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For couples seeking to conceive, offer advice on reducing the risk of schizophrenia in their child
I explained to them that schizophrenia is a neurodevelopmental syndrome that comprises hundreds of different disorders of genetic or non-genetic etiology, all of which share a similar psychotic phenotype. Although the various genetic causes of schizophrenia are difficult to prevent—but may be prevented in the future with epigenetic techniques—the many non-genetic (environmental) pathways to schizophrenia can be avoided to significantly reduce the incidence of schizophrenia by 40% to 50%, according to some estimates.
I will share what I told this couple, because even couples without any family history of psychosis may have a child who develops schizophrenia because of a variety of environmental risk factors.
Genetic risk factors
One-half of the 20,000 genes in the 23 chromosomes of the human genome participate in constructing and sculpting the extremely intricate and complex human brain. There are many ways that genetic factors can increase the risk of schizophrenia,1 and only some are transmitted by parents:
Risk genes. More than 30 risk genes have been identified as heritable in schizophrenia. They are spread over many chromosomes and more are likely to be discovered. Most of those risk genes regulate glutamate— not dopamine—pathways, and each increases the risk by 2% to 4%.
Copy number variations (CNVs) are produced via meiosis mishaps, where 1 or 3 alleles of certain genes are formed instead of the usual 2. A high frequency of CNVs have been found in schizophrenia compared with the general population—but also are found in autism and bipolar disorders—and are believed to disrupt brain development in various ways.
De novo mutations. Recent studies on large samples of people with schizophrenia (50,000 to 100,000) uncovered a much higher rate of mutations (some code for proteins while others are nonsense mutations that code for nothing). Obviously, these mutations led to anomalous neurodevelopment.
There are hundreds, maybe thousands, of genetic subtypes within the schizophrenia syndrome. Advances in epigenetics, which allow silencing of culprit genes or overexpression of protective genes, one day may enable psychiatric geneticists to prevent schizophrenia in fetuses at risk.
Non-genetic risk factors
Just as with the genetic patho-genic heterogeneity, the schizophrenia syndrome can be caused by numerous environmental adverse events,2 many of which can be avoided, including:
Older paternal age (>45) at time of conception doubles or triples the risk of schizophrenia3 as well as autism and bipolar disorder. Aging sperm are associated with a higher rate of DNA fragmentation and genetic mutations.
Prenatal complications, especially during the second trimester when CNS development takes place. These adverse prenatal events skew fetal brain development to produce psychosis in adulthood and can be minimized with optimal prenatal care, which sadly is lacking among the poor. These include:
• Vaginal infections before pregnancy,4 such as herpes simplex virus, can cause fetal brain inflammation and increased risk of schizophrenia.
• Infections during pregnancy— whether bacterial, viral, or protozoan (Toxoplasma gondii)—have been shown to significantly increase the risk of schizophrenia in offspring.5 An increase in serum C-reactive protein during pregnancy also is a biomarker of increased risk.
• Poor diet, especially starvation, can double or triple the risk of schizophrenia.
• Vitamin deficiency, especially folate and vitamin D, are critical for normal brain development.6 Vitamin D is vital to mitigate neuroinflammation.
• Smoking before and during pregnancy.4
• Medical illness during pregnancy, especially gestational diabetes, increases the risk of schizophrenia in the fetus by 800%.7
• Severe stress during pregnancy, such as the death of the spouse, doubles the risk of schizophrenia.2
• Schizophrenia risk is 400% to 500% higher among those born and raised in an urban area, compared with a rural area.8
• Babies born in northern latitudes, such as in Sweden, Norway, or Canada, have a 10-fold risk of schizophrenia in adulthood compared with babies born near the equator.6 This has been attributed to lack of sunshine and the risk of severe vitamin D deficiency in northern latitudes.
• High maternal body mass index during the first trimester7 increases the child’s risk of schizophrenia.
• Low number of prenatal visits is associated with higher risk of schizophrenia.
• Obstetric complications that cause hypoxia and a low Apgar score after birth increase the risk of schizophrenia. This includes long labor, cord around the neck, meconium spillage into the amniotic fluid, and mechanical injury with forceps delivery.
• Infection in the newborn shortly after birth.
Severe physical or sexual abuse before age 5 is associated with increased risk of schizophrenia in adulthood.2 This may be because of stress-induced epigenetic mechanisms (silencing or overexpressing certain genes).
Migration has been shown to increase the risk of schizophrenia by 3 to 5 fold. The exact reason is unclear, but it could be a combination of social stress, exposure to new types of germs, less sunshine, and even a different diet.
My advice to the couple? Get a good obstetrician well before conception; get the mother immunized against infections; eat a lot of fish (omega-3 fatty acids); take adequate doses of folate and vitamin D, perhaps even choline9; avoid smoking before and during pregnancy; adopt a healthy, balanced diet; avoid excessive weight gain and/or gestational diabetes; avoid contact with people with infections; avoid exposure to cat feces (toxoplasmosis); schedule frequent prenatal visits; and hope for a smooth and uneventful delivery and a newborn with an Apgar score of 9 or 10. All this will greatly reduce the non-genetic risks of schizophrenia, but is unlikely to modify the genetic risks. However, it has been shown that a combination of both genetic and non-genetic risk factors is associated with a more severe form of schizophrenia.10
Optimal prenatal and postnatal care can be helpful for couples with a family history of schizophrenia (without moving to deliver their baby in a rural village near the equator). However, if their child starts using marijuana during adolescence, all bets are off. The risk of schizophrenia and serious cortical tissue loss increases dramatically when a carrier of risk genes use Cannabis. But that’s another editorial, to be read by clinicians in states where marijuana has been (foolishly, I believe) legalized.
1. Rodriguez-Murillo L, Gogos JA, Karayiorgou M. The genetic architecture of schizophrenia: new mutations and emerging paradigms. Annu Rev Med. 2012;63:63-80.
2. van Os J, Kenis G, Rutten BP. The environment and schizophrenia. Nature. 2010;468(7321):203-212.
3. Brown AS, Schefer CA, Wyatt RJ, et al. Paternal age and risk of schizophrenia in adult offspring. Am J Psychiatry. 2002;159(9):1528-1533.
4. Betts KS, Williams GM, Najman JM, et al. Maternal prenatal infection, early susceptibility to illness and adult psychotic experiences: a birth cohort study. Schizophr Res. 2014;156(2- 3):161-167.
5. Brown AS, Derkits EJ. Prental infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry. 2010;167(3):261-280.
6. Kinney DK, Teixeira P, Hsu D, et al. Relation of schizophrenia prevalence to latitude, climate, fish consumption, infant mortality, and skin color: a role for prenatal vitamin d deficiency and infections? Schizophr Bull. 2009;35(3): 582-595.
7. Kawai M, Minabe Y, Takagai S, et al. Poor maternal care and high maternal body mass index in pregnancy as a risk factor for schizophrenia in offspring. Acta Psychiatry Scand. 2004;110(4):257-263.
8. Kelly BD, O’Callaghan E, Waddington JL, et al. Schizophrenia and the city: a review of literature and prospective study of psychosis and urbanicity in Ireland. Schizophr Res. 2010;116(1):75-89.
9. Ross RG, Hunter SK, McCarthy L, et al. Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk. Am J Psychiatry. 2013; 170(3):290-298.
10. Maynard TM, Sikich L, Lieberman JA, et al. Neural development, cell-cell signaling, and the “two-hit” hypothesis of schizophrenia. Schizophr Bull. 2001;27(3): 457-476.
I explained to them that schizophrenia is a neurodevelopmental syndrome that comprises hundreds of different disorders of genetic or non-genetic etiology, all of which share a similar psychotic phenotype. Although the various genetic causes of schizophrenia are difficult to prevent—but may be prevented in the future with epigenetic techniques—the many non-genetic (environmental) pathways to schizophrenia can be avoided to significantly reduce the incidence of schizophrenia by 40% to 50%, according to some estimates.
I will share what I told this couple, because even couples without any family history of psychosis may have a child who develops schizophrenia because of a variety of environmental risk factors.
Genetic risk factors
One-half of the 20,000 genes in the 23 chromosomes of the human genome participate in constructing and sculpting the extremely intricate and complex human brain. There are many ways that genetic factors can increase the risk of schizophrenia,1 and only some are transmitted by parents:
Risk genes. More than 30 risk genes have been identified as heritable in schizophrenia. They are spread over many chromosomes and more are likely to be discovered. Most of those risk genes regulate glutamate— not dopamine—pathways, and each increases the risk by 2% to 4%.
Copy number variations (CNVs) are produced via meiosis mishaps, where 1 or 3 alleles of certain genes are formed instead of the usual 2. A high frequency of CNVs have been found in schizophrenia compared with the general population—but also are found in autism and bipolar disorders—and are believed to disrupt brain development in various ways.
De novo mutations. Recent studies on large samples of people with schizophrenia (50,000 to 100,000) uncovered a much higher rate of mutations (some code for proteins while others are nonsense mutations that code for nothing). Obviously, these mutations led to anomalous neurodevelopment.
There are hundreds, maybe thousands, of genetic subtypes within the schizophrenia syndrome. Advances in epigenetics, which allow silencing of culprit genes or overexpression of protective genes, one day may enable psychiatric geneticists to prevent schizophrenia in fetuses at risk.
Non-genetic risk factors
Just as with the genetic patho-genic heterogeneity, the schizophrenia syndrome can be caused by numerous environmental adverse events,2 many of which can be avoided, including:
Older paternal age (>45) at time of conception doubles or triples the risk of schizophrenia3 as well as autism and bipolar disorder. Aging sperm are associated with a higher rate of DNA fragmentation and genetic mutations.
Prenatal complications, especially during the second trimester when CNS development takes place. These adverse prenatal events skew fetal brain development to produce psychosis in adulthood and can be minimized with optimal prenatal care, which sadly is lacking among the poor. These include:
• Vaginal infections before pregnancy,4 such as herpes simplex virus, can cause fetal brain inflammation and increased risk of schizophrenia.
• Infections during pregnancy— whether bacterial, viral, or protozoan (Toxoplasma gondii)—have been shown to significantly increase the risk of schizophrenia in offspring.5 An increase in serum C-reactive protein during pregnancy also is a biomarker of increased risk.
• Poor diet, especially starvation, can double or triple the risk of schizophrenia.
• Vitamin deficiency, especially folate and vitamin D, are critical for normal brain development.6 Vitamin D is vital to mitigate neuroinflammation.
• Smoking before and during pregnancy.4
• Medical illness during pregnancy, especially gestational diabetes, increases the risk of schizophrenia in the fetus by 800%.7
• Severe stress during pregnancy, such as the death of the spouse, doubles the risk of schizophrenia.2
• Schizophrenia risk is 400% to 500% higher among those born and raised in an urban area, compared with a rural area.8
• Babies born in northern latitudes, such as in Sweden, Norway, or Canada, have a 10-fold risk of schizophrenia in adulthood compared with babies born near the equator.6 This has been attributed to lack of sunshine and the risk of severe vitamin D deficiency in northern latitudes.
• High maternal body mass index during the first trimester7 increases the child’s risk of schizophrenia.
• Low number of prenatal visits is associated with higher risk of schizophrenia.
• Obstetric complications that cause hypoxia and a low Apgar score after birth increase the risk of schizophrenia. This includes long labor, cord around the neck, meconium spillage into the amniotic fluid, and mechanical injury with forceps delivery.
• Infection in the newborn shortly after birth.
Severe physical or sexual abuse before age 5 is associated with increased risk of schizophrenia in adulthood.2 This may be because of stress-induced epigenetic mechanisms (silencing or overexpressing certain genes).
Migration has been shown to increase the risk of schizophrenia by 3 to 5 fold. The exact reason is unclear, but it could be a combination of social stress, exposure to new types of germs, less sunshine, and even a different diet.
My advice to the couple? Get a good obstetrician well before conception; get the mother immunized against infections; eat a lot of fish (omega-3 fatty acids); take adequate doses of folate and vitamin D, perhaps even choline9; avoid smoking before and during pregnancy; adopt a healthy, balanced diet; avoid excessive weight gain and/or gestational diabetes; avoid contact with people with infections; avoid exposure to cat feces (toxoplasmosis); schedule frequent prenatal visits; and hope for a smooth and uneventful delivery and a newborn with an Apgar score of 9 or 10. All this will greatly reduce the non-genetic risks of schizophrenia, but is unlikely to modify the genetic risks. However, it has been shown that a combination of both genetic and non-genetic risk factors is associated with a more severe form of schizophrenia.10
Optimal prenatal and postnatal care can be helpful for couples with a family history of schizophrenia (without moving to deliver their baby in a rural village near the equator). However, if their child starts using marijuana during adolescence, all bets are off. The risk of schizophrenia and serious cortical tissue loss increases dramatically when a carrier of risk genes use Cannabis. But that’s another editorial, to be read by clinicians in states where marijuana has been (foolishly, I believe) legalized.
I explained to them that schizophrenia is a neurodevelopmental syndrome that comprises hundreds of different disorders of genetic or non-genetic etiology, all of which share a similar psychotic phenotype. Although the various genetic causes of schizophrenia are difficult to prevent—but may be prevented in the future with epigenetic techniques—the many non-genetic (environmental) pathways to schizophrenia can be avoided to significantly reduce the incidence of schizophrenia by 40% to 50%, according to some estimates.
I will share what I told this couple, because even couples without any family history of psychosis may have a child who develops schizophrenia because of a variety of environmental risk factors.
Genetic risk factors
One-half of the 20,000 genes in the 23 chromosomes of the human genome participate in constructing and sculpting the extremely intricate and complex human brain. There are many ways that genetic factors can increase the risk of schizophrenia,1 and only some are transmitted by parents:
Risk genes. More than 30 risk genes have been identified as heritable in schizophrenia. They are spread over many chromosomes and more are likely to be discovered. Most of those risk genes regulate glutamate— not dopamine—pathways, and each increases the risk by 2% to 4%.
Copy number variations (CNVs) are produced via meiosis mishaps, where 1 or 3 alleles of certain genes are formed instead of the usual 2. A high frequency of CNVs have been found in schizophrenia compared with the general population—but also are found in autism and bipolar disorders—and are believed to disrupt brain development in various ways.
De novo mutations. Recent studies on large samples of people with schizophrenia (50,000 to 100,000) uncovered a much higher rate of mutations (some code for proteins while others are nonsense mutations that code for nothing). Obviously, these mutations led to anomalous neurodevelopment.
There are hundreds, maybe thousands, of genetic subtypes within the schizophrenia syndrome. Advances in epigenetics, which allow silencing of culprit genes or overexpression of protective genes, one day may enable psychiatric geneticists to prevent schizophrenia in fetuses at risk.
Non-genetic risk factors
Just as with the genetic patho-genic heterogeneity, the schizophrenia syndrome can be caused by numerous environmental adverse events,2 many of which can be avoided, including:
Older paternal age (>45) at time of conception doubles or triples the risk of schizophrenia3 as well as autism and bipolar disorder. Aging sperm are associated with a higher rate of DNA fragmentation and genetic mutations.
Prenatal complications, especially during the second trimester when CNS development takes place. These adverse prenatal events skew fetal brain development to produce psychosis in adulthood and can be minimized with optimal prenatal care, which sadly is lacking among the poor. These include:
• Vaginal infections before pregnancy,4 such as herpes simplex virus, can cause fetal brain inflammation and increased risk of schizophrenia.
• Infections during pregnancy— whether bacterial, viral, or protozoan (Toxoplasma gondii)—have been shown to significantly increase the risk of schizophrenia in offspring.5 An increase in serum C-reactive protein during pregnancy also is a biomarker of increased risk.
• Poor diet, especially starvation, can double or triple the risk of schizophrenia.
• Vitamin deficiency, especially folate and vitamin D, are critical for normal brain development.6 Vitamin D is vital to mitigate neuroinflammation.
• Smoking before and during pregnancy.4
• Medical illness during pregnancy, especially gestational diabetes, increases the risk of schizophrenia in the fetus by 800%.7
• Severe stress during pregnancy, such as the death of the spouse, doubles the risk of schizophrenia.2
• Schizophrenia risk is 400% to 500% higher among those born and raised in an urban area, compared with a rural area.8
• Babies born in northern latitudes, such as in Sweden, Norway, or Canada, have a 10-fold risk of schizophrenia in adulthood compared with babies born near the equator.6 This has been attributed to lack of sunshine and the risk of severe vitamin D deficiency in northern latitudes.
• High maternal body mass index during the first trimester7 increases the child’s risk of schizophrenia.
• Low number of prenatal visits is associated with higher risk of schizophrenia.
• Obstetric complications that cause hypoxia and a low Apgar score after birth increase the risk of schizophrenia. This includes long labor, cord around the neck, meconium spillage into the amniotic fluid, and mechanical injury with forceps delivery.
• Infection in the newborn shortly after birth.
Severe physical or sexual abuse before age 5 is associated with increased risk of schizophrenia in adulthood.2 This may be because of stress-induced epigenetic mechanisms (silencing or overexpressing certain genes).
Migration has been shown to increase the risk of schizophrenia by 3 to 5 fold. The exact reason is unclear, but it could be a combination of social stress, exposure to new types of germs, less sunshine, and even a different diet.
My advice to the couple? Get a good obstetrician well before conception; get the mother immunized against infections; eat a lot of fish (omega-3 fatty acids); take adequate doses of folate and vitamin D, perhaps even choline9; avoid smoking before and during pregnancy; adopt a healthy, balanced diet; avoid excessive weight gain and/or gestational diabetes; avoid contact with people with infections; avoid exposure to cat feces (toxoplasmosis); schedule frequent prenatal visits; and hope for a smooth and uneventful delivery and a newborn with an Apgar score of 9 or 10. All this will greatly reduce the non-genetic risks of schizophrenia, but is unlikely to modify the genetic risks. However, it has been shown that a combination of both genetic and non-genetic risk factors is associated with a more severe form of schizophrenia.10
Optimal prenatal and postnatal care can be helpful for couples with a family history of schizophrenia (without moving to deliver their baby in a rural village near the equator). However, if their child starts using marijuana during adolescence, all bets are off. The risk of schizophrenia and serious cortical tissue loss increases dramatically when a carrier of risk genes use Cannabis. But that’s another editorial, to be read by clinicians in states where marijuana has been (foolishly, I believe) legalized.
1. Rodriguez-Murillo L, Gogos JA, Karayiorgou M. The genetic architecture of schizophrenia: new mutations and emerging paradigms. Annu Rev Med. 2012;63:63-80.
2. van Os J, Kenis G, Rutten BP. The environment and schizophrenia. Nature. 2010;468(7321):203-212.
3. Brown AS, Schefer CA, Wyatt RJ, et al. Paternal age and risk of schizophrenia in adult offspring. Am J Psychiatry. 2002;159(9):1528-1533.
4. Betts KS, Williams GM, Najman JM, et al. Maternal prenatal infection, early susceptibility to illness and adult psychotic experiences: a birth cohort study. Schizophr Res. 2014;156(2- 3):161-167.
5. Brown AS, Derkits EJ. Prental infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry. 2010;167(3):261-280.
6. Kinney DK, Teixeira P, Hsu D, et al. Relation of schizophrenia prevalence to latitude, climate, fish consumption, infant mortality, and skin color: a role for prenatal vitamin d deficiency and infections? Schizophr Bull. 2009;35(3): 582-595.
7. Kawai M, Minabe Y, Takagai S, et al. Poor maternal care and high maternal body mass index in pregnancy as a risk factor for schizophrenia in offspring. Acta Psychiatry Scand. 2004;110(4):257-263.
8. Kelly BD, O’Callaghan E, Waddington JL, et al. Schizophrenia and the city: a review of literature and prospective study of psychosis and urbanicity in Ireland. Schizophr Res. 2010;116(1):75-89.
9. Ross RG, Hunter SK, McCarthy L, et al. Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk. Am J Psychiatry. 2013; 170(3):290-298.
10. Maynard TM, Sikich L, Lieberman JA, et al. Neural development, cell-cell signaling, and the “two-hit” hypothesis of schizophrenia. Schizophr Bull. 2001;27(3): 457-476.
1. Rodriguez-Murillo L, Gogos JA, Karayiorgou M. The genetic architecture of schizophrenia: new mutations and emerging paradigms. Annu Rev Med. 2012;63:63-80.
2. van Os J, Kenis G, Rutten BP. The environment and schizophrenia. Nature. 2010;468(7321):203-212.
3. Brown AS, Schefer CA, Wyatt RJ, et al. Paternal age and risk of schizophrenia in adult offspring. Am J Psychiatry. 2002;159(9):1528-1533.
4. Betts KS, Williams GM, Najman JM, et al. Maternal prenatal infection, early susceptibility to illness and adult psychotic experiences: a birth cohort study. Schizophr Res. 2014;156(2- 3):161-167.
5. Brown AS, Derkits EJ. Prental infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry. 2010;167(3):261-280.
6. Kinney DK, Teixeira P, Hsu D, et al. Relation of schizophrenia prevalence to latitude, climate, fish consumption, infant mortality, and skin color: a role for prenatal vitamin d deficiency and infections? Schizophr Bull. 2009;35(3): 582-595.
7. Kawai M, Minabe Y, Takagai S, et al. Poor maternal care and high maternal body mass index in pregnancy as a risk factor for schizophrenia in offspring. Acta Psychiatry Scand. 2004;110(4):257-263.
8. Kelly BD, O’Callaghan E, Waddington JL, et al. Schizophrenia and the city: a review of literature and prospective study of psychosis and urbanicity in Ireland. Schizophr Res. 2010;116(1):75-89.
