Henry A. Nasrallah, MD

Snake venom is deadly but is being used to treat some cancers,¹ because it produces contortrostatin, a protein that “paralyzes” cancer cells and prevents them from migrating. Venoms from spiders are being investigated as a treatment to slow the progression of muscular dystrophy by preventing muscle cells from deteriorating. Venom from tarantulas can relieve chronic pain, and those from centipedes help rodents tolerate thermal, chemical, or acid pain. Scorpion venom can cause cancer cells to glow under a flashlight, enabling surgeons to locate and remove them. Anemones toxin could be used to treat autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and lupus.

Vaccines are an excellent example of how deadly pathogens can be transformed into life-saving therapies. Billions of people have been protected from polio, smallpox, tetanus, diphtheria, measles, mumps, rubella, influenza, pneumococcus, hepatitis A and B, rabies, shingles, typhoid, meningitis, or cholera. Turning killers into saviors is one of the most remarkable miracles of medical research.²

The mind-boggling transformation of mind-altering drugs

In psychiatry, psychedelic drugs have been repurposed into useful therapies for mental illness. As recently as a decade ago, psychiatric practitioners—physicians and nurse practitioners—regarded hallucinogens as dangerous, “must-avoid” drugs of abuse that could trigger or exacerbate serious psychiatric disorders. Then, thanks to ongoing research, the psychedelic “caterpillars” transformed into therapeutic “butterflies,” and the despised drugs of abuse became welcome adjuncts for treating some stubborn psychopathologies. Such paradoxical developments are emblematic of how one can always find a silver lining.

Consider the following transformations of various psychedelics and hallucinogens—also called “entheogens”—into novel pharmacotherapies. Note that in most cases, the application of these mind-altering drugs into useful medications is still a work in progress.

Lysergic acid diethylamide (LSD) was used extensively for treating mood disorders in the pre-antidepressant era, before it was prohibited in the late 1960s. A review of 19 studies—many uncontrolled—concluded that approximately 80% of patients improved, according to the treating physicians.³ However, research on LSD was halted for several decades after it became illegal, and resumed in 2010. Neuropsychiatrists and neuroscience researchers are now employing advanced techniques, such as neuroimaging, molecular pharmacology, and connectomics, to study its therapeutic effects.⁴ LSD is not only being used for treatment-resistant depression but also anxiety, alcoholism, autism, and even schizophrenia. However, despite its potential uses for treating alcoholism and anxiety, enhancing creativity, or caring for terminally ill patients, using LSD requires expertise, caution, and adherence to ethical standards.⁵

In healthy individuals, the effects of LSD include visual hallucinations, audiovisual synesthesia, depersonalization and derealization, and a sense of well-being, happiness, closeness to others, and trust.

Biologic effects include increased heart rate and blood pressure, elevated temperature, dilated pupils, and increased serum cortisol, prolactin, oxytocin, and epinephrine. All effects subside within 3 days.⁶

Psilocybin

Psilocybin, a component of some mushrooms that is known for its use during rituals in some cultures, has been discovered to have antidepressant, anxiolytic, and anti-addictive effects.⁷ Recent controlled studies at Johns Hopkins University reported that a single dose of psilocybin can relieve anxiety or depression for up to 6 months, which, if replicated, could lead to a remarkable paradigm shift in treating mood and anxiety disorders, especially if patients do not respond to standard antidepressants.³ Other emerging uses of both psilocybin and LSD are in treating addictions⁸ where psychiatry is desperately looking for innovative new therapies.

Ecstasy

MDMA (3,4-methylenedioxymethamphetamine), also known as ecstasy, is widely regarded as a harmful party drug that produces euphoria, but not hallucinations. However, it has emerged as a useful treatment for posttraumatic stress disorder (PTSD). In one study of female sexual abuse victims, 80% of the patients who received MDMA with psychotherapy no longer met diagnostic criteria for PTSD after 2 months.⁹ Other studies showed no effects. Despite persistent skepticisms by many, the Multidisciplinary Association for Psychedelics Studies organization is investing millions of dollars into studying MDMA for PTSD in several countries.^9,10 One hurdle is that it is difficult to conduct truly blind studies with psychedelic drugs because of their profound effects. MDMA releases cortisol, oxytocin—which are known to facilitate psychotherapy—and testosterone, but the debate about the risk–benefit ratio will continue.¹¹ MDMA also is being studied for treating social anxiety in adults with autism.¹²

Ketamine

Ketamine is a weaker cousin of the potent psychotogenic phencyclidine (approximately one-fiftieth the potency) and is a well-known drug of abuse that causes dissociation and hallucinations. It is used as an anesthetic in veterinary medicine and in children undergoing surgical procedures. Until recently, its only use in psychiatry has been as an anesthetic during electroconvulsive therapy. However, over the past few years, IV ketamine has been in the spotlight as a breakthrough, rapid-onset antidepressant and anti-suicidal agent in several controlled studies.¹³ This drug is revolutionizing the management of treatment-resistant depression and suicidal ideation and generating new insights into the neurobiology of depression.

Cannabis

Last, but certainly not least, is marijuana, which is more widely used than all the other psychedelics combined, and is currently at the center of a national debate about its legalization. Although the director of the National Institute on Drug Abuse highlighted the many risk of marijuana,¹⁴ studies have pointed to the myriad medical uses of Cannabis.^15,16 An editorial in Nature Medicine recently urged that regulators reconsider the tight constraints on marijuana research.¹⁷ Some of the medical applications of marijuana include:

• psychiatry (anxiety, PTSD)
• neurology (severe epilepsy, tremors in Parkinson’s disease, traumatic brain injury, pain of multiple sclerosis, muscle spasms, and progression of Alzheimer’s disease)
• oncology (nausea and pain of chemotherapy, reduction of metastasis)
• ophthalmology (decrease of intraocular pressure in glaucoma)
• autoimmune disorders (rheumatoid arthritis, Crohn’s disease, lupus).

However, as a schizophrenia researcher, I am wary about marijuana’s high risk of triggering psychosis in young adults with a family history of schizophrenia spectrum disorders.¹⁸

The above are examples of how psychiatry is finally recognizing the therapeutic value inherent in traditionally “evil” street drugs that we euphemistically refer to as “recreational drugs.” Even methamphetamine, the universally condemned and clearly harmful drug, was recently reported to be neuroprotective at low dosages!¹⁹ Could our field have suffered from a blind eye to the benefits of these hallucinogens and ignored the possibility that some persons with addiction who use these “recreational drugs” may have been self-medicating to alleviate their un-diagnosed psychiatric disorder? We need to reconceptualize the pejorative term “mind-altering drug” because of its implicitly negative connotation. After all, alteration may indicate a favorable, not just a deleterious, outcome.

