Henry A. Nasrallah, MD

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You may have noticed the buzz about Charles Darwin in the news: 2009 marks the 200th anniversary of his birth and the 150th anniversary of his monumental description of evolution in On the Origin of Species. Celebrations are scheduled around the world to honor the scientist who coined the phrase “natural selection” to explain the heritable process by which adaptive evolution occurs.

But is Darwin’s theory of evolution still relevant? The “game-changer” that is transforming evolution is the genetic mutation that led to dramatic growth in the primate cortex—especially the frontal lobe—culminating in the emergence of Homo sapiens. The overdeveloped brain that has helped our species adapt and survive may be transforming us into predators of all other species and a hazard to our planet.

Survival regardless of ‘fitness’

Humans are discovering so much about biology and treatment of disease that we are disrupting natural selection and undermining the tyranny of “survival of the fittest.” A triumph of modern medicine (the antithesis of eugenics) is salvaging those who in Darwin’s day would have died and allowing them to survive and perpetuate their genes:

• Children born with metabolic errors no longer are doomed to succumb before their childbearing years.
• Premature 1-pound infants who never would have survived before are routinely doing so now.
• Women can conceive in their 60s, well after menopause.
• Medical advances have enabled humans to parry the deadly assaults of bacteria, viruses, and parasites.
• Future scientific advances will certainly include genetic engineering, which will eliminate the sometimes grim determinism of heredity.

Conversely, humans’ intelligence has enabled us to wreak havoc on other species. Tens of thousands of animals and plants have vanished because flourishing humans have survived and wittingly or unwittingly exploited, polluted, and injured the environment. Of course, a pathologic evolution may backfire on us, despite our highly evolved brain. However, humans may still adapt and survive, albeit in a dramatically altered, even inhospitable world. Or maybe not, as war and weapons of mass destruction appear to be unique inventions of the human brain.

Darwin’s psychiatric challenges

What does this have to do with psychiatry? Disorders of thought, emotions, cognition, and volition are probably the price humans paid for a dramatically evolved brain. Evolutionary psychiatrists have linked these disorders to traits that may have survival value in carriers but cause maladaptive behaviors in some individuals.

Darwin’s own struggles with disabling mental illness^1-5 are perhaps the most eloquent testimonial that classic evolutionary principles may not apply to humans. His symptoms included panic attacks, agoraphobia, social anxiety, depersonalization, obsessions and compulsions, depression, suicidal impulses, visual hallucinations, and psychosomatic complaints (eczema, dizziness, and irritable bowel syndrome). Beginning in his 20s, he confined himself to his home for decades, undergoing futile interventions (such as water therapy) and taking antiquated remedies for his afflictions.

Yet Darwin’s genius was never compromised by his lack of psychiatric or physical fitness. His explanation for evolution—which made him one of the most famous scientists of all time—emerged in the midst of and despite his overwhelming health problems.

Thus, Darwin’s achievements embody the notion that the mutation that led to the hyper-developed human brain is the nemesis of evolution as he conceived it. He also serves as an inspiration to everyone who suffers from mental illness. His landmark contribution to science is a forceful rebuttal to anyone who regards psychiatric illness as synonymous with “lack of fitness.”

Happy birthday, Darwin!

Comment on this article

You may have noticed the buzz about Charles Darwin in the news: 2009 marks the 200th anniversary of his birth and the 150th anniversary of his monumental description of evolution in On the Origin of Species. Celebrations are scheduled around the world to honor the scientist who coined the phrase “natural selection” to explain the heritable process by which adaptive evolution occurs.

But is Darwin’s theory of evolution still relevant? The “game-changer” that is transforming evolution is the genetic mutation that led to dramatic growth in the primate cortex—especially the frontal lobe—culminating in the emergence of Homo sapiens. The overdeveloped brain that has helped our species adapt and survive may be transforming us into predators of all other species and a hazard to our planet.

Survival regardless of ‘fitness’

Humans are discovering so much about biology and treatment of disease that we are disrupting natural selection and undermining the tyranny of “survival of the fittest.” A triumph of modern medicine (the antithesis of eugenics) is salvaging those who in Darwin’s day would have died and allowing them to survive and perpetuate their genes:

• Children born with metabolic errors no longer are doomed to succumb before their childbearing years.
• Premature 1-pound infants who never would have survived before are routinely doing so now.
• Women can conceive in their 60s, well after menopause.
• Medical advances have enabled humans to parry the deadly assaults of bacteria, viruses, and parasites.
• Future scientific advances will certainly include genetic engineering, which will eliminate the sometimes grim determinism of heredity.

Conversely, humans’ intelligence has enabled us to wreak havoc on other species. Tens of thousands of animals and plants have vanished because flourishing humans have survived and wittingly or unwittingly exploited, polluted, and injured the environment. Of course, a pathologic evolution may backfire on us, despite our highly evolved brain. However, humans may still adapt and survive, albeit in a dramatically altered, even inhospitable world. Or maybe not, as war and weapons of mass destruction appear to be unique inventions of the human brain.

Darwin’s psychiatric challenges

What does this have to do with psychiatry? Disorders of thought, emotions, cognition, and volition are probably the price humans paid for a dramatically evolved brain. Evolutionary psychiatrists have linked these disorders to traits that may have survival value in carriers but cause maladaptive behaviors in some individuals.

Darwin’s own struggles with disabling mental illness^1-5 are perhaps the most eloquent testimonial that classic evolutionary principles may not apply to humans. His symptoms included panic attacks, agoraphobia, social anxiety, depersonalization, obsessions and compulsions, depression, suicidal impulses, visual hallucinations, and psychosomatic complaints (eczema, dizziness, and irritable bowel syndrome). Beginning in his 20s, he confined himself to his home for decades, undergoing futile interventions (such as water therapy) and taking antiquated remedies for his afflictions.

Yet Darwin’s genius was never compromised by his lack of psychiatric or physical fitness. His explanation for evolution—which made him one of the most famous scientists of all time—emerged in the midst of and despite his overwhelming health problems.

Thus, Darwin’s achievements embody the notion that the mutation that led to the hyper-developed human brain is the nemesis of evolution as he conceived it. He also serves as an inspiration to everyone who suffers from mental illness. His landmark contribution to science is a forceful rebuttal to anyone who regards psychiatric illness as synonymous with “lack of fitness.”

Happy birthday, Darwin!

Comment on this article

You may have noticed the buzz about Charles Darwin in the news: 2009 marks the 200th anniversary of his birth and the 150th anniversary of his monumental description of evolution in On the Origin of Species. Celebrations are scheduled around the world to honor the scientist who coined the phrase “natural selection” to explain the heritable process by which adaptive evolution occurs.

But is Darwin’s theory of evolution still relevant? The “game-changer” that is transforming evolution is the genetic mutation that led to dramatic growth in the primate cortex—especially the frontal lobe—culminating in the emergence of Homo sapiens. The overdeveloped brain that has helped our species adapt and survive may be transforming us into predators of all other species and a hazard to our planet.

Survival regardless of ‘fitness’

Humans are discovering so much about biology and treatment of disease that we are disrupting natural selection and undermining the tyranny of “survival of the fittest.” A triumph of modern medicine (the antithesis of eugenics) is salvaging those who in Darwin’s day would have died and allowing them to survive and perpetuate their genes:

• Children born with metabolic errors no longer are doomed to succumb before their childbearing years.
• Premature 1-pound infants who never would have survived before are routinely doing so now.
• Women can conceive in their 60s, well after menopause.
• Medical advances have enabled humans to parry the deadly assaults of bacteria, viruses, and parasites.
• Future scientific advances will certainly include genetic engineering, which will eliminate the sometimes grim determinism of heredity.

Conversely, humans’ intelligence has enabled us to wreak havoc on other species. Tens of thousands of animals and plants have vanished because flourishing humans have survived and wittingly or unwittingly exploited, polluted, and injured the environment. Of course, a pathologic evolution may backfire on us, despite our highly evolved brain. However, humans may still adapt and survive, albeit in a dramatically altered, even inhospitable world. Or maybe not, as war and weapons of mass destruction appear to be unique inventions of the human brain.

Darwin’s psychiatric challenges

What does this have to do with psychiatry? Disorders of thought, emotions, cognition, and volition are probably the price humans paid for a dramatically evolved brain. Evolutionary psychiatrists have linked these disorders to traits that may have survival value in carriers but cause maladaptive behaviors in some individuals.

Darwin’s own struggles with disabling mental illness^1-5 are perhaps the most eloquent testimonial that classic evolutionary principles may not apply to humans. His symptoms included panic attacks, agoraphobia, social anxiety, depersonalization, obsessions and compulsions, depression, suicidal impulses, visual hallucinations, and psychosomatic complaints (eczema, dizziness, and irritable bowel syndrome). Beginning in his 20s, he confined himself to his home for decades, undergoing futile interventions (such as water therapy) and taking antiquated remedies for his afflictions.

Yet Darwin’s genius was never compromised by his lack of psychiatric or physical fitness. His explanation for evolution—which made him one of the most famous scientists of all time—emerged in the midst of and despite his overwhelming health problems.

Thus, Darwin’s achievements embody the notion that the mutation that led to the hyper-developed human brain is the nemesis of evolution as he conceived it. He also serves as an inspiration to everyone who suffers from mental illness. His landmark contribution to science is a forceful rebuttal to anyone who regards psychiatric illness as synonymous with “lack of fitness.”

Happy birthday, Darwin!

Do you sometimes wonder what psychiatry’s future holds? Wonder no more: abundant clues point to exciting innovations in our field. Let me highlight 6 trends that will shape how we practice psychiatry.

1. Earlier diagnosis and early intervention. The past decade has witnessed a surge of progress in identifying individuals at high risk for psychosis or mood disorders. The “prodrome” has become a fertile area of research, with a focus on early “treatment” even before the clinical syndrome of schizophrenia or mania appears. The goal is to try to delay, modify, or ameliorate incipient serious mental illness by using both pharmacotherapy and psychotherapy.

2. A tsunami of genetic discoveries. Almost weekly, psychiatric geneticists are discovering genes associated with serious psychiatric disorders. Neuregulin 1, dysbindin, DISC1, DAOA (G72), PRODH, and COMT are among the many odd-sounding genes located on various chromosomes. These discoveries confirm the “complex genetics” of psychiatric disorders involving dozens—even hundreds—of susceptibility genes, in contrast to the “1 gene, 1 disease” Mendelian paradigm.

Ultimately, these genetic discoveries will provide clues to the molecular pathophysiology of major mental disorders, leading to the holy grail of psychiatric treatment: specific, biotechnology-driven, disease-modifying pharmacotherapeutics rather than merely symptom-control agents.

3. Neuroplasticity as treatment target. Over the past few years, structural atrophy of the brain at the cellular and molecular levels has been documented in psychosis, mania, depression, and anxiety. These findings have shifted our perspective of mental illness beyond the simplistic notions of “chemical imbalance.” The new model is progressive neuroplasticity changes in neurons, dendritic spines, neurite extensions, and synapses, (ie, the neuropil), with both grey and white matter reductions impairing brain connectivity and functioning.

In response, researchers are developing a neuro-protective paradigm to reverse neuroplastic changes as a new brain-repair strategy. Thus, therapeutic agents and their targets may include:

• caspase inhibitors to stop apoptosis
• neurogenesis stimulators to replenish neurons
• neurotropic enhancers to reverse deficits in various growth factors, such as nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), vascular endothelial growth factor (VEGF), etc.
• antioxidants to neutralize excess free radicals
• glia-proliferation enhancers to rebuild white matter
• tumor necrosis factor-alpha (TNF-α) inhibitors to combat the inflammatory process reflected by high cytokine levels in psychotic and mood disorders.

Interestingly, many existing psychotropic agents have one or more of these neurotropic effects.

4. Neurostimulation for brain repair. Electroconvulsive therapy has been an effective (though sparingly used) psychiatric treatment for decades. Now, a new era of brain stimulation for psychiatric disorders is evolving with the FDA-approved modalities of repetitive transcranial magnetic stimulation (rTMS) and vagal nerve stimulation (VNS). But the next “big thing” may be deep-brain stimulation (DBS), which is becoming a routine treatment for neurologic conditions such as Parkinson’s disease. DBS has potential to provide major treatment breakthroughs, and DBS research is progressing rapidly.