9. Ross RG, Hunter SK, McCarthy L, et al. Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk. Am J Psychiatry. 2013; 170(3):290-298.
10. Maynard TM, Sikich L, Lieberman JA, et al. Neural development, cell-cell signaling, and the “two-hit” hypothesis of schizophrenia. Schizophr Bull. 2001;27(3): 457-476.
Post-World War II psychiatry: 70 years of momentous change
A large percentage of psychiatrists practicing today are Boomers, and have experienced the tumultuous change in their profession since the end of World War II. At a recent Grand Rounds presentation in the Department of Neurology & Psychiatry at Saint Louis University, participants examined major changes and paradigm shifts that have reshaped psychiatry since 1946. The audience, which included me, contributed historical observations to the list of those changes and shifts, which I’ve classified here for your benefit, whether or not you are a Boomer.
Medical advances
Consider these discoveries and developments:
• Penicillin in 1947, which led to a reduction in cases of psychosis caused by tertiary syphilis, a disease that accounted for 10% to 15% of state hospital admissions.
• Lithium in 1948, the first pharmaceutical treatment for mania.
• Chlorpromazine, the first antipsychotic drug, in 1952, launching the psychopharmacology era and ending lifetime institutional sequestration as the only “treatment” for serious mental disorders.
• Monoamine oxidase inhibitors in 1959, from observations that iproniazid, a drug used in tuberculosis sanitariums, improved the mood of tuberculosis patients. This was the first pharmacotherapy for depression, which had been treated with electroconvulsive therapy (ECT), developed in the 1930s.
• Tricyclic antidepressants, starting with imipramine in the late 1950s, during attempts to synthesize additional phenothiazine antipsychotics.
• Diazepam, introduced in 1963 for its anti-anxiety effects, became the most widely used drug in the world over the next 2 decades.
• Pre-frontal lobotomy to treat severe psychiatric disorders. The neurosurgeon-inventor of this so-called medical advance won the 1949 Nobel Prize for Medicine or Physiology. The procedure was rapidly discredited after the development of antipsychotic drugs.
• Fluoxetine, the first selective serotonin reuptake inhibitor, in 1987, revolutionized the treatment of depression, especially in primary care settings.
• Clozapine, as an effective treatment for refractory and suicidal schizophrenia, and the spawning of second-generation antipsychotics. These newer agents shifted focus from neurologic adverse effects (extrapyramidal symptoms, tardive dyskinesia) to cardio-metabolic side effects (obesity, diabetes, dyslipidemia, and hypertension).
Changes to the landscape of health care
Three noteworthy developments made the list:
• The Community Mental Health Act of 1963, signed into law by President John F. Kennedy, revolutionized psychiatric care by shifting delivery of care from inpatient, hospital-based facilities to outpatient, clinic-based centers. There are now close to 800 community mental health centers in the United States, where care is dominated by non-physician mental health providers—in contrast to the era of state hospitals, during which physicians and nurses provided care for mentally ill patients.
• Deinstitutionalization. This move-ment gathered momentum in the 1970s and 1980s, leading to closing of the majority of state hospitals, with tragic consequences for the seriously mentally ill—including early demise, homelessness, substance abuse, and incarceration. In fact, the large percentage of mentally ill people in U.S. jails and prisons, instead of in a hospital, represents what has been labeled trans-institutionalization (see my March 2008 editorial, “Bring back the asylums?,” available at CurrentPsychiatry.com).
• Managed care, emerging in the late 1980s and early 1990s, caused a seismic disturbance in the delivery of, and reimbursement for, psychiatric care. The result was a significant decline in access to, and quality of, care—especially the so-called carve-out model that reduced payment for psychiatric care even more drastically than for general medical care. Under managed care, the priority became saving money, rather than saving lives. Average hospital stay for patients who had a psychiatric disorder, which was years in the pre-pharmacotherapy era, and weeks or months after that, shrunk to a few days under managed care.
Changes in professional direction
Two major shifts in the complexion of the specialty were identified:
• The decline of psychoanalysis, which had dominated psychiatry for decades (the 1940s through the 1970s), was a major shift in the conceptualization, training, and delivery of care in psychiatry. The rise of biological psychiatry and the medical model of psychiatric brain disorders, as well as the emergence of evidence-based (and briefer) psychotherapies (eg, cognitive-behavioral therapy, dialectical behavior therapy, and interpersonal therapy), gradually replaced the Freudian model of mental illness.
As a result, it became no longer necessary to be a certified psychoanalyst to be named chair of a department of psychiatry. The impact of this change on psychiatric training has been profound, because medical management by psychiatrists superseded psychotherapy— given the brief hospitalization that is required and the diminishing coverage for psychotherapy by insurers.
• Delegation of psychosocial treatments to non-psychiatrists. The unintended consequences of psychiatrists’ change of focus to 1) consultation on medical/surgical patients and 2) the medical evaluation, diagnosis, and pharmacotherapy of mental disorders led to the so-called “dual treatment model” for the most seriously mentally ill patients: The physician provides medical management and non-physician mental health professionals provide counseling, psychosocial therapy, and rehabilitation.
Disruptive breakthroughs
Several are notable:
• National Institute of Mental Health (NIMH). Establishment of NIMH in April 1949 was a major step toward funding research into psychiatric disorders. Billions of dollars have been invested to generate knowledge about the causes, treatment, course, and prevention of mental illness. No other country has spent as much on psychiatric research. It would have been nearly impossible to discover what we know today without the work of NIMH.
• Neuroscience. The meteoric rise of neuroscience from the 1960s to the present has had a dramatic effect, transforming old psychiatry and the study and therapy of the mind to a focus on the brain-mind continuum and the prospects of brain repair and neuroplasticity. Psychiatry is now regarded as a clinical neuroscience specialty of brain disorders that manifest as changes in thought, affect, mood, cognition, and behavior.
• Brain imaging. Techniques developed since the 1970s—the veritable alphabet soup of CT, PET, SPECT, MRI, MRS, fMRI, and DTI— has revolutionized understanding of brain structure and function in all psychiatric disorders but especially in psychotic and mood disorders.
• Molecular genetics. Advances over the past 2 decades have shed unprecedented light on the complex genetics of psychiatric disorders. It is becoming apparent that most psychiatric disorders are caused via gene-by-environment interaction; etiology is therefore a consequence of genetic and non-genetic variables. Risk genes, copy number variants, and de novo mutations are being discovered almost weekly, and progress in epigenetics holds promise for preventing medical disorders, including psychiatric illness.
• Neuromodulation. Advances represent an important paradigm shift, from pharmacotherapy to brain stimulation. Several techniques have been approved by the FDA, including transcranial magnetic stimulation, vagus nerve stimulation, and deep brain stimulation, to supplement, and perhaps eventually supplant, ECT.
Legal intrusiveness
No other medical specialty has been subject to laws governing clinical practice as psychiatry has been. Progressive intrusion of laws (ostensibly, enacted to protect the civil rights of “the disabled”) ends up hurting patients who refuse admission and then often harm themselves or others or decline urgent treatment, which can be associated with loss of brain tissue in acute psychotic, manic, and depressed states. No legal shackles apply to treating unconscious stroke patients, delirious geriatric patients, or semiconscious myocardial infarction patients when they are admitted to a hospital.
Distortions of the anti-psychiatry movement
The antipsychiatry movement preceded the Baby Boomer era by a century but has continued unabated. The movement gained momentum and became more defamatory after release of the movie One Flew Over the Cuckoo’s Nest in 1975, which portrayed psychiatry in a purely negative light. Despite progress in public understanding of psychiatry, and tangible improvements in practice, the stigma of mental illness persists. Media portrayals, including motion pictures, continue to distort the good that psychiatrists do for their patients.
Gender and sexuality
• Gender distribution of psychiatrists. A major shift occurred over the past 7 decades, reflecting the same pattern that has been documented in other medical specialties. At least one-half of psychiatry residents are now women—a welcome change from the pre-1946 era, when nearly all psychiatrists were men. This demographic transformation has had an impact on the dynamics of psychiatric practice.
• Acceptance and depathologization of homosexuality. Until 1974, homosexuality was considered a psychiatric disorder, and many homosexual persons sought treatment. That year, membership of the American Psychiatric Association voted to remove homosexuality from DSM-II and to no longer regard it as a behavioral abnormality. This was a huge step toward de-pathologizing same-sex orientation and love, and might have been the major impetus for the progressive social acceptance of gay, lesbian, and transgendered people over the past 4 decades.
The DSM paradigm shift in psychiatric diagnosis
• DSM-III. Perhaps the most radical change in the diagnostic criteria of psychiatric disorders occurred in 1980, with introduction of DSM-III to replace DSM-I and DSM-II, which were absurdly vague, unreliable, and with poor validity.
The move toward more operational and reliable diagnostic requirements began with the Research Diagnostic Criteria, developed by the Department of Psychiatry at Washington University in St. Louis. DSM-III represented a complete paradigm shift in psychiatric diagnosis. Subsequent editions maintained the same methodology, with relatively modest changes. The field expects continued evolution in DSM diagnostic criteria, including the future inclusion of biomarkers, based on sound, controlled studies.
• Recognizing PTSD. Develop-ment of posttraumatic stress disorder (PTSD) as a diagnostic entity, and its inclusion in DSM-III, were major changes in psychiatric nosology. At last, the old terms—shell shock, battle fatigue, neurasthenia—were legitimized as a recognizable syndrome secondary to major life trauma, including war and rape. That legitimacy has instigated substantial clinical and research interest in identifying how serious psychopathology can be triggered by life events.
Pharmaceutical industry debacle
Few industries have fallen so far from grace in the eyes of psychiatric professionals and the public as the manufacturers of psychotropic drugs.
At the dawn of the psychopharmacology era (the 1950s, 1960s, and 1970s) pharmaceutical companies were respected and regarded by physicians and patients as a vital partner in health care for their discovery and development of medications to treat psychiatric disorders. That image was tarnished in the 1990s, however, with the approval and release of several atypical antipsychotics. Cutthroat competition, questionable publication methods, concealment of negative findings, and excessive spending on marketing, including FDA-approved educational programs for clinicians on efficacy, safety, and dosing, all contributed to escalating cynicism about the industry. Academic faculty who received research grants to conduct FDA-required clinical trials of new agents were painted with the same brush.
Disclosure of potential conflict of interest became a mandatory procedure at universities and for NIMH grant applicants and journal publishers. Class-action lawsuits against companies that manufacture second-generation antipsychotics—filed for lack of transparency about metabolic side effects—exacerbated the intensity of criticism and condemnation.
Although new drug development has become measurably more rigorous and ethical because of self-regulation, combined with vigorous government scrutiny and regulation, demonization of the pharmaceutical industry remains unabated. That might be the reason why several major pharmaceutical companies have abandoned research and development of psychotropic drugs. That is likely to impede progress in psychopharmacotherapeutics; after all, no other private or government entity develops drugs for patients who have a psychiatric illness. The need for such agents is great: There is no FDA-indicated drug for the majority of DSM-5 diagnoses.
We entrust the future to next generations
Momentous events have transformed psychiatry during the lifespan of Baby Boomers like me and many of you. Because the cohort of 80 million Baby Boomers has comprised a significant percentage of the nation’s scientists, media representatives, members of the American Psychiatric Association, academicians, and community leaders over the past few decades, it is conceivable that the Baby Boomer generation helped trigger most of the transformative changes in psychiatry we have seen over the past 70 years.
I can only wonder: What direction will psychiatry take in the age of Generation X, Generation Y, and the Millennials? Only this is certain: Psychiatry will continue to evolve— long after Baby Boomers are gone.
A large percentage of psychiatrists practicing today are Boomers, and have experienced the tumultuous change in their profession since the end of World War II. At a recent Grand Rounds presentation in the Department of Neurology & Psychiatry at Saint Louis University, participants examined major changes and paradigm shifts that have reshaped psychiatry since 1946. The audience, which included me, contributed historical observations to the list of those changes and shifts, which I’ve classified here for your benefit, whether or not you are a Boomer.
Medical advances
Consider these discoveries and developments:
• Penicillin in 1947, which led to a reduction in cases of psychosis caused by tertiary syphilis, a disease that accounted for 10% to 15% of state hospital admissions.
• Lithium in 1948, the first pharmaceutical treatment for mania.
• Chlorpromazine, the first antipsychotic drug, in 1952, launching the psychopharmacology era and ending lifetime institutional sequestration as the only “treatment” for serious mental disorders.
• Monoamine oxidase inhibitors in 1959, from observations that iproniazid, a drug used in tuberculosis sanitariums, improved the mood of tuberculosis patients. This was the first pharmacotherapy for depression, which had been treated with electroconvulsive therapy (ECT), developed in the 1930s.
• Tricyclic antidepressants, starting with imipramine in the late 1950s, during attempts to synthesize additional phenothiazine antipsychotics.
• Diazepam, introduced in 1963 for its anti-anxiety effects, became the most widely used drug in the world over the next 2 decades.
• Pre-frontal lobotomy to treat severe psychiatric disorders. The neurosurgeon-inventor of this so-called medical advance won the 1949 Nobel Prize for Medicine or Physiology. The procedure was rapidly discredited after the development of antipsychotic drugs.
• Fluoxetine, the first selective serotonin reuptake inhibitor, in 1987, revolutionized the treatment of depression, especially in primary care settings.
• Clozapine, as an effective treatment for refractory and suicidal schizophrenia, and the spawning of second-generation antipsychotics. These newer agents shifted focus from neurologic adverse effects (extrapyramidal symptoms, tardive dyskinesia) to cardio-metabolic side effects (obesity, diabetes, dyslipidemia, and hypertension).
Changes to the landscape of health care
Three noteworthy developments made the list:
• The Community Mental Health Act of 1963, signed into law by President John F. Kennedy, revolutionized psychiatric care by shifting delivery of care from inpatient, hospital-based facilities to outpatient, clinic-based centers. There are now close to 800 community mental health centers in the United States, where care is dominated by non-physician mental health providers—in contrast to the era of state hospitals, during which physicians and nurses provided care for mentally ill patients.
• Deinstitutionalization. This move-ment gathered momentum in the 1970s and 1980s, leading to closing of the majority of state hospitals, with tragic consequences for the seriously mentally ill—including early demise, homelessness, substance abuse, and incarceration. In fact, the large percentage of mentally ill people in U.S. jails and prisons, instead of in a hospital, represents what has been labeled trans-institutionalization (see my March 2008 editorial, “Bring back the asylums?,” available at CurrentPsychiatry.com).
• Managed care, emerging in the late 1980s and early 1990s, caused a seismic disturbance in the delivery of, and reimbursement for, psychiatric care. The result was a significant decline in access to, and quality of, care—especially the so-called carve-out model that reduced payment for psychiatric care even more drastically than for general medical care. Under managed care, the priority became saving money, rather than saving lives. Average hospital stay for patients who had a psychiatric disorder, which was years in the pre-pharmacotherapy era, and weeks or months after that, shrunk to a few days under managed care.
Changes in professional direction
Two major shifts in the complexion of the specialty were identified:
• The decline of psychoanalysis, which had dominated psychiatry for decades (the 1940s through the 1970s), was a major shift in the conceptualization, training, and delivery of care in psychiatry. The rise of biological psychiatry and the medical model of psychiatric brain disorders, as well as the emergence of evidence-based (and briefer) psychotherapies (eg, cognitive-behavioral therapy, dialectical behavior therapy, and interpersonal therapy), gradually replaced the Freudian model of mental illness.
As a result, it became no longer necessary to be a certified psychoanalyst to be named chair of a department of psychiatry. The impact of this change on psychiatric training has been profound, because medical management by psychiatrists superseded psychotherapy— given the brief hospitalization that is required and the diminishing coverage for psychotherapy by insurers.
• Delegation of psychosocial treatments to non-psychiatrists. The unintended consequences of psychiatrists’ change of focus to 1) consultation on medical/surgical patients and 2) the medical evaluation, diagnosis, and pharmacotherapy of mental disorders led to the so-called “dual treatment model” for the most seriously mentally ill patients: The physician provides medical management and non-physician mental health professionals provide counseling, psychosocial therapy, and rehabilitation.
Disruptive breakthroughs
Several are notable:
• National Institute of Mental Health (NIMH). Establishment of NIMH in April 1949 was a major step toward funding research into psychiatric disorders. Billions of dollars have been invested to generate knowledge about the causes, treatment, course, and prevention of mental illness. No other country has spent as much on psychiatric research. It would have been nearly impossible to discover what we know today without the work of NIMH.
• Neuroscience. The meteoric rise of neuroscience from the 1960s to the present has had a dramatic effect, transforming old psychiatry and the study and therapy of the mind to a focus on the brain-mind continuum and the prospects of brain repair and neuroplasticity. Psychiatry is now regarded as a clinical neuroscience specialty of brain disorders that manifest as changes in thought, affect, mood, cognition, and behavior.
• Brain imaging. Techniques developed since the 1970s—the veritable alphabet soup of CT, PET, SPECT, MRI, MRS, fMRI, and DTI— has revolutionized understanding of brain structure and function in all psychiatric disorders but especially in psychotic and mood disorders.
• Molecular genetics. Advances over the past 2 decades have shed unprecedented light on the complex genetics of psychiatric disorders. It is becoming apparent that most psychiatric disorders are caused via gene-by-environment interaction; etiology is therefore a consequence of genetic and non-genetic variables. Risk genes, copy number variants, and de novo mutations are being discovered almost weekly, and progress in epigenetics holds promise for preventing medical disorders, including psychiatric illness.
• Neuromodulation. Advances represent an important paradigm shift, from pharmacotherapy to brain stimulation. Several techniques have been approved by the FDA, including transcranial magnetic stimulation, vagus nerve stimulation, and deep brain stimulation, to supplement, and perhaps eventually supplant, ECT.
Legal intrusiveness
No other medical specialty has been subject to laws governing clinical practice as psychiatry has been. Progressive intrusion of laws (ostensibly, enacted to protect the civil rights of “the disabled”) ends up hurting patients who refuse admission and then often harm themselves or others or decline urgent treatment, which can be associated with loss of brain tissue in acute psychotic, manic, and depressed states. No legal shackles apply to treating unconscious stroke patients, delirious geriatric patients, or semiconscious myocardial infarction patients when they are admitted to a hospital.
Distortions of the anti-psychiatry movement
The antipsychiatry movement preceded the Baby Boomer era by a century but has continued unabated. The movement gained momentum and became more defamatory after release of the movie One Flew Over the Cuckoo’s Nest in 1975, which portrayed psychiatry in a purely negative light. Despite progress in public understanding of psychiatry, and tangible improvements in practice, the stigma of mental illness persists. Media portrayals, including motion pictures, continue to distort the good that psychiatrists do for their patients.
Gender and sexuality
• Gender distribution of psychiatrists. A major shift occurred over the past 7 decades, reflecting the same pattern that has been documented in other medical specialties. At least one-half of psychiatry residents are now women—a welcome change from the pre-1946 era, when nearly all psychiatrists were men. This demographic transformation has had an impact on the dynamics of psychiatric practice.
• Acceptance and depathologization of homosexuality. Until 1974, homosexuality was considered a psychiatric disorder, and many homosexual persons sought treatment. That year, membership of the American Psychiatric Association voted to remove homosexuality from DSM-II and to no longer regard it as a behavioral abnormality. This was a huge step toward de-pathologizing same-sex orientation and love, and might have been the major impetus for the progressive social acceptance of gay, lesbian, and transgendered people over the past 4 decades.
The DSM paradigm shift in psychiatric diagnosis
• DSM-III. Perhaps the most radical change in the diagnostic criteria of psychiatric disorders occurred in 1980, with introduction of DSM-III to replace DSM-I and DSM-II, which were absurdly vague, unreliable, and with poor validity.
The move toward more operational and reliable diagnostic requirements began with the Research Diagnostic Criteria, developed by the Department of Psychiatry at Washington University in St. Louis. DSM-III represented a complete paradigm shift in psychiatric diagnosis. Subsequent editions maintained the same methodology, with relatively modest changes. The field expects continued evolution in DSM diagnostic criteria, including the future inclusion of biomarkers, based on sound, controlled studies.
• Recognizing PTSD. Develop-ment of posttraumatic stress disorder (PTSD) as a diagnostic entity, and its inclusion in DSM-III, were major changes in psychiatric nosology. At last, the old terms—shell shock, battle fatigue, neurasthenia—were legitimized as a recognizable syndrome secondary to major life trauma, including war and rape. That legitimacy has instigated substantial clinical and research interest in identifying how serious psychopathology can be triggered by life events.
Pharmaceutical industry debacle
Few industries have fallen so far from grace in the eyes of psychiatric professionals and the public as the manufacturers of psychotropic drugs.
At the dawn of the psychopharmacology era (the 1950s, 1960s, and 1970s) pharmaceutical companies were respected and regarded by physicians and patients as a vital partner in health care for their discovery and development of medications to treat psychiatric disorders. That image was tarnished in the 1990s, however, with the approval and release of several atypical antipsychotics. Cutthroat competition, questionable publication methods, concealment of negative findings, and excessive spending on marketing, including FDA-approved educational programs for clinicians on efficacy, safety, and dosing, all contributed to escalating cynicism about the industry. Academic faculty who received research grants to conduct FDA-required clinical trials of new agents were painted with the same brush.
Disclosure of potential conflict of interest became a mandatory procedure at universities and for NIMH grant applicants and journal publishers. Class-action lawsuits against companies that manufacture second-generation antipsychotics—filed for lack of transparency about metabolic side effects—exacerbated the intensity of criticism and condemnation.