Snake venom is deadly but is being used to treat some cancers,¹ because it produces contortrostatin, a protein that “paralyzes” cancer cells and prevents them from migrating. Venoms from spiders are being investigated as a treatment to slow the progression of muscular dystrophy by preventing muscle cells from deteriorating. Venom from tarantulas can relieve chronic pain, and those from centipedes help rodents tolerate thermal, chemical, or acid pain. Scorpion venom can cause cancer cells to glow under a flashlight, enabling surgeons to locate and remove them. Anemones toxin could be used to treat autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and lupus.

Vaccines are an excellent example of how deadly pathogens can be transformed into life-saving therapies. Billions of people have been protected from polio, smallpox, tetanus, diphtheria, measles, mumps, rubella, influenza, pneumococcus, hepatitis A and B, rabies, shingles, typhoid, meningitis, or cholera. Turning killers into saviors is one of the most remarkable miracles of medical research.²

The mind-boggling transformation of mind-altering drugs

In psychiatry, psychedelic drugs have been repurposed into useful therapies for mental illness. As recently as a decade ago, psychiatric practitioners—physicians and nurse practitioners—regarded hallucinogens as dangerous, “must-avoid” drugs of abuse that could trigger or exacerbate serious psychiatric disorders. Then, thanks to ongoing research, the psychedelic “caterpillars” transformed into therapeutic “butterflies,” and the despised drugs of abuse became welcome adjuncts for treating some stubborn psychopathologies. Such paradoxical developments are emblematic of how one can always find a silver lining.

Consider the following transformations of various psychedelics and hallucinogens—also called “entheogens”—into novel pharmacotherapies. Note that in most cases, the application of these mind-altering drugs into useful medications is still a work in progress.

Lysergic acid diethylamide (LSD) was used extensively for treating mood disorders in the pre-antidepressant era, before it was prohibited in the late 1960s. A review of 19 studies—many uncontrolled—concluded that approximately 80% of patients improved, according to the treating physicians.³ However, research on LSD was halted for several decades after it became illegal, and resumed in 2010. Neuropsychiatrists and neuroscience researchers are now employing advanced techniques, such as neuroimaging, molecular pharmacology, and connectomics, to study its therapeutic effects.⁴ LSD is not only being used for treatment-resistant depression but also anxiety, alcoholism, autism, and even schizophrenia. However, despite its potential uses for treating alcoholism and anxiety, enhancing creativity, or caring for terminally ill patients, using LSD requires expertise, caution, and adherence to ethical standards.⁵

In healthy individuals, the effects of LSD include visual hallucinations, audiovisual synesthesia, depersonalization and derealization, and a sense of well-being, happiness, closeness to others, and trust.

Biologic effects include increased heart rate and blood pressure, elevated temperature, dilated pupils, and increased serum cortisol, prolactin, oxytocin, and epinephrine. All effects subside within 3 days.⁶

Psilocybin

Psilocybin, a component of some mushrooms that is known for its use during rituals in some cultures, has been discovered to have antidepressant, anxiolytic, and anti-addictive effects.⁷ Recent controlled studies at Johns Hopkins University reported that a single dose of psilocybin can relieve anxiety or depression for up to 6 months, which, if replicated, could lead to a remarkable paradigm shift in treating mood and anxiety disorders, especially if patients do not respond to standard antidepressants.³ Other emerging uses of both psilocybin and LSD are in treating addictions⁸ where psychiatry is desperately looking for innovative new therapies.

Ecstasy

MDMA (3,4-methylenedioxymethamphetamine), also known as ecstasy, is widely regarded as a harmful party drug that produces euphoria, but not hallucinations. However, it has emerged as a useful treatment for posttraumatic stress disorder (PTSD). In one study of female sexual abuse victims, 80% of the patients who received MDMA with psychotherapy no longer met diagnostic criteria for PTSD after 2 months.⁹ Other studies showed no effects. Despite persistent skepticisms by many, the Multidisciplinary Association for Psychedelics Studies organization is investing millions of dollars into studying MDMA for PTSD in several countries.^9,10 One hurdle is that it is difficult to conduct truly blind studies with psychedelic drugs because of their profound effects. MDMA releases cortisol, oxytocin—which are known to facilitate psychotherapy—and testosterone, but the debate about the risk–benefit ratio will continue.¹¹ MDMA also is being studied for treating social anxiety in adults with autism.¹²

Ketamine

Ketamine is a weaker cousin of the potent psychotogenic phencyclidine (approximately one-fiftieth the potency) and is a well-known drug of abuse that causes dissociation and hallucinations. It is used as an anesthetic in veterinary medicine and in children undergoing surgical procedures. Until recently, its only use in psychiatry has been as an anesthetic during electroconvulsive therapy. However, over the past few years, IV ketamine has been in the spotlight as a breakthrough, rapid-onset antidepressant and anti-suicidal agent in several controlled studies.¹³ This drug is revolutionizing the management of treatment-resistant depression and suicidal ideation and generating new insights into the neurobiology of depression.

Cannabis

Last, but certainly not least, is marijuana, which is more widely used than all the other psychedelics combined, and is currently at the center of a national debate about its legalization. Although the director of the National Institute on Drug Abuse highlighted the many risk of marijuana,¹⁴ studies have pointed to the myriad medical uses of Cannabis.^15,16 An editorial in Nature Medicine recently urged that regulators reconsider the tight constraints on marijuana research.¹⁷ Some of the medical applications of marijuana include:

• psychiatry (anxiety, PTSD)
• neurology (severe epilepsy, tremors in Parkinson’s disease, traumatic brain injury, pain of multiple sclerosis, muscle spasms, and progression of Alzheimer’s disease)
• oncology (nausea and pain of chemotherapy, reduction of metastasis)
• ophthalmology (decrease of intraocular pressure in glaucoma)
• autoimmune disorders (rheumatoid arthritis, Crohn’s disease, lupus).