Welcome, Dr. Goldberg

Dr. Goldberg

Joseph F. Goldberg, MD, has joined CURRENT PSYCHIATRY’s editorial board as Deputy Editor. Dr. Goldberg is associate clinical professor of psychiatry at Mount Sinai School of Medicine, New York, NY, and director of the affective disorders research program at Silver Hill Hospital, New Canaan, CT. He has published >100 peer-reviewed papers on bipolar disorder, his specialty in both research and clinical practice.

5. Pharmacogenomics in clinical practice. Psychiatrists are aware that inherited genetic variations (such as in cytochrome enzymes) can influence the body’s response to drugs. Thus, patients who are poor metabolizers often experience side effects at usual clinical doses and may discontinue medications that could help them. Similarly, fast metabolizers may fail to respond to drugs that should work and are labeled as “treatment-resistant.”

Pharmacogenetic screening in clinical practice soon will become routine—it already is at a few U.S. academic hospitals—and will enable psychiatrists to customize drug treatment to achieve better efficacy and tolerability for each patient. This will help us adapt therapies to address genetic variations within our ethnically diverse society.

6. Intertwining of physical and mental disorders. A comparatively high mortality rate from cardiovascular disease has been documented in persons with serious psychiatric disorders, especially schizophrenia, bipolar disorder, major depression, and anxiety. Similarly, persons with obesity, diabetes, dyslipidemia, and hypertension suffer from higher rates of psychiatric disorders. Inflammatory factors, in part secreted from visceral adipose tissue, appear to be a common pathway.

The optimal psychiatric practice is becoming a collaborative model of care between psychiatrists and family physicians, so that patients receive integrated, comprehensive physical and mental treatments.

What this all means. The journey to the future of psychiatric practice is underway. In many respects, the future is already here. I encourage you to join the excitement.

Do you sometimes wonder what psychiatry’s future holds? Wonder no more: abundant clues point to exciting innovations in our field. Let me highlight 6 trends that will shape how we practice psychiatry.

1. Earlier diagnosis and early intervention. The past decade has witnessed a surge of progress in identifying individuals at high risk for psychosis or mood disorders. The “prodrome” has become a fertile area of research, with a focus on early “treatment” even before the clinical syndrome of schizophrenia or mania appears. The goal is to try to delay, modify, or ameliorate incipient serious mental illness by using both pharmacotherapy and psychotherapy.

2. A tsunami of genetic discoveries. Almost weekly, psychiatric geneticists are discovering genes associated with serious psychiatric disorders. Neuregulin 1, dysbindin, DISC1, DAOA (G72), PRODH, and COMT are among the many odd-sounding genes located on various chromosomes. These discoveries confirm the “complex genetics” of psychiatric disorders involving dozens—even hundreds—of susceptibility genes, in contrast to the “1 gene, 1 disease” Mendelian paradigm.

Ultimately, these genetic discoveries will provide clues to the molecular pathophysiology of major mental disorders, leading to the holy grail of psychiatric treatment: specific, biotechnology-driven, disease-modifying pharmacotherapeutics rather than merely symptom-control agents.

3. Neuroplasticity as treatment target. Over the past few years, structural atrophy of the brain at the cellular and molecular levels has been documented in psychosis, mania, depression, and anxiety. These findings have shifted our perspective of mental illness beyond the simplistic notions of “chemical imbalance.” The new model is progressive neuroplasticity changes in neurons, dendritic spines, neurite extensions, and synapses, (ie, the neuropil), with both grey and white matter reductions impairing brain connectivity and functioning.

In response, researchers are developing a neuro-protective paradigm to reverse neuroplastic changes as a new brain-repair strategy. Thus, therapeutic agents and their targets may include:

• caspase inhibitors to stop apoptosis
• neurogenesis stimulators to replenish neurons
• neurotropic enhancers to reverse deficits in various growth factors, such as nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), vascular endothelial growth factor (VEGF), etc.
• antioxidants to neutralize excess free radicals
• glia-proliferation enhancers to rebuild white matter
• tumor necrosis factor-alpha (TNF-α) inhibitors to combat the inflammatory process reflected by high cytokine levels in psychotic and mood disorders.

Interestingly, many existing psychotropic agents have one or more of these neurotropic effects.

4. Neurostimulation for brain repair. Electroconvulsive therapy has been an effective (though sparingly used) psychiatric treatment for decades. Now, a new era of brain stimulation for psychiatric disorders is evolving with the FDA-approved modalities of repetitive transcranial magnetic stimulation (rTMS) and vagal nerve stimulation (VNS). But the next “big thing” may be deep-brain stimulation (DBS), which is becoming a routine treatment for neurologic conditions such as Parkinson’s disease. DBS has potential to provide major treatment breakthroughs, and DBS research is progressing rapidly.

Welcome, Dr. Goldberg

Dr. Goldberg

Joseph F. Goldberg, MD, has joined CURRENT PSYCHIATRY’s editorial board as Deputy Editor. Dr. Goldberg is associate clinical professor of psychiatry at Mount Sinai School of Medicine, New York, NY, and director of the affective disorders research program at Silver Hill Hospital, New Canaan, CT. He has published >100 peer-reviewed papers on bipolar disorder, his specialty in both research and clinical practice.

5. Pharmacogenomics in clinical practice. Psychiatrists are aware that inherited genetic variations (such as in cytochrome enzymes) can influence the body’s response to drugs. Thus, patients who are poor metabolizers often experience side effects at usual clinical doses and may discontinue medications that could help them. Similarly, fast metabolizers may fail to respond to drugs that should work and are labeled as “treatment-resistant.”

Pharmacogenetic screening in clinical practice soon will become routine—it already is at a few U.S. academic hospitals—and will enable psychiatrists to customize drug treatment to achieve better efficacy and tolerability for each patient. This will help us adapt therapies to address genetic variations within our ethnically diverse society.

6. Intertwining of physical and mental disorders. A comparatively high mortality rate from cardiovascular disease has been documented in persons with serious psychiatric disorders, especially schizophrenia, bipolar disorder, major depression, and anxiety. Similarly, persons with obesity, diabetes, dyslipidemia, and hypertension suffer from higher rates of psychiatric disorders. Inflammatory factors, in part secreted from visceral adipose tissue, appear to be a common pathway.

The optimal psychiatric practice is becoming a collaborative model of care between psychiatrists and family physicians, so that patients receive integrated, comprehensive physical and mental treatments.

What this all means. The journey to the future of psychiatric practice is underway. In many respects, the future is already here. I encourage you to join the excitement.

Do you sometimes wonder what psychiatry’s future holds? Wonder no more: abundant clues point to exciting innovations in our field. Let me highlight 6 trends that will shape how we practice psychiatry.

1. Earlier diagnosis and early intervention. The past decade has witnessed a surge of progress in identifying individuals at high risk for psychosis or mood disorders. The “prodrome” has become a fertile area of research, with a focus on early “treatment” even before the clinical syndrome of schizophrenia or mania appears. The goal is to try to delay, modify, or ameliorate incipient serious mental illness by using both pharmacotherapy and psychotherapy.

2. A tsunami of genetic discoveries. Almost weekly, psychiatric geneticists are discovering genes associated with serious psychiatric disorders. Neuregulin 1, dysbindin, DISC1, DAOA (G72), PRODH, and COMT are among the many odd-sounding genes located on various chromosomes. These discoveries confirm the “complex genetics” of psychiatric disorders involving dozens—even hundreds—of susceptibility genes, in contrast to the “1 gene, 1 disease” Mendelian paradigm.

Ultimately, these genetic discoveries will provide clues to the molecular pathophysiology of major mental disorders, leading to the holy grail of psychiatric treatment: specific, biotechnology-driven, disease-modifying pharmacotherapeutics rather than merely symptom-control agents.

3. Neuroplasticity as treatment target. Over the past few years, structural atrophy of the brain at the cellular and molecular levels has been documented in psychosis, mania, depression, and anxiety. These findings have shifted our perspective of mental illness beyond the simplistic notions of “chemical imbalance.” The new model is progressive neuroplasticity changes in neurons, dendritic spines, neurite extensions, and synapses, (ie, the neuropil), with both grey and white matter reductions impairing brain connectivity and functioning.

In response, researchers are developing a neuro-protective paradigm to reverse neuroplastic changes as a new brain-repair strategy. Thus, therapeutic agents and their targets may include:

• caspase inhibitors to stop apoptosis
• neurogenesis stimulators to replenish neurons
• neurotropic enhancers to reverse deficits in various growth factors, such as nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), vascular endothelial growth factor (VEGF), etc.
• antioxidants to neutralize excess free radicals
• glia-proliferation enhancers to rebuild white matter
• tumor necrosis factor-alpha (TNF-α) inhibitors to combat the inflammatory process reflected by high cytokine levels in psychotic and mood disorders.

Interestingly, many existing psychotropic agents have one or more of these neurotropic effects.

4. Neurostimulation for brain repair. Electroconvulsive therapy has been an effective (though sparingly used) psychiatric treatment for decades. Now, a new era of brain stimulation for psychiatric disorders is evolving with the FDA-approved modalities of repetitive transcranial magnetic stimulation (rTMS) and vagal nerve stimulation (VNS). But the next “big thing” may be deep-brain stimulation (DBS), which is becoming a routine treatment for neurologic conditions such as Parkinson’s disease. DBS has potential to provide major treatment breakthroughs, and DBS research is progressing rapidly.

Welcome, Dr. Goldberg

Dr. Goldberg

Joseph F. Goldberg, MD, has joined CURRENT PSYCHIATRY’s editorial board as Deputy Editor. Dr. Goldberg is associate clinical professor of psychiatry at Mount Sinai School of Medicine, New York, NY, and director of the affective disorders research program at Silver Hill Hospital, New Canaan, CT. He has published >100 peer-reviewed papers on bipolar disorder, his specialty in both research and clinical practice.

5. Pharmacogenomics in clinical practice. Psychiatrists are aware that inherited genetic variations (such as in cytochrome enzymes) can influence the body’s response to drugs. Thus, patients who are poor metabolizers often experience side effects at usual clinical doses and may discontinue medications that could help them. Similarly, fast metabolizers may fail to respond to drugs that should work and are labeled as “treatment-resistant.”

Pharmacogenetic screening in clinical practice soon will become routine—it already is at a few U.S. academic hospitals—and will enable psychiatrists to customize drug treatment to achieve better efficacy and tolerability for each patient. This will help us adapt therapies to address genetic variations within our ethnically diverse society.

6. Intertwining of physical and mental disorders. A comparatively high mortality rate from cardiovascular disease has been documented in persons with serious psychiatric disorders, especially schizophrenia, bipolar disorder, major depression, and anxiety. Similarly, persons with obesity, diabetes, dyslipidemia, and hypertension suffer from higher rates of psychiatric disorders. Inflammatory factors, in part secreted from visceral adipose tissue, appear to be a common pathway.

The optimal psychiatric practice is becoming a collaborative model of care between psychiatrists and family physicians, so that patients receive integrated, comprehensive physical and mental treatments.

What this all means. The journey to the future of psychiatric practice is underway. In many respects, the future is already here. I encourage you to join the excitement.

A major challenge for the DSM-V committees as they revise the diagnostic “bible” of psychiatric disorders is to determine whether mental illnesses are diseases, disorders, or syndromes.

Here’s how my version of Webster’s dictionary defines these terms:

• Disease: A particular distinctive process in the body with a specific cause and characteristic symptoms.
• Disorder: Irregularity, disturbance, or interruption of normal functions.
• Syndrome: A number of symptoms occurring together and characterizing a specific disease.

Let’s consider 4 facts that may be relevant for this decision.

Probably not ‘diseases’

No objective laboratory test can differentiate 1 psychiatric malady from another, and this lack of specificity casts doubt on the disease model. However, many documented perturbations of normal brain functions are consistent with a disorder paradigm.