Although new drug development has become measurably more rigorous and ethical because of self-regulation, combined with vigorous government scrutiny and regulation, demonization of the pharmaceutical industry remains unabated. That might be the reason why several major pharmaceutical companies have abandoned research and development of psychotropic drugs. That is likely to impede progress in psychopharmacotherapeutics; after all, no other private or government entity develops drugs for patients who have a psychiatric illness. The need for such agents is great: There is no FDA-indicated drug for the majority of DSM-5 diagnoses.
We entrust the future to next generations
Momentous events have transformed psychiatry during the lifespan of Baby Boomers like me and many of you. Because the cohort of 80 million Baby Boomers has comprised a significant percentage of the nation’s scientists, media representatives, members of the American Psychiatric Association, academicians, and community leaders over the past few decades, it is conceivable that the Baby Boomer generation helped trigger most of the transformative changes in psychiatry we have seen over the past 70 years.
I can only wonder: What direction will psychiatry take in the age of Generation X, Generation Y, and the Millennials? Only this is certain: Psychiatry will continue to evolve— long after Baby Boomers are gone.
A large percentage of psychiatrists practicing today are Boomers, and have experienced the tumultuous change in their profession since the end of World War II. At a recent Grand Rounds presentation in the Department of Neurology & Psychiatry at Saint Louis University, participants examined major changes and paradigm shifts that have reshaped psychiatry since 1946. The audience, which included me, contributed historical observations to the list of those changes and shifts, which I’ve classified here for your benefit, whether or not you are a Boomer.
Medical advances
Consider these discoveries and developments:
• Penicillin in 1947, which led to a reduction in cases of psychosis caused by tertiary syphilis, a disease that accounted for 10% to 15% of state hospital admissions.
• Lithium in 1948, the first pharmaceutical treatment for mania.
• Chlorpromazine, the first antipsychotic drug, in 1952, launching the psychopharmacology era and ending lifetime institutional sequestration as the only “treatment” for serious mental disorders.
• Monoamine oxidase inhibitors in 1959, from observations that iproniazid, a drug used in tuberculosis sanitariums, improved the mood of tuberculosis patients. This was the first pharmacotherapy for depression, which had been treated with electroconvulsive therapy (ECT), developed in the 1930s.
• Tricyclic antidepressants, starting with imipramine in the late 1950s, during attempts to synthesize additional phenothiazine antipsychotics.
• Diazepam, introduced in 1963 for its anti-anxiety effects, became the most widely used drug in the world over the next 2 decades.
• Pre-frontal lobotomy to treat severe psychiatric disorders. The neurosurgeon-inventor of this so-called medical advance won the 1949 Nobel Prize for Medicine or Physiology. The procedure was rapidly discredited after the development of antipsychotic drugs.
• Fluoxetine, the first selective serotonin reuptake inhibitor, in 1987, revolutionized the treatment of depression, especially in primary care settings.
• Clozapine, as an effective treatment for refractory and suicidal schizophrenia, and the spawning of second-generation antipsychotics. These newer agents shifted focus from neurologic adverse effects (extrapyramidal symptoms, tardive dyskinesia) to cardio-metabolic side effects (obesity, diabetes, dyslipidemia, and hypertension).
Changes to the landscape of health care
Three noteworthy developments made the list:
• The Community Mental Health Act of 1963, signed into law by President John F. Kennedy, revolutionized psychiatric care by shifting delivery of care from inpatient, hospital-based facilities to outpatient, clinic-based centers. There are now close to 800 community mental health centers in the United States, where care is dominated by non-physician mental health providers—in contrast to the era of state hospitals, during which physicians and nurses provided care for mentally ill patients.
• Deinstitutionalization. This move-ment gathered momentum in the 1970s and 1980s, leading to closing of the majority of state hospitals, with tragic consequences for the seriously mentally ill—including early demise, homelessness, substance abuse, and incarceration. In fact, the large percentage of mentally ill people in U.S. jails and prisons, instead of in a hospital, represents what has been labeled trans-institutionalization (see my March 2008 editorial, “Bring back the asylums?,” available at CurrentPsychiatry.com).
• Managed care, emerging in the late 1980s and early 1990s, caused a seismic disturbance in the delivery of, and reimbursement for, psychiatric care. The result was a significant decline in access to, and quality of, care—especially the so-called carve-out model that reduced payment for psychiatric care even more drastically than for general medical care. Under managed care, the priority became saving money, rather than saving lives. Average hospital stay for patients who had a psychiatric disorder, which was years in the pre-pharmacotherapy era, and weeks or months after that, shrunk to a few days under managed care.
Changes in professional direction
Two major shifts in the complexion of the specialty were identified:
• The decline of psychoanalysis, which had dominated psychiatry for decades (the 1940s through the 1970s), was a major shift in the conceptualization, training, and delivery of care in psychiatry. The rise of biological psychiatry and the medical model of psychiatric brain disorders, as well as the emergence of evidence-based (and briefer) psychotherapies (eg, cognitive-behavioral therapy, dialectical behavior therapy, and interpersonal therapy), gradually replaced the Freudian model of mental illness.
As a result, it became no longer necessary to be a certified psychoanalyst to be named chair of a department of psychiatry. The impact of this change on psychiatric training has been profound, because medical management by psychiatrists superseded psychotherapy— given the brief hospitalization that is required and the diminishing coverage for psychotherapy by insurers.
• Delegation of psychosocial treatments to non-psychiatrists. The unintended consequences of psychiatrists’ change of focus to 1) consultation on medical/surgical patients and 2) the medical evaluation, diagnosis, and pharmacotherapy of mental disorders led to the so-called “dual treatment model” for the most seriously mentally ill patients: The physician provides medical management and non-physician mental health professionals provide counseling, psychosocial therapy, and rehabilitation.
Disruptive breakthroughs
Several are notable:
• National Institute of Mental Health (NIMH). Establishment of NIMH in April 1949 was a major step toward funding research into psychiatric disorders. Billions of dollars have been invested to generate knowledge about the causes, treatment, course, and prevention of mental illness. No other country has spent as much on psychiatric research. It would have been nearly impossible to discover what we know today without the work of NIMH.
• Neuroscience. The meteoric rise of neuroscience from the 1960s to the present has had a dramatic effect, transforming old psychiatry and the study and therapy of the mind to a focus on the brain-mind continuum and the prospects of brain repair and neuroplasticity. Psychiatry is now regarded as a clinical neuroscience specialty of brain disorders that manifest as changes in thought, affect, mood, cognition, and behavior.
• Brain imaging. Techniques developed since the 1970s—the veritable alphabet soup of CT, PET, SPECT, MRI, MRS, fMRI, and DTI— has revolutionized understanding of brain structure and function in all psychiatric disorders but especially in psychotic and mood disorders.
• Molecular genetics. Advances over the past 2 decades have shed unprecedented light on the complex genetics of psychiatric disorders. It is becoming apparent that most psychiatric disorders are caused via gene-by-environment interaction; etiology is therefore a consequence of genetic and non-genetic variables. Risk genes, copy number variants, and de novo mutations are being discovered almost weekly, and progress in epigenetics holds promise for preventing medical disorders, including psychiatric illness.
• Neuromodulation. Advances represent an important paradigm shift, from pharmacotherapy to brain stimulation. Several techniques have been approved by the FDA, including transcranial magnetic stimulation, vagus nerve stimulation, and deep brain stimulation, to supplement, and perhaps eventually supplant, ECT.
Legal intrusiveness
No other medical specialty has been subject to laws governing clinical practice as psychiatry has been. Progressive intrusion of laws (ostensibly, enacted to protect the civil rights of “the disabled”) ends up hurting patients who refuse admission and then often harm themselves or others or decline urgent treatment, which can be associated with loss of brain tissue in acute psychotic, manic, and depressed states. No legal shackles apply to treating unconscious stroke patients, delirious geriatric patients, or semiconscious myocardial infarction patients when they are admitted to a hospital.
Distortions of the anti-psychiatry movement
The antipsychiatry movement preceded the Baby Boomer era by a century but has continued unabated. The movement gained momentum and became more defamatory after release of the movie One Flew Over the Cuckoo’s Nest in 1975, which portrayed psychiatry in a purely negative light. Despite progress in public understanding of psychiatry, and tangible improvements in practice, the stigma of mental illness persists. Media portrayals, including motion pictures, continue to distort the good that psychiatrists do for their patients.
Gender and sexuality
• Gender distribution of psychiatrists. A major shift occurred over the past 7 decades, reflecting the same pattern that has been documented in other medical specialties. At least one-half of psychiatry residents are now women—a welcome change from the pre-1946 era, when nearly all psychiatrists were men. This demographic transformation has had an impact on the dynamics of psychiatric practice.
• Acceptance and depathologization of homosexuality. Until 1974, homosexuality was considered a psychiatric disorder, and many homosexual persons sought treatment. That year, membership of the American Psychiatric Association voted to remove homosexuality from DSM-II and to no longer regard it as a behavioral abnormality. This was a huge step toward de-pathologizing same-sex orientation and love, and might have been the major impetus for the progressive social acceptance of gay, lesbian, and transgendered people over the past 4 decades.
The DSM paradigm shift in psychiatric diagnosis
• DSM-III. Perhaps the most radical change in the diagnostic criteria of psychiatric disorders occurred in 1980, with introduction of DSM-III to replace DSM-I and DSM-II, which were absurdly vague, unreliable, and with poor validity.
The move toward more operational and reliable diagnostic requirements began with the Research Diagnostic Criteria, developed by the Department of Psychiatry at Washington University in St. Louis. DSM-III represented a complete paradigm shift in psychiatric diagnosis. Subsequent editions maintained the same methodology, with relatively modest changes. The field expects continued evolution in DSM diagnostic criteria, including the future inclusion of biomarkers, based on sound, controlled studies.
• Recognizing PTSD. Develop-ment of posttraumatic stress disorder (PTSD) as a diagnostic entity, and its inclusion in DSM-III, were major changes in psychiatric nosology. At last, the old terms—shell shock, battle fatigue, neurasthenia—were legitimized as a recognizable syndrome secondary to major life trauma, including war and rape. That legitimacy has instigated substantial clinical and research interest in identifying how serious psychopathology can be triggered by life events.
Pharmaceutical industry debacle
Few industries have fallen so far from grace in the eyes of psychiatric professionals and the public as the manufacturers of psychotropic drugs.
At the dawn of the psychopharmacology era (the 1950s, 1960s, and 1970s) pharmaceutical companies were respected and regarded by physicians and patients as a vital partner in health care for their discovery and development of medications to treat psychiatric disorders. That image was tarnished in the 1990s, however, with the approval and release of several atypical antipsychotics. Cutthroat competition, questionable publication methods, concealment of negative findings, and excessive spending on marketing, including FDA-approved educational programs for clinicians on efficacy, safety, and dosing, all contributed to escalating cynicism about the industry. Academic faculty who received research grants to conduct FDA-required clinical trials of new agents were painted with the same brush.
Disclosure of potential conflict of interest became a mandatory procedure at universities and for NIMH grant applicants and journal publishers. Class-action lawsuits against companies that manufacture second-generation antipsychotics—filed for lack of transparency about metabolic side effects—exacerbated the intensity of criticism and condemnation.
Although new drug development has become measurably more rigorous and ethical because of self-regulation, combined with vigorous government scrutiny and regulation, demonization of the pharmaceutical industry remains unabated. That might be the reason why several major pharmaceutical companies have abandoned research and development of psychotropic drugs. That is likely to impede progress in psychopharmacotherapeutics; after all, no other private or government entity develops drugs for patients who have a psychiatric illness. The need for such agents is great: There is no FDA-indicated drug for the majority of DSM-5 diagnoses.
We entrust the future to next generations
Momentous events have transformed psychiatry during the lifespan of Baby Boomers like me and many of you. Because the cohort of 80 million Baby Boomers has comprised a significant percentage of the nation’s scientists, media representatives, members of the American Psychiatric Association, academicians, and community leaders over the past few decades, it is conceivable that the Baby Boomer generation helped trigger most of the transformative changes in psychiatry we have seen over the past 70 years.
I can only wonder: What direction will psychiatry take in the age of Generation X, Generation Y, and the Millennials? Only this is certain: Psychiatry will continue to evolve— long after Baby Boomers are gone.
The transient truths of medical ‘progress’
I might have a jaundiced view of progress but, across most medical specialties, diseases are still managed, not cured. Chronicity is almost ubiquitous among medical ailments, and no specialty can boast that it restores function completely and fully restores patients’ quality of life.
Psychiatry has had its share of missteps
Prefrontal lobotomy is perhaps the most infamous of many discredited treatments that were introduced as a great solution to severe brain disorders such as schizophrenia.1 Prefrontal lobotomy (leucotomy) was initially heralded as a major medical advance in 1935; its originator, neurosurgeon António Egas Moniz, shared the Nobel Prize in Medicine or Physiology in 1949 for what is now regarded as mayhem. Prefrontal lobotomy was widely used for many conditions—not just for psychosis—but it fell from favor rapidly after the discovery of anti-psychotic drugs.
A similar fate befell other treatments that were introduced to psychiatry:
• malaria therapy (1917) for general paresis of the insane (the condition was later recognized as tertiary syphilis)
• deep sleep therapy (1920) for schizophrenia
• insulin shock therapy (1933), also for schizophrenia.
Those discredited therapies were lauded as significant advances, only to be shunned later as harmful, even barbaric.
Treating addiction is another saga of false steps. Fifty-nine different treatments for addiction have been introduced over the past few decades, many later discredited as “psychoquackery.”2 In the breathless rush to cure desperate conditions, there often is the risk that pseudoscience will masquerade as science. Many patients suffer needlessly before the medical community examines the accumulated evidence and discredits useless or harmful treatments.
Psychiatry isn’t alone in lacking cures
A fitting slogan of many non-psychiatric medical specialties is “to treat, perchance to cure.” Consider some examples:
• In cardiology, congestive heart failure, a chronic illness, is managed but rarely cured, and leads to early mortality.
• Nephrologists struggle to maintain a semblance of kidney function in renal failure patients, before placing them on the long waiting list for a kidney transplant.
• Gastroenterologists can only hope to maintain liver function in severe hepatitis, or to alleviate the misery of ulcerative colitis.
• Rheumatologists do what they can to relieve the debilitating symptoms of rheumatoid arthritis, systemic lupus erythematosus, and Sjögren’s syndrome.
• Pulmonologists know they can never restore normal lung function for their patients with chronic obstructive pulmonary disease; they can only help them hang on with partial function.
• Oncologists valiantly fight aggressive cancers with the hope of prolonging life for a few months or years.
• Neurologists valiantly try to manage multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, epilepsy, stroke, myasthenia gravis, and amyotrophic lateral sclerosis—often with limited, if any, success at achieving remission.
Internal medicine has had its share of discredited therapies, too—ones that were withdrawn because they caused harm or were of dubious or inconclusive efficacy.3 Thanks to careful analysis of the efficacy and safety of medical procedures introduced during the past decade, we know that 40% of 146 procedures examined were eventually discredited and withdrawn. (That kind of analysis should be undertaken in psychotherapy, where evidence-based therapies can be counted on one hand but dozens more are promoted as legitimate.4 Psychotherapy can be harmful.5)
As with patients in psychiatry, patients of all these specialties are at risk of suffering disruptive iatrogenic side effects that, at times, approach torture—just to have progression of disease halted but not necessarily to deliver full remission. The quality of life for patients who have a chronic disease ranges from barely tolerable to poor, but is rarely good or optimal—and that is the case across all of medicine, including psychiatry.
Desperation often drives dubious innovation
There are numerous “desperate” diseases across all medical specialties, including psychiatry. Radical and harmful measures are sometimes proposed and marketed to treat many of those conditions; more often, useless, ineffective, futile “treatments” are introduced, and it might take years before they are discredited and withdrawn.6,7 Useless treatments can be harmful, too, because they delay the use of potentially effective procedures.
Move forward with caution!
What does this brief look at the missteps of medicine tell us? First, medical progress is like the mambo: We take steps forward but then step backward again; and, as Karl Popper noted, science learns more from its failures than from its successes.8 Second, all physicians must be judicious and guided by evidence when they select treatments.
For your patients’ sake, choose wisely!9
1. Valenstein ES. Great and desperate cures: The rise and decline of psychosurgery and other radical treatments for mental illness. New York, NY: Basic Books; 1986.
2. Norcross JC, Koocher GP, Fala NC, et al. What does not work? Expert consensus on discredited treatments in the addictions. J Addic Med. 2010;4(3):174-180.
3. Prasad V, Vandross A, Toomey C, et al. A decade of reversal: an analysis of 146 contradicted medical practices. Mayo Clin Proc. 2013;88(8):790-798.
4. Corsini RJ. Handbook of innovative therapy. Philadelphia, PA: John Wiley & Sons, Inc; 2001.
5. Berk M, Parker G. The elephant on the couch: side-effects of psychotherapy. Austr N Z J Psychiatry. 2009;43(9):787-794.
6. Iaonnidis JP. Contradicted and initially stronger effects in highly cited clinical research. JAMA. 2005;294(2): 218-228.
7. Elshang AG, Watt AM, Mundy L, et al. Over 150 potentially low-value health care practices: an Australian study. Med J Aust. 2012;197(10):556-560.
8. Popper K. The logic of scientific discovery. London, United Kingdom: Hutchinson & Co.; 1959.
9. Cassel CK, Guest JA. Choosing wisely: helping physicians and patients make smart decision about their care. JAMA. 2012;307(17):1801-1802.
I might have a jaundiced view of progress but, across most medical specialties, diseases are still managed, not cured. Chronicity is almost ubiquitous among medical ailments, and no specialty can boast that it restores function completely and fully restores patients’ quality of life.
Psychiatry has had its share of missteps
Prefrontal lobotomy is perhaps the most infamous of many discredited treatments that were introduced as a great solution to severe brain disorders such as schizophrenia.1 Prefrontal lobotomy (leucotomy) was initially heralded as a major medical advance in 1935; its originator, neurosurgeon António Egas Moniz, shared the Nobel Prize in Medicine or Physiology in 1949 for what is now regarded as mayhem. Prefrontal lobotomy was widely used for many conditions—not just for psychosis—but it fell from favor rapidly after the discovery of anti-psychotic drugs.
A similar fate befell other treatments that were introduced to psychiatry:
• malaria therapy (1917) for general paresis of the insane (the condition was later recognized as tertiary syphilis)
• deep sleep therapy (1920) for schizophrenia
• insulin shock therapy (1933), also for schizophrenia.
Those discredited therapies were lauded as significant advances, only to be shunned later as harmful, even barbaric.
Treating addiction is another saga of false steps. Fifty-nine different treatments for addiction have been introduced over the past few decades, many later discredited as “psychoquackery.”2 In the breathless rush to cure desperate conditions, there often is the risk that pseudoscience will masquerade as science. Many patients suffer needlessly before the medical community examines the accumulated evidence and discredits useless or harmful treatments.
Psychiatry isn’t alone in lacking cures
A fitting slogan of many non-psychiatric medical specialties is “to treat, perchance to cure.” Consider some examples:
• In cardiology, congestive heart failure, a chronic illness, is managed but rarely cured, and leads to early mortality.
• Nephrologists struggle to maintain a semblance of kidney function in renal failure patients, before placing them on the long waiting list for a kidney transplant.
• Gastroenterologists can only hope to maintain liver function in severe hepatitis, or to alleviate the misery of ulcerative colitis.
• Rheumatologists do what they can to relieve the debilitating symptoms of rheumatoid arthritis, systemic lupus erythematosus, and Sjögren’s syndrome.
• Pulmonologists know they can never restore normal lung function for their patients with chronic obstructive pulmonary disease; they can only help them hang on with partial function.
• Oncologists valiantly fight aggressive cancers with the hope of prolonging life for a few months or years.
• Neurologists valiantly try to manage multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, epilepsy, stroke, myasthenia gravis, and amyotrophic lateral sclerosis—often with limited, if any, success at achieving remission.
Internal medicine has had its share of discredited therapies, too—ones that were withdrawn because they caused harm or were of dubious or inconclusive efficacy.3 Thanks to careful analysis of the efficacy and safety of medical procedures introduced during the past decade, we know that 40% of 146 procedures examined were eventually discredited and withdrawn. (That kind of analysis should be undertaken in psychotherapy, where evidence-based therapies can be counted on one hand but dozens more are promoted as legitimate.4 Psychotherapy can be harmful.5)
As with patients in psychiatry, patients of all these specialties are at risk of suffering disruptive iatrogenic side effects that, at times, approach torture—just to have progression of disease halted but not necessarily to deliver full remission. The quality of life for patients who have a chronic disease ranges from barely tolerable to poor, but is rarely good or optimal—and that is the case across all of medicine, including psychiatry.
Desperation often drives dubious innovation
There are numerous “desperate” diseases across all medical specialties, including psychiatry. Radical and harmful measures are sometimes proposed and marketed to treat many of those conditions; more often, useless, ineffective, futile “treatments” are introduced, and it might take years before they are discredited and withdrawn.6,7 Useless treatments can be harmful, too, because they delay the use of potentially effective procedures.
Move forward with caution!
What does this brief look at the missteps of medicine tell us? First, medical progress is like the mambo: We take steps forward but then step backward again; and, as Karl Popper noted, science learns more from its failures than from its successes.8 Second, all physicians must be judicious and guided by evidence when they select treatments.
For your patients’ sake, choose wisely!9
I might have a jaundiced view of progress but, across most medical specialties, diseases are still managed, not cured. Chronicity is almost ubiquitous among medical ailments, and no specialty can boast that it restores function completely and fully restores patients’ quality of life.