However, as a schizophrenia researcher, I am wary about marijuana’s high risk of triggering psychosis in young adults with a family history of schizophrenia spectrum disorders.¹⁸

The above are examples of how psychiatry is finally recognizing the therapeutic value inherent in traditionally “evil” street drugs that we euphemistically refer to as “recreational drugs.” Even methamphetamine, the universally condemned and clearly harmful drug, was recently reported to be neuroprotective at low dosages!¹⁹ Could our field have suffered from a blind eye to the benefits of these hallucinogens and ignored the possibility that some persons with addiction who use these “recreational drugs” may have been self-medicating to alleviate their un-diagnosed psychiatric disorder? We need to reconceptualize the pejorative term “mind-altering drug” because of its implicitly negative connotation. After all, alteration may indicate a favorable, not just a deleterious, outcome.

Snake venom is deadly but is being used to treat some cancers,¹ because it produces contortrostatin, a protein that “paralyzes” cancer cells and prevents them from migrating. Venoms from spiders are being investigated as a treatment to slow the progression of muscular dystrophy by preventing muscle cells from deteriorating. Venom from tarantulas can relieve chronic pain, and those from centipedes help rodents tolerate thermal, chemical, or acid pain. Scorpion venom can cause cancer cells to glow under a flashlight, enabling surgeons to locate and remove them. Anemones toxin could be used to treat autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and lupus.

Vaccines are an excellent example of how deadly pathogens can be transformed into life-saving therapies. Billions of people have been protected from polio, smallpox, tetanus, diphtheria, measles, mumps, rubella, influenza, pneumococcus, hepatitis A and B, rabies, shingles, typhoid, meningitis, or cholera. Turning killers into saviors is one of the most remarkable miracles of medical research.²

The mind-boggling transformation of mind-altering drugs

In psychiatry, psychedelic drugs have been repurposed into useful therapies for mental illness. As recently as a decade ago, psychiatric practitioners—physicians and nurse practitioners—regarded hallucinogens as dangerous, “must-avoid” drugs of abuse that could trigger or exacerbate serious psychiatric disorders. Then, thanks to ongoing research, the psychedelic “caterpillars” transformed into therapeutic “butterflies,” and the despised drugs of abuse became welcome adjuncts for treating some stubborn psychopathologies. Such paradoxical developments are emblematic of how one can always find a silver lining.

Consider the following transformations of various psychedelics and hallucinogens—also called “entheogens”—into novel pharmacotherapies. Note that in most cases, the application of these mind-altering drugs into useful medications is still a work in progress.

Lysergic acid diethylamide (LSD) was used extensively for treating mood disorders in the pre-antidepressant era, before it was prohibited in the late 1960s. A review of 19 studies—many uncontrolled—concluded that approximately 80% of patients improved, according to the treating physicians.³ However, research on LSD was halted for several decades after it became illegal, and resumed in 2010. Neuropsychiatrists and neuroscience researchers are now employing advanced techniques, such as neuroimaging, molecular pharmacology, and connectomics, to study its therapeutic effects.⁴ LSD is not only being used for treatment-resistant depression but also anxiety, alcoholism, autism, and even schizophrenia. However, despite its potential uses for treating alcoholism and anxiety, enhancing creativity, or caring for terminally ill patients, using LSD requires expertise, caution, and adherence to ethical standards.⁵

In healthy individuals, the effects of LSD include visual hallucinations, audiovisual synesthesia, depersonalization and derealization, and a sense of well-being, happiness, closeness to others, and trust.

Biologic effects include increased heart rate and blood pressure, elevated temperature, dilated pupils, and increased serum cortisol, prolactin, oxytocin, and epinephrine. All effects subside within 3 days.⁶

Psilocybin

Psilocybin, a component of some mushrooms that is known for its use during rituals in some cultures, has been discovered to have antidepressant, anxiolytic, and anti-addictive effects.⁷ Recent controlled studies at Johns Hopkins University reported that a single dose of psilocybin can relieve anxiety or depression for up to 6 months, which, if replicated, could lead to a remarkable paradigm shift in treating mood and anxiety disorders, especially if patients do not respond to standard antidepressants.³ Other emerging uses of both psilocybin and LSD are in treating addictions⁸ where psychiatry is desperately looking for innovative new therapies.

Ecstasy

MDMA (3,4-methylenedioxymethamphetamine), also known as ecstasy, is widely regarded as a harmful party drug that produces euphoria, but not hallucinations. However, it has emerged as a useful treatment for posttraumatic stress disorder (PTSD). In one study of female sexual abuse victims, 80% of the patients who received MDMA with psychotherapy no longer met diagnostic criteria for PTSD after 2 months.⁹ Other studies showed no effects. Despite persistent skepticisms by many, the Multidisciplinary Association for Psychedelics Studies organization is investing millions of dollars into studying MDMA for PTSD in several countries.^9,10 One hurdle is that it is difficult to conduct truly blind studies with psychedelic drugs because of their profound effects. MDMA releases cortisol, oxytocin—which are known to facilitate psychotherapy—and testosterone, but the debate about the risk–benefit ratio will continue.¹¹ MDMA also is being studied for treating social anxiety in adults with autism.¹²

Ketamine

Ketamine is a weaker cousin of the potent psychotogenic phencyclidine (approximately one-fiftieth the potency) and is a well-known drug of abuse that causes dissociation and hallucinations. It is used as an anesthetic in veterinary medicine and in children undergoing surgical procedures. Until recently, its only use in psychiatry has been as an anesthetic during electroconvulsive therapy. However, over the past few years, IV ketamine has been in the spotlight as a breakthrough, rapid-onset antidepressant and anti-suicidal agent in several controlled studies.¹³ This drug is revolutionizing the management of treatment-resistant depression and suicidal ideation and generating new insights into the neurobiology of depression.

Cannabis

Last, but certainly not least, is marijuana, which is more widely used than all the other psychedelics combined, and is currently at the center of a national debate about its legalization. Although the director of the National Institute on Drug Abuse highlighted the many risk of marijuana,¹⁴ studies have pointed to the myriad medical uses of Cannabis.^15,16 An editorial in Nature Medicine recently urged that regulators reconsider the tight constraints on marijuana research.¹⁷ Some of the medical applications of marijuana include:

• psychiatry (anxiety, PTSD)
• neurology (severe epilepsy, tremors in Parkinson’s disease, traumatic brain injury, pain of multiple sclerosis, muscle spasms, and progression of Alzheimer’s disease)
• oncology (nausea and pain of chemotherapy, reduction of metastasis)
• ophthalmology (decrease of intraocular pressure in glaucoma)
• autoimmune disorders (rheumatoid arthritis, Crohn’s disease, lupus).