Symptom overlap

The signs and symptoms of psychiatric ailments overlap considerably. Depression and anxiety share many symptoms and frequently co-occur. Bipolar mania and schizophrenia share psychotic features, cognitive deficits, agitation, suicidality, aggressive behavior, etc. The obsessions of obsessive-compulsive disorder (OCD) resemble and sometimes morph into the fixed false beliefs (delusions) of psychosis, and OCD’s compulsions often characterize the behaviors of other psychiatric disorders, such as anorexia or bulimia nervosa.

Personality disorder features essentially are attenuated but enduring forms of Axis I conditions. Nearly all psychiatric illnesses have some degree of suicidality, insomnia, and addictive behavior. Posttraumatic stress disorder’s symptoms recapitulate those of numerous diagnostic categories, such as anxiety, depression, psychosis, negative symptoms, mania, OCD, impulsive behavior, and personality changes.

Common neurobiology

Most diagnostic categories in psychiatry share some neurobiologic features, such as:

• neurotransmitter pathways (serotonin, dopamine, norepinephrine, or glutamate)
• structural abnormalities on neuroimaging (cortical atrophy, ventriculomegaly, gray and/or white matter abnormalities) or
• genetic predispositions.

Medical and psychiatric comorbidities (migraine, chronic pain, diabetes, obesity, alcohol abuse, anxiety, eating disorders, and Axis II features) occur across all major psychiatric diagnoses.

Nonspecific medications

Psychotropics approved for treating 1 condition are frequently useful for others:

• Selective serotonin reuptake inhibitors initially were indicated for depression but soon were found to have efficacy for panic attacks, social phobia, OCD, bulimia, impulse dyscontrol, and fibromyalgia.
• Atypical antipsychotics indicated for schizophrenia have been found useful in bipolar mania, treatment-resistant OCD, treatment-resistant depression, borderline personality disorder, delirium, anxiety, etc.
• Anticonvulsants indicated for epilepsy later were approved for bipolar mania and then found to have uses in alcoholism and drug abuse, aggressive behavior, impulsivity, treatment-resistant anxiety, and psychosis.

The multiple efficacies of psychiatric drug classes strongly suggest shared pharmacotherapeutic responsiveness across psychiatric diagnoses, including those without any FDA-approved medication. They also render the opinionated and uninformed criticism of “off-label” prescribing practices hollow, effete, and counterproductive.

Back to definitions

So, should DSM-V committees define diagnostic categories as diseases, disorders, or syndromes? The state of knowledge points to disorders and syndromes rather than diseases. There very well could be a specific disease within a syndrome, but many phenotypes and genotypes manifest with similar clusters of psychiatric signs and symptoms. As research identifies each syndrome’s components, future DSM editions can systematically incorporate them and their specific pathophysiologies that converge into common neural and behavioral pathways.

Until neuroscience elucidates the pathogenesis of psychiatric diseases, wouldn’t it make sense to recognize 4 major syndromes: mood, anxiety, psychosis, and addiction? This might prompt the FDA to approve drugs for clusters of symptoms rather than for arbitrarily defined diagnostic categories that appear distinct but in fact share many signs and symptoms.

Psychiatrists, then, could reconceptualize how primary and secondary psychopathologic disorders can produce common symptoms that do not constitute a specific disease but do aggregate into treatable syndromes, the underpinning of which may be shared biological mechanisms.

A major challenge for the DSM-V committees as they revise the diagnostic “bible” of psychiatric disorders is to determine whether mental illnesses are diseases, disorders, or syndromes.

Here’s how my version of Webster’s dictionary defines these terms:

• Disease: A particular distinctive process in the body with a specific cause and characteristic symptoms.
• Disorder: Irregularity, disturbance, or interruption of normal functions.
• Syndrome: A number of symptoms occurring together and characterizing a specific disease.

Let’s consider 4 facts that may be relevant for this decision.

Probably not ‘diseases’

No objective laboratory test can differentiate 1 psychiatric malady from another, and this lack of specificity casts doubt on the disease model. However, many documented perturbations of normal brain functions are consistent with a disorder paradigm.

Symptom overlap

The signs and symptoms of psychiatric ailments overlap considerably. Depression and anxiety share many symptoms and frequently co-occur. Bipolar mania and schizophrenia share psychotic features, cognitive deficits, agitation, suicidality, aggressive behavior, etc. The obsessions of obsessive-compulsive disorder (OCD) resemble and sometimes morph into the fixed false beliefs (delusions) of psychosis, and OCD’s compulsions often characterize the behaviors of other psychiatric disorders, such as anorexia or bulimia nervosa.

Personality disorder features essentially are attenuated but enduring forms of Axis I conditions. Nearly all psychiatric illnesses have some degree of suicidality, insomnia, and addictive behavior. Posttraumatic stress disorder’s symptoms recapitulate those of numerous diagnostic categories, such as anxiety, depression, psychosis, negative symptoms, mania, OCD, impulsive behavior, and personality changes.

Common neurobiology

Most diagnostic categories in psychiatry share some neurobiologic features, such as:

• neurotransmitter pathways (serotonin, dopamine, norepinephrine, or glutamate)
• structural abnormalities on neuroimaging (cortical atrophy, ventriculomegaly, gray and/or white matter abnormalities) or
• genetic predispositions.

Medical and psychiatric comorbidities (migraine, chronic pain, diabetes, obesity, alcohol abuse, anxiety, eating disorders, and Axis II features) occur across all major psychiatric diagnoses.

Nonspecific medications

Psychotropics approved for treating 1 condition are frequently useful for others:

• Selective serotonin reuptake inhibitors initially were indicated for depression but soon were found to have efficacy for panic attacks, social phobia, OCD, bulimia, impulse dyscontrol, and fibromyalgia.
• Atypical antipsychotics indicated for schizophrenia have been found useful in bipolar mania, treatment-resistant OCD, treatment-resistant depression, borderline personality disorder, delirium, anxiety, etc.
• Anticonvulsants indicated for epilepsy later were approved for bipolar mania and then found to have uses in alcoholism and drug abuse, aggressive behavior, impulsivity, treatment-resistant anxiety, and psychosis.

The multiple efficacies of psychiatric drug classes strongly suggest shared pharmacotherapeutic responsiveness across psychiatric diagnoses, including those without any FDA-approved medication. They also render the opinionated and uninformed criticism of “off-label” prescribing practices hollow, effete, and counterproductive.

Back to definitions

So, should DSM-V committees define diagnostic categories as diseases, disorders, or syndromes? The state of knowledge points to disorders and syndromes rather than diseases. There very well could be a specific disease within a syndrome, but many phenotypes and genotypes manifest with similar clusters of psychiatric signs and symptoms. As research identifies each syndrome’s components, future DSM editions can systematically incorporate them and their specific pathophysiologies that converge into common neural and behavioral pathways.

Until neuroscience elucidates the pathogenesis of psychiatric diseases, wouldn’t it make sense to recognize 4 major syndromes: mood, anxiety, psychosis, and addiction? This might prompt the FDA to approve drugs for clusters of symptoms rather than for arbitrarily defined diagnostic categories that appear distinct but in fact share many signs and symptoms.

Psychiatrists, then, could reconceptualize how primary and secondary psychopathologic disorders can produce common symptoms that do not constitute a specific disease but do aggregate into treatable syndromes, the underpinning of which may be shared biological mechanisms.

A major challenge for the DSM-V committees as they revise the diagnostic “bible” of psychiatric disorders is to determine whether mental illnesses are diseases, disorders, or syndromes.

Here’s how my version of Webster’s dictionary defines these terms:

• Disease: A particular distinctive process in the body with a specific cause and characteristic symptoms.
• Disorder: Irregularity, disturbance, or interruption of normal functions.
• Syndrome: A number of symptoms occurring together and characterizing a specific disease.

Let’s consider 4 facts that may be relevant for this decision.

Probably not ‘diseases’

No objective laboratory test can differentiate 1 psychiatric malady from another, and this lack of specificity casts doubt on the disease model. However, many documented perturbations of normal brain functions are consistent with a disorder paradigm.

Symptom overlap

The signs and symptoms of psychiatric ailments overlap considerably. Depression and anxiety share many symptoms and frequently co-occur. Bipolar mania and schizophrenia share psychotic features, cognitive deficits, agitation, suicidality, aggressive behavior, etc. The obsessions of obsessive-compulsive disorder (OCD) resemble and sometimes morph into the fixed false beliefs (delusions) of psychosis, and OCD’s compulsions often characterize the behaviors of other psychiatric disorders, such as anorexia or bulimia nervosa.

Personality disorder features essentially are attenuated but enduring forms of Axis I conditions. Nearly all psychiatric illnesses have some degree of suicidality, insomnia, and addictive behavior. Posttraumatic stress disorder’s symptoms recapitulate those of numerous diagnostic categories, such as anxiety, depression, psychosis, negative symptoms, mania, OCD, impulsive behavior, and personality changes.

Common neurobiology

Most diagnostic categories in psychiatry share some neurobiologic features, such as:

• neurotransmitter pathways (serotonin, dopamine, norepinephrine, or glutamate)
• structural abnormalities on neuroimaging (cortical atrophy, ventriculomegaly, gray and/or white matter abnormalities) or
• genetic predispositions.

Medical and psychiatric comorbidities (migraine, chronic pain, diabetes, obesity, alcohol abuse, anxiety, eating disorders, and Axis II features) occur across all major psychiatric diagnoses.

Nonspecific medications

Psychotropics approved for treating 1 condition are frequently useful for others:

• Selective serotonin reuptake inhibitors initially were indicated for depression but soon were found to have efficacy for panic attacks, social phobia, OCD, bulimia, impulse dyscontrol, and fibromyalgia.
• Atypical antipsychotics indicated for schizophrenia have been found useful in bipolar mania, treatment-resistant OCD, treatment-resistant depression, borderline personality disorder, delirium, anxiety, etc.
• Anticonvulsants indicated for epilepsy later were approved for bipolar mania and then found to have uses in alcoholism and drug abuse, aggressive behavior, impulsivity, treatment-resistant anxiety, and psychosis.

The multiple efficacies of psychiatric drug classes strongly suggest shared pharmacotherapeutic responsiveness across psychiatric diagnoses, including those without any FDA-approved medication. They also render the opinionated and uninformed criticism of “off-label” prescribing practices hollow, effete, and counterproductive.

Back to definitions

So, should DSM-V committees define diagnostic categories as diseases, disorders, or syndromes? The state of knowledge points to disorders and syndromes rather than diseases. There very well could be a specific disease within a syndrome, but many phenotypes and genotypes manifest with similar clusters of psychiatric signs and symptoms. As research identifies each syndrome’s components, future DSM editions can systematically incorporate them and their specific pathophysiologies that converge into common neural and behavioral pathways.

Until neuroscience elucidates the pathogenesis of psychiatric diseases, wouldn’t it make sense to recognize 4 major syndromes: mood, anxiety, psychosis, and addiction? This might prompt the FDA to approve drugs for clusters of symptoms rather than for arbitrarily defined diagnostic categories that appear distinct but in fact share many signs and symptoms.

Psychiatrists, then, could reconceptualize how primary and secondary psychopathologic disorders can produce common symptoms that do not constitute a specific disease but do aggregate into treatable syndromes, the underpinning of which may be shared biological mechanisms.

A recent book contends that psychiatry has transformed normal sadness and sorrow into a depressive disorder,¹ which would be akin to saying primary care physicians diagnose every mild cough as pneumonia. The book’s premise is not true, of course, but it’s a perfect example of how misunderstood serious mental illness is.

Psychiatric disorders deal with extreme, pathologic changes in behavior, thoughts and emotions, perception, or will. Psychiatrists do not pathologize normal sadness over a missed opportunity nor noticeable grief over the death of a loved one. We do, however, recognize the substantial disruption that clinical depression brings to a person’s life and the potential for suicidal acts during major depressive illness.

Similarly, being happy about a minor achievement does not affect one’s life as much as the giddiness of infatuation and certainly is not as serious as the grandiose euphoria of a manic episode. Psychiatrists would intervene with a diagnosis and treatment plan only if the condition were severe enough to impair social and vocational functioning.

Cataloging human flaws

Let’s assume, just for fun, that psychiatrists did decide to pathologize common human traits. Consider the many categories we would need to add to DSM-V!