Psychiatry has had its share of missteps
Prefrontal lobotomy is perhaps the most infamous of many discredited treatments that were introduced as a great solution to severe brain disorders such as schizophrenia.1 Prefrontal lobotomy (leucotomy) was initially heralded as a major medical advance in 1935; its originator, neurosurgeon António Egas Moniz, shared the Nobel Prize in Medicine or Physiology in 1949 for what is now regarded as mayhem. Prefrontal lobotomy was widely used for many conditions—not just for psychosis—but it fell from favor rapidly after the discovery of anti-psychotic drugs.
A similar fate befell other treatments that were introduced to psychiatry:
• malaria therapy (1917) for general paresis of the insane (the condition was later recognized as tertiary syphilis)
• deep sleep therapy (1920) for schizophrenia
• insulin shock therapy (1933), also for schizophrenia.
Those discredited therapies were lauded as significant advances, only to be shunned later as harmful, even barbaric.
Treating addiction is another saga of false steps. Fifty-nine different treatments for addiction have been introduced over the past few decades, many later discredited as “psychoquackery.”2 In the breathless rush to cure desperate conditions, there often is the risk that pseudoscience will masquerade as science. Many patients suffer needlessly before the medical community examines the accumulated evidence and discredits useless or harmful treatments.
Psychiatry isn’t alone in lacking cures
A fitting slogan of many non-psychiatric medical specialties is “to treat, perchance to cure.” Consider some examples:
• In cardiology, congestive heart failure, a chronic illness, is managed but rarely cured, and leads to early mortality.
• Nephrologists struggle to maintain a semblance of kidney function in renal failure patients, before placing them on the long waiting list for a kidney transplant.
• Gastroenterologists can only hope to maintain liver function in severe hepatitis, or to alleviate the misery of ulcerative colitis.
• Rheumatologists do what they can to relieve the debilitating symptoms of rheumatoid arthritis, systemic lupus erythematosus, and Sjögren’s syndrome.
• Pulmonologists know they can never restore normal lung function for their patients with chronic obstructive pulmonary disease; they can only help them hang on with partial function.
• Oncologists valiantly fight aggressive cancers with the hope of prolonging life for a few months or years.
• Neurologists valiantly try to manage multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, epilepsy, stroke, myasthenia gravis, and amyotrophic lateral sclerosis—often with limited, if any, success at achieving remission.
Internal medicine has had its share of discredited therapies, too—ones that were withdrawn because they caused harm or were of dubious or inconclusive efficacy.3 Thanks to careful analysis of the efficacy and safety of medical procedures introduced during the past decade, we know that 40% of 146 procedures examined were eventually discredited and withdrawn. (That kind of analysis should be undertaken in psychotherapy, where evidence-based therapies can be counted on one hand but dozens more are promoted as legitimate.4 Psychotherapy can be harmful.5)
As with patients in psychiatry, patients of all these specialties are at risk of suffering disruptive iatrogenic side effects that, at times, approach torture—just to have progression of disease halted but not necessarily to deliver full remission. The quality of life for patients who have a chronic disease ranges from barely tolerable to poor, but is rarely good or optimal—and that is the case across all of medicine, including psychiatry.
Desperation often drives dubious innovation
There are numerous “desperate” diseases across all medical specialties, including psychiatry. Radical and harmful measures are sometimes proposed and marketed to treat many of those conditions; more often, useless, ineffective, futile “treatments” are introduced, and it might take years before they are discredited and withdrawn.6,7 Useless treatments can be harmful, too, because they delay the use of potentially effective procedures.
Move forward with caution!
What does this brief look at the missteps of medicine tell us? First, medical progress is like the mambo: We take steps forward but then step backward again; and, as Karl Popper noted, science learns more from its failures than from its successes.8 Second, all physicians must be judicious and guided by evidence when they select treatments.
For your patients’ sake, choose wisely!9
1. Valenstein ES. Great and desperate cures: The rise and decline of psychosurgery and other radical treatments for mental illness. New York, NY: Basic Books; 1986.
2. Norcross JC, Koocher GP, Fala NC, et al. What does not work? Expert consensus on discredited treatments in the addictions. J Addic Med. 2010;4(3):174-180.
3. Prasad V, Vandross A, Toomey C, et al. A decade of reversal: an analysis of 146 contradicted medical practices. Mayo Clin Proc. 2013;88(8):790-798.
4. Corsini RJ. Handbook of innovative therapy. Philadelphia, PA: John Wiley & Sons, Inc; 2001.
5. Berk M, Parker G. The elephant on the couch: side-effects of psychotherapy. Austr N Z J Psychiatry. 2009;43(9):787-794.
6. Iaonnidis JP. Contradicted and initially stronger effects in highly cited clinical research. JAMA. 2005;294(2): 218-228.
7. Elshang AG, Watt AM, Mundy L, et al. Over 150 potentially low-value health care practices: an Australian study. Med J Aust. 2012;197(10):556-560.
8. Popper K. The logic of scientific discovery. London, United Kingdom: Hutchinson & Co.; 1959.
9. Cassel CK, Guest JA. Choosing wisely: helping physicians and patients make smart decision about their care. JAMA. 2012;307(17):1801-1802.
1. Valenstein ES. Great and desperate cures: The rise and decline of psychosurgery and other radical treatments for mental illness. New York, NY: Basic Books; 1986.
2. Norcross JC, Koocher GP, Fala NC, et al. What does not work? Expert consensus on discredited treatments in the addictions. J Addic Med. 2010;4(3):174-180.
3. Prasad V, Vandross A, Toomey C, et al. A decade of reversal: an analysis of 146 contradicted medical practices. Mayo Clin Proc. 2013;88(8):790-798.
4. Corsini RJ. Handbook of innovative therapy. Philadelphia, PA: John Wiley & Sons, Inc; 2001.
5. Berk M, Parker G. The elephant on the couch: side-effects of psychotherapy. Austr N Z J Psychiatry. 2009;43(9):787-794.
6. Iaonnidis JP. Contradicted and initially stronger effects in highly cited clinical research. JAMA. 2005;294(2): 218-228.
7. Elshang AG, Watt AM, Mundy L, et al. Over 150 potentially low-value health care practices: an Australian study. Med J Aust. 2012;197(10):556-560.
8. Popper K. The logic of scientific discovery. London, United Kingdom: Hutchinson & Co.; 1959.
9. Cassel CK, Guest JA. Choosing wisely: helping physicians and patients make smart decision about their care. JAMA. 2012;307(17):1801-1802.
100 years of solicitude: Do global traumatic events have a transgenerational effect?
Yet, important questions about the impact of these events have not been asked: Can there be a transgenerational neurobiological effect on the children and grandchildren of people who have been subjected to life-threatening, traumatic societal events? Could the psychobiology of widespread anxiety and worry (solicitude) be experienced not only by the generation that witnessed and lived through those devastating events, but also by their progeny, who were not yet born during the traumatic events? And could there be epigenetic consequences on a large scale, producing a generation that shares traits induced by the trauma experienced by the previous generation?
Did the rise of delinquency in the 1950s, followed by the anti-war rebellion, unprecedented sexual promiscuity, and substance abuse of the 1960s, be the result of genetic changes in the previous generation induced by living through World War II—after which the generation that grew up in the 1960s was born?
In the late Gabriel García Márquez’s masterpiece novel, One Hundred Years of Solitude, the 1982 Nobel Laureate’s chronicle of the Buendía family across 7 generations is replete with dark and insalubrious events. The fictional family’s story is considered a metaphor for the tumultuous evolution of Márquez’s native Colombia, but that story is consistent with the concept of transgenerational transmission of the biologic effects of stress, as each generation of the Buendía family manifests unusual, even pathological behaviors.
One hundred years of alarm, panic, and anxiety
Psychiatrists are keenly aware of the impact of stressful events on their patients’ mood and behavior, and of the association of life-threatening events with posttraumatic stress disorder (PTSD). For persons who suffer the generalized anxiety of PTSD, further stressful life events can aggravate their condition and result in additional anxiety and solicitude.
It is not surprising that anxiety has been documented as the most common psychiatric condition in the United States.1 Consider the variety of perturbations that have induced alarm, panic, fear, and simmering anxiety on a global scale over the past 100 years— starting with World War I, exactly a century ago.
War. The ruinous 4-year Great War was followed 20 years later by World War II, which caused tens of millions of casualties and the annihilation of Hiroshima and Nagasaki by the atomic bomb— escalating fear of nuclear warfare and radiation poisoning for decades to come. Add to that the Korean War, the Vietnam conflict, the First Gulf War, and the Iraq and Afghanistan wars. The war fatigue and mental exhaustion of the population are palpable.
Economic upheaval. After the Stock Market Crash of 1929 came the Great Depression, the recessions of the 1970s and early 1980s, another stock market crash in 1987, and, most recently, the financial crisis of 2008. Millions saw their wealth wiped out and their livelihoods disrupted, exerting enormous life-changing stresses on countless families.
Disasters. The sinking of the Titanic in 1912, the crash of the Hindenburg, the Three Mile Island nuclear accident, the meltdown of the Chernobyl and Fukushima Daiichi reactors, the space shuttle disasters, and the 9/11 terrorist attacks—all these trigger and perpetuate fear and worry about the one’s own, and one’s loved ones, abrupt and premature mortality.
Epidemics. Millions died in the 1918 influenza pandemic, prompting widespread societal fears that re-intensified during subsequent epidemics: polio in the 1950s, swine flu in the 1970s, SARS (severe acute respiratory syndrome) in the 1990s, West Nile Virus, and avian influenza.
Assassination. The shooting of Archduke Franz Ferdinand of Austria sparked World War I a century ago, but what baby boomers, such as me, vividly remember is our angst over the assassinations of President John F. Kennedy, his brother Robert, and Rev. Dr. Martin Luther King, Jr; the attempted assassination of President Ronald Reagan; and the murder of John Lennon. Each assassination leaves a communal scar on millions, forever reminding them of the ephemeral nature of life at any rung of the social ladder.
Mass murder. The past 100 years began with the Armenian genocide in 1918, followed by the Holocaust of World War II, the Munich Olympics killings, the Jonestown massacre, the Oklahoma City bombing, and, to name a few, the mass murders at Columbine, Virginia Tech, Newtown, and Fort Hood.
Natural disasters can wreak havoc on peoples’ lives. Consider the annual tally of hurricanes (a long list, some—such as Katrina and Sandy—more infamous than others). Add to those storms the earthquakes, tsunamis, erupting volcanoes, floods, and blizzards, and the result is suffering and anxiety on a massive scale, even among those who are not affected directly.
A surprising facet of these disquieting events is the resiliency of people. Life goes on, despite the agony, despair, and solicitude instigated by deadly events. But of those who buckle under the weight of adversity, many end up in a psychiatric clinic or hospital, and are disabled by their symptoms.
Even ‘good’ change can be disquieting
Juxtaposed against these awful events are 100 years of an array of positive, uplifting discoveries, inventions, and medical advances that have completely transformed our lives. Consider: electricity, clean water, women’s right to vote, automobiles, air and space travel, air conditioning, and highway systems; the momentous discoveries of penicillin, antipsychotics, antidepressants, and mood stabilizers; television, the telephone (evolving from dumb to smart), vaccines, oral contraceptives, genetic discoveries, brain imaging technology, and home appliances (refrigerators, microwave ovens, dishwashers); and not at all least, personal computers and the Internet.
But even these advances can generate anxiety and solicitude: Fear of flying, anyone? Embarrassment about a selfie gone viral on the Web? Worry about being a carrier of a breast cancer gene? Claustrophobia inside an MRI scanner?
Hypothesizing about the transfer of anxiety
Could PTSD and solicitude in one generation be transmitted to the next via epigenetic mechanisms (that is, by over-expression or silencing of genes involved in brain development) and could this transmission result in unusual wide-scale stress reactivity? Might this be an example of the infamous Lamarckian “inheritance of acquired characteristics” at the molecular genetic level, in which the anxiety of traumatized parents is transmitted to their offspring? Or could transmission be mediated by being reared in the emotionally oppressive environment of a family still reeling from the effects of war, disaster, and mass murder?
Such questions might sound rhetorical, but they present a reasonable hypothesis that can be answered by research. Findings from animal studies suggest that such a phenomenon might occur in humans.2 If those findings are validated, opportunities for preventing societal solicitude might emerge.
1. Robins LN, Regier DA, eds. Psychiatric disorders in America: The Epidemiologic Catchment Area Study. New York, New York: The Free Press; 1991.
2. Rechavi O, Minevich G, Hobert O. Transgenerational inheritance of an acquired small RNA-based antiviral response in C. elegans. Cell. 2011;147(6):1248-1256.
Yet, important questions about the impact of these events have not been asked: Can there be a transgenerational neurobiological effect on the children and grandchildren of people who have been subjected to life-threatening, traumatic societal events? Could the psychobiology of widespread anxiety and worry (solicitude) be experienced not only by the generation that witnessed and lived through those devastating events, but also by their progeny, who were not yet born during the traumatic events? And could there be epigenetic consequences on a large scale, producing a generation that shares traits induced by the trauma experienced by the previous generation?
Did the rise of delinquency in the 1950s, followed by the anti-war rebellion, unprecedented sexual promiscuity, and substance abuse of the 1960s, be the result of genetic changes in the previous generation induced by living through World War II—after which the generation that grew up in the 1960s was born?
In the late Gabriel García Márquez’s masterpiece novel, One Hundred Years of Solitude, the 1982 Nobel Laureate’s chronicle of the Buendía family across 7 generations is replete with dark and insalubrious events. The fictional family’s story is considered a metaphor for the tumultuous evolution of Márquez’s native Colombia, but that story is consistent with the concept of transgenerational transmission of the biologic effects of stress, as each generation of the Buendía family manifests unusual, even pathological behaviors.
One hundred years of alarm, panic, and anxiety
Psychiatrists are keenly aware of the impact of stressful events on their patients’ mood and behavior, and of the association of life-threatening events with posttraumatic stress disorder (PTSD). For persons who suffer the generalized anxiety of PTSD, further stressful life events can aggravate their condition and result in additional anxiety and solicitude.
It is not surprising that anxiety has been documented as the most common psychiatric condition in the United States.1 Consider the variety of perturbations that have induced alarm, panic, fear, and simmering anxiety on a global scale over the past 100 years— starting with World War I, exactly a century ago.
War. The ruinous 4-year Great War was followed 20 years later by World War II, which caused tens of millions of casualties and the annihilation of Hiroshima and Nagasaki by the atomic bomb— escalating fear of nuclear warfare and radiation poisoning for decades to come. Add to that the Korean War, the Vietnam conflict, the First Gulf War, and the Iraq and Afghanistan wars. The war fatigue and mental exhaustion of the population are palpable.
Economic upheaval. After the Stock Market Crash of 1929 came the Great Depression, the recessions of the 1970s and early 1980s, another stock market crash in 1987, and, most recently, the financial crisis of 2008. Millions saw their wealth wiped out and their livelihoods disrupted, exerting enormous life-changing stresses on countless families.
Disasters. The sinking of the Titanic in 1912, the crash of the Hindenburg, the Three Mile Island nuclear accident, the meltdown of the Chernobyl and Fukushima Daiichi reactors, the space shuttle disasters, and the 9/11 terrorist attacks—all these trigger and perpetuate fear and worry about the one’s own, and one’s loved ones, abrupt and premature mortality.
Epidemics. Millions died in the 1918 influenza pandemic, prompting widespread societal fears that re-intensified during subsequent epidemics: polio in the 1950s, swine flu in the 1970s, SARS (severe acute respiratory syndrome) in the 1990s, West Nile Virus, and avian influenza.
Assassination. The shooting of Archduke Franz Ferdinand of Austria sparked World War I a century ago, but what baby boomers, such as me, vividly remember is our angst over the assassinations of President John F. Kennedy, his brother Robert, and Rev. Dr. Martin Luther King, Jr; the attempted assassination of President Ronald Reagan; and the murder of John Lennon. Each assassination leaves a communal scar on millions, forever reminding them of the ephemeral nature of life at any rung of the social ladder.
Mass murder. The past 100 years began with the Armenian genocide in 1918, followed by the Holocaust of World War II, the Munich Olympics killings, the Jonestown massacre, the Oklahoma City bombing, and, to name a few, the mass murders at Columbine, Virginia Tech, Newtown, and Fort Hood.
Natural disasters can wreak havoc on peoples’ lives. Consider the annual tally of hurricanes (a long list, some—such as Katrina and Sandy—more infamous than others). Add to those storms the earthquakes, tsunamis, erupting volcanoes, floods, and blizzards, and the result is suffering and anxiety on a massive scale, even among those who are not affected directly.
A surprising facet of these disquieting events is the resiliency of people. Life goes on, despite the agony, despair, and solicitude instigated by deadly events. But of those who buckle under the weight of adversity, many end up in a psychiatric clinic or hospital, and are disabled by their symptoms.
Even ‘good’ change can be disquieting
Juxtaposed against these awful events are 100 years of an array of positive, uplifting discoveries, inventions, and medical advances that have completely transformed our lives. Consider: electricity, clean water, women’s right to vote, automobiles, air and space travel, air conditioning, and highway systems; the momentous discoveries of penicillin, antipsychotics, antidepressants, and mood stabilizers; television, the telephone (evolving from dumb to smart), vaccines, oral contraceptives, genetic discoveries, brain imaging technology, and home appliances (refrigerators, microwave ovens, dishwashers); and not at all least, personal computers and the Internet.
But even these advances can generate anxiety and solicitude: Fear of flying, anyone? Embarrassment about a selfie gone viral on the Web? Worry about being a carrier of a breast cancer gene? Claustrophobia inside an MRI scanner?
Hypothesizing about the transfer of anxiety
Could PTSD and solicitude in one generation be transmitted to the next via epigenetic mechanisms (that is, by over-expression or silencing of genes involved in brain development) and could this transmission result in unusual wide-scale stress reactivity? Might this be an example of the infamous Lamarckian “inheritance of acquired characteristics” at the molecular genetic level, in which the anxiety of traumatized parents is transmitted to their offspring? Or could transmission be mediated by being reared in the emotionally oppressive environment of a family still reeling from the effects of war, disaster, and mass murder?
Such questions might sound rhetorical, but they present a reasonable hypothesis that can be answered by research. Findings from animal studies suggest that such a phenomenon might occur in humans.2 If those findings are validated, opportunities for preventing societal solicitude might emerge.
Yet, important questions about the impact of these events have not been asked: Can there be a transgenerational neurobiological effect on the children and grandchildren of people who have been subjected to life-threatening, traumatic societal events? Could the psychobiology of widespread anxiety and worry (solicitude) be experienced not only by the generation that witnessed and lived through those devastating events, but also by their progeny, who were not yet born during the traumatic events? And could there be epigenetic consequences on a large scale, producing a generation that shares traits induced by the trauma experienced by the previous generation?
Did the rise of delinquency in the 1950s, followed by the anti-war rebellion, unprecedented sexual promiscuity, and substance abuse of the 1960s, be the result of genetic changes in the previous generation induced by living through World War II—after which the generation that grew up in the 1960s was born?
In the late Gabriel García Márquez’s masterpiece novel, One Hundred Years of Solitude, the 1982 Nobel Laureate’s chronicle of the Buendía family across 7 generations is replete with dark and insalubrious events. The fictional family’s story is considered a metaphor for the tumultuous evolution of Márquez’s native Colombia, but that story is consistent with the concept of transgenerational transmission of the biologic effects of stress, as each generation of the Buendía family manifests unusual, even pathological behaviors.
One hundred years of alarm, panic, and anxiety
Psychiatrists are keenly aware of the impact of stressful events on their patients’ mood and behavior, and of the association of life-threatening events with posttraumatic stress disorder (PTSD). For persons who suffer the generalized anxiety of PTSD, further stressful life events can aggravate their condition and result in additional anxiety and solicitude.
It is not surprising that anxiety has been documented as the most common psychiatric condition in the United States.1 Consider the variety of perturbations that have induced alarm, panic, fear, and simmering anxiety on a global scale over the past 100 years— starting with World War I, exactly a century ago.
War. The ruinous 4-year Great War was followed 20 years later by World War II, which caused tens of millions of casualties and the annihilation of Hiroshima and Nagasaki by the atomic bomb— escalating fear of nuclear warfare and radiation poisoning for decades to come. Add to that the Korean War, the Vietnam conflict, the First Gulf War, and the Iraq and Afghanistan wars. The war fatigue and mental exhaustion of the population are palpable.
Economic upheaval. After the Stock Market Crash of 1929 came the Great Depression, the recessions of the 1970s and early 1980s, another stock market crash in 1987, and, most recently, the financial crisis of 2008. Millions saw their wealth wiped out and their livelihoods disrupted, exerting enormous life-changing stresses on countless families.
Disasters. The sinking of the Titanic in 1912, the crash of the Hindenburg, the Three Mile Island nuclear accident, the meltdown of the Chernobyl and Fukushima Daiichi reactors, the space shuttle disasters, and the 9/11 terrorist attacks—all these trigger and perpetuate fear and worry about the one’s own, and one’s loved ones, abrupt and premature mortality.
Epidemics. Millions died in the 1918 influenza pandemic, prompting widespread societal fears that re-intensified during subsequent epidemics: polio in the 1950s, swine flu in the 1970s, SARS (severe acute respiratory syndrome) in the 1990s, West Nile Virus, and avian influenza.