However, as a schizophrenia researcher, I am wary about marijuana’s high risk of triggering psychosis in young adults with a family history of schizophrenia spectrum disorders.¹⁸

The above are examples of how psychiatry is finally recognizing the therapeutic value inherent in traditionally “evil” street drugs that we euphemistically refer to as “recreational drugs.” Even methamphetamine, the universally condemned and clearly harmful drug, was recently reported to be neuroprotective at low dosages!¹⁹ Could our field have suffered from a blind eye to the benefits of these hallucinogens and ignored the possibility that some persons with addiction who use these “recreational drugs” may have been self-medicating to alleviate their un-diagnosed psychiatric disorder? We need to reconceptualize the pejorative term “mind-altering drug” because of its implicitly negative connotation. After all, alteration may indicate a favorable, not just a deleterious, outcome.

Are you ‘neuroprotecting’ your patients?

Fortunately, many studies have demonstrated that in addition to controlling clinical symptoms, antidepressants, mood stabilizers, and atypical antipsychotics all have neuroprotective effects, including stimulating neurogenesis, preventing apoptosis, and increasing neurotrophins. However, more needs to be done to protect the brain’s gray and white matter and to prevent negative neuroplasticity and disconnectivity of brain circuits that often are documented in patients with psychotic and mood disorders.

There are, in fact, many off-label supplements with strong neuroprotective effects that psychiatrists can use as an adjunct to standard evidence-based pharmacotherapy. These agents generally are safe and well tolerated and often are sold over the counter, but are not covered by insurance. However, considering the disability that often is associated with schizophrenia, treatment-resistant depression, or psychotic mania, it is reasonable to consider using these agents, many of which are supported by studies published in peer-reviewed journals. However, because they are widely available and not proprietary and large, expensive registration trials such as the ones conducted by the pharmaceutical industry are not done, none is likely to receive FDA approval. Therefore, it is up to psychiatrists and nurse practitioners to use them judiciously in patients at risk for neurotoxicity.

Here are 10 agents with neuroprotective effects supported by published data that can be considered as add-on to the standard treatments in an effort to mitigate neurotoxicity and protect the brain from the destructive processes that accompany acute episodes of psychosis, mania, and depression.

Omega-3 fatty acids have been shown in several studies to help reduce psychopathology of psychosis, mania, or depression when used as an adjunctive agent.¹ It appears to be more effective in the early stages of psychiatric disorders than in the chronic phase. It has anti-inflammatory, anti-oxidant, and anti-apoptotic effects; activates cell-signaling pathways; and prevents synaptic loss as well as neuronal and glial death.²

N-acetylcysteine (NAC) is a powerful antioxidant that increases glutathione, which is produced in the mitochondria. Schizophrenia is associated with mitochondrial dysfunction with low levels of glutathione, which puts the brain at risk for neurodegeneration caused by high levels of free radicals produced during psychosis. Adding NAC to antipsychotics during acute psychotic episodes—especially the first episode—can significantly reduce the neurotoxic effects of reactive oxygen and nitrogen species, also known as free radicals.³ In studies of traumatic brain injury in rats, NAC reduced brain edema, neuro­inflammation, blood–brain barrier permeability, and apoptosis.⁴

Minocycline. This antibiotic has been studied extensively as an adjunctive treatment in schizophrenia and has proven to have several neuroprotective effects including anti-inflammatory, anti-oxidant, and anti-apoptotic, and reduces glutamate excitotoxicity.⁵ Several studies have documented its usefulness in acute psychotic episodes.

Vitamin D. Because of its vital role in neurodevelopment (neuronal differentiation, axonal connectivity), vitamin D deficiency has been associated with several psychiatric disorders including autism, schizophrenia, depression, and Alzheimer’s disease.⁶ Measure serum levels of vitamin D in patients with psychotic and mood disorders and implement supplementation if it is low—and it often is in these patients.

Nicotine is neuroprotective against glutamate excitotoxicity and it also inhibits apoptosis.⁷ However, it should never be administered via cigarettes, which are loaded with hundreds of toxic substances! It can be administered via patches or nicotine gum, which are usually used to help in smoking cessation. Nicotine also also can have a pro-cognitive effect.

Melatonin. Many people associate melatonin with sleep. However, it has multiple neuroprotective effects by being an antioxidant, protecting mitochondrial integrity, and modulating the immune system, as well as attenuating microglial activation, which triggers neuroinflammation and oxidative stress. It also protects against cellular senescence, which is due to inflammation and reactive oxygen species. Furthermore, melatonin is useful in ameliorating the metabolic syndrome, which is associated with neurotoxic effects on brain tissue caused by the pro-inflammatory effects of peri-omental fat in obesity.⁸ Adjunctive melatonin could be helpful in patients with schizophrenia or depression who suffer from metabolic syndrome.

Erythropoietin is a hormone produced by the kidneys to promote the formation of red blood cells. It is a potent neuroprotective cytokine that promotes neuronal survival via anti-apoptotic effects. It protects against glutamate and nitrous oxide toxicity⁹ and haloperidol-induced neuronal death.¹⁰ It is clinically used (since FDA approval in 1989) in severe anemia due to chronic kidney disease or chemotherapy, as well as in inflammatory bowel disease. It does have some “black-box” warnings so its use should be limited.

The above interventions may be helpful for some patients but not others. Practitioners should consider using 1 or more of those adjunctive neuroprotective agents in patients who are at risk for neurodegenerative changes secondary to recurrences of acute and severe psychosis or mood episodes. Although clinicians cannot monitor brain structural integrity, they can assess the rate of symptomatic improvement and degree of functional restoration in their patients. Until a cure is found, these little steps—taken cautiously and judiciously—could help alleviate our patients’ suffering and the risk of neurotoxicity associated with their serious psychiatric disorder.

Are you ‘neuroprotecting’ your patients?

Fortunately, many studies have demonstrated that in addition to controlling clinical symptoms, antidepressants, mood stabilizers, and atypical antipsychotics all have neuroprotective effects, including stimulating neurogenesis, preventing apoptosis, and increasing neurotrophins. However, more needs to be done to protect the brain’s gray and white matter and to prevent negative neuroplasticity and disconnectivity of brain circuits that often are documented in patients with psychotic and mood disorders.

There are, in fact, many off-label supplements with strong neuroprotective effects that psychiatrists can use as an adjunct to standard evidence-based pharmacotherapy. These agents generally are safe and well tolerated and often are sold over the counter, but are not covered by insurance. However, considering the disability that often is associated with schizophrenia, treatment-resistant depression, or psychotic mania, it is reasonable to consider using these agents, many of which are supported by studies published in peer-reviewed journals. However, because they are widely available and not proprietary and large, expensive registration trials such as the ones conducted by the pharmaceutical industry are not done, none is likely to receive FDA approval. Therefore, it is up to psychiatrists and nurse practitioners to use them judiciously in patients at risk for neurotoxicity.