Take the worldwide financial meltdown triggered by questionable practices of banking executives who thought they would never fail or be caught on their way to accumulating obscene wealth. They certainly left a lot of wreckage in their wake, so perhaps psychiatry should create new diagnostic entities of “Horrendous Hubris” and “Gargantuan Greed.”

But why stop there? How about “Verbal Diarrhea” for folks who chatter incessantly at a cocktail party or committee meeting, or “Intellectual Constipation” for our friends with exasperating narrow-mindedness. And for the painfully irritating person, “Social Hemorrhoid” might be apropos.

Let’s not forget those who throw temper tantrums when they can’t have their way: they may suffer from “Temperamental Arrhythmia.” And for chronic complainers who never stop whining, let’s go with “Emotive Angina.” I’d better stop here and not go into the garden variety of human flaws: gluttony, sloth, fanaticism, indecisiveness, cowardice, chicanery, snobbishness, rudeness, and plain old stupidity.

Normal vs pathologic

My point is that the social retina of psychiatry does not perceive ordinary human traits and emotions such as normal sadness as pathologic behavior. But psychiatrists certainly are willing to intervene when people seek help on their own for problems such as depressive episodes that are disrupting their lives or are referred by physicians or brought in by family or friends who recognize the potential gravity of their afflictions.

A recent book contends that psychiatry has transformed normal sadness and sorrow into a depressive disorder,¹ which would be akin to saying primary care physicians diagnose every mild cough as pneumonia. The book’s premise is not true, of course, but it’s a perfect example of how misunderstood serious mental illness is.

Psychiatric disorders deal with extreme, pathologic changes in behavior, thoughts and emotions, perception, or will. Psychiatrists do not pathologize normal sadness over a missed opportunity nor noticeable grief over the death of a loved one. We do, however, recognize the substantial disruption that clinical depression brings to a person’s life and the potential for suicidal acts during major depressive illness.

Similarly, being happy about a minor achievement does not affect one’s life as much as the giddiness of infatuation and certainly is not as serious as the grandiose euphoria of a manic episode. Psychiatrists would intervene with a diagnosis and treatment plan only if the condition were severe enough to impair social and vocational functioning.

Cataloging human flaws

Let’s assume, just for fun, that psychiatrists did decide to pathologize common human traits. Consider the many categories we would need to add to DSM-V!

Take the worldwide financial meltdown triggered by questionable practices of banking executives who thought they would never fail or be caught on their way to accumulating obscene wealth. They certainly left a lot of wreckage in their wake, so perhaps psychiatry should create new diagnostic entities of “Horrendous Hubris” and “Gargantuan Greed.”

But why stop there? How about “Verbal Diarrhea” for folks who chatter incessantly at a cocktail party or committee meeting, or “Intellectual Constipation” for our friends with exasperating narrow-mindedness. And for the painfully irritating person, “Social Hemorrhoid” might be apropos.

Let’s not forget those who throw temper tantrums when they can’t have their way: they may suffer from “Temperamental Arrhythmia.” And for chronic complainers who never stop whining, let’s go with “Emotive Angina.” I’d better stop here and not go into the garden variety of human flaws: gluttony, sloth, fanaticism, indecisiveness, cowardice, chicanery, snobbishness, rudeness, and plain old stupidity.

Normal vs pathologic

My point is that the social retina of psychiatry does not perceive ordinary human traits and emotions such as normal sadness as pathologic behavior. But psychiatrists certainly are willing to intervene when people seek help on their own for problems such as depressive episodes that are disrupting their lives or are referred by physicians or brought in by family or friends who recognize the potential gravity of their afflictions.

A recent book contends that psychiatry has transformed normal sadness and sorrow into a depressive disorder,¹ which would be akin to saying primary care physicians diagnose every mild cough as pneumonia. The book’s premise is not true, of course, but it’s a perfect example of how misunderstood serious mental illness is.

Psychiatric disorders deal with extreme, pathologic changes in behavior, thoughts and emotions, perception, or will. Psychiatrists do not pathologize normal sadness over a missed opportunity nor noticeable grief over the death of a loved one. We do, however, recognize the substantial disruption that clinical depression brings to a person’s life and the potential for suicidal acts during major depressive illness.

Similarly, being happy about a minor achievement does not affect one’s life as much as the giddiness of infatuation and certainly is not as serious as the grandiose euphoria of a manic episode. Psychiatrists would intervene with a diagnosis and treatment plan only if the condition were severe enough to impair social and vocational functioning.

Cataloging human flaws

Let’s assume, just for fun, that psychiatrists did decide to pathologize common human traits. Consider the many categories we would need to add to DSM-V!

Take the worldwide financial meltdown triggered by questionable practices of banking executives who thought they would never fail or be caught on their way to accumulating obscene wealth. They certainly left a lot of wreckage in their wake, so perhaps psychiatry should create new diagnostic entities of “Horrendous Hubris” and “Gargantuan Greed.”

But why stop there? How about “Verbal Diarrhea” for folks who chatter incessantly at a cocktail party or committee meeting, or “Intellectual Constipation” for our friends with exasperating narrow-mindedness. And for the painfully irritating person, “Social Hemorrhoid” might be apropos.

Let’s not forget those who throw temper tantrums when they can’t have their way: they may suffer from “Temperamental Arrhythmia.” And for chronic complainers who never stop whining, let’s go with “Emotive Angina.” I’d better stop here and not go into the garden variety of human flaws: gluttony, sloth, fanaticism, indecisiveness, cowardice, chicanery, snobbishness, rudeness, and plain old stupidity.

Normal vs pathologic

My point is that the social retina of psychiatry does not perceive ordinary human traits and emotions such as normal sadness as pathologic behavior. But psychiatrists certainly are willing to intervene when people seek help on their own for problems such as depressive episodes that are disrupting their lives or are referred by physicians or brought in by family or friends who recognize the potential gravity of their afflictions.

Ever since Kraepelin used the label “dementia praecox” for the disorder Bleuler later renamed “schizophrenia,” psychiatrists have recognized cognitive impairment as a central feature of schizophrenia.¹ Cognitive deficits are an important component of many psychiatric disorders, but formal cognitive assessment still is not a part of standard clinical evaluation in psychiatric practice. It’s time that it becomes so.

Almost 2 decades ago, studies in my laboratory discovered that patients with bipolar disorder have significant deficits in cognition—including short-term memory and executive function—similar to those seen in schizophrenia.² This finding has been replicated extensively, and a book on the subject was published recently.³ Cognitive dysfunction also has been reported in unipolar depression,⁴ obsessive-compulsive disorder,⁵ posttraumatic stress disorder (PTSD),⁶ attention-deficit/hyperactivity disorder,⁷ and borderline personality disorder.⁸

This should not be surprising. Cognition is a major brain function, and mental illnesses are neurobiologic disorders in which cognitive domains can be moderately or seriously disrupted. Neurocognitive studies have established that specific cognitive dysfunctions correlate with brain pathology in specific regions. For example, because the hippocampus is a key brain region for memory, memory deficits are observed in any disorder that disrupts hippocampal structure, including Alzheimer’s disease, alcoholism, PTSD, schizophrenia, and depression.

Why assess cognition?

Cognitive measurement using validated test batteries as part of a thorough and systematic mental status examination is becoming essential—even required—in psychiatric practice. Formal cognitive assessment is useful for many clinical reasons:

• for diagnosis (the upcoming fifth edition of the Diagnostic and statistical manual of mental disorders [DSM-V] is sure to include cognitive performance in schizophrenia’s diagnostic criteria)
• to assess illness severity
• to localize dysfunctional neural pathways
• to formulate a reasonable prognosis
• to rule out possible mental retardation
• to tailor a pharmacologic treatment plan that does not further impair cognition but may enhance it
• to monitor response to treatment
• to assess cognitive side effects of pharmacotherapy
• to develop social and vocational rehabilitation programs that build on patients’ cognitive abilities.

‘Cognition enhancers’

The pharmaceutical industry’s recent surge of interest in developing cognition-enhancing (“nootropic”) drugs is timely, welcome, and supported by the National Institute of Mental Health. Initial targets of nootropic drug development are Alzheimer’s dementia and schizophrenia, but research is likely to extend to other psychiatric disorders.

When effective cognition-enhancing agents are developed and approved for use in dementia and schizophrenia, they undoubtedly will be tested in other neuropsychiatric disorders as well. They will be used as “add-on” medications to target cognitive deficits in many psychopathologic states.

Getting started

The time to vigorously assess and treat cognitive dysfunction is here. You can start—if you haven’t already—by incorporating into your practice a brief cognitive battery that measures performance on several key domains. One example is the Brief Assessment of Cognition in Schizophrenia (BACS)⁹ that was used in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. You not only will be ahead of the curve, but your patients will benefit from increased attention to cognition in their diagnosis and treatment.

Ever since Kraepelin used the label “dementia praecox” for the disorder Bleuler later renamed “schizophrenia,” psychiatrists have recognized cognitive impairment as a central feature of schizophrenia.¹ Cognitive deficits are an important component of many psychiatric disorders, but formal cognitive assessment still is not a part of standard clinical evaluation in psychiatric practice. It’s time that it becomes so.

Almost 2 decades ago, studies in my laboratory discovered that patients with bipolar disorder have significant deficits in cognition—including short-term memory and executive function—similar to those seen in schizophrenia.² This finding has been replicated extensively, and a book on the subject was published recently.³ Cognitive dysfunction also has been reported in unipolar depression,⁴ obsessive-compulsive disorder,⁵ posttraumatic stress disorder (PTSD),⁶ attention-deficit/hyperactivity disorder,⁷ and borderline personality disorder.⁸

This should not be surprising. Cognition is a major brain function, and mental illnesses are neurobiologic disorders in which cognitive domains can be moderately or seriously disrupted. Neurocognitive studies have established that specific cognitive dysfunctions correlate with brain pathology in specific regions. For example, because the hippocampus is a key brain region for memory, memory deficits are observed in any disorder that disrupts hippocampal structure, including Alzheimer’s disease, alcoholism, PTSD, schizophrenia, and depression.

Why assess cognition?

Cognitive measurement using validated test batteries as part of a thorough and systematic mental status examination is becoming essential—even required—in psychiatric practice. Formal cognitive assessment is useful for many clinical reasons:

• for diagnosis (the upcoming fifth edition of the Diagnostic and statistical manual of mental disorders [DSM-V] is sure to include cognitive performance in schizophrenia’s diagnostic criteria)
• to assess illness severity
• to localize dysfunctional neural pathways
• to formulate a reasonable prognosis
• to rule out possible mental retardation
• to tailor a pharmacologic treatment plan that does not further impair cognition but may enhance it
• to monitor response to treatment
• to assess cognitive side effects of pharmacotherapy
• to develop social and vocational rehabilitation programs that build on patients’ cognitive abilities.

‘Cognition enhancers’

The pharmaceutical industry’s recent surge of interest in developing cognition-enhancing (“nootropic”) drugs is timely, welcome, and supported by the National Institute of Mental Health. Initial targets of nootropic drug development are Alzheimer’s dementia and schizophrenia, but research is likely to extend to other psychiatric disorders.

When effective cognition-enhancing agents are developed and approved for use in dementia and schizophrenia, they undoubtedly will be tested in other neuropsychiatric disorders as well. They will be used as “add-on” medications to target cognitive deficits in many psychopathologic states.

Getting started

The time to vigorously assess and treat cognitive dysfunction is here. You can start—if you haven’t already—by incorporating into your practice a brief cognitive battery that measures performance on several key domains. One example is the Brief Assessment of Cognition in Schizophrenia (BACS)⁹ that was used in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. You not only will be ahead of the curve, but your patients will benefit from increased attention to cognition in their diagnosis and treatment.

Ever since Kraepelin used the label “dementia praecox” for the disorder Bleuler later renamed “schizophrenia,” psychiatrists have recognized cognitive impairment as a central feature of schizophrenia.¹ Cognitive deficits are an important component of many psychiatric disorders, but formal cognitive assessment still is not a part of standard clinical evaluation in psychiatric practice. It’s time that it becomes so.