Assassination. The shooting of Archduke Franz Ferdinand of Austria sparked World War I a century ago, but what baby boomers, such as me, vividly remember is our angst over the assassinations of President John F. Kennedy, his brother Robert, and Rev. Dr. Martin Luther King, Jr; the attempted assassination of President Ronald Reagan; and the murder of John Lennon. Each assassination leaves a communal scar on millions, forever reminding them of the ephemeral nature of life at any rung of the social ladder.
Mass murder. The past 100 years began with the Armenian genocide in 1918, followed by the Holocaust of World War II, the Munich Olympics killings, the Jonestown massacre, the Oklahoma City bombing, and, to name a few, the mass murders at Columbine, Virginia Tech, Newtown, and Fort Hood.
Natural disasters can wreak havoc on peoples’ lives. Consider the annual tally of hurricanes (a long list, some—such as Katrina and Sandy—more infamous than others). Add to those storms the earthquakes, tsunamis, erupting volcanoes, floods, and blizzards, and the result is suffering and anxiety on a massive scale, even among those who are not affected directly.
A surprising facet of these disquieting events is the resiliency of people. Life goes on, despite the agony, despair, and solicitude instigated by deadly events. But of those who buckle under the weight of adversity, many end up in a psychiatric clinic or hospital, and are disabled by their symptoms.
Even ‘good’ change can be disquieting
Juxtaposed against these awful events are 100 years of an array of positive, uplifting discoveries, inventions, and medical advances that have completely transformed our lives. Consider: electricity, clean water, women’s right to vote, automobiles, air and space travel, air conditioning, and highway systems; the momentous discoveries of penicillin, antipsychotics, antidepressants, and mood stabilizers; television, the telephone (evolving from dumb to smart), vaccines, oral contraceptives, genetic discoveries, brain imaging technology, and home appliances (refrigerators, microwave ovens, dishwashers); and not at all least, personal computers and the Internet.
But even these advances can generate anxiety and solicitude: Fear of flying, anyone? Embarrassment about a selfie gone viral on the Web? Worry about being a carrier of a breast cancer gene? Claustrophobia inside an MRI scanner?
Hypothesizing about the transfer of anxiety
Could PTSD and solicitude in one generation be transmitted to the next via epigenetic mechanisms (that is, by over-expression or silencing of genes involved in brain development) and could this transmission result in unusual wide-scale stress reactivity? Might this be an example of the infamous Lamarckian “inheritance of acquired characteristics” at the molecular genetic level, in which the anxiety of traumatized parents is transmitted to their offspring? Or could transmission be mediated by being reared in the emotionally oppressive environment of a family still reeling from the effects of war, disaster, and mass murder?
Such questions might sound rhetorical, but they present a reasonable hypothesis that can be answered by research. Findings from animal studies suggest that such a phenomenon might occur in humans.2 If those findings are validated, opportunities for preventing societal solicitude might emerge.
1. Robins LN, Regier DA, eds. Psychiatric disorders in America: The Epidemiologic Catchment Area Study. New York, New York: The Free Press; 1991.
2. Rechavi O, Minevich G, Hobert O. Transgenerational inheritance of an acquired small RNA-based antiviral response in C. elegans. Cell. 2011;147(6):1248-1256.
1. Robins LN, Regier DA, eds. Psychiatric disorders in America: The Epidemiologic Catchment Area Study. New York, New York: The Free Press; 1991.
2. Rechavi O, Minevich G, Hobert O. Transgenerational inheritance of an acquired small RNA-based antiviral response in C. elegans. Cell. 2011;147(6):1248-1256.
Borderline personality disorder is a heritable brain disease
The prevailing view among many psychiatrists and mental health professionals is that borderline personality disorder (BPD) is a “psychological” condition. BPD often is conceptualized as a behavioral consequence of childhood trauma; treatment approaches have emphasized intensive psychotherapeutic modalities, less so biologic interventions. You might not be aware that a large body of research over the past decade provides strong evidence that BPD is a neurobiological illness—a finding that would drastically alter how the disorder should be conceptualized and managed.
Neuropathology underpins the personality disorder
Foremost, BPD must be regarded as a serious, disabling brain disorder, not simply an aberration of personality. In DSM-5, symptoms of BPD are listed as: feelings of abandonment; unstable and intense interpersonal relationships; unstable sense of self; impulsivity; suicidal or self-mutilating behavior; affective instability (dysphoria, irritability, anxiety); chronic feelings of emptiness; intense anger episodes; and transient paranoid or dissociative symptoms. Clearly, these clusters of psychopathological and behavioral symptoms reflect a pervasive brain disorder associated with abnormal neurobiology and neural circuitry that might, at times, stubbornly defy therapeutic intervention.
No wonder that 42 published studies report that, compared with healthy controls, people who have BPD display extensive cortical and subcortical abnormalities in brain structure and function.1 These anomalous patterns have been detected across all 4 available neuroimaging techniques.
Magnetic resonance imaging. MRI studies have revealed the following abnormalities in BPD:
• hypoplasia of the hippocampus, caudate, and dorsolateral prefrontal cortex
• variations in the CA1 region of the hippocampus and subiculum
• smaller-than-normal orbitofrontal cortex (by 24%, compared with healthy controls) and the mid-temporal and left cingulate gyrii (by 26%)
• larger-than-normal volume of the right inferior parietal cortex and the right parahippocampal gyrus
• loss of gray matter in the frontal, temporal, and parietal cortices
• an enlarged third cerebral ventricle
• in women, reduced size of the medial temporal lobe and amygdala
• in men, a decreased concentration of gray matter in the anterior cingulate
• reversal of normal right-greater-than-left asymmetry of the orbitofrontal cortex gray matter, reflecting loss of gray matter on the right side
• a lower concentration of gray matter in the rostral/subgenual anterior cingulate cortex
• a smaller frontal lobe.
In an analysis of MRI studies,2 correlation was found between structural brain abnormalities and specific symptoms of BPD, such as impulsivity, suicidality, and aggression. These findings might someday guide personalized interventions—for example, using neurostimulation techniques such as repetitive transcranial magnetic stimulation and deep brain stimulation—to modulate the activity of a given region of the brain (depending on which symptom is most prominent or disabling).
Magnetic resonance spectroscopy. In BPD, MRS studies reveal:
• compared with controls, a higher glutamate level in the anterior cingulate cortex
• reduced levels of N-acetyl aspartate (NAA; found in neurons) and creatinine in the left amygdala
• a reduction (on average, 19%) in the NAA concentration in the dorsolateral prefrontal cortex.
Functional magnetic resonance imaging. From fMRI studies, there is evidence in BPD of:
• greater activation of the amygdala and prolonged return to baseline
• increased functional connectivity in the left frontopolar cortex and left insula
• decreased connectivity in the left cuneus and left inferior parietal and the right middle temporal lobes
• marked frontal hypometabolism
• hypermetabolism in the motor cortex, medial and anterior cingulate, and occipital and temporal poles
• lower connectivity between the amygdala during a neutral stimulus
• higher connectivity between the amygdala during fear stimulus
• higher connectivity between the amygdala during fear stimulus
• deactivation of the opioid system in the left nucleus accumbens, hypothalamus, and hippocampus
• hyperactivation of the left medial prefrontal cortex during social exclusion
• more mistakes made in differentiating an emotional and a neutral facial expression.
Diffusion tensor imaging. DTI white-matter integrity studies of BPD show:
• a bilateral decrease in fractional anisotropy (FA) in frontal, uncinated, and occipitalfrontal fasciculi
• a decrease in FA in the genu and rostrum of the corpus callosum
• a decrease in inter-hemispheric connectivity between right and left anterior cigulate cortices.
Genetic Studies
There is substantial scientific evidence that BPD is highly heritable—a finding that suggests that brain abnormalities of this disorder are a consequence of genes involved in brain development (similar to what is known about schizophrenia, bipolar disorder, and autism).
A systematic review of the heritability of BPD examined 59 published studies that were categorized into 12 family studies, 18 twin studies, 24 association studies, and 5 gene-environment interaction studies.3 The authors concluded that BPD has a strong genetic component, although there also is evidence of gene-environment (G.E) interactions (ie, how nature and nurture influence each other).
The G.E interaction model appears to be consistent with the theory that expression of plasticity genes is modified by childhood experiences and environment, such as physical or sexual abuse. Some studies have found evidence of hypermethylation in BPD, which can exert epigenetic effects. Childhood abuse might, therefore, disrupt certain neuroplasticity genes, culminating in morphological, neurochemical, metabolic, and white-matter aberrations—leading to pathological behavioral patterns identified as BPD.
The neuropsychiatric basis of BPD must guide treatment
There is no such thing as a purely psychological disorder: Invariably, it is an abnormality of brain circuits that disrupts normal development of emotions, thought, behavior, and social cognition. BPD is an exemplar of such neuropsychiatric illness, and treatment should support psychotherapeutic approaches to mend the mind at the same time it moves aggressively to repair the brain.
1. McKenzie CE, Nasrallah HA. Neuroimaging abnormalities in borderline personality disorder: MRI, MRS, fMRI and DTI findings. Poster presented at: 52nd Annual Meeting of the American College of Neuropsychopharmacology; December 8-12, 2013; Hollywood, FL.
2. McKenzie CE, Nasrallah HA. Clinical symptoms of borderline personality disorder are associated with cortical and subcortical abnormalities on brain magnetic resonance imaging (MRI). Poster presented at: 26th Annual Meeting of the U.S. Psychiatric and Mental Health Congress; September 31-October 3, 2013; Las Vegas, NV.
3. Amad A, Ramoz N, Thomas P, et al. Genetics of borderline personality disorder: systematic review and proposal of an integrative model. Neurosci Biobehav Rev. 2014;40C:6-19.
The prevailing view among many psychiatrists and mental health professionals is that borderline personality disorder (BPD) is a “psychological” condition. BPD often is conceptualized as a behavioral consequence of childhood trauma; treatment approaches have emphasized intensive psychotherapeutic modalities, less so biologic interventions. You might not be aware that a large body of research over the past decade provides strong evidence that BPD is a neurobiological illness—a finding that would drastically alter how the disorder should be conceptualized and managed.
Neuropathology underpins the personality disorder
Foremost, BPD must be regarded as a serious, disabling brain disorder, not simply an aberration of personality. In DSM-5, symptoms of BPD are listed as: feelings of abandonment; unstable and intense interpersonal relationships; unstable sense of self; impulsivity; suicidal or self-mutilating behavior; affective instability (dysphoria, irritability, anxiety); chronic feelings of emptiness; intense anger episodes; and transient paranoid or dissociative symptoms. Clearly, these clusters of psychopathological and behavioral symptoms reflect a pervasive brain disorder associated with abnormal neurobiology and neural circuitry that might, at times, stubbornly defy therapeutic intervention.
No wonder that 42 published studies report that, compared with healthy controls, people who have BPD display extensive cortical and subcortical abnormalities in brain structure and function.1 These anomalous patterns have been detected across all 4 available neuroimaging techniques.
Magnetic resonance imaging. MRI studies have revealed the following abnormalities in BPD:
• hypoplasia of the hippocampus, caudate, and dorsolateral prefrontal cortex
• variations in the CA1 region of the hippocampus and subiculum
• smaller-than-normal orbitofrontal cortex (by 24%, compared with healthy controls) and the mid-temporal and left cingulate gyrii (by 26%)
• larger-than-normal volume of the right inferior parietal cortex and the right parahippocampal gyrus
• loss of gray matter in the frontal, temporal, and parietal cortices
• an enlarged third cerebral ventricle
• in women, reduced size of the medial temporal lobe and amygdala
• in men, a decreased concentration of gray matter in the anterior cingulate
• reversal of normal right-greater-than-left asymmetry of the orbitofrontal cortex gray matter, reflecting loss of gray matter on the right side
• a lower concentration of gray matter in the rostral/subgenual anterior cingulate cortex
• a smaller frontal lobe.
In an analysis of MRI studies,2 correlation was found between structural brain abnormalities and specific symptoms of BPD, such as impulsivity, suicidality, and aggression. These findings might someday guide personalized interventions—for example, using neurostimulation techniques such as repetitive transcranial magnetic stimulation and deep brain stimulation—to modulate the activity of a given region of the brain (depending on which symptom is most prominent or disabling).
Magnetic resonance spectroscopy. In BPD, MRS studies reveal:
• compared with controls, a higher glutamate level in the anterior cingulate cortex
• reduced levels of N-acetyl aspartate (NAA; found in neurons) and creatinine in the left amygdala
• a reduction (on average, 19%) in the NAA concentration in the dorsolateral prefrontal cortex.
Functional magnetic resonance imaging. From fMRI studies, there is evidence in BPD of:
• greater activation of the amygdala and prolonged return to baseline
• increased functional connectivity in the left frontopolar cortex and left insula
• decreased connectivity in the left cuneus and left inferior parietal and the right middle temporal lobes
• marked frontal hypometabolism
• hypermetabolism in the motor cortex, medial and anterior cingulate, and occipital and temporal poles
• lower connectivity between the amygdala during a neutral stimulus
• higher connectivity between the amygdala during fear stimulus
• higher connectivity between the amygdala during fear stimulus
• deactivation of the opioid system in the left nucleus accumbens, hypothalamus, and hippocampus
• hyperactivation of the left medial prefrontal cortex during social exclusion
• more mistakes made in differentiating an emotional and a neutral facial expression.
Diffusion tensor imaging. DTI white-matter integrity studies of BPD show:
• a bilateral decrease in fractional anisotropy (FA) in frontal, uncinated, and occipitalfrontal fasciculi
• a decrease in FA in the genu and rostrum of the corpus callosum
• a decrease in inter-hemispheric connectivity between right and left anterior cigulate cortices.
Genetic Studies
There is substantial scientific evidence that BPD is highly heritable—a finding that suggests that brain abnormalities of this disorder are a consequence of genes involved in brain development (similar to what is known about schizophrenia, bipolar disorder, and autism).
A systematic review of the heritability of BPD examined 59 published studies that were categorized into 12 family studies, 18 twin studies, 24 association studies, and 5 gene-environment interaction studies.3 The authors concluded that BPD has a strong genetic component, although there also is evidence of gene-environment (G.E) interactions (ie, how nature and nurture influence each other).
The G.E interaction model appears to be consistent with the theory that expression of plasticity genes is modified by childhood experiences and environment, such as physical or sexual abuse. Some studies have found evidence of hypermethylation in BPD, which can exert epigenetic effects. Childhood abuse might, therefore, disrupt certain neuroplasticity genes, culminating in morphological, neurochemical, metabolic, and white-matter aberrations—leading to pathological behavioral patterns identified as BPD.
The neuropsychiatric basis of BPD must guide treatment
There is no such thing as a purely psychological disorder: Invariably, it is an abnormality of brain circuits that disrupts normal development of emotions, thought, behavior, and social cognition. BPD is an exemplar of such neuropsychiatric illness, and treatment should support psychotherapeutic approaches to mend the mind at the same time it moves aggressively to repair the brain.
The prevailing view among many psychiatrists and mental health professionals is that borderline personality disorder (BPD) is a “psychological” condition. BPD often is conceptualized as a behavioral consequence of childhood trauma; treatment approaches have emphasized intensive psychotherapeutic modalities, less so biologic interventions. You might not be aware that a large body of research over the past decade provides strong evidence that BPD is a neurobiological illness—a finding that would drastically alter how the disorder should be conceptualized and managed.
Neuropathology underpins the personality disorder
Foremost, BPD must be regarded as a serious, disabling brain disorder, not simply an aberration of personality. In DSM-5, symptoms of BPD are listed as: feelings of abandonment; unstable and intense interpersonal relationships; unstable sense of self; impulsivity; suicidal or self-mutilating behavior; affective instability (dysphoria, irritability, anxiety); chronic feelings of emptiness; intense anger episodes; and transient paranoid or dissociative symptoms. Clearly, these clusters of psychopathological and behavioral symptoms reflect a pervasive brain disorder associated with abnormal neurobiology and neural circuitry that might, at times, stubbornly defy therapeutic intervention.
No wonder that 42 published studies report that, compared with healthy controls, people who have BPD display extensive cortical and subcortical abnormalities in brain structure and function.1 These anomalous patterns have been detected across all 4 available neuroimaging techniques.
Magnetic resonance imaging. MRI studies have revealed the following abnormalities in BPD:
• hypoplasia of the hippocampus, caudate, and dorsolateral prefrontal cortex
• variations in the CA1 region of the hippocampus and subiculum
• smaller-than-normal orbitofrontal cortex (by 24%, compared with healthy controls) and the mid-temporal and left cingulate gyrii (by 26%)
• larger-than-normal volume of the right inferior parietal cortex and the right parahippocampal gyrus
• loss of gray matter in the frontal, temporal, and parietal cortices
• an enlarged third cerebral ventricle
• in women, reduced size of the medial temporal lobe and amygdala
• in men, a decreased concentration of gray matter in the anterior cingulate
• reversal of normal right-greater-than-left asymmetry of the orbitofrontal cortex gray matter, reflecting loss of gray matter on the right side
• a lower concentration of gray matter in the rostral/subgenual anterior cingulate cortex
• a smaller frontal lobe.
In an analysis of MRI studies,2 correlation was found between structural brain abnormalities and specific symptoms of BPD, such as impulsivity, suicidality, and aggression. These findings might someday guide personalized interventions—for example, using neurostimulation techniques such as repetitive transcranial magnetic stimulation and deep brain stimulation—to modulate the activity of a given region of the brain (depending on which symptom is most prominent or disabling).
Magnetic resonance spectroscopy. In BPD, MRS studies reveal:
• compared with controls, a higher glutamate level in the anterior cingulate cortex
• reduced levels of N-acetyl aspartate (NAA; found in neurons) and creatinine in the left amygdala
• a reduction (on average, 19%) in the NAA concentration in the dorsolateral prefrontal cortex.
Functional magnetic resonance imaging. From fMRI studies, there is evidence in BPD of:
• greater activation of the amygdala and prolonged return to baseline
• increased functional connectivity in the left frontopolar cortex and left insula
• decreased connectivity in the left cuneus and left inferior parietal and the right middle temporal lobes
• marked frontal hypometabolism
• hypermetabolism in the motor cortex, medial and anterior cingulate, and occipital and temporal poles
• lower connectivity between the amygdala during a neutral stimulus
• higher connectivity between the amygdala during fear stimulus
• higher connectivity between the amygdala during fear stimulus
• deactivation of the opioid system in the left nucleus accumbens, hypothalamus, and hippocampus
• hyperactivation of the left medial prefrontal cortex during social exclusion
• more mistakes made in differentiating an emotional and a neutral facial expression.
Diffusion tensor imaging. DTI white-matter integrity studies of BPD show:
• a bilateral decrease in fractional anisotropy (FA) in frontal, uncinated, and occipitalfrontal fasciculi
• a decrease in FA in the genu and rostrum of the corpus callosum
• a decrease in inter-hemispheric connectivity between right and left anterior cigulate cortices.
Genetic Studies
There is substantial scientific evidence that BPD is highly heritable—a finding that suggests that brain abnormalities of this disorder are a consequence of genes involved in brain development (similar to what is known about schizophrenia, bipolar disorder, and autism).
A systematic review of the heritability of BPD examined 59 published studies that were categorized into 12 family studies, 18 twin studies, 24 association studies, and 5 gene-environment interaction studies.3 The authors concluded that BPD has a strong genetic component, although there also is evidence of gene-environment (G.E) interactions (ie, how nature and nurture influence each other).
The G.E interaction model appears to be consistent with the theory that expression of plasticity genes is modified by childhood experiences and environment, such as physical or sexual abuse. Some studies have found evidence of hypermethylation in BPD, which can exert epigenetic effects. Childhood abuse might, therefore, disrupt certain neuroplasticity genes, culminating in morphological, neurochemical, metabolic, and white-matter aberrations—leading to pathological behavioral patterns identified as BPD.
The neuropsychiatric basis of BPD must guide treatment
There is no such thing as a purely psychological disorder: Invariably, it is an abnormality of brain circuits that disrupts normal development of emotions, thought, behavior, and social cognition. BPD is an exemplar of such neuropsychiatric illness, and treatment should support psychotherapeutic approaches to mend the mind at the same time it moves aggressively to repair the brain.
1. McKenzie CE, Nasrallah HA. Neuroimaging abnormalities in borderline personality disorder: MRI, MRS, fMRI and DTI findings. Poster presented at: 52nd Annual Meeting of the American College of Neuropsychopharmacology; December 8-12, 2013; Hollywood, FL.
2. McKenzie CE, Nasrallah HA. Clinical symptoms of borderline personality disorder are associated with cortical and subcortical abnormalities on brain magnetic resonance imaging (MRI). Poster presented at: 26th Annual Meeting of the U.S. Psychiatric and Mental Health Congress; September 31-October 3, 2013; Las Vegas, NV.
3. Amad A, Ramoz N, Thomas P, et al. Genetics of borderline personality disorder: systematic review and proposal of an integrative model. Neurosci Biobehav Rev. 2014;40C:6-19.
1. McKenzie CE, Nasrallah HA. Neuroimaging abnormalities in borderline personality disorder: MRI, MRS, fMRI and DTI findings. Poster presented at: 52nd Annual Meeting of the American College of Neuropsychopharmacology; December 8-12, 2013; Hollywood, FL.
2. McKenzie CE, Nasrallah HA. Clinical symptoms of borderline personality disorder are associated with cortical and subcortical abnormalities on brain magnetic resonance imaging (MRI). Poster presented at: 26th Annual Meeting of the U.S. Psychiatric and Mental Health Congress; September 31-October 3, 2013; Las Vegas, NV.