Here are 10 agents with neuroprotective effects supported by published data that can be considered as add-on to the standard treatments in an effort to mitigate neurotoxicity and protect the brain from the destructive processes that accompany acute episodes of psychosis, mania, and depression.

Omega-3 fatty acids have been shown in several studies to help reduce psychopathology of psychosis, mania, or depression when used as an adjunctive agent.¹ It appears to be more effective in the early stages of psychiatric disorders than in the chronic phase. It has anti-inflammatory, anti-oxidant, and anti-apoptotic effects; activates cell-signaling pathways; and prevents synaptic loss as well as neuronal and glial death.²

N-acetylcysteine (NAC) is a powerful antioxidant that increases glutathione, which is produced in the mitochondria. Schizophrenia is associated with mitochondrial dysfunction with low levels of glutathione, which puts the brain at risk for neurodegeneration caused by high levels of free radicals produced during psychosis. Adding NAC to antipsychotics during acute psychotic episodes—especially the first episode—can significantly reduce the neurotoxic effects of reactive oxygen and nitrogen species, also known as free radicals.³ In studies of traumatic brain injury in rats, NAC reduced brain edema, neuro­inflammation, blood–brain barrier permeability, and apoptosis.⁴

Minocycline. This antibiotic has been studied extensively as an adjunctive treatment in schizophrenia and has proven to have several neuroprotective effects including anti-inflammatory, anti-oxidant, and anti-apoptotic, and reduces glutamate excitotoxicity.⁵ Several studies have documented its usefulness in acute psychotic episodes.

Vitamin D. Because of its vital role in neurodevelopment (neuronal differentiation, axonal connectivity), vitamin D deficiency has been associated with several psychiatric disorders including autism, schizophrenia, depression, and Alzheimer’s disease.⁶ Measure serum levels of vitamin D in patients with psychotic and mood disorders and implement supplementation if it is low—and it often is in these patients.

Nicotine is neuroprotective against glutamate excitotoxicity and it also inhibits apoptosis.⁷ However, it should never be administered via cigarettes, which are loaded with hundreds of toxic substances! It can be administered via patches or nicotine gum, which are usually used to help in smoking cessation. Nicotine also also can have a pro-cognitive effect.

Melatonin. Many people associate melatonin with sleep. However, it has multiple neuroprotective effects by being an antioxidant, protecting mitochondrial integrity, and modulating the immune system, as well as attenuating microglial activation, which triggers neuroinflammation and oxidative stress. It also protects against cellular senescence, which is due to inflammation and reactive oxygen species. Furthermore, melatonin is useful in ameliorating the metabolic syndrome, which is associated with neurotoxic effects on brain tissue caused by the pro-inflammatory effects of peri-omental fat in obesity.⁸ Adjunctive melatonin could be helpful in patients with schizophrenia or depression who suffer from metabolic syndrome.

Erythropoietin is a hormone produced by the kidneys to promote the formation of red blood cells. It is a potent neuroprotective cytokine that promotes neuronal survival via anti-apoptotic effects. It protects against glutamate and nitrous oxide toxicity⁹ and haloperidol-induced neuronal death.¹⁰ It is clinically used (since FDA approval in 1989) in severe anemia due to chronic kidney disease or chemotherapy, as well as in inflammatory bowel disease. It does have some “black-box” warnings so its use should be limited.

The above interventions may be helpful for some patients but not others. Practitioners should consider using 1 or more of those adjunctive neuroprotective agents in patients who are at risk for neurodegenerative changes secondary to recurrences of acute and severe psychosis or mood episodes. Although clinicians cannot monitor brain structural integrity, they can assess the rate of symptomatic improvement and degree of functional restoration in their patients. Until a cure is found, these little steps—taken cautiously and judiciously—could help alleviate our patients’ suffering and the risk of neurotoxicity associated with their serious psychiatric disorder.

Are you ‘neuroprotecting’ your patients?

Fortunately, many studies have demonstrated that in addition to controlling clinical symptoms, antidepressants, mood stabilizers, and atypical antipsychotics all have neuroprotective effects, including stimulating neurogenesis, preventing apoptosis, and increasing neurotrophins. However, more needs to be done to protect the brain’s gray and white matter and to prevent negative neuroplasticity and disconnectivity of brain circuits that often are documented in patients with psychotic and mood disorders.

There are, in fact, many off-label supplements with strong neuroprotective effects that psychiatrists can use as an adjunct to standard evidence-based pharmacotherapy. These agents generally are safe and well tolerated and often are sold over the counter, but are not covered by insurance. However, considering the disability that often is associated with schizophrenia, treatment-resistant depression, or psychotic mania, it is reasonable to consider using these agents, many of which are supported by studies published in peer-reviewed journals. However, because they are widely available and not proprietary and large, expensive registration trials such as the ones conducted by the pharmaceutical industry are not done, none is likely to receive FDA approval. Therefore, it is up to psychiatrists and nurse practitioners to use them judiciously in patients at risk for neurotoxicity.

Here are 10 agents with neuroprotective effects supported by published data that can be considered as add-on to the standard treatments in an effort to mitigate neurotoxicity and protect the brain from the destructive processes that accompany acute episodes of psychosis, mania, and depression.

Omega-3 fatty acids have been shown in several studies to help reduce psychopathology of psychosis, mania, or depression when used as an adjunctive agent.¹ It appears to be more effective in the early stages of psychiatric disorders than in the chronic phase. It has anti-inflammatory, anti-oxidant, and anti-apoptotic effects; activates cell-signaling pathways; and prevents synaptic loss as well as neuronal and glial death.²

N-acetylcysteine (NAC) is a powerful antioxidant that increases glutathione, which is produced in the mitochondria. Schizophrenia is associated with mitochondrial dysfunction with low levels of glutathione, which puts the brain at risk for neurodegeneration caused by high levels of free radicals produced during psychosis. Adding NAC to antipsychotics during acute psychotic episodes—especially the first episode—can significantly reduce the neurotoxic effects of reactive oxygen and nitrogen species, also known as free radicals.³ In studies of traumatic brain injury in rats, NAC reduced brain edema, neuro­inflammation, blood–brain barrier permeability, and apoptosis.⁴

Minocycline. This antibiotic has been studied extensively as an adjunctive treatment in schizophrenia and has proven to have several neuroprotective effects including anti-inflammatory, anti-oxidant, and anti-apoptotic, and reduces glutamate excitotoxicity.⁵ Several studies have documented its usefulness in acute psychotic episodes.