Almost 2 decades ago, studies in my laboratory discovered that patients with bipolar disorder have significant deficits in cognition—including short-term memory and executive function—similar to those seen in schizophrenia.² This finding has been replicated extensively, and a book on the subject was published recently.³ Cognitive dysfunction also has been reported in unipolar depression,⁴ obsessive-compulsive disorder,⁵ posttraumatic stress disorder (PTSD),⁶ attention-deficit/hyperactivity disorder,⁷ and borderline personality disorder.⁸

This should not be surprising. Cognition is a major brain function, and mental illnesses are neurobiologic disorders in which cognitive domains can be moderately or seriously disrupted. Neurocognitive studies have established that specific cognitive dysfunctions correlate with brain pathology in specific regions. For example, because the hippocampus is a key brain region for memory, memory deficits are observed in any disorder that disrupts hippocampal structure, including Alzheimer’s disease, alcoholism, PTSD, schizophrenia, and depression.

Why assess cognition?

Cognitive measurement using validated test batteries as part of a thorough and systematic mental status examination is becoming essential—even required—in psychiatric practice. Formal cognitive assessment is useful for many clinical reasons:

• for diagnosis (the upcoming fifth edition of the Diagnostic and statistical manual of mental disorders [DSM-V] is sure to include cognitive performance in schizophrenia’s diagnostic criteria)
• to assess illness severity
• to localize dysfunctional neural pathways
• to formulate a reasonable prognosis
• to rule out possible mental retardation
• to tailor a pharmacologic treatment plan that does not further impair cognition but may enhance it
• to monitor response to treatment
• to assess cognitive side effects of pharmacotherapy
• to develop social and vocational rehabilitation programs that build on patients’ cognitive abilities.

‘Cognition enhancers’

The pharmaceutical industry’s recent surge of interest in developing cognition-enhancing (“nootropic”) drugs is timely, welcome, and supported by the National Institute of Mental Health. Initial targets of nootropic drug development are Alzheimer’s dementia and schizophrenia, but research is likely to extend to other psychiatric disorders.

When effective cognition-enhancing agents are developed and approved for use in dementia and schizophrenia, they undoubtedly will be tested in other neuropsychiatric disorders as well. They will be used as “add-on” medications to target cognitive deficits in many psychopathologic states.

Getting started

The time to vigorously assess and treat cognitive dysfunction is here. You can start—if you haven’t already—by incorporating into your practice a brief cognitive battery that measures performance on several key domains. One example is the Brief Assessment of Cognition in Schizophrenia (BACS)⁹ that was used in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. You not only will be ahead of the curve, but your patients will benefit from increased attention to cognition in their diagnosis and treatment.

Medication side effects are generally regarded as the Achilles’ heel of pharmacologic treatment. And who can argue with that? Adverse effects are the downside of drug treatment of psychiatric disorders and are blamed for tolerability and adherence problems. Patients dread side effects, physicians feel uncomfortable or even guilty about them, and litigation lawyers thrive on them.

Psychotropics’ package inserts are loaded with side-effect descriptions. The precautions, warnings, and black boxes frequently make patients anxious about taking medications, even when the diseases they suffer from pose far greater risk to their lives and health.

Are side effects entirely bad, or is there a possible upside lurking within them? Psychiatrists know, for example, that a common adverse effect of selective serotonin reuptake inhibitor (SSRI) antidepressants/anxiolytics is delayed orgasm. But because of this side effect, SSRIs can be dramatically helpful for treating premature ejaculation in nondepressed men.

Let’s consider some effects of atypical antipsychotics that usually are considered a downside of antipsychotic treatment yet appear to be associated with advantages for the same patients.

Therapeutic sedation

Sedation was considered a major adverse effect of quetiapine when this antipsychotic was approved for treating schizophrenia. Yet with time—and as the drug received additional indications for bipolar mania and bipolar depression—it became apparent to psychiatrists that quetiapine’s sedative effects could be useful for treating insomnia in individuals with psychotic and mood disorders. Thus, practitioners saw an advantage in using a sedating antipsychotic, instead of adding a sedative/hypnotic, for psychotic or manic patients suffering from agitation, anxiety, and insomnia. Three advantages of this approach for patients are:

• fewer medications to manage
• lower costs without an additional sedative/hypnotic
• avoiding the potential addictive effects of a sedative/hypnotic.

Hyperprolactinemia and myelin repair

Some patients receiving risperidone or paliperidone for psychotic symptoms develop sexual dysfunction because of the side effect of increased serum prolactin. On the other hand, recent research indicates that prolactin enhances the synthesis of oligodendrocytes, which are critical for myelin (white matter) integrity in brain tissue.

In a recent study, researchers used a toxin to destroy patches of white matter in the brains of nonpregnant mice. Subsequent pregnancy and prolactin elevation repaired the myelin lesions completely, whereas no changes occurred in the white matter lesions in the brains of control mice that remained nonpregnant.¹

This suggested myelin-repairing property of prolactin is highly relevant to the development of potential therapies, not only for demyelinating disorders such as multiple sclerosis but also for schizophrenia. Numerous studies have demonstrated that schizophrenia is associated with serious white-matter pathology,² which may account for many of the disorder’s thought, emotional, and cognitive impairments.

Weight gain as marker for antipsychotic efficacy

Some weight increase is observed with all antipsychotics, although certain atypicals such as olanzapine and clozapine are associated with more weight gain than others. No clinician would see anything except a downside to weight gain, which may lead to metabolic complications such as diabetes, hyperlipidemia, and hypertension.

However, some weight gain appears to be related to the efficacy of all antipsychotics (first- and second-generation), according to the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)³ and previous sporadic observations in the literature. Even Kraepelin noted in the 1920s—long before the era of antipsychotics—that patients with psychosis gained weight when they spontaneously improved.

Thus, some weight gain appears to be a necessary correlate of improvement in persons treated with antipsychotics. The reasons are still unclear, but weight gain may be a modulator, mediator, or marker of antipsychotic efficacy.

In summary, there appears to be at least some upside to the downside of certain drug side effects. In other words, every dark cloud has a silver lining, and it might be helpful for patients and physicians to see more than just the cloud.

Medication side effects are generally regarded as the Achilles’ heel of pharmacologic treatment. And who can argue with that? Adverse effects are the downside of drug treatment of psychiatric disorders and are blamed for tolerability and adherence problems. Patients dread side effects, physicians feel uncomfortable or even guilty about them, and litigation lawyers thrive on them.

Psychotropics’ package inserts are loaded with side-effect descriptions. The precautions, warnings, and black boxes frequently make patients anxious about taking medications, even when the diseases they suffer from pose far greater risk to their lives and health.

Are side effects entirely bad, or is there a possible upside lurking within them? Psychiatrists know, for example, that a common adverse effect of selective serotonin reuptake inhibitor (SSRI) antidepressants/anxiolytics is delayed orgasm. But because of this side effect, SSRIs can be dramatically helpful for treating premature ejaculation in nondepressed men.

Let’s consider some effects of atypical antipsychotics that usually are considered a downside of antipsychotic treatment yet appear to be associated with advantages for the same patients.

Therapeutic sedation

Sedation was considered a major adverse effect of quetiapine when this antipsychotic was approved for treating schizophrenia. Yet with time—and as the drug received additional indications for bipolar mania and bipolar depression—it became apparent to psychiatrists that quetiapine’s sedative effects could be useful for treating insomnia in individuals with psychotic and mood disorders. Thus, practitioners saw an advantage in using a sedating antipsychotic, instead of adding a sedative/hypnotic, for psychotic or manic patients suffering from agitation, anxiety, and insomnia. Three advantages of this approach for patients are:

• fewer medications to manage
• lower costs without an additional sedative/hypnotic
• avoiding the potential addictive effects of a sedative/hypnotic.

Hyperprolactinemia and myelin repair

Some patients receiving risperidone or paliperidone for psychotic symptoms develop sexual dysfunction because of the side effect of increased serum prolactin. On the other hand, recent research indicates that prolactin enhances the synthesis of oligodendrocytes, which are critical for myelin (white matter) integrity in brain tissue.

In a recent study, researchers used a toxin to destroy patches of white matter in the brains of nonpregnant mice. Subsequent pregnancy and prolactin elevation repaired the myelin lesions completely, whereas no changes occurred in the white matter lesions in the brains of control mice that remained nonpregnant.¹

This suggested myelin-repairing property of prolactin is highly relevant to the development of potential therapies, not only for demyelinating disorders such as multiple sclerosis but also for schizophrenia. Numerous studies have demonstrated that schizophrenia is associated with serious white-matter pathology,² which may account for many of the disorder’s thought, emotional, and cognitive impairments.

Weight gain as marker for antipsychotic efficacy

Some weight increase is observed with all antipsychotics, although certain atypicals such as olanzapine and clozapine are associated with more weight gain than others. No clinician would see anything except a downside to weight gain, which may lead to metabolic complications such as diabetes, hyperlipidemia, and hypertension.

However, some weight gain appears to be related to the efficacy of all antipsychotics (first- and second-generation), according to the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)³ and previous sporadic observations in the literature. Even Kraepelin noted in the 1920s—long before the era of antipsychotics—that patients with psychosis gained weight when they spontaneously improved.

Thus, some weight gain appears to be a necessary correlate of improvement in persons treated with antipsychotics. The reasons are still unclear, but weight gain may be a modulator, mediator, or marker of antipsychotic efficacy.

In summary, there appears to be at least some upside to the downside of certain drug side effects. In other words, every dark cloud has a silver lining, and it might be helpful for patients and physicians to see more than just the cloud.

Medication side effects are generally regarded as the Achilles’ heel of pharmacologic treatment. And who can argue with that? Adverse effects are the downside of drug treatment of psychiatric disorders and are blamed for tolerability and adherence problems. Patients dread side effects, physicians feel uncomfortable or even guilty about them, and litigation lawyers thrive on them.

Psychotropics’ package inserts are loaded with side-effect descriptions. The precautions, warnings, and black boxes frequently make patients anxious about taking medications, even when the diseases they suffer from pose far greater risk to their lives and health.

Are side effects entirely bad, or is there a possible upside lurking within them? Psychiatrists know, for example, that a common adverse effect of selective serotonin reuptake inhibitor (SSRI) antidepressants/anxiolytics is delayed orgasm. But because of this side effect, SSRIs can be dramatically helpful for treating premature ejaculation in nondepressed men.

Let’s consider some effects of atypical antipsychotics that usually are considered a downside of antipsychotic treatment yet appear to be associated with advantages for the same patients.

Therapeutic sedation

Sedation was considered a major adverse effect of quetiapine when this antipsychotic was approved for treating schizophrenia. Yet with time—and as the drug received additional indications for bipolar mania and bipolar depression—it became apparent to psychiatrists that quetiapine’s sedative effects could be useful for treating insomnia in individuals with psychotic and mood disorders. Thus, practitioners saw an advantage in using a sedating antipsychotic, instead of adding a sedative/hypnotic, for psychotic or manic patients suffering from agitation, anxiety, and insomnia. Three advantages of this approach for patients are:

• fewer medications to manage
• lower costs without an additional sedative/hypnotic
• avoiding the potential addictive effects of a sedative/hypnotic.

Hyperprolactinemia and myelin repair

Some patients receiving risperidone or paliperidone for psychotic symptoms develop sexual dysfunction because of the side effect of increased serum prolactin. On the other hand, recent research indicates that prolactin enhances the synthesis of oligodendrocytes, which are critical for myelin (white matter) integrity in brain tissue.

In a recent study, researchers used a toxin to destroy patches of white matter in the brains of nonpregnant mice. Subsequent pregnancy and prolactin elevation repaired the myelin lesions completely, whereas no changes occurred in the white matter lesions in the brains of control mice that remained nonpregnant.¹

This suggested myelin-repairing property of prolactin is highly relevant to the development of potential therapies, not only for demyelinating disorders such as multiple sclerosis but also for schizophrenia. Numerous studies have demonstrated that schizophrenia is associated with serious white-matter pathology,² which may account for many of the disorder’s thought, emotional, and cognitive impairments.

Weight gain as marker for antipsychotic efficacy

Some weight increase is observed with all antipsychotics, although certain atypicals such as olanzapine and clozapine are associated with more weight gain than others. No clinician would see anything except a downside to weight gain, which may lead to metabolic complications such as diabetes, hyperlipidemia, and hypertension.