3. Amad A, Ramoz N, Thomas P, et al. Genetics of borderline personality disorder: systematic review and proposal of an integrative model. Neurosci Biobehav Rev. 2014;40C:6-19.
A brave new era of IV psychopharmacotherapy
Most psychiatrists generally avoid starting an IV line on their patients these days, but delivering psychotropic medications by infusion has been employed in psychiatry for decades—mainly in cases of acute psychiatric emergencies.
IV pharmacotherapy might be evolving, however, to address the treatment of severe, chronic, intractable, and disabling disorders that have failed to respond to multiple oral formulations. In addition, IV therapy might be exploited to hasten onset of a therapeutic response.
In short, IV delivery of psychotropics might soon become a routine psychiatric “procedure.”
In the past
Apart from the desperate measures of pentylenetetrazol-induced seizures for depression and insulin coma for schizophrenia—both eventually discarded—psychiatrists have used IV pharmacotherapeutic interventions since the dawn of psychopharmacology in the 1950s. These include:
• Droperidol (the highly sedating cousin of haloperidol) for severe agitation
or aggressive behavior in an emergency setting
• Haloperidol for delirium in the intensive care unit
• Benzodiazepines for severe anxiety and panic attacks (although the IM
route is preferable)
• Clomipramine to potentiate the effect of a selective serotonin reuptake inhibitor in treatment-resistant depression
• Valproate to accelerate mood stabilization in acute mania.
The present
Recently, a mini-avalanche of novel studies has signaled a paradigm shift to IV therapy for refractory unipolar and bipolar depression.
Ketamine. Administering the N-methyl-d-aspartate (NMDA) glutamate receptor antagonist ketamine (a cousin of phencyclidine and a well-known drug of abuse with psychotogenic properties) by IV infusion (0.5 mg/kg) produces rapid improvement, sometimes complete remission, of chronic, treatment-resistant depression. The effect seen in 1 or 2 hours matches what oral antidepressants accomplish in 6 to 8 weeks in a responsive patient.1,2 The response to IV ketamine lasts approximately 1 week and is initially associated with transient dissociation.
Another reported benefit of IV ketamine is rapid reversal of suicidal intent.3 This effect is envisioned as a future alternative to hospitalizing patients brought to the emergency room after a suicide attempt.
To be clear: The long-term (maintenance) safety and efficacy of repeated infusions of IV ketamine to maintain response in chronic, treatment-resistant depression has not been studied.
IV ketamine therapy for severe depression is a dual paradigm shift: 1) it uses the IV route and 2) it modulates the glutamate ion-channel receptor NMDA—a major departure from the 50-year-old monoamine hypothesis of depression, in which a deficit of serotonin and/or norepinephrine was proposed. The mechanism of action of IV ketamine appears to be instant triggering of neuroplasticity in the mammalian target of rapamycin (mTOR), as observed in animal studies. A significant surge in brain-derived neurotrophic factor appears to be involved as well.
Scopolamine. Another novel IV treatment for depression was reported recently,4 based on old studies in which tearfulness and dysphoria were induced by increasing cholinergic activity with IV physostigmine. The anticholinergic drug scopolamine was administered to depressed patients by pulsed IV infusion (4.0 μg/kg over 15 minutes), and rapid improvement in depression was observed within 72 hours in patients with unipolar and bipolar depression. Anticholinergic side effects were mild; women responded better than men.
Nitroprusside. A similar breakthrough with IV pharmacotherapy was recently reported in schizophrenia, in which traditional oral antipsychotic treatment is limited to suppressing positive symptoms, leaving negative symptoms and cognitive deficits unchanged. The old antihypertensive drug nitroprusside, which modulates nitrous oxide and, by extension, NMDA, was administered IV to a small sample of patients with schizophrenia.5 Significant improvement was observed not only in positive (psychotic) symptoms, but also in negative and cognitive symptoms. Improvement occurred within a few hours and lasted for as long as 4 weeks. Studies are underway to replicate the investigators’ findings about this potentially ground-breaking and novel approach to schizophrenia.
For the future
Given these recent successes, it is reasonable to speculate that IV drugs might someday become a major tool in the practice of psychiatry—transcending emergent uses (suicidal, homicidal, and delirious states) and becoming a mainstream treatment for acute episodes of psychosis, mania, depression, and anxiety. In addition, research might reveal that medications already approved for oral delivery exert a more robust response and a more rapid onset of action when delivered IV—assuming no serious safety issues arise.
Advances in our understanding of the neurobiologic basis and pathophysiology of psychiatric disorders might provide clues to agents that are not even on the current radar screen of psychiatry’s pharmacopoeia. Treatment-resistant conditions are obvious initial candidates for IV pharmacotherapy, but so might be acute episodes of psychosis, mania, and depression, and panic attacks. Just as status epilepticus requires IV, rather than oral, delivery of an anticonvulsant, we might conceptualize acute psychotic, mood, and anxiety episodes as emergent conditions of status psychiatricus that require rapid stabilization with IV medication instead of a pill.
The bottom line?
IV delivery of drugs might soon be a routine psychiatric “procedure.” Better brush up on your skills for starting an infusion!
Drug Brand Names
Benztropine • Cogentin Pentylenetetrazol • Metrazol
Clomipramine • Anafranil Physostigmine • Antilirium
Diphenhydramine• Benadryl Scopolamine • Scopace, Transderm-Scop
Droperidol • Inapsine Valproate • Depacon
Haloperidol • Haldol
Ketamine • Ketalar
Nitroprusside • Nitropress
1. DiazGranados N, Ibrahim LA, Brutsche NE, et al. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry. 2010;71(12):1605-1611.
2. Rasmussen KG, Lineberry TW, Galardy CW, et al. Serial infusions of low-dose ketamine for major depression. J Psychopharmacol. 2013;27(5):444-450.
3. Zarate CA Jr, Brutsche NE, Ibrahim L, et al. Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry. 2012;71(11):939-946.
4. Drevets WC, Furey ML. Replication of scopolamine’s antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial. Biol Psychiatry. 2010;67(5):432-438.
5. Hallak JE, Maia-de-Oliveira JP, Abrao J, et al. Rapid improvement of acute schizophrenia symptoms after intravenous sodium nitroprusside: a randomized, double-blind, placebo-controlled trial. JAMA Psychiatry. 2013;70(7):668-676.
Most psychiatrists generally avoid starting an IV line on their patients these days, but delivering psychotropic medications by infusion has been employed in psychiatry for decades—mainly in cases of acute psychiatric emergencies.
IV pharmacotherapy might be evolving, however, to address the treatment of severe, chronic, intractable, and disabling disorders that have failed to respond to multiple oral formulations. In addition, IV therapy might be exploited to hasten onset of a therapeutic response.
In short, IV delivery of psychotropics might soon become a routine psychiatric “procedure.”
In the past
Apart from the desperate measures of pentylenetetrazol-induced seizures for depression and insulin coma for schizophrenia—both eventually discarded—psychiatrists have used IV pharmacotherapeutic interventions since the dawn of psychopharmacology in the 1950s. These include:
• Droperidol (the highly sedating cousin of haloperidol) for severe agitation
or aggressive behavior in an emergency setting
• Haloperidol for delirium in the intensive care unit
• Benzodiazepines for severe anxiety and panic attacks (although the IM
route is preferable)
• Clomipramine to potentiate the effect of a selective serotonin reuptake inhibitor in treatment-resistant depression
• Valproate to accelerate mood stabilization in acute mania.
The present
Recently, a mini-avalanche of novel studies has signaled a paradigm shift to IV therapy for refractory unipolar and bipolar depression.
Ketamine. Administering the N-methyl-d-aspartate (NMDA) glutamate receptor antagonist ketamine (a cousin of phencyclidine and a well-known drug of abuse with psychotogenic properties) by IV infusion (0.5 mg/kg) produces rapid improvement, sometimes complete remission, of chronic, treatment-resistant depression. The effect seen in 1 or 2 hours matches what oral antidepressants accomplish in 6 to 8 weeks in a responsive patient.1,2 The response to IV ketamine lasts approximately 1 week and is initially associated with transient dissociation.
Another reported benefit of IV ketamine is rapid reversal of suicidal intent.3 This effect is envisioned as a future alternative to hospitalizing patients brought to the emergency room after a suicide attempt.
To be clear: The long-term (maintenance) safety and efficacy of repeated infusions of IV ketamine to maintain response in chronic, treatment-resistant depression has not been studied.
IV ketamine therapy for severe depression is a dual paradigm shift: 1) it uses the IV route and 2) it modulates the glutamate ion-channel receptor NMDA—a major departure from the 50-year-old monoamine hypothesis of depression, in which a deficit of serotonin and/or norepinephrine was proposed. The mechanism of action of IV ketamine appears to be instant triggering of neuroplasticity in the mammalian target of rapamycin (mTOR), as observed in animal studies. A significant surge in brain-derived neurotrophic factor appears to be involved as well.
Scopolamine. Another novel IV treatment for depression was reported recently,4 based on old studies in which tearfulness and dysphoria were induced by increasing cholinergic activity with IV physostigmine. The anticholinergic drug scopolamine was administered to depressed patients by pulsed IV infusion (4.0 μg/kg over 15 minutes), and rapid improvement in depression was observed within 72 hours in patients with unipolar and bipolar depression. Anticholinergic side effects were mild; women responded better than men.
Nitroprusside. A similar breakthrough with IV pharmacotherapy was recently reported in schizophrenia, in which traditional oral antipsychotic treatment is limited to suppressing positive symptoms, leaving negative symptoms and cognitive deficits unchanged. The old antihypertensive drug nitroprusside, which modulates nitrous oxide and, by extension, NMDA, was administered IV to a small sample of patients with schizophrenia.5 Significant improvement was observed not only in positive (psychotic) symptoms, but also in negative and cognitive symptoms. Improvement occurred within a few hours and lasted for as long as 4 weeks. Studies are underway to replicate the investigators’ findings about this potentially ground-breaking and novel approach to schizophrenia.
For the future
Given these recent successes, it is reasonable to speculate that IV drugs might someday become a major tool in the practice of psychiatry—transcending emergent uses (suicidal, homicidal, and delirious states) and becoming a mainstream treatment for acute episodes of psychosis, mania, depression, and anxiety. In addition, research might reveal that medications already approved for oral delivery exert a more robust response and a more rapid onset of action when delivered IV—assuming no serious safety issues arise.
Advances in our understanding of the neurobiologic basis and pathophysiology of psychiatric disorders might provide clues to agents that are not even on the current radar screen of psychiatry’s pharmacopoeia. Treatment-resistant conditions are obvious initial candidates for IV pharmacotherapy, but so might be acute episodes of psychosis, mania, and depression, and panic attacks. Just as status epilepticus requires IV, rather than oral, delivery of an anticonvulsant, we might conceptualize acute psychotic, mood, and anxiety episodes as emergent conditions of status psychiatricus that require rapid stabilization with IV medication instead of a pill.
The bottom line?
IV delivery of drugs might soon be a routine psychiatric “procedure.” Better brush up on your skills for starting an infusion!
Drug Brand Names
Benztropine • Cogentin Pentylenetetrazol • Metrazol
Clomipramine • Anafranil Physostigmine • Antilirium
Diphenhydramine• Benadryl Scopolamine • Scopace, Transderm-Scop
Droperidol • Inapsine Valproate • Depacon
Haloperidol • Haldol
Ketamine • Ketalar
Nitroprusside • Nitropress
Most psychiatrists generally avoid starting an IV line on their patients these days, but delivering psychotropic medications by infusion has been employed in psychiatry for decades—mainly in cases of acute psychiatric emergencies.
IV pharmacotherapy might be evolving, however, to address the treatment of severe, chronic, intractable, and disabling disorders that have failed to respond to multiple oral formulations. In addition, IV therapy might be exploited to hasten onset of a therapeutic response.
In short, IV delivery of psychotropics might soon become a routine psychiatric “procedure.”
In the past
Apart from the desperate measures of pentylenetetrazol-induced seizures for depression and insulin coma for schizophrenia—both eventually discarded—psychiatrists have used IV pharmacotherapeutic interventions since the dawn of psychopharmacology in the 1950s. These include:
• Droperidol (the highly sedating cousin of haloperidol) for severe agitation
or aggressive behavior in an emergency setting
• Haloperidol for delirium in the intensive care unit
• Benzodiazepines for severe anxiety and panic attacks (although the IM
route is preferable)
• Clomipramine to potentiate the effect of a selective serotonin reuptake inhibitor in treatment-resistant depression
• Valproate to accelerate mood stabilization in acute mania.
The present
Recently, a mini-avalanche of novel studies has signaled a paradigm shift to IV therapy for refractory unipolar and bipolar depression.
Ketamine. Administering the N-methyl-d-aspartate (NMDA) glutamate receptor antagonist ketamine (a cousin of phencyclidine and a well-known drug of abuse with psychotogenic properties) by IV infusion (0.5 mg/kg) produces rapid improvement, sometimes complete remission, of chronic, treatment-resistant depression. The effect seen in 1 or 2 hours matches what oral antidepressants accomplish in 6 to 8 weeks in a responsive patient.1,2 The response to IV ketamine lasts approximately 1 week and is initially associated with transient dissociation.
Another reported benefit of IV ketamine is rapid reversal of suicidal intent.3 This effect is envisioned as a future alternative to hospitalizing patients brought to the emergency room after a suicide attempt.
To be clear: The long-term (maintenance) safety and efficacy of repeated infusions of IV ketamine to maintain response in chronic, treatment-resistant depression has not been studied.
IV ketamine therapy for severe depression is a dual paradigm shift: 1) it uses the IV route and 2) it modulates the glutamate ion-channel receptor NMDA—a major departure from the 50-year-old monoamine hypothesis of depression, in which a deficit of serotonin and/or norepinephrine was proposed. The mechanism of action of IV ketamine appears to be instant triggering of neuroplasticity in the mammalian target of rapamycin (mTOR), as observed in animal studies. A significant surge in brain-derived neurotrophic factor appears to be involved as well.
Scopolamine. Another novel IV treatment for depression was reported recently,4 based on old studies in which tearfulness and dysphoria were induced by increasing cholinergic activity with IV physostigmine. The anticholinergic drug scopolamine was administered to depressed patients by pulsed IV infusion (4.0 μg/kg over 15 minutes), and rapid improvement in depression was observed within 72 hours in patients with unipolar and bipolar depression. Anticholinergic side effects were mild; women responded better than men.
Nitroprusside. A similar breakthrough with IV pharmacotherapy was recently reported in schizophrenia, in which traditional oral antipsychotic treatment is limited to suppressing positive symptoms, leaving negative symptoms and cognitive deficits unchanged. The old antihypertensive drug nitroprusside, which modulates nitrous oxide and, by extension, NMDA, was administered IV to a small sample of patients with schizophrenia.5 Significant improvement was observed not only in positive (psychotic) symptoms, but also in negative and cognitive symptoms. Improvement occurred within a few hours and lasted for as long as 4 weeks. Studies are underway to replicate the investigators’ findings about this potentially ground-breaking and novel approach to schizophrenia.
For the future
Given these recent successes, it is reasonable to speculate that IV drugs might someday become a major tool in the practice of psychiatry—transcending emergent uses (suicidal, homicidal, and delirious states) and becoming a mainstream treatment for acute episodes of psychosis, mania, depression, and anxiety. In addition, research might reveal that medications already approved for oral delivery exert a more robust response and a more rapid onset of action when delivered IV—assuming no serious safety issues arise.
Advances in our understanding of the neurobiologic basis and pathophysiology of psychiatric disorders might provide clues to agents that are not even on the current radar screen of psychiatry’s pharmacopoeia. Treatment-resistant conditions are obvious initial candidates for IV pharmacotherapy, but so might be acute episodes of psychosis, mania, and depression, and panic attacks. Just as status epilepticus requires IV, rather than oral, delivery of an anticonvulsant, we might conceptualize acute psychotic, mood, and anxiety episodes as emergent conditions of status psychiatricus that require rapid stabilization with IV medication instead of a pill.
The bottom line?
IV delivery of drugs might soon be a routine psychiatric “procedure.” Better brush up on your skills for starting an infusion!
Drug Brand Names
Benztropine • Cogentin Pentylenetetrazol • Metrazol
Clomipramine • Anafranil Physostigmine • Antilirium
Diphenhydramine• Benadryl Scopolamine • Scopace, Transderm-Scop
Droperidol • Inapsine Valproate • Depacon
Haloperidol • Haldol
Ketamine • Ketalar
Nitroprusside • Nitropress
1. DiazGranados N, Ibrahim LA, Brutsche NE, et al. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry. 2010;71(12):1605-1611.
2. Rasmussen KG, Lineberry TW, Galardy CW, et al. Serial infusions of low-dose ketamine for major depression. J Psychopharmacol. 2013;27(5):444-450.
3. Zarate CA Jr, Brutsche NE, Ibrahim L, et al. Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry. 2012;71(11):939-946.
4. Drevets WC, Furey ML. Replication of scopolamine’s antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial. Biol Psychiatry. 2010;67(5):432-438.
5. Hallak JE, Maia-de-Oliveira JP, Abrao J, et al. Rapid improvement of acute schizophrenia symptoms after intravenous sodium nitroprusside: a randomized, double-blind, placebo-controlled trial. JAMA Psychiatry. 2013;70(7):668-676.
1. DiazGranados N, Ibrahim LA, Brutsche NE, et al. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry. 2010;71(12):1605-1611.
2. Rasmussen KG, Lineberry TW, Galardy CW, et al. Serial infusions of low-dose ketamine for major depression. J Psychopharmacol. 2013;27(5):444-450.
3. Zarate CA Jr, Brutsche NE, Ibrahim L, et al. Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry. 2012;71(11):939-946.
4. Drevets WC, Furey ML. Replication of scopolamine’s antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial. Biol Psychiatry. 2010;67(5):432-438.
5. Hallak JE, Maia-de-Oliveira JP, Abrao J, et al. Rapid improvement of acute schizophrenia symptoms after intravenous sodium nitroprusside: a randomized, double-blind, placebo-controlled trial. JAMA Psychiatry. 2013;70(7):668-676.
Psychiatry’s future shock
It might seem business as usual in clinical psychiatry, but major transformative changes in the scientific foundation of the specialty are taking place. The “neuroscientification” of psychiatry, ongoing for more than 3 decades, is now approaching a tipping point: The specialty is on the verge of an unprecedented denouement of the old tenets and assumptions. Just as smartphones have made a 25-volume encyclopedia set obsolete, coming changes in scientific psychiatry will be fully disruptive to your father’s practice of psychiatry.
Many psychiatrists still practice like it’s 1999
That situation will change, soon—as surely as medieval times gave way to the Renaissance. Psychiatry of the future will be drastically different once new models of objective diagnostic tests and physiologically specific interventions emerge from fast-moving discoveries of the molecular biology of the mind and its pathologies.
Most psychiatric practitioners do not regularly read neuroscience journals that describe the accelerating progress in molecular psychiatry, where the text is replete with an alphabet soup of terminology that one day will permeate the medical practice of the new psychiatry.
Fuzzy ambiguities will be cleared away
There are many reasons to be optimistic that transcendent scientific transformations will sweep away the fuzzy biologic, diagnostic, and therapeutic ambiguities that have plagued psychiatry for so long—plagued us because of the herculean challenges of investigating the divinely complex brain and its gloriously enigmatic mind. New methods and tools for exploration and paradigmatic shifts in conceptualizing the etiopathogenesis of psychiatric brain disorders are rapidly leading to a discarding of many simplistic, even primitive, notions that have guided psychiatry over the past century. Psychopharmacological breakthroughs of the past 50 years, which, admittedly, have yet to cure or eliminate disabilities associated with major psychiatric disorders, are only a prologue to the coming revolution in neuropsychiatry, in which prevention, not just intervention, will change everything. Curing deteriorative brain disorders will be a reality once that revolution in neuroscience enters its propitious translational phase.
The Table presents a sampling of scientific progress that is setting the stage for disruptive technologies and probes that will lead to far more advanced diagnosis, prevention, and treatment of neuropsychiatric diseases.
Prepare for psychiatry’s future shock!
We psychiatrists must keep up, regularly reading the latest literature to learn about the latest advances and to make sure we are familiar with the emerging language of psychiatric neuroscience. Instead of remaining fondly attached to ancient constructs such as id, ego, superego, and defense mechanisms, we should be thinking about the default mode network, seeking to understand the connectome, the envirome, the metabolome, and the proteome; microglial activation, inflammatory markers, IL-6, TNF alpha, oxidative and nitrosative stress, and physiologic vs pathologic apoptosis; BDNF, FGF, VEGF, MIF, GFAP, and S100B; neuroplasticity and dendritic spines; and genes such as CLOCK, NOTCH3, and Met-to-Val mutations—and so on.
Those of us who do not adapt to swift transition of knowledge might suffer the fate of clinical dinosaurs, as the massive asteroid of neuroscientific advances smashes into the placid landscape of psychiatry. As Alvin Toffler, author of Future Shock, proposed, the illiterates of the future will not be the people who cannot read or write. They will be the ones who fail to learn.
It might seem business as usual in clinical psychiatry, but major transformative changes in the scientific foundation of the specialty are taking place. The “neuroscientification” of psychiatry, ongoing for more than 3 decades, is now approaching a tipping point: The specialty is on the verge of an unprecedented denouement of the old tenets and assumptions. Just as smartphones have made a 25-volume encyclopedia set obsolete, coming changes in scientific psychiatry will be fully disruptive to your father’s practice of psychiatry.