Vitamin D. Because of its vital role in neurodevelopment (neuronal differentiation, axonal connectivity), vitamin D deficiency has been associated with several psychiatric disorders including autism, schizophrenia, depression, and Alzheimer’s disease.⁶ Measure serum levels of vitamin D in patients with psychotic and mood disorders and implement supplementation if it is low—and it often is in these patients.

Nicotine is neuroprotective against glutamate excitotoxicity and it also inhibits apoptosis.⁷ However, it should never be administered via cigarettes, which are loaded with hundreds of toxic substances! It can be administered via patches or nicotine gum, which are usually used to help in smoking cessation. Nicotine also also can have a pro-cognitive effect.

Melatonin. Many people associate melatonin with sleep. However, it has multiple neuroprotective effects by being an antioxidant, protecting mitochondrial integrity, and modulating the immune system, as well as attenuating microglial activation, which triggers neuroinflammation and oxidative stress. It also protects against cellular senescence, which is due to inflammation and reactive oxygen species. Furthermore, melatonin is useful in ameliorating the metabolic syndrome, which is associated with neurotoxic effects on brain tissue caused by the pro-inflammatory effects of peri-omental fat in obesity.⁸ Adjunctive melatonin could be helpful in patients with schizophrenia or depression who suffer from metabolic syndrome.

Erythropoietin is a hormone produced by the kidneys to promote the formation of red blood cells. It is a potent neuroprotective cytokine that promotes neuronal survival via anti-apoptotic effects. It protects against glutamate and nitrous oxide toxicity⁹ and haloperidol-induced neuronal death.¹⁰ It is clinically used (since FDA approval in 1989) in severe anemia due to chronic kidney disease or chemotherapy, as well as in inflammatory bowel disease. It does have some “black-box” warnings so its use should be limited.

The above interventions may be helpful for some patients but not others. Practitioners should consider using 1 or more of those adjunctive neuroprotective agents in patients who are at risk for neurodegenerative changes secondary to recurrences of acute and severe psychosis or mood episodes. Although clinicians cannot monitor brain structural integrity, they can assess the rate of symptomatic improvement and degree of functional restoration in their patients. Until a cure is found, these little steps—taken cautiously and judiciously—could help alleviate our patients’ suffering and the risk of neurotoxicity associated with their serious psychiatric disorder.

This implies early senescence, segmental aging, and, in young adult patients, premature onset of multi-system medical illnesses associated with aging, including cardiovascular disease, cancer, brain atrophy, and cognitive decline. This might be the real reason why persons with schizophrenia die 25 to 30 years too early, not only because of an unhealthy lifestyle and iatrogenic cardio-metabolic adverse effects.

One of the most consistent observations pointing to accelerated aging in schizophrenia is shortened telomeres.^2,3 Telomeres are the terminal part of chromosomes (similar to the plastic aglets of shoelaces), which are known to shorten with each cell division because of “end replication losses.” Telomeres are measured in lymphocytes, which researchers regard as “windows to the brain” because they reflect brain aging.⁴ One study of lymphocytes in patients with schizophrenia found that they appear to be approximately 25 years older than the lymphocytes of healthy individuals!⁴

Possible causes of accelerated aging

Inflammation. The leading hypothesis for accelerated aging in schizophrenia is based on the inflammatory theory of aging. Schizophrenia has been strongly linked to immune dysregulation and neuroinflammation.⁵ Other components of the accelerated aging hypothesis include oxidative and nitrosative stress, which is associated with high levels of free radicals, and, importantly, mitochondrial dysfunction that fails to generate antioxidants (glutathione peroxidase, superoxide dismutase, and catalase) that can neutralize free radicals and reverse oxidative stress, as numerous studies have shown.

Clinically, and at a relatively young age, persons with schizophrenia show many physical features consistent with aging,⁶ including the following system changes:

• CNS: dilated ventricles, reduced brain volume and gray matter volume; hypofrontality, neurocognitive deficits such as executive functioning, working memory, and attention; neurophysiologic (low amplitudes on evoked potentials)
• Musculoskeletal system: abnormalities in muscle fibers; altered nerve conduction velocity; reduced bone density
• Skin: aging skin
• Eyes: increased rate of cataracts (not caused by medications); degradation in motion discrimination
• Endocrine system: abnormal gonadal hormones; low estrogen; low androgen; thyroid dysfunction, elevated cortisol
• Metabolism: increased rates of obesity; glucose dysregulation even before antipsychotic treatment; increased insulin resistance; abnormal glucose tolerance; reduced insulin-like growth factor-1 levels
• Immune system: increased pro-inflammatory cytokines (interleukin [IL]-1B, IL-6, IL-3, IL-4, IL-10, IL-13, tumor necrosis factor-Symbol Stdα) and decrease in anti-inflammatory cytokines (IL-2, interferon [INF]-Symbol Stdα, INF-Symbol Stdγ) and vitamin D
• Cardiovascular: systolic hypertension, increased pulse pressure
• Oxidative stress and mitochondrial dysfunction: increase in reactive oxygen species in brain tissue and increased DNA and RNA oxidation markers
• Telomere dynamics: significantly higher rates of telomere loss.

The mitochondrial theory of aging.⁷ The origin of this theory dates back to the landmark work of Denham Harman more than 2 decades ago in which he proposed a connection between free radicals and aging, which is associated with cell mutations and cancer.⁸ He suggested that because mitochondrial DNA is not protected by histones as DNA in the nucleus is, it might be the main target for free radicals, making the mitochondria more susceptible to oxidative damage. Therefore, it is possible that the high oxidative stress of schizophrenia could contribute to mitochondrial dysfunction, which leads to further telomere erosion.⁹ Perhaps reducing oxidative stress in schizophrenia with a powerful antioxidant, such as the supplement N-acetylcysteine,¹⁰ could help repair the dysfunctional mitochondria found in patients with schizophrenia and might mitigate accelerated aging.