However, some weight gain appears to be related to the efficacy of all antipsychotics (first- and second-generation), according to the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)³ and previous sporadic observations in the literature. Even Kraepelin noted in the 1920s—long before the era of antipsychotics—that patients with psychosis gained weight when they spontaneously improved.

Thus, some weight gain appears to be a necessary correlate of improvement in persons treated with antipsychotics. The reasons are still unclear, but weight gain may be a modulator, mediator, or marker of antipsychotic efficacy.

In summary, there appears to be at least some upside to the downside of certain drug side effects. In other words, every dark cloud has a silver lining, and it might be helpful for patients and physicians to see more than just the cloud.

Current Psychiatry has built its reputation as the clinical journal that provides psychiatrists with peer-reviewed, practical advice by leading authorities, emphasizing up-to-date solutions to common clinical problems. As Editor-in-Chief, I’m pleased to announce that Current Psychiatry is expanding its mission to you and your patients through an agreement with the American Academy of Clinical Psychiatrists (AACP).

Quadrant HealthCom Inc., publisher of Current Psychiatry, will collaborate with the AACP by:

• publishing its official journal, the Annals of Clinical Psychiatry
• managing and co-sponsoring its annual conference, beginning in 2009
• developing and managing www.aacp.com, the official Web site of the AACP and the Annals.

This agreement provides excellent synergy. As a past president of the AACP and a founding editorial board member of the Annals, I believe it offers exciting and important benefits for psychiatry professionals.

Emphasis: Clinical psychiatry

The AACP is a unique professional society that encourages the exchange of information between clinicians interested in evidence-based practice and academicians involved in clinical research. It is the type of psychiatric association that Current Psychiatry readers should seriously consider joining. Its founder, the late George Winokur, MD, played a leading role in developing the first diagnostic criteria for use in psychiatric research—a prototype for the Diagnostic and Statistical Manual of Mental Disorders.¹ A cherished mentor, Dr. Winokur trained a generation of outstanding psychiatrists during 24 years as professor and head of the University of Iowa’s department of psychiatry. He was my role model when I was on the faculty at Iowa in the 1980s.

Donald W. Black, MD, professor of psychiatry at the University of Iowa College of Medicine, has served as Editor-in-Chief of the Annals since 2004 and will continue in this role. Dr. Black also trained with Dr. Winokur and is recognized as an outstanding educator, researcher, and clinician.

The AACP launched the Annals in 1989 to provide clinical psychiatrists with up-to-date information on the symptoms, diagnosis, and treatment of mental disorders. The quarterly journal, which emphasizes the results of controlled clinical studies, is abstracted/indexed in Index Medicus, Excerpta Medica, Current Contents, EMBASE, PsychINFO, and other databases.

The AACP will continue to select and appoint the Annals’ Editor-in-Chief, set the journal’s editorial mission, recruit the editorial board, invite authors, and implement peer review. Quadrant HealthCom Inc. will be responsible for production, mailing, and other publishing duties. Continuing medical education (CME) supplements to the Annals will be distributed to Current Psychiatry’s circulation as well.

The AACP’s annual meetings provide educational updates that Current Psychiatry readers will find useful and relevant to clinical practice. “Bipolar disorder and ADHD: Solving clinical challenges, improving patient care” is the theme of the April 2009 conference, which will be held in Chicago. An outstanding faculty is onboard for this CME opportunity, which is open to AACP members and nonmembers alike.

Quadrant HealthCom Inc. will develop and relaunch the AACP Web site. Its content will be expanded to include materials from presentations at AACP annual meetings and industry-sponsored programs.

Benefits for all

I am very enthusiastic about this agreement. Current Psychiatry—a clinical journal that reaches more than 39,000 psychiatrists and psychiatric nurse practitioners—is joining forces with the Annals of Clinical Psychiatry, a well-established scientific journal that focuses on the latest clinical research. As a result:

• Readers of both journals will benefit from expanded CME opportunities as funding becomes available for industry-sponsored programs and supplements.
• Members of the AACP gain Quadrant HealthCom Inc.’s publishing expertise for their respected scientific publication and meeting planning experience to grow their annual meeting.
• The AACP and Current Psychiatry Web sites will complement each other in serving the needs of clinical practitioners with expanded content and educational offerings.

I predict that a vibrant community of clinical psychiatrists will emerge from this collaboration and energize psychiatric education, both online and in print.

Current Psychiatry has built its reputation as the clinical journal that provides psychiatrists with peer-reviewed, practical advice by leading authorities, emphasizing up-to-date solutions to common clinical problems. As Editor-in-Chief, I’m pleased to announce that Current Psychiatry is expanding its mission to you and your patients through an agreement with the American Academy of Clinical Psychiatrists (AACP).

Quadrant HealthCom Inc., publisher of Current Psychiatry, will collaborate with the AACP by:

• publishing its official journal, the Annals of Clinical Psychiatry
• managing and co-sponsoring its annual conference, beginning in 2009
• developing and managing www.aacp.com, the official Web site of the AACP and the Annals.

This agreement provides excellent synergy. As a past president of the AACP and a founding editorial board member of the Annals, I believe it offers exciting and important benefits for psychiatry professionals.

Emphasis: Clinical psychiatry

The AACP is a unique professional society that encourages the exchange of information between clinicians interested in evidence-based practice and academicians involved in clinical research. It is the type of psychiatric association that Current Psychiatry readers should seriously consider joining. Its founder, the late George Winokur, MD, played a leading role in developing the first diagnostic criteria for use in psychiatric research—a prototype for the Diagnostic and Statistical Manual of Mental Disorders.¹ A cherished mentor, Dr. Winokur trained a generation of outstanding psychiatrists during 24 years as professor and head of the University of Iowa’s department of psychiatry. He was my role model when I was on the faculty at Iowa in the 1980s.

Donald W. Black, MD, professor of psychiatry at the University of Iowa College of Medicine, has served as Editor-in-Chief of the Annals since 2004 and will continue in this role. Dr. Black also trained with Dr. Winokur and is recognized as an outstanding educator, researcher, and clinician.

The AACP launched the Annals in 1989 to provide clinical psychiatrists with up-to-date information on the symptoms, diagnosis, and treatment of mental disorders. The quarterly journal, which emphasizes the results of controlled clinical studies, is abstracted/indexed in Index Medicus, Excerpta Medica, Current Contents, EMBASE, PsychINFO, and other databases.

The AACP will continue to select and appoint the Annals’ Editor-in-Chief, set the journal’s editorial mission, recruit the editorial board, invite authors, and implement peer review. Quadrant HealthCom Inc. will be responsible for production, mailing, and other publishing duties. Continuing medical education (CME) supplements to the Annals will be distributed to Current Psychiatry’s circulation as well.

The AACP’s annual meetings provide educational updates that Current Psychiatry readers will find useful and relevant to clinical practice. “Bipolar disorder and ADHD: Solving clinical challenges, improving patient care” is the theme of the April 2009 conference, which will be held in Chicago. An outstanding faculty is onboard for this CME opportunity, which is open to AACP members and nonmembers alike.

Quadrant HealthCom Inc. will develop and relaunch the AACP Web site. Its content will be expanded to include materials from presentations at AACP annual meetings and industry-sponsored programs.

Benefits for all

I am very enthusiastic about this agreement. Current Psychiatry—a clinical journal that reaches more than 39,000 psychiatrists and psychiatric nurse practitioners—is joining forces with the Annals of Clinical Psychiatry, a well-established scientific journal that focuses on the latest clinical research. As a result:

• Readers of both journals will benefit from expanded CME opportunities as funding becomes available for industry-sponsored programs and supplements.
• Members of the AACP gain Quadrant HealthCom Inc.’s publishing expertise for their respected scientific publication and meeting planning experience to grow their annual meeting.
• The AACP and Current Psychiatry Web sites will complement each other in serving the needs of clinical practitioners with expanded content and educational offerings.

I predict that a vibrant community of clinical psychiatrists will emerge from this collaboration and energize psychiatric education, both online and in print.

Current Psychiatry has built its reputation as the clinical journal that provides psychiatrists with peer-reviewed, practical advice by leading authorities, emphasizing up-to-date solutions to common clinical problems. As Editor-in-Chief, I’m pleased to announce that Current Psychiatry is expanding its mission to you and your patients through an agreement with the American Academy of Clinical Psychiatrists (AACP).

Quadrant HealthCom Inc., publisher of Current Psychiatry, will collaborate with the AACP by:

• publishing its official journal, the Annals of Clinical Psychiatry
• managing and co-sponsoring its annual conference, beginning in 2009
• developing and managing www.aacp.com, the official Web site of the AACP and the Annals.

This agreement provides excellent synergy. As a past president of the AACP and a founding editorial board member of the Annals, I believe it offers exciting and important benefits for psychiatry professionals.

Emphasis: Clinical psychiatry

The AACP is a unique professional society that encourages the exchange of information between clinicians interested in evidence-based practice and academicians involved in clinical research. It is the type of psychiatric association that Current Psychiatry readers should seriously consider joining. Its founder, the late George Winokur, MD, played a leading role in developing the first diagnostic criteria for use in psychiatric research—a prototype for the Diagnostic and Statistical Manual of Mental Disorders.¹ A cherished mentor, Dr. Winokur trained a generation of outstanding psychiatrists during 24 years as professor and head of the University of Iowa’s department of psychiatry. He was my role model when I was on the faculty at Iowa in the 1980s.

Donald W. Black, MD, professor of psychiatry at the University of Iowa College of Medicine, has served as Editor-in-Chief of the Annals since 2004 and will continue in this role. Dr. Black also trained with Dr. Winokur and is recognized as an outstanding educator, researcher, and clinician.

The AACP launched the Annals in 1989 to provide clinical psychiatrists with up-to-date information on the symptoms, diagnosis, and treatment of mental disorders. The quarterly journal, which emphasizes the results of controlled clinical studies, is abstracted/indexed in Index Medicus, Excerpta Medica, Current Contents, EMBASE, PsychINFO, and other databases.

The AACP will continue to select and appoint the Annals’ Editor-in-Chief, set the journal’s editorial mission, recruit the editorial board, invite authors, and implement peer review. Quadrant HealthCom Inc. will be responsible for production, mailing, and other publishing duties. Continuing medical education (CME) supplements to the Annals will be distributed to Current Psychiatry’s circulation as well.

The AACP’s annual meetings provide educational updates that Current Psychiatry readers will find useful and relevant to clinical practice. “Bipolar disorder and ADHD: Solving clinical challenges, improving patient care” is the theme of the April 2009 conference, which will be held in Chicago. An outstanding faculty is onboard for this CME opportunity, which is open to AACP members and nonmembers alike.

Quadrant HealthCom Inc. will develop and relaunch the AACP Web site. Its content will be expanded to include materials from presentations at AACP annual meetings and industry-sponsored programs.

Benefits for all

I am very enthusiastic about this agreement. Current Psychiatry—a clinical journal that reaches more than 39,000 psychiatrists and psychiatric nurse practitioners—is joining forces with the Annals of Clinical Psychiatry, a well-established scientific journal that focuses on the latest clinical research. As a result:

• Readers of both journals will benefit from expanded CME opportunities as funding becomes available for industry-sponsored programs and supplements.
• Members of the AACP gain Quadrant HealthCom Inc.’s publishing expertise for their respected scientific publication and meeting planning experience to grow their annual meeting.
• The AACP and Current Psychiatry Web sites will complement each other in serving the needs of clinical practitioners with expanded content and educational offerings.

I predict that a vibrant community of clinical psychiatrists will emerge from this collaboration and energize psychiatric education, both online and in print.

The complex process by which psychiatric medications are discovered, developed, and tested culminates in “evidence-based medicine”—the backbone of psychopharmacology. Large controlled clinical trials are designed to demonstrate under highly controlled conditions that a newly synthesized molecule has sufficient efficacy and a reasonable side-effect profile to warrant FDA approval. Results are published, and the pharmaceutical company launches the approved medication in the community.

Not usually recognized is that a treasure trove of information may be buried in a preapproval clinical trial’s massive database. The pharmaceutical company might not “mine” this information without the likelihood of revenue enhancement, but the raw data may hold clinically useful revelations.