Many psychiatrists still practice like it’s 1999
That situation will change, soon—as surely as medieval times gave way to the Renaissance. Psychiatry of the future will be drastically different once new models of objective diagnostic tests and physiologically specific interventions emerge from fast-moving discoveries of the molecular biology of the mind and its pathologies.
Most psychiatric practitioners do not regularly read neuroscience journals that describe the accelerating progress in molecular psychiatry, where the text is replete with an alphabet soup of terminology that one day will permeate the medical practice of the new psychiatry.
Fuzzy ambiguities will be cleared away
There are many reasons to be optimistic that transcendent scientific transformations will sweep away the fuzzy biologic, diagnostic, and therapeutic ambiguities that have plagued psychiatry for so long—plagued us because of the herculean challenges of investigating the divinely complex brain and its gloriously enigmatic mind. New methods and tools for exploration and paradigmatic shifts in conceptualizing the etiopathogenesis of psychiatric brain disorders are rapidly leading to a discarding of many simplistic, even primitive, notions that have guided psychiatry over the past century. Psychopharmacological breakthroughs of the past 50 years, which, admittedly, have yet to cure or eliminate disabilities associated with major psychiatric disorders, are only a prologue to the coming revolution in neuropsychiatry, in which prevention, not just intervention, will change everything. Curing deteriorative brain disorders will be a reality once that revolution in neuroscience enters its propitious translational phase.
The Table presents a sampling of scientific progress that is setting the stage for disruptive technologies and probes that will lead to far more advanced diagnosis, prevention, and treatment of neuropsychiatric diseases.
Prepare for psychiatry’s future shock!
We psychiatrists must keep up, regularly reading the latest literature to learn about the latest advances and to make sure we are familiar with the emerging language of psychiatric neuroscience. Instead of remaining fondly attached to ancient constructs such as id, ego, superego, and defense mechanisms, we should be thinking about the default mode network, seeking to understand the connectome, the envirome, the metabolome, and the proteome; microglial activation, inflammatory markers, IL-6, TNF alpha, oxidative and nitrosative stress, and physiologic vs pathologic apoptosis; BDNF, FGF, VEGF, MIF, GFAP, and S100B; neuroplasticity and dendritic spines; and genes such as CLOCK, NOTCH3, and Met-to-Val mutations—and so on.
Those of us who do not adapt to swift transition of knowledge might suffer the fate of clinical dinosaurs, as the massive asteroid of neuroscientific advances smashes into the placid landscape of psychiatry. As Alvin Toffler, author of Future Shock, proposed, the illiterates of the future will not be the people who cannot read or write. They will be the ones who fail to learn.
It might seem business as usual in clinical psychiatry, but major transformative changes in the scientific foundation of the specialty are taking place. The “neuroscientification” of psychiatry, ongoing for more than 3 decades, is now approaching a tipping point: The specialty is on the verge of an unprecedented denouement of the old tenets and assumptions. Just as smartphones have made a 25-volume encyclopedia set obsolete, coming changes in scientific psychiatry will be fully disruptive to your father’s practice of psychiatry.
Many psychiatrists still practice like it’s 1999
That situation will change, soon—as surely as medieval times gave way to the Renaissance. Psychiatry of the future will be drastically different once new models of objective diagnostic tests and physiologically specific interventions emerge from fast-moving discoveries of the molecular biology of the mind and its pathologies.
Most psychiatric practitioners do not regularly read neuroscience journals that describe the accelerating progress in molecular psychiatry, where the text is replete with an alphabet soup of terminology that one day will permeate the medical practice of the new psychiatry.
Fuzzy ambiguities will be cleared away
There are many reasons to be optimistic that transcendent scientific transformations will sweep away the fuzzy biologic, diagnostic, and therapeutic ambiguities that have plagued psychiatry for so long—plagued us because of the herculean challenges of investigating the divinely complex brain and its gloriously enigmatic mind. New methods and tools for exploration and paradigmatic shifts in conceptualizing the etiopathogenesis of psychiatric brain disorders are rapidly leading to a discarding of many simplistic, even primitive, notions that have guided psychiatry over the past century. Psychopharmacological breakthroughs of the past 50 years, which, admittedly, have yet to cure or eliminate disabilities associated with major psychiatric disorders, are only a prologue to the coming revolution in neuropsychiatry, in which prevention, not just intervention, will change everything. Curing deteriorative brain disorders will be a reality once that revolution in neuroscience enters its propitious translational phase.
The Table presents a sampling of scientific progress that is setting the stage for disruptive technologies and probes that will lead to far more advanced diagnosis, prevention, and treatment of neuropsychiatric diseases.
Prepare for psychiatry’s future shock!
We psychiatrists must keep up, regularly reading the latest literature to learn about the latest advances and to make sure we are familiar with the emerging language of psychiatric neuroscience. Instead of remaining fondly attached to ancient constructs such as id, ego, superego, and defense mechanisms, we should be thinking about the default mode network, seeking to understand the connectome, the envirome, the metabolome, and the proteome; microglial activation, inflammatory markers, IL-6, TNF alpha, oxidative and nitrosative stress, and physiologic vs pathologic apoptosis; BDNF, FGF, VEGF, MIF, GFAP, and S100B; neuroplasticity and dendritic spines; and genes such as CLOCK, NOTCH3, and Met-to-Val mutations—and so on.
Those of us who do not adapt to swift transition of knowledge might suffer the fate of clinical dinosaurs, as the massive asteroid of neuroscientific advances smashes into the placid landscape of psychiatry. As Alvin Toffler, author of Future Shock, proposed, the illiterates of the future will not be the people who cannot read or write. They will be the ones who fail to learn.
The travesty of disparity and non-parity
Staggering disparities and lack of parity mark many aspects of mental health care, at huge cost to the 25% of Americans who suffer a mental disorder. It’s time to correct this unconscionable discrepancy.
Imagine a world in which aortic stenosis is fully covered by health insurance but coverage for atrial fibrillation is carved out and assigned partial coverage, with a high copayment, a limit on physician visits and hospital days, and a lifetime cap on coverage. If it strikes you as outrageous that disorders of the same organ could be treated so differently, with irrational discrimination, think again! Such an egregious injustice has been going on for a long time against disorders of the brain.
Care provided for stroke, brain tumor, and epilepsy is given full coverage—but not so for depression, psychosis, and panic disorder. To make the matter more bizarre, depression is a known complication of certain types of stroke; some brain tumors are associated with psychosis; and panic attacks can occur with complex partial seizures—demonstrating that the pathways of so-called “mental” illnesses are as “physical” as any neurological disorder of the brain.
Welcome to the absurd world of lack of parity for psychiatric brain disorders!
Senseless, unethical discrimination against mental illness goes on unabated, despite lip service by politicians and policy-makers. The lack of parity adds insult to injury for psychiatric patients, inflicting a financial burden atop unbearable suffering and functional disability.
How long will this injustice endure?
For a civilized society, in which discrimination based on skin color, sex, sexual orientation, and religious belief is prohibited, discrimination by medical illness seems to be tolerated with impunity. This is a blind spot of unimaginable magnitude in the conscience of society and a cancerous lesion on its ethical standards.
The lack of parity in health-care coverage for psychiatric disorders is compounded by several other disparities. Consider this array of discriminatory actions and conditions directed at psychiatrists and their patients:
• The mentally ill endure a stigma that deprives them of the compassion and sympathy that people who have other medical disorders routinely receive.
• Managed-care organizations and some health-maintenance organizations are reluctant to allow the use of newer, more tolerable, and less neurotoxic psychoactive medications by psychiatrists and nurse practitioners; instead, they impose a fail-first policy with decades-old generic drugs to save money—although newer drugs are readily available for oncologists, cardiologists, and neurologists to use.
• Behavioral health is always “carved out”—that obscene word—in insurance contracts. This is overt discrimination against the mentally ill and mental health professionals that the government should not allow, in its role as a watchdog of human rights.
• Psychiatric wards usually are the most poorly renovated and oldest section of hospitals, while obstetrics, oncology, cardiology, and orthopedics units have state-of-the-art facilities. Many inner-city community mental health centers look tad better than a war zone, with dilapidated buildings, stained and broken furniture, and peeling walls. Where are the funds that were supposed to be recovered by shuttering asylums and to flow into community care for outpatient mental health care?
• It’s the height of discrimination that the relapsed mentally ill have no place to go but jail or prison. Isn’t it the worst injustice to transform medical illness into a felony? Why are there few long-term facilities for severe mental illness any more—the equivalent of refractory patients? In a civilized nation, why is homelessness among people who have a brain disorder tolerated?
• The medical records of psychiatric patients are segregated and set aside, perpetuating the unfair shame and guilt associated with mental illness. When will a history of depression and a broken spirit be no more secretive than having a broken leg?
• The lack of regard for psychiatry as a vital medical specialty reflects medieval-like ignorance and discrimination in an age when the neurobiology of psychiatric brain disorders is unfolding with dazzling scientific elegance. When will those who treat mood, thought, behavior, and cognition receive the same respect as a surgeon who transplants a liver or a cardiologist who manages heart failure?
• The disparity in access by the seriously mentally ill to primary, secondary, and tertiary care has, literally, fatal consequences. Despite the high prevalence of serious cardio-metabolic, pulmonary, infectious, and gastrointestinal disorders among the mentally ill, a large percentage do not receive the most basic primary care to manage their ailments—let alone undergo special procedures or advanced surgical interventions. This shameful neglect and health-care disparity contribute to early mortality (by 20 to 25 years) among people who suffer a serious mental disorder. This is a deadly disparity, yet it goes unaddressed.
• Last, a disparity exists in funding for research to find the causes of, and cures for, disorders of the brain’s mind. Psychiatric disorders and substance use cost society more than $300 billion annually in the United States, yet investment in research on those disorders pales compared with the support provided to the study of other medical disorders.
It’s time society closed this ugly gap
Lack of parity extends across a broad swath of issues related to mental illness, with a huge personal and material cost to the 25% of the US population that suffers a mental disorder. It’s time to close the shameful gap and end this harmful discrimination. Let’s hope that ongoing changes in health care will, finally, reverse the injustice. Given the broken promises of the past, however, let’s not count our chickens before they hatch….
Staggering disparities and lack of parity mark many aspects of mental health care, at huge cost to the 25% of Americans who suffer a mental disorder. It’s time to correct this unconscionable discrepancy.
Imagine a world in which aortic stenosis is fully covered by health insurance but coverage for atrial fibrillation is carved out and assigned partial coverage, with a high copayment, a limit on physician visits and hospital days, and a lifetime cap on coverage. If it strikes you as outrageous that disorders of the same organ could be treated so differently, with irrational discrimination, think again! Such an egregious injustice has been going on for a long time against disorders of the brain.
Care provided for stroke, brain tumor, and epilepsy is given full coverage—but not so for depression, psychosis, and panic disorder. To make the matter more bizarre, depression is a known complication of certain types of stroke; some brain tumors are associated with psychosis; and panic attacks can occur with complex partial seizures—demonstrating that the pathways of so-called “mental” illnesses are as “physical” as any neurological disorder of the brain.
Welcome to the absurd world of lack of parity for psychiatric brain disorders!
Senseless, unethical discrimination against mental illness goes on unabated, despite lip service by politicians and policy-makers. The lack of parity adds insult to injury for psychiatric patients, inflicting a financial burden atop unbearable suffering and functional disability.
How long will this injustice endure?
For a civilized society, in which discrimination based on skin color, sex, sexual orientation, and religious belief is prohibited, discrimination by medical illness seems to be tolerated with impunity. This is a blind spot of unimaginable magnitude in the conscience of society and a cancerous lesion on its ethical standards.
The lack of parity in health-care coverage for psychiatric disorders is compounded by several other disparities. Consider this array of discriminatory actions and conditions directed at psychiatrists and their patients:
• The mentally ill endure a stigma that deprives them of the compassion and sympathy that people who have other medical disorders routinely receive.
• Managed-care organizations and some health-maintenance organizations are reluctant to allow the use of newer, more tolerable, and less neurotoxic psychoactive medications by psychiatrists and nurse practitioners; instead, they impose a fail-first policy with decades-old generic drugs to save money—although newer drugs are readily available for oncologists, cardiologists, and neurologists to use.
• Behavioral health is always “carved out”—that obscene word—in insurance contracts. This is overt discrimination against the mentally ill and mental health professionals that the government should not allow, in its role as a watchdog of human rights.
• Psychiatric wards usually are the most poorly renovated and oldest section of hospitals, while obstetrics, oncology, cardiology, and orthopedics units have state-of-the-art facilities. Many inner-city community mental health centers look tad better than a war zone, with dilapidated buildings, stained and broken furniture, and peeling walls. Where are the funds that were supposed to be recovered by shuttering asylums and to flow into community care for outpatient mental health care?
• It’s the height of discrimination that the relapsed mentally ill have no place to go but jail or prison. Isn’t it the worst injustice to transform medical illness into a felony? Why are there few long-term facilities for severe mental illness any more—the equivalent of refractory patients? In a civilized nation, why is homelessness among people who have a brain disorder tolerated?
• The medical records of psychiatric patients are segregated and set aside, perpetuating the unfair shame and guilt associated with mental illness. When will a history of depression and a broken spirit be no more secretive than having a broken leg?
• The lack of regard for psychiatry as a vital medical specialty reflects medieval-like ignorance and discrimination in an age when the neurobiology of psychiatric brain disorders is unfolding with dazzling scientific elegance. When will those who treat mood, thought, behavior, and cognition receive the same respect as a surgeon who transplants a liver or a cardiologist who manages heart failure?
• The disparity in access by the seriously mentally ill to primary, secondary, and tertiary care has, literally, fatal consequences. Despite the high prevalence of serious cardio-metabolic, pulmonary, infectious, and gastrointestinal disorders among the mentally ill, a large percentage do not receive the most basic primary care to manage their ailments—let alone undergo special procedures or advanced surgical interventions. This shameful neglect and health-care disparity contribute to early mortality (by 20 to 25 years) among people who suffer a serious mental disorder. This is a deadly disparity, yet it goes unaddressed.
• Last, a disparity exists in funding for research to find the causes of, and cures for, disorders of the brain’s mind. Psychiatric disorders and substance use cost society more than $300 billion annually in the United States, yet investment in research on those disorders pales compared with the support provided to the study of other medical disorders.
It’s time society closed this ugly gap
Lack of parity extends across a broad swath of issues related to mental illness, with a huge personal and material cost to the 25% of the US population that suffers a mental disorder. It’s time to close the shameful gap and end this harmful discrimination. Let’s hope that ongoing changes in health care will, finally, reverse the injustice. Given the broken promises of the past, however, let’s not count our chickens before they hatch….
Staggering disparities and lack of parity mark many aspects of mental health care, at huge cost to the 25% of Americans who suffer a mental disorder. It’s time to correct this unconscionable discrepancy.
Imagine a world in which aortic stenosis is fully covered by health insurance but coverage for atrial fibrillation is carved out and assigned partial coverage, with a high copayment, a limit on physician visits and hospital days, and a lifetime cap on coverage. If it strikes you as outrageous that disorders of the same organ could be treated so differently, with irrational discrimination, think again! Such an egregious injustice has been going on for a long time against disorders of the brain.
Care provided for stroke, brain tumor, and epilepsy is given full coverage—but not so for depression, psychosis, and panic disorder. To make the matter more bizarre, depression is a known complication of certain types of stroke; some brain tumors are associated with psychosis; and panic attacks can occur with complex partial seizures—demonstrating that the pathways of so-called “mental” illnesses are as “physical” as any neurological disorder of the brain.
Welcome to the absurd world of lack of parity for psychiatric brain disorders!
Senseless, unethical discrimination against mental illness goes on unabated, despite lip service by politicians and policy-makers. The lack of parity adds insult to injury for psychiatric patients, inflicting a financial burden atop unbearable suffering and functional disability.
How long will this injustice endure?
For a civilized society, in which discrimination based on skin color, sex, sexual orientation, and religious belief is prohibited, discrimination by medical illness seems to be tolerated with impunity. This is a blind spot of unimaginable magnitude in the conscience of society and a cancerous lesion on its ethical standards.
The lack of parity in health-care coverage for psychiatric disorders is compounded by several other disparities. Consider this array of discriminatory actions and conditions directed at psychiatrists and their patients:
• The mentally ill endure a stigma that deprives them of the compassion and sympathy that people who have other medical disorders routinely receive.
• Managed-care organizations and some health-maintenance organizations are reluctant to allow the use of newer, more tolerable, and less neurotoxic psychoactive medications by psychiatrists and nurse practitioners; instead, they impose a fail-first policy with decades-old generic drugs to save money—although newer drugs are readily available for oncologists, cardiologists, and neurologists to use.
• Behavioral health is always “carved out”—that obscene word—in insurance contracts. This is overt discrimination against the mentally ill and mental health professionals that the government should not allow, in its role as a watchdog of human rights.
• Psychiatric wards usually are the most poorly renovated and oldest section of hospitals, while obstetrics, oncology, cardiology, and orthopedics units have state-of-the-art facilities. Many inner-city community mental health centers look tad better than a war zone, with dilapidated buildings, stained and broken furniture, and peeling walls. Where are the funds that were supposed to be recovered by shuttering asylums and to flow into community care for outpatient mental health care?
• It’s the height of discrimination that the relapsed mentally ill have no place to go but jail or prison. Isn’t it the worst injustice to transform medical illness into a felony? Why are there few long-term facilities for severe mental illness any more—the equivalent of refractory patients? In a civilized nation, why is homelessness among people who have a brain disorder tolerated?
• The medical records of psychiatric patients are segregated and set aside, perpetuating the unfair shame and guilt associated with mental illness. When will a history of depression and a broken spirit be no more secretive than having a broken leg?
• The lack of regard for psychiatry as a vital medical specialty reflects medieval-like ignorance and discrimination in an age when the neurobiology of psychiatric brain disorders is unfolding with dazzling scientific elegance. When will those who treat mood, thought, behavior, and cognition receive the same respect as a surgeon who transplants a liver or a cardiologist who manages heart failure?
• The disparity in access by the seriously mentally ill to primary, secondary, and tertiary care has, literally, fatal consequences. Despite the high prevalence of serious cardio-metabolic, pulmonary, infectious, and gastrointestinal disorders among the mentally ill, a large percentage do not receive the most basic primary care to manage their ailments—let alone undergo special procedures or advanced surgical interventions. This shameful neglect and health-care disparity contribute to early mortality (by 20 to 25 years) among people who suffer a serious mental disorder. This is a deadly disparity, yet it goes unaddressed.
• Last, a disparity exists in funding for research to find the causes of, and cures for, disorders of the brain’s mind. Psychiatric disorders and substance use cost society more than $300 billion annually in the United States, yet investment in research on those disorders pales compared with the support provided to the study of other medical disorders.
It’s time society closed this ugly gap
Lack of parity extends across a broad swath of issues related to mental illness, with a huge personal and material cost to the 25% of the US population that suffers a mental disorder. It’s time to close the shameful gap and end this harmful discrimination. Let’s hope that ongoing changes in health care will, finally, reverse the injustice. Given the broken promises of the past, however, let’s not count our chickens before they hatch….
Repositioning psychotherapy as a neurobiological intervention
Despite its well-documented efficacy in a myriad of neuropsychiatric conditions, psychotherapy has never been able to shrug off an unwarranted aura of fuzziness as a legitimate medical intervention. To many uninformed people, psychotherapy isn’t a “real” treatment, such as medication or a surgical procedure. It often is referred to as “talk therapy,” which provokes skepticism, even snickering, because talking is a ubiquitous social activity.
Psychotherapy is sometimes perceived as a scam—that is, a placebo packaged and propagated as treatment; after all, how can spoken words “heal” the wounds of the soul? Paradoxically, skepticism about the vague and mysterious mechanism of action of psychotherapy might make things worse by adding to the stigma that mental illness is a spurious “all-in-your-head” complaint and not a genuine medical disorder.
Giving psychotherapy the respect it deserves
To the chagrin of many in our field, this image problem persists, despite psychotherapy having helped millions of people. It is widely used in conjunction with pharmacotherapy by psychiatrists and nurse practitioners, and as a sole therapeutic modality by psychologists and other therapists. This image problem has emboldened health insurance companies to arbitrarily limit reimbursement for psychotherapy, compared with psychopharmacology, to the detriment of patients who often can benefit significantly from psychotherapy alone, without medication.
So, how can psychotherapy capture the respect it deserves as a vital and valid therapeutic modality?
For one, psychotherapy has to be evidence-based and rigorously proven to be superior to placebo—the same standard that drugs are held to before they are approved by the FDA. But there are hundreds of psychotherapies, of which only a minority are evidence-based (eg, cognitive-behavioral therapy, dialectical behavior therapy, and interpersonal therapy), based on findings of controlled trials in which they were documented to be efficacious.
There is a dearth of data about the safety and tolerability of, and indications for, specific psychotherapies—criteria that are major factors in determining whether the FDA approves a medication. Also, dosing of psychotherapy remains ambiguous, subjective, and lacking solid clinical guidelines, and the frequency of visits, duration of each visit, and need for maintenance of psychotherapy lack solid scientific evidence.
Patients therefore seem to receive psychotherapy for as long as health insurance pays for it, even if they need more of it. Frequency of treatment is determined by the therapist, or at the convenience of the patient or the therapist. Long-term psychotherapy—1 or 2 years—once was common, but short-term psychotherapy of fewer than 10 sessions has become the rage since managed care curtailed reimbursement. It is curious that, although most practitioners agree that serious psychiatric disorders can require ongoing, even lifelong maintenance of a drug beyond the acute phase, no one ever argues for indefinite continuation of psychotherapy (although Sigmund Freud did discuss terminable and interminable psychoanalysis).