I would like to propose a bolder, even radical, “out-of-the-box” therapeutic strategy for accelerated aging: mitochondrial transplantation. In fact, “mitochondrial donation” and transplant has been performed on fetuses with genetically defective mitochondria, which has prevented rapid death after birth.¹¹

Similarities with progeria. The accumulating evidence for accelerated aging in schizophrenia has promoted some researchers to consider it a form of progeria¹² because of the accelerated aging features that patients with schizophrenia manifest. Patients with schizophrenia share some risk factors with patients with progeria, including high paternal age, prenatal stress, prenatal famine, low birth weight, and premature cognitive decline. Both progeria and schizophrenia are associated with increased apoptosis and cell senescence, which could reduce the risk of cancer but result in premature aging along with age-related medical disorders that lead to mortality in the elderly.

This is why collaborative care between psychiatrists and primary care providers is so vital for patients with schizophrenia from the onset of the illness during the teens and young adulthood, not after years of treatment and unhealthy lifestyle habits (smoking, sedentary living, high-fat and high-calorie diet), which add insult to injury, culminating in loss of 25 to 30 years of potential life. Preventative medical care starting when schizophrenia is first diagnosed is vital, in addition to comprehensive psychiatric care, because premature mortality is the worst outcome in medicine.

Henry A. Nasrallah, MD

Editor-in-Chief

This implies early senescence, segmental aging, and, in young adult patients, premature onset of multi-system medical illnesses associated with aging, including cardiovascular disease, cancer, brain atrophy, and cognitive decline. This might be the real reason why persons with schizophrenia die 25 to 30 years too early, not only because of an unhealthy lifestyle and iatrogenic cardio-metabolic adverse effects.

One of the most consistent observations pointing to accelerated aging in schizophrenia is shortened telomeres.^2,3 Telomeres are the terminal part of chromosomes (similar to the plastic aglets of shoelaces), which are known to shorten with each cell division because of “end replication losses.” Telomeres are measured in lymphocytes, which researchers regard as “windows to the brain” because they reflect brain aging.⁴ One study of lymphocytes in patients with schizophrenia found that they appear to be approximately 25 years older than the lymphocytes of healthy individuals!⁴

Possible causes of accelerated aging

Inflammation. The leading hypothesis for accelerated aging in schizophrenia is based on the inflammatory theory of aging. Schizophrenia has been strongly linked to immune dysregulation and neuroinflammation.⁵ Other components of the accelerated aging hypothesis include oxidative and nitrosative stress, which is associated with high levels of free radicals, and, importantly, mitochondrial dysfunction that fails to generate antioxidants (glutathione peroxidase, superoxide dismutase, and catalase) that can neutralize free radicals and reverse oxidative stress, as numerous studies have shown.

Clinically, and at a relatively young age, persons with schizophrenia show many physical features consistent with aging,⁶ including the following system changes:

• CNS: dilated ventricles, reduced brain volume and gray matter volume; hypofrontality, neurocognitive deficits such as executive functioning, working memory, and attention; neurophysiologic (low amplitudes on evoked potentials)
• Musculoskeletal system: abnormalities in muscle fibers; altered nerve conduction velocity; reduced bone density
• Skin: aging skin
• Eyes: increased rate of cataracts (not caused by medications); degradation in motion discrimination
• Endocrine system: abnormal gonadal hormones; low estrogen; low androgen; thyroid dysfunction, elevated cortisol
• Metabolism: increased rates of obesity; glucose dysregulation even before antipsychotic treatment; increased insulin resistance; abnormal glucose tolerance; reduced insulin-like growth factor-1 levels
• Immune system: increased pro-inflammatory cytokines (interleukin [IL]-1B, IL-6, IL-3, IL-4, IL-10, IL-13, tumor necrosis factor-Symbol Stdα) and decrease in anti-inflammatory cytokines (IL-2, interferon [INF]-Symbol Stdα, INF-Symbol Stdγ) and vitamin D
• Cardiovascular: systolic hypertension, increased pulse pressure
• Oxidative stress and mitochondrial dysfunction: increase in reactive oxygen species in brain tissue and increased DNA and RNA oxidation markers
• Telomere dynamics: significantly higher rates of telomere loss.

The mitochondrial theory of aging.⁷ The origin of this theory dates back to the landmark work of Denham Harman more than 2 decades ago in which he proposed a connection between free radicals and aging, which is associated with cell mutations and cancer.⁸ He suggested that because mitochondrial DNA is not protected by histones as DNA in the nucleus is, it might be the main target for free radicals, making the mitochondria more susceptible to oxidative damage. Therefore, it is possible that the high oxidative stress of schizophrenia could contribute to mitochondrial dysfunction, which leads to further telomere erosion.⁹ Perhaps reducing oxidative stress in schizophrenia with a powerful antioxidant, such as the supplement N-acetylcysteine,¹⁰ could help repair the dysfunctional mitochondria found in patients with schizophrenia and might mitigate accelerated aging.

I would like to propose a bolder, even radical, “out-of-the-box” therapeutic strategy for accelerated aging: mitochondrial transplantation. In fact, “mitochondrial donation” and transplant has been performed on fetuses with genetically defective mitochondria, which has prevented rapid death after birth.¹¹

Similarities with progeria. The accumulating evidence for accelerated aging in schizophrenia has promoted some researchers to consider it a form of progeria¹² because of the accelerated aging features that patients with schizophrenia manifest. Patients with schizophrenia share some risk factors with patients with progeria, including high paternal age, prenatal stress, prenatal famine, low birth weight, and premature cognitive decline. Both progeria and schizophrenia are associated with increased apoptosis and cell senescence, which could reduce the risk of cancer but result in premature aging along with age-related medical disorders that lead to mortality in the elderly.

This is why collaborative care between psychiatrists and primary care providers is so vital for patients with schizophrenia from the onset of the illness during the teens and young adulthood, not after years of treatment and unhealthy lifestyle habits (smoking, sedentary living, high-fat and high-calorie diet), which add insult to injury, culminating in loss of 25 to 30 years of potential life. Preventative medical care starting when schizophrenia is first diagnosed is vital, in addition to comprehensive psychiatric care, because premature mortality is the worst outcome in medicine.

Henry A. Nasrallah, MD

Editor-in-Chief

This implies early senescence, segmental aging, and, in young adult patients, premature onset of multi-system medical illnesses associated with aging, including cardiovascular disease, cancer, brain atrophy, and cognitive decline. This might be the real reason why persons with schizophrenia die 25 to 30 years too early, not only because of an unhealthy lifestyle and iatrogenic cardio-metabolic adverse effects.

One of the most consistent observations pointing to accelerated aging in schizophrenia is shortened telomeres.^2,3 Telomeres are the terminal part of chromosomes (similar to the plastic aglets of shoelaces), which are known to shorten with each cell division because of “end replication losses.” Telomeres are measured in lymphocytes, which researchers regard as “windows to the brain” because they reflect brain aging.⁴ One study of lymphocytes in patients with schizophrenia found that they appear to be approximately 25 years older than the lymphocytes of healthy individuals!⁴

Possible causes of accelerated aging

Inflammation. The leading hypothesis for accelerated aging in schizophrenia is based on the inflammatory theory of aging. Schizophrenia has been strongly linked to immune dysregulation and neuroinflammation.⁵ Other components of the accelerated aging hypothesis include oxidative and nitrosative stress, which is associated with high levels of free radicals, and, importantly, mitochondrial dysfunction that fails to generate antioxidants (glutathione peroxidase, superoxide dismutase, and catalase) that can neutralize free radicals and reverse oxidative stress, as numerous studies have shown.

Clinically, and at a relatively young age, persons with schizophrenia show many physical features consistent with aging,⁶ including the following system changes:

• CNS: dilated ventricles, reduced brain volume and gray matter volume; hypofrontality, neurocognitive deficits such as executive functioning, working memory, and attention; neurophysiologic (low amplitudes on evoked potentials)
• Musculoskeletal system: abnormalities in muscle fibers; altered nerve conduction velocity; reduced bone density
• Skin: aging skin
• Eyes: increased rate of cataracts (not caused by medications); degradation in motion discrimination
• Endocrine system: abnormal gonadal hormones; low estrogen; low androgen; thyroid dysfunction, elevated cortisol
• Metabolism: increased rates of obesity; glucose dysregulation even before antipsychotic treatment; increased insulin resistance; abnormal glucose tolerance; reduced insulin-like growth factor-1 levels
• Immune system: increased pro-inflammatory cytokines (interleukin [IL]-1B, IL-6, IL-3, IL-4, IL-10, IL-13, tumor necrosis factor-Symbol Stdα) and decrease in anti-inflammatory cytokines (IL-2, interferon [INF]-Symbol Stdα, INF-Symbol Stdγ) and vitamin D
• Cardiovascular: systolic hypertension, increased pulse pressure
• Oxidative stress and mitochondrial dysfunction: increase in reactive oxygen species in brain tissue and increased DNA and RNA oxidation markers
• Telomere dynamics: significantly higher rates of telomere loss.

The mitochondrial theory of aging.⁷ The origin of this theory dates back to the landmark work of Denham Harman more than 2 decades ago in which he proposed a connection between free radicals and aging, which is associated with cell mutations and cancer.⁸ He suggested that because mitochondrial DNA is not protected by histones as DNA in the nucleus is, it might be the main target for free radicals, making the mitochondria more susceptible to oxidative damage. Therefore, it is possible that the high oxidative stress of schizophrenia could contribute to mitochondrial dysfunction, which leads to further telomere erosion.⁹ Perhaps reducing oxidative stress in schizophrenia with a powerful antioxidant, such as the supplement N-acetylcysteine,¹⁰ could help repair the dysfunctional mitochondria found in patients with schizophrenia and might mitigate accelerated aging.

I would like to propose a bolder, even radical, “out-of-the-box” therapeutic strategy for accelerated aging: mitochondrial transplantation. In fact, “mitochondrial donation” and transplant has been performed on fetuses with genetically defective mitochondria, which has prevented rapid death after birth.¹¹

Similarities with progeria. The accumulating evidence for accelerated aging in schizophrenia has promoted some researchers to consider it a form of progeria¹² because of the accelerated aging features that patients with schizophrenia manifest. Patients with schizophrenia share some risk factors with patients with progeria, including high paternal age, prenatal stress, prenatal famine, low birth weight, and premature cognitive decline. Both progeria and schizophrenia are associated with increased apoptosis and cell senescence, which could reduce the risk of cancer but result in premature aging along with age-related medical disorders that lead to mortality in the elderly.

This is why collaborative care between psychiatrists and primary care providers is so vital for patients with schizophrenia from the onset of the illness during the teens and young adulthood, not after years of treatment and unhealthy lifestyle habits (smoking, sedentary living, high-fat and high-calorie diet), which add insult to injury, culminating in loss of 25 to 30 years of potential life. Preventative medical care starting when schizophrenia is first diagnosed is vital, in addition to comprehensive psychiatric care, because premature mortality is the worst outcome in medicine.

Henry A. Nasrallah, MD

Editor-in-Chief

The dilemma of a diminishing workforce pool might seem more the province of medical school deans, psychiatry department chairs, and psychiatry residency training directors, but our ability to recruit and retain psychiatrists is, in reality, everyone’s concern—including hospitals, clinics, and, especially, patients and their families. Even without knowledge of the specialty or any numerical appraisal, for example, it is common knowledge that we have a dire shortage of child and adolescent and geriatric psychiatrists—a topic of widespread interest and great consequence for access to mental health care.

Tracking a decline

The very title of a recent provocative paper¹ in Health Affairs says it all: “Population of US practicing psychiatrists declined 2003-13, which may help explain poor access to mental health care.” In an elegant analysis, the authors expose (1) a 10% decline in the number of psychiatrists for every 100,000 people and (2) wide regional variability in the availability of psychiatrists. In stark contrast, the number of neurologists increased by >15% and the primary care workforce remained stable, with a 1.3% increase in the number of physicians, over the same 10 years.

At the beginning of the psychiatry workforce pipeline, the number of medical students who choose psychiatry remains both small (typically, slightly more than 4% of graduating students) and remarkably stable over time. Wilbanks et al,² in a thoughtful analysis of the 2011 to 2013 Medical School Graduation Questionnaire of the Association of American Medical Colleges, affirm and, in part, explain this consistent pattern. They note that the 4 most important considerations among students who select psychiatry are:

• personality fit
• specialty content
• work–life balance
• role model influences.

Some of these considerations also overlap with those of students in other specialties; the authors also note that older medical students and women are more likely to choose psychiatry.

Here is what we must do to erase the shortage

It does appear that, despite scientific advances in brain and behavior, expanding therapeutic options, and unique patient interactions that, taken together, should make a career in psychiatry exciting and appealing, there are simply not enough of us to meet the population’s mental health needs. This is a serious problem. It is our professional obligation—all of us—that we take on this shortage and develop solutions to it.

At its zenith, only about 7% of medical students chose psychiatry. We need to proactively prime the pump for our specialty by encouraging more observerships and promoting