These may include clues about which patients are likely to respond (or not) or experience a serious side effect with the drug (or placebo). Some-times examining contrarian psychopharmacology—unexpected patterns of response or adverse effects—provides valuable insights with clinical applications. Here are some questions we could explore beyond the efficacy-safety-tolerability data published on atypical antipsychotics.

Drug efficacy

• What are the demographic, biologic, and clinical profiles of rapid responders vs delayed responders vs nonresponders?
• How do full responders differ from partial responders or complete nonresponders? Can we identify them in clinical settings?
• Can we predict who will respond or not to a particular antipsychotic? Why not report whether the nonresponders in a clinical trial responded to some other antipsychotic after the trial was completed? That information would be tremendously useful and cost-effective in clinical practice.

Placebo efficacy

• How do placebo responders differ from nonresponders?
• Are placebo nonresponders similar in some ways to drug nonresponders?
• Would placebo nonresponders respond to the active drug after the controlled trial is completed?

Side effects

Each atypical has common side effects, but we know little about patients who buck the trend. Consider the potentially useful insights from studying patients who:

• lose weight on olanzapine
• gain weight on ziprasidone
• get sedated with aripiprazole
• develop insomnia or extrapyramidal symptoms with quetiapine
• continue to menstruate regularly on risperidone.

Patients such as these are reported in clinical trials but not monitored or compared for their response rates.

Placebo

• What would we learn if we compared psychotic patients who developed sedation with those who developed insomnia while receiving placebo in a clinical trial? Would these 2 groups differ in their response to the antipsychotic?
• Some psychotic patients gain substantial weight (>7%) on placebo, whereas others lose quite a bit of weight. Do they differ in response rates or other traits?

Individualized therapy

Contrarian patients who develop unexpected responses (such as strong improvement on placebo or side effects the opposite of what is expected) represent missed opportunities for research to elucidate the heterogeneity of psychosis (as well as mania, depression, or anxiety). Understanding individual differences could enable practitioners to predict efficacy and tolerability and to match patients with the most suitable medications from the start. These insights could save time, reduce duration of illness, predict likely side effects, and ultimately reduce the costs of treatment.

The complex process by which psychiatric medications are discovered, developed, and tested culminates in “evidence-based medicine”—the backbone of psychopharmacology. Large controlled clinical trials are designed to demonstrate under highly controlled conditions that a newly synthesized molecule has sufficient efficacy and a reasonable side-effect profile to warrant FDA approval. Results are published, and the pharmaceutical company launches the approved medication in the community.

Not usually recognized is that a treasure trove of information may be buried in a preapproval clinical trial’s massive database. The pharmaceutical company might not “mine” this information without the likelihood of revenue enhancement, but the raw data may hold clinically useful revelations.

These may include clues about which patients are likely to respond (or not) or experience a serious side effect with the drug (or placebo). Some-times examining contrarian psychopharmacology—unexpected patterns of response or adverse effects—provides valuable insights with clinical applications. Here are some questions we could explore beyond the efficacy-safety-tolerability data published on atypical antipsychotics.

Drug efficacy

• What are the demographic, biologic, and clinical profiles of rapid responders vs delayed responders vs nonresponders?
• How do full responders differ from partial responders or complete nonresponders? Can we identify them in clinical settings?
• Can we predict who will respond or not to a particular antipsychotic? Why not report whether the nonresponders in a clinical trial responded to some other antipsychotic after the trial was completed? That information would be tremendously useful and cost-effective in clinical practice.

Placebo efficacy

• How do placebo responders differ from nonresponders?
• Are placebo nonresponders similar in some ways to drug nonresponders?
• Would placebo nonresponders respond to the active drug after the controlled trial is completed?

Side effects

Each atypical has common side effects, but we know little about patients who buck the trend. Consider the potentially useful insights from studying patients who:

• lose weight on olanzapine
• gain weight on ziprasidone
• get sedated with aripiprazole
• develop insomnia or extrapyramidal symptoms with quetiapine
• continue to menstruate regularly on risperidone.

Patients such as these are reported in clinical trials but not monitored or compared for their response rates.

Placebo

• What would we learn if we compared psychotic patients who developed sedation with those who developed insomnia while receiving placebo in a clinical trial? Would these 2 groups differ in their response to the antipsychotic?
• Some psychotic patients gain substantial weight (>7%) on placebo, whereas others lose quite a bit of weight. Do they differ in response rates or other traits?

Individualized therapy

Contrarian patients who develop unexpected responses (such as strong improvement on placebo or side effects the opposite of what is expected) represent missed opportunities for research to elucidate the heterogeneity of psychosis (as well as mania, depression, or anxiety). Understanding individual differences could enable practitioners to predict efficacy and tolerability and to match patients with the most suitable medications from the start. These insights could save time, reduce duration of illness, predict likely side effects, and ultimately reduce the costs of treatment.

The complex process by which psychiatric medications are discovered, developed, and tested culminates in “evidence-based medicine”—the backbone of psychopharmacology. Large controlled clinical trials are designed to demonstrate under highly controlled conditions that a newly synthesized molecule has sufficient efficacy and a reasonable side-effect profile to warrant FDA approval. Results are published, and the pharmaceutical company launches the approved medication in the community.

Not usually recognized is that a treasure trove of information may be buried in a preapproval clinical trial’s massive database. The pharmaceutical company might not “mine” this information without the likelihood of revenue enhancement, but the raw data may hold clinically useful revelations.

These may include clues about which patients are likely to respond (or not) or experience a serious side effect with the drug (or placebo). Some-times examining contrarian psychopharmacology—unexpected patterns of response or adverse effects—provides valuable insights with clinical applications. Here are some questions we could explore beyond the efficacy-safety-tolerability data published on atypical antipsychotics.

Drug efficacy

• What are the demographic, biologic, and clinical profiles of rapid responders vs delayed responders vs nonresponders?
• How do full responders differ from partial responders or complete nonresponders? Can we identify them in clinical settings?
• Can we predict who will respond or not to a particular antipsychotic? Why not report whether the nonresponders in a clinical trial responded to some other antipsychotic after the trial was completed? That information would be tremendously useful and cost-effective in clinical practice.

Placebo efficacy

• How do placebo responders differ from nonresponders?
• Are placebo nonresponders similar in some ways to drug nonresponders?
• Would placebo nonresponders respond to the active drug after the controlled trial is completed?

Side effects

Each atypical has common side effects, but we know little about patients who buck the trend. Consider the potentially useful insights from studying patients who:

• lose weight on olanzapine
• gain weight on ziprasidone
• get sedated with aripiprazole
• develop insomnia or extrapyramidal symptoms with quetiapine
• continue to menstruate regularly on risperidone.

Patients such as these are reported in clinical trials but not monitored or compared for their response rates.

Placebo

• What would we learn if we compared psychotic patients who developed sedation with those who developed insomnia while receiving placebo in a clinical trial? Would these 2 groups differ in their response to the antipsychotic?
• Some psychotic patients gain substantial weight (>7%) on placebo, whereas others lose quite a bit of weight. Do they differ in response rates or other traits?

Individualized therapy

Contrarian patients who develop unexpected responses (such as strong improvement on placebo or side effects the opposite of what is expected) represent missed opportunities for research to elucidate the heterogeneity of psychosis (as well as mania, depression, or anxiety). Understanding individual differences could enable practitioners to predict efficacy and tolerability and to match patients with the most suitable medications from the start. These insights could save time, reduce duration of illness, predict likely side effects, and ultimately reduce the costs of treatment.

Consider these common human tales:

• A prominent politician who made his reputation combating prostitution loses his job after being discovered to have consorted with many "escorts." He believed he would never be caught.
• A sociopathic man charms a young woman and convinces her he will love her forever. She is infatuated with him. He dumps her a month later.
• A gambler is "convinced" his next bet will win back his previous losses and ends up losing his shirt again.
• Voters elect a politician who promises to solve all their problems but are disillusioned a few years later when things have barely changed.
• A woman with severe chronic fibromyalgia seeks the help of a shaman in her village in Haiti. He pain amazingly disappears for a few days before recurring.

The human brain has been both blessed and cursed during its evolutionary journey by developing the capacity for self-deception. Unlike other living things, humans are capable of massive self-deception—as these tales show.

Advantage: survival

Self-deception's upside is obvious, with established survival value. Hope, optimism, and self-confidence in dark times are antidotes to capitulation, despair, and inaction. Infatuation helps perpetuate the human species, and "eternal love" leads to other obligatory self-deceptions such as "till death do us part." Sometimes self-deception helps communities survive by promoting altruism, charity, and compassion for strangers.

For us in the health professions—especially psychiatry—self-deception's benefits for patients are well recognized: a remarkable healing capacity, an almost magical placebo effect from drug therapy or psychotherapy, and the advantages of positive transference toward the physician. Without self-deception, our patients could not respond to support and reassurance or resist hopelessness and the urge to give up and end their lives.

Disadvantage: suffering

But self-deception has a serious downside as well, from hubris and arrogance that end badly to blind faith and gullibility that lead to joining cults and "drinking the Kool-Aid," from unshakable belief in astrology or fanatical pursuit of a cause to believing in nothing and wasting one's life with nihilism.

The biology of self-deception also may represent the foundation of psychopathology, such as:

• unremitting panic and anxiety associated with a firm belief in impending doom
• bizarre, fixed, false beliefs of schizophrenia
• grandiose delusions of bipolar mania
• melancholia's profound and inconsolable sorrow, futility, and worthlessness
• pervasive belief in one's repulsiveness by attractive women with dysmorphic body disorder
• distorted conviction of obesity in skin-and-bones teenagers with anorexia nervosa
• unshakable parasitosis of a delusional disorder
• tortured and agonizing obsessions to perform meaningless rituals.

Psychiatric disorders are extremes of self-deception gone awry across complex neural pathways, encompassing emotions, thoughts, behavior, and cognitions. Human adaptation to stress or serious illness is often enhanced by the blissful escape of self-deception, but its curse can destroy lives and cause untold suffering.

So, are nonhuman creatures spared the double-edged sword of self-deception? If so, then why do dogs have unshakable loyalty, even when their owners abuse them? Maybe self-deception is not uniquely human after all.

Consider these common human tales:

• A prominent politician who made his reputation combating prostitution loses his job after being discovered to have consorted with many "escorts." He believed he would never be caught.
• A sociopathic man charms a young woman and convinces her he will love her forever. She is infatuated with him. He dumps her a month later.
• A gambler is "convinced" his next bet will win back his previous losses and ends up losing his shirt again.
• Voters elect a politician who promises to solve all their problems but are disillusioned a few years later when things have barely changed.
• A woman with severe chronic fibromyalgia seeks the help of a shaman in her village in Haiti. He pain amazingly disappears for a few days before recurring.

The human brain has been both blessed and cursed during its evolutionary journey by developing the capacity for self-deception. Unlike other living things, humans are capable of massive self-deception—as these tales show.

Advantage: survival

Self-deception's upside is obvious, with established survival value. Hope, optimism, and self-confidence in dark times are antidotes to capitulation, despair, and inaction. Infatuation helps perpetuate the human species, and "eternal love" leads to other obligatory self-deceptions such as "till death do us part." Sometimes self-deception helps communities survive by promoting altruism, charity, and compassion for strangers.

For us in the health professions—especially psychiatry—self-deception's benefits for patients are well recognized: a remarkable healing capacity, an almost magical placebo effect from drug therapy or psychotherapy, and the advantages of positive transference toward the physician. Without self-deception, our patients could not respond to support and reassurance or resist hopelessness and the urge to give up and end their lives.

Disadvantage: suffering

But self-deception has a serious downside as well, from hubris and arrogance that end badly to blind faith and gullibility that lead to joining cults and "drinking the Kool-Aid," from unshakable belief in astrology or fanatical pursuit of a cause to believing in nothing and wasting one's life with nihilism.

The biology of self-deception also may represent the foundation of psychopathology, such as:

• unremitting panic and anxiety associated with a firm belief in impending doom
• bizarre, fixed, false beliefs of schizophrenia
• grandiose delusions of bipolar mania
• melancholia's profound and inconsolable sorrow, futility, and worthlessness
• pervasive belief in one's repulsiveness by attractive women with dysmorphic body disorder
• distorted conviction of obesity in skin-and-bones teenagers with anorexia nervosa
• unshakable parasitosis of a delusional disorder
• tortured and agonizing obsessions to perform meaningless rituals.