Rx: A ’makeover’
Psychotherapy needs to be reconceptualized, rebranded, and repositioned as a neurobiological treatment—because, in fact, that’s what it is. This notion goes hand-in-hand with unimpeachable evidence that the mind is an integral component of the brain and mental illness is generated from genetic or environmentally-induced dysregulation of neurobiological homeostasis.
An important line of evidence for the neurologic effects of psychotherapy are studies of positron-emission tomography showing that psychotherapy induces changes in specific brain regions that are identical to changes induced by drug therapy.1,2 The component activities of psychotherapy—verbal and nonverbal communication, evocation of memories, empathizing, challenging, connecting the dots, triggering insights, and reducing anguish—are transduced into instantaneous neuroplastic changes, which can be lasting and lead to corrective modification of the neural circuitry of feelings, thinking, and behavior.
Most non-neuroscientists might not be aware that the brain changes continuously, moment to moment, forming dendritic spines that immediately encode verbal and nonverbal memories in response to experiences throughout life. A skilled psychotherapist exploits this biological property of the brain to modify its molecular and cellular structure to relieve the anguish and psychopathology of its avatar, the mind.
What might silence the skeptics?
Psychotherapy legitimately could be relabeled “neuropsychotherapy” to indicate that it has an impact on the neural structure and function that underpin the “psyche”—that collection of thoughts, feelings, memories, and impulses that are a product of activity in specific brain pathways, just as other brain pathways produce movement and sensation. Future studies, using innovative biotechnological imaging methods, will demonstrate the tangible neurobiological impact of neuropsychotherapy and erase the skepticism that shrouds its nature. At that point, neuropsychotherapy will get the respect it deserves as a tool to heal the mind by repairing the brain.
1. Brody AL, Saxena S, Stoessel P, et al. Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings. Arch Gen Psychiatry. 2001;58(7):631-640.
2. Baxter LR Jr, Schwartz JM, Bergman KS, et al. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry. 1992;49(9):681-689.
Despite its well-documented efficacy in a myriad of neuropsychiatric conditions, psychotherapy has never been able to shrug off an unwarranted aura of fuzziness as a legitimate medical intervention. To many uninformed people, psychotherapy isn’t a “real” treatment, such as medication or a surgical procedure. It often is referred to as “talk therapy,” which provokes skepticism, even snickering, because talking is a ubiquitous social activity.
Psychotherapy is sometimes perceived as a scam—that is, a placebo packaged and propagated as treatment; after all, how can spoken words “heal” the wounds of the soul? Paradoxically, skepticism about the vague and mysterious mechanism of action of psychotherapy might make things worse by adding to the stigma that mental illness is a spurious “all-in-your-head” complaint and not a genuine medical disorder.
Giving psychotherapy the respect it deserves
To the chagrin of many in our field, this image problem persists, despite psychotherapy having helped millions of people. It is widely used in conjunction with pharmacotherapy by psychiatrists and nurse practitioners, and as a sole therapeutic modality by psychologists and other therapists. This image problem has emboldened health insurance companies to arbitrarily limit reimbursement for psychotherapy, compared with psychopharmacology, to the detriment of patients who often can benefit significantly from psychotherapy alone, without medication.
So, how can psychotherapy capture the respect it deserves as a vital and valid therapeutic modality?
For one, psychotherapy has to be evidence-based and rigorously proven to be superior to placebo—the same standard that drugs are held to before they are approved by the FDA. But there are hundreds of psychotherapies, of which only a minority are evidence-based (eg, cognitive-behavioral therapy, dialectical behavior therapy, and interpersonal therapy), based on findings of controlled trials in which they were documented to be efficacious.
There is a dearth of data about the safety and tolerability of, and indications for, specific psychotherapies—criteria that are major factors in determining whether the FDA approves a medication. Also, dosing of psychotherapy remains ambiguous, subjective, and lacking solid clinical guidelines, and the frequency of visits, duration of each visit, and need for maintenance of psychotherapy lack solid scientific evidence.
Patients therefore seem to receive psychotherapy for as long as health insurance pays for it, even if they need more of it. Frequency of treatment is determined by the therapist, or at the convenience of the patient or the therapist. Long-term psychotherapy—1 or 2 years—once was common, but short-term psychotherapy of fewer than 10 sessions has become the rage since managed care curtailed reimbursement. It is curious that, although most practitioners agree that serious psychiatric disorders can require ongoing, even lifelong maintenance of a drug beyond the acute phase, no one ever argues for indefinite continuation of psychotherapy (although Sigmund Freud did discuss terminable and interminable psychoanalysis).
Rx: A ’makeover’
Psychotherapy needs to be reconceptualized, rebranded, and repositioned as a neurobiological treatment—because, in fact, that’s what it is. This notion goes hand-in-hand with unimpeachable evidence that the mind is an integral component of the brain and mental illness is generated from genetic or environmentally-induced dysregulation of neurobiological homeostasis.
An important line of evidence for the neurologic effects of psychotherapy are studies of positron-emission tomography showing that psychotherapy induces changes in specific brain regions that are identical to changes induced by drug therapy.1,2 The component activities of psychotherapy—verbal and nonverbal communication, evocation of memories, empathizing, challenging, connecting the dots, triggering insights, and reducing anguish—are transduced into instantaneous neuroplastic changes, which can be lasting and lead to corrective modification of the neural circuitry of feelings, thinking, and behavior.
Most non-neuroscientists might not be aware that the brain changes continuously, moment to moment, forming dendritic spines that immediately encode verbal and nonverbal memories in response to experiences throughout life. A skilled psychotherapist exploits this biological property of the brain to modify its molecular and cellular structure to relieve the anguish and psychopathology of its avatar, the mind.
What might silence the skeptics?
Psychotherapy legitimately could be relabeled “neuropsychotherapy” to indicate that it has an impact on the neural structure and function that underpin the “psyche”—that collection of thoughts, feelings, memories, and impulses that are a product of activity in specific brain pathways, just as other brain pathways produce movement and sensation. Future studies, using innovative biotechnological imaging methods, will demonstrate the tangible neurobiological impact of neuropsychotherapy and erase the skepticism that shrouds its nature. At that point, neuropsychotherapy will get the respect it deserves as a tool to heal the mind by repairing the brain.
Despite its well-documented efficacy in a myriad of neuropsychiatric conditions, psychotherapy has never been able to shrug off an unwarranted aura of fuzziness as a legitimate medical intervention. To many uninformed people, psychotherapy isn’t a “real” treatment, such as medication or a surgical procedure. It often is referred to as “talk therapy,” which provokes skepticism, even snickering, because talking is a ubiquitous social activity.
Psychotherapy is sometimes perceived as a scam—that is, a placebo packaged and propagated as treatment; after all, how can spoken words “heal” the wounds of the soul? Paradoxically, skepticism about the vague and mysterious mechanism of action of psychotherapy might make things worse by adding to the stigma that mental illness is a spurious “all-in-your-head” complaint and not a genuine medical disorder.
Giving psychotherapy the respect it deserves
To the chagrin of many in our field, this image problem persists, despite psychotherapy having helped millions of people. It is widely used in conjunction with pharmacotherapy by psychiatrists and nurse practitioners, and as a sole therapeutic modality by psychologists and other therapists. This image problem has emboldened health insurance companies to arbitrarily limit reimbursement for psychotherapy, compared with psychopharmacology, to the detriment of patients who often can benefit significantly from psychotherapy alone, without medication.
So, how can psychotherapy capture the respect it deserves as a vital and valid therapeutic modality?
For one, psychotherapy has to be evidence-based and rigorously proven to be superior to placebo—the same standard that drugs are held to before they are approved by the FDA. But there are hundreds of psychotherapies, of which only a minority are evidence-based (eg, cognitive-behavioral therapy, dialectical behavior therapy, and interpersonal therapy), based on findings of controlled trials in which they were documented to be efficacious.
There is a dearth of data about the safety and tolerability of, and indications for, specific psychotherapies—criteria that are major factors in determining whether the FDA approves a medication. Also, dosing of psychotherapy remains ambiguous, subjective, and lacking solid clinical guidelines, and the frequency of visits, duration of each visit, and need for maintenance of psychotherapy lack solid scientific evidence.
Patients therefore seem to receive psychotherapy for as long as health insurance pays for it, even if they need more of it. Frequency of treatment is determined by the therapist, or at the convenience of the patient or the therapist. Long-term psychotherapy—1 or 2 years—once was common, but short-term psychotherapy of fewer than 10 sessions has become the rage since managed care curtailed reimbursement. It is curious that, although most practitioners agree that serious psychiatric disorders can require ongoing, even lifelong maintenance of a drug beyond the acute phase, no one ever argues for indefinite continuation of psychotherapy (although Sigmund Freud did discuss terminable and interminable psychoanalysis).
Rx: A ’makeover’
Psychotherapy needs to be reconceptualized, rebranded, and repositioned as a neurobiological treatment—because, in fact, that’s what it is. This notion goes hand-in-hand with unimpeachable evidence that the mind is an integral component of the brain and mental illness is generated from genetic or environmentally-induced dysregulation of neurobiological homeostasis.
An important line of evidence for the neurologic effects of psychotherapy are studies of positron-emission tomography showing that psychotherapy induces changes in specific brain regions that are identical to changes induced by drug therapy.1,2 The component activities of psychotherapy—verbal and nonverbal communication, evocation of memories, empathizing, challenging, connecting the dots, triggering insights, and reducing anguish—are transduced into instantaneous neuroplastic changes, which can be lasting and lead to corrective modification of the neural circuitry of feelings, thinking, and behavior.
Most non-neuroscientists might not be aware that the brain changes continuously, moment to moment, forming dendritic spines that immediately encode verbal and nonverbal memories in response to experiences throughout life. A skilled psychotherapist exploits this biological property of the brain to modify its molecular and cellular structure to relieve the anguish and psychopathology of its avatar, the mind.
What might silence the skeptics?
Psychotherapy legitimately could be relabeled “neuropsychotherapy” to indicate that it has an impact on the neural structure and function that underpin the “psyche”—that collection of thoughts, feelings, memories, and impulses that are a product of activity in specific brain pathways, just as other brain pathways produce movement and sensation. Future studies, using innovative biotechnological imaging methods, will demonstrate the tangible neurobiological impact of neuropsychotherapy and erase the skepticism that shrouds its nature. At that point, neuropsychotherapy will get the respect it deserves as a tool to heal the mind by repairing the brain.
1. Brody AL, Saxena S, Stoessel P, et al. Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings. Arch Gen Psychiatry. 2001;58(7):631-640.
2. Baxter LR Jr, Schwartz JM, Bergman KS, et al. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry. 1992;49(9):681-689.
1. Brody AL, Saxena S, Stoessel P, et al. Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings. Arch Gen Psychiatry. 2001;58(7):631-640.
2. Baxter LR Jr, Schwartz JM, Bergman KS, et al. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry. 1992;49(9):681-689.
One shade of gray, 50 shades of ignorance
With its tissue a unique shade of gray, the brain is a glorious organ: Although it is only 1 of 200 types of tissue in the body, 50% of the approximately 22,000 genes in the human karyotype are dedicated to brain development.
The brain’s supremacy among all organs is readily attributable to its transcendent mind, comprising the essence of personhood in the individual. The mental functions of the mind, such as self-awareness, thinking, speaking, feeling, remembering, communicating, and deciding, are by far the most advanced traits of Homo sapiens.
The profound complexity of the brain and its mind has triggered the explosive growth of neuroscience research over the past few decades, thanks to remarkable advances in neuroimaging and molecular biology. Scientists are perpetually humbled by the divine complexity of the brain, and readily admit to ignorance about many of its functions—despite astonishing increases in
knowledge they have generated about the physical brain and its avatar, the mind.
Ignorance has many faces
The incomplete understanding of brain and mind that neuroscience
researchers admit to is a shade of insightful ignorance, one that fuels intense motivation to persist in exploring it to elucidate its stunning enigmas. There are, however, other shades of ignorance, especially surrounding the mind and its “mental” disorders. Several adjectives come to mind: blatant, partial, smug, inexcusable, malicious, stupid, and dangerous ignorance. When prominent persons, who have an advanced degree in their field of study, demonstrate a shocking lack of understanding of psychiatric disorders emanating from brain pathology, however, I label that disappointing ignorance.
Take David Brooks, renowned syndicated New York Times columnist whose political analysis and insights I have always enjoyed. My heart sank in dismay when, in a column earlier this year, he stated—emphatically—that psychiatry is not a “real science,” a status he does bestow on physics and biology!1 Brooks disparaged DSM-5
(a popular blood sport these days) and called psychiatrists “heroes of uncertainty.”
I wish this esteemed writer had stuck to one of his areas of expertise, such as politics, and abstained from remarks that betray a surprising shade of ignorance. My disappointment escalated into alarm when I considered the millions of readers who regard him as credible and will be misled by his erroneous comments, which perpetuate ugly misconceptions about mental illness and disparage the people who seek help for a psychiatric medical disorder. Anti-psychiatry fanatics and professional detractors will be emboldened by misstatements such as “psychiatry is not a real science,” which help them spread virulent falsehoods and malicious propaganda against psychiatry.
A ‘colossal body of scientific evidence’ informs psychiatry
There was a time when physics, Brooks’s favorite science, was in a primitive stage of knowledge and would not have qualified as “real science.” Gravity, the laws of thermodynamics, quantum physics, the theory of relativity, the structure of the atom, the astrophysics of our solar system—all these were unknown until a short historical time ago. The scientific transformation of psychiatry is even more recent because of the past challenges of studying the brain and understanding the neurobiology of its mental processes in vivo.
There exists a colossal body of elegant scientific evidence for the biological basis of mental illness and brain-behavior links. Perhaps we psychiatrists aren’t doing a good job disseminating scientific discoveries about the neuro-anatomic, neurophysiologic, neurochemical, and molecular underpinnings of perceptual, affective, thought, behavioral, and cognitive disorders.
The hazard of obsolete knowledge
Emily Dickinson said, “The truth must dazzle gradually/Or every man be blind.” The scientific truth of psychiatry is unfolding at a breathtaking pace, yet even intelligent people continue to harbor decades-old misconceptions about the mind and its disorders. Indeed, “A little learning is a dangerous thing,” as Alexander Pope asserted, especially when it is obsolete. And, whoever said, “Ignorance is bliss” was in utter denial—perhaps the worst shade of ignorance.
Reference
1. Brooks D. Heroes of uncertainty. The New York Times. May 27, 2013:A19.
With its tissue a unique shade of gray, the brain is a glorious organ: Although it is only 1 of 200 types of tissue in the body, 50% of the approximately 22,000 genes in the human karyotype are dedicated to brain development.
The brain’s supremacy among all organs is readily attributable to its transcendent mind, comprising the essence of personhood in the individual. The mental functions of the mind, such as self-awareness, thinking, speaking, feeling, remembering, communicating, and deciding, are by far the most advanced traits of Homo sapiens.
The profound complexity of the brain and its mind has triggered the explosive growth of neuroscience research over the past few decades, thanks to remarkable advances in neuroimaging and molecular biology. Scientists are perpetually humbled by the divine complexity of the brain, and readily admit to ignorance about many of its functions—despite astonishing increases in
knowledge they have generated about the physical brain and its avatar, the mind.
Ignorance has many faces
The incomplete understanding of brain and mind that neuroscience
researchers admit to is a shade of insightful ignorance, one that fuels intense motivation to persist in exploring it to elucidate its stunning enigmas. There are, however, other shades of ignorance, especially surrounding the mind and its “mental” disorders. Several adjectives come to mind: blatant, partial, smug, inexcusable, malicious, stupid, and dangerous ignorance. When prominent persons, who have an advanced degree in their field of study, demonstrate a shocking lack of understanding of psychiatric disorders emanating from brain pathology, however, I label that disappointing ignorance.
Take David Brooks, renowned syndicated New York Times columnist whose political analysis and insights I have always enjoyed. My heart sank in dismay when, in a column earlier this year, he stated—emphatically—that psychiatry is not a “real science,” a status he does bestow on physics and biology!1 Brooks disparaged DSM-5
(a popular blood sport these days) and called psychiatrists “heroes of uncertainty.”
I wish this esteemed writer had stuck to one of his areas of expertise, such as politics, and abstained from remarks that betray a surprising shade of ignorance. My disappointment escalated into alarm when I considered the millions of readers who regard him as credible and will be misled by his erroneous comments, which perpetuate ugly misconceptions about mental illness and disparage the people who seek help for a psychiatric medical disorder. Anti-psychiatry fanatics and professional detractors will be emboldened by misstatements such as “psychiatry is not a real science,” which help them spread virulent falsehoods and malicious propaganda against psychiatry.
A ‘colossal body of scientific evidence’ informs psychiatry
There was a time when physics, Brooks’s favorite science, was in a primitive stage of knowledge and would not have qualified as “real science.” Gravity, the laws of thermodynamics, quantum physics, the theory of relativity, the structure of the atom, the astrophysics of our solar system—all these were unknown until a short historical time ago. The scientific transformation of psychiatry is even more recent because of the past challenges of studying the brain and understanding the neurobiology of its mental processes in vivo.
There exists a colossal body of elegant scientific evidence for the biological basis of mental illness and brain-behavior links. Perhaps we psychiatrists aren’t doing a good job disseminating scientific discoveries about the neuro-anatomic, neurophysiologic, neurochemical, and molecular underpinnings of perceptual, affective, thought, behavioral, and cognitive disorders.
The hazard of obsolete knowledge
Emily Dickinson said, “The truth must dazzle gradually/Or every man be blind.” The scientific truth of psychiatry is unfolding at a breathtaking pace, yet even intelligent people continue to harbor decades-old misconceptions about the mind and its disorders. Indeed, “A little learning is a dangerous thing,” as Alexander Pope asserted, especially when it is obsolete. And, whoever said, “Ignorance is bliss” was in utter denial—perhaps the worst shade of ignorance.
With its tissue a unique shade of gray, the brain is a glorious organ: Although it is only 1 of 200 types of tissue in the body, 50% of the approximately 22,000 genes in the human karyotype are dedicated to brain development.
The brain’s supremacy among all organs is readily attributable to its transcendent mind, comprising the essence of personhood in the individual. The mental functions of the mind, such as self-awareness, thinking, speaking, feeling, remembering, communicating, and deciding, are by far the most advanced traits of Homo sapiens.
The profound complexity of the brain and its mind has triggered the explosive growth of neuroscience research over the past few decades, thanks to remarkable advances in neuroimaging and molecular biology. Scientists are perpetually humbled by the divine complexity of the brain, and readily admit to ignorance about many of its functions—despite astonishing increases in
knowledge they have generated about the physical brain and its avatar, the mind.
Ignorance has many faces
The incomplete understanding of brain and mind that neuroscience
researchers admit to is a shade of insightful ignorance, one that fuels intense motivation to persist in exploring it to elucidate its stunning enigmas. There are, however, other shades of ignorance, especially surrounding the mind and its “mental” disorders. Several adjectives come to mind: blatant, partial, smug, inexcusable, malicious, stupid, and dangerous ignorance. When prominent persons, who have an advanced degree in their field of study, demonstrate a shocking lack of understanding of psychiatric disorders emanating from brain pathology, however, I label that disappointing ignorance.
Take David Brooks, renowned syndicated New York Times columnist whose political analysis and insights I have always enjoyed. My heart sank in dismay when, in a column earlier this year, he stated—emphatically—that psychiatry is not a “real science,” a status he does bestow on physics and biology!1 Brooks disparaged DSM-5
(a popular blood sport these days) and called psychiatrists “heroes of uncertainty.”
I wish this esteemed writer had stuck to one of his areas of expertise, such as politics, and abstained from remarks that betray a surprising shade of ignorance. My disappointment escalated into alarm when I considered the millions of readers who regard him as credible and will be misled by his erroneous comments, which perpetuate ugly misconceptions about mental illness and disparage the people who seek help for a psychiatric medical disorder. Anti-psychiatry fanatics and professional detractors will be emboldened by misstatements such as “psychiatry is not a real science,” which help them spread virulent falsehoods and malicious propaganda against psychiatry.
A ‘colossal body of scientific evidence’ informs psychiatry
There was a time when physics, Brooks’s favorite science, was in a primitive stage of knowledge and would not have qualified as “real science.” Gravity, the laws of thermodynamics, quantum physics, the theory of relativity, the structure of the atom, the astrophysics of our solar system—all these were unknown until a short historical time ago. The scientific transformation of psychiatry is even more recent because of the past challenges of studying the brain and understanding the neurobiology of its mental processes in vivo.
There exists a colossal body of elegant scientific evidence for the biological basis of mental illness and brain-behavior links. Perhaps we psychiatrists aren’t doing a good job disseminating scientific discoveries about the neuro-anatomic, neurophysiologic, neurochemical, and molecular underpinnings of perceptual, affective, thought, behavioral, and cognitive disorders.
The hazard of obsolete knowledge
Emily Dickinson said, “The truth must dazzle gradually/Or every man be blind.” The scientific truth of psychiatry is unfolding at a breathtaking pace, yet even intelligent people continue to harbor decades-old misconceptions about the mind and its disorders. Indeed, “A little learning is a dangerous thing,” as Alexander Pope asserted, especially when it is obsolete. And, whoever said, “Ignorance is bliss” was in utter denial—perhaps the worst shade of ignorance.
Reference
1. Brooks D. Heroes of uncertainty. The New York Times. May 27, 2013:A19.
Reference
1. Brooks D. Heroes of uncertainty. The New York Times. May 27, 2013:A19.