Psychiatric disorders are extremes of self-deception gone awry across complex neural pathways, encompassing emotions, thoughts, behavior, and cognitions. Human adaptation to stress or serious illness is often enhanced by the blissful escape of self-deception, but its curse can destroy lives and cause untold suffering.

So, are nonhuman creatures spared the double-edged sword of self-deception? If so, then why do dogs have unshakable loyalty, even when their owners abuse them? Maybe self-deception is not uniquely human after all.

Consider these common human tales:

• A prominent politician who made his reputation combating prostitution loses his job after being discovered to have consorted with many "escorts." He believed he would never be caught.
• A sociopathic man charms a young woman and convinces her he will love her forever. She is infatuated with him. He dumps her a month later.
• A gambler is "convinced" his next bet will win back his previous losses and ends up losing his shirt again.
• Voters elect a politician who promises to solve all their problems but are disillusioned a few years later when things have barely changed.
• A woman with severe chronic fibromyalgia seeks the help of a shaman in her village in Haiti. He pain amazingly disappears for a few days before recurring.

The human brain has been both blessed and cursed during its evolutionary journey by developing the capacity for self-deception. Unlike other living things, humans are capable of massive self-deception—as these tales show.

Advantage: survival

Self-deception's upside is obvious, with established survival value. Hope, optimism, and self-confidence in dark times are antidotes to capitulation, despair, and inaction. Infatuation helps perpetuate the human species, and "eternal love" leads to other obligatory self-deceptions such as "till death do us part." Sometimes self-deception helps communities survive by promoting altruism, charity, and compassion for strangers.

For us in the health professions—especially psychiatry—self-deception's benefits for patients are well recognized: a remarkable healing capacity, an almost magical placebo effect from drug therapy or psychotherapy, and the advantages of positive transference toward the physician. Without self-deception, our patients could not respond to support and reassurance or resist hopelessness and the urge to give up and end their lives.

Disadvantage: suffering

But self-deception has a serious downside as well, from hubris and arrogance that end badly to blind faith and gullibility that lead to joining cults and "drinking the Kool-Aid," from unshakable belief in astrology or fanatical pursuit of a cause to believing in nothing and wasting one's life with nihilism.

The biology of self-deception also may represent the foundation of psychopathology, such as:

• unremitting panic and anxiety associated with a firm belief in impending doom
• bizarre, fixed, false beliefs of schizophrenia
• grandiose delusions of bipolar mania
• melancholia's profound and inconsolable sorrow, futility, and worthlessness
• pervasive belief in one's repulsiveness by attractive women with dysmorphic body disorder
• distorted conviction of obesity in skin-and-bones teenagers with anorexia nervosa
• unshakable parasitosis of a delusional disorder
• tortured and agonizing obsessions to perform meaningless rituals.

Psychiatric disorders are extremes of self-deception gone awry across complex neural pathways, encompassing emotions, thoughts, behavior, and cognitions. Human adaptation to stress or serious illness is often enhanced by the blissful escape of self-deception, but its curse can destroy lives and cause untold suffering.

So, are nonhuman creatures spared the double-edged sword of self-deception? If so, then why do dogs have unshakable loyalty, even when their owners abuse them? Maybe self-deception is not uniquely human after all.

Psychiatry has become a mature neuroscience discipline and medical specialty, helping millions of Americans suffering from mental illness. Neurobiologic and psychosocial research into causes of and treatments for psychiatric brain disorders is booming, and molecular genetic discoveries promise unprecedented insights into the neural mechanisms of thought, feeling, emotional, behavioral, and cognitive disturbances.

As psychiatry’s promise grows, however, so do its frustrations. I list here 17 challenges psychiatrists face, and I would like to know how important you feel each challenge is to our profession.

Please visit the HTML version of this article to rank each challenge from 10 (highest importance) to 1 (lowest importance). To add other challenges not on my list, simply use the comments field at the bottom of the survey. We will share the results with you in Current Psychiatry, and you can compare your opinions with those of your colleagues.

1. Still-elusive pathophysiology of psychiatric disorders, despite the abundance of new knowledge.
2. Lack of an objective diagnostic schema, including laboratory tests to confirm diagnoses.
3. High rates of off-label psychotropic use because >80% of DSM-IV-TR psychiatric disorders have no approved medications and practitioners have few options.
4. Tightening regulations, suffocating litigation, and a demoralized drug-discovery industry that have blunted innovation and threaten drug development.
5. Limited evidence-based psychotherapy research, compared with controlled FDA trials for drug therapy or medical devices.
6. Persistent stigma of mental illness interfering with prevention and early intervention.
7. Lack of full parity for mental illness with physical illness.
8. Excessive, harmful intrusion of the courts into psychiatric care, more than any other medical specialty.
9. A “broken” public mental health system with red tape, inadequate funding, nonevidence-based treatments, homelessness, drug abuse, and lack of primary care.
10. Far less private philanthropy bestowed on psychiatry compared with cancer, cardiology, or other medical specialities.
11. Shrinking funds for psychiatric research because of National Institutes of Health belt-tightening and dwindling of unrestricted pharmaceutical industry research grants.
12. Atrociously low compensation for psychiatrists, with hourly earnings a fraction of those for procedural specialists (such as surgeons or radiologists), although the years of training are similar.
13. Unreimbursed time spent on paperwork or phone calls related to patient care.
14. Little time to read journals or attend continuing medical education meetings to keep up with rapid advances in psychiatry.
15. Lack of primary care for the seriously mentally ill because of barriers to collaborative care between psychiatrists and primary care providers.
16. Shortage of psychiatric beds, both acute and longterm, and a ridiculously brief length of stay for psychotic or suicidal patients.
17. Too few academic psychiatrists to train and mentor young clinicians, researchers, and educators who represent the cutting edge of the speciality.

I am very interested in knowing your opinions. Ranking the importance of these challenges may be a sobering task, but problem solving always starts by assessing the challenges and developing strategies to address them in a targeted, systematic manner.

Finally, it is interesting that while there is a serious national shortage of psychiatrists, there is certainly no shortage of challenges. Psychiatrists, patients, families, and advocates should combine their efforts to find effective solutions, one challenge at a time.

Psychiatry has become a mature neuroscience discipline and medical specialty, helping millions of Americans suffering from mental illness. Neurobiologic and psychosocial research into causes of and treatments for psychiatric brain disorders is booming, and molecular genetic discoveries promise unprecedented insights into the neural mechanisms of thought, feeling, emotional, behavioral, and cognitive disturbances.

As psychiatry’s promise grows, however, so do its frustrations. I list here 17 challenges psychiatrists face, and I would like to know how important you feel each challenge is to our profession.

Please visit the HTML version of this article to rank each challenge from 10 (highest importance) to 1 (lowest importance). To add other challenges not on my list, simply use the comments field at the bottom of the survey. We will share the results with you in Current Psychiatry, and you can compare your opinions with those of your colleagues.

1. Still-elusive pathophysiology of psychiatric disorders, despite the abundance of new knowledge.
2. Lack of an objective diagnostic schema, including laboratory tests to confirm diagnoses.
3. High rates of off-label psychotropic use because >80% of DSM-IV-TR psychiatric disorders have no approved medications and practitioners have few options.
4. Tightening regulations, suffocating litigation, and a demoralized drug-discovery industry that have blunted innovation and threaten drug development.
5. Limited evidence-based psychotherapy research, compared with controlled FDA trials for drug therapy or medical devices.
6. Persistent stigma of mental illness interfering with prevention and early intervention.
7. Lack of full parity for mental illness with physical illness.
8. Excessive, harmful intrusion of the courts into psychiatric care, more than any other medical specialty.
9. A “broken” public mental health system with red tape, inadequate funding, nonevidence-based treatments, homelessness, drug abuse, and lack of primary care.
10. Far less private philanthropy bestowed on psychiatry compared with cancer, cardiology, or other medical specialities.
11. Shrinking funds for psychiatric research because of National Institutes of Health belt-tightening and dwindling of unrestricted pharmaceutical industry research grants.
12. Atrociously low compensation for psychiatrists, with hourly earnings a fraction of those for procedural specialists (such as surgeons or radiologists), although the years of training are similar.
13. Unreimbursed time spent on paperwork or phone calls related to patient care.
14. Little time to read journals or attend continuing medical education meetings to keep up with rapid advances in psychiatry.
15. Lack of primary care for the seriously mentally ill because of barriers to collaborative care between psychiatrists and primary care providers.
16. Shortage of psychiatric beds, both acute and longterm, and a ridiculously brief length of stay for psychotic or suicidal patients.
17. Too few academic psychiatrists to train and mentor young clinicians, researchers, and educators who represent the cutting edge of the speciality.

I am very interested in knowing your opinions. Ranking the importance of these challenges may be a sobering task, but problem solving always starts by assessing the challenges and developing strategies to address them in a targeted, systematic manner.

Finally, it is interesting that while there is a serious national shortage of psychiatrists, there is certainly no shortage of challenges. Psychiatrists, patients, families, and advocates should combine their efforts to find effective solutions, one challenge at a time.

Psychiatry has become a mature neuroscience discipline and medical specialty, helping millions of Americans suffering from mental illness. Neurobiologic and psychosocial research into causes of and treatments for psychiatric brain disorders is booming, and molecular genetic discoveries promise unprecedented insights into the neural mechanisms of thought, feeling, emotional, behavioral, and cognitive disturbances.

As psychiatry’s promise grows, however, so do its frustrations. I list here 17 challenges psychiatrists face, and I would like to know how important you feel each challenge is to our profession.

Please visit the HTML version of this article to rank each challenge from 10 (highest importance) to 1 (lowest importance). To add other challenges not on my list, simply use the comments field at the bottom of the survey. We will share the results with you in Current Psychiatry, and you can compare your opinions with those of your colleagues.

1. Still-elusive pathophysiology of psychiatric disorders, despite the abundance of new knowledge.
2. Lack of an objective diagnostic schema, including laboratory tests to confirm diagnoses.
3. High rates of off-label psychotropic use because >80% of DSM-IV-TR psychiatric disorders have no approved medications and practitioners have few options.
4. Tightening regulations, suffocating litigation, and a demoralized drug-discovery industry that have blunted innovation and threaten drug development.
5. Limited evidence-based psychotherapy research, compared with controlled FDA trials for drug therapy or medical devices.
6. Persistent stigma of mental illness interfering with prevention and early intervention.
7. Lack of full parity for mental illness with physical illness.
8. Excessive, harmful intrusion of the courts into psychiatric care, more than any other medical specialty.
9. A “broken” public mental health system with red tape, inadequate funding, nonevidence-based treatments, homelessness, drug abuse, and lack of primary care.
10. Far less private philanthropy bestowed on psychiatry compared with cancer, cardiology, or other medical specialities.
11. Shrinking funds for psychiatric research because of National Institutes of Health belt-tightening and dwindling of unrestricted pharmaceutical industry research grants.
12. Atrociously low compensation for psychiatrists, with hourly earnings a fraction of those for procedural specialists (such as surgeons or radiologists), although the years of training are similar.
13. Unreimbursed time spent on paperwork or phone calls related to patient care.
14. Little time to read journals or attend continuing medical education meetings to keep up with rapid advances in psychiatry.
15. Lack of primary care for the seriously mentally ill because of barriers to collaborative care between psychiatrists and primary care providers.
16. Shortage of psychiatric beds, both acute and longterm, and a ridiculously brief length of stay for psychotic or suicidal patients.
17. Too few academic psychiatrists to train and mentor young clinicians, researchers, and educators who represent the cutting edge of the speciality.

I am very interested in knowing your opinions. Ranking the importance of these challenges may be a sobering task, but problem solving always starts by assessing the challenges and developing strategies to address them in a targeted, systematic manner.

Finally, it is interesting that while there is a serious national shortage of psychiatrists, there is certainly no shortage of challenges. Psychiatrists, patients, families, and advocates should combine their efforts to find effective solutions, one challenge at a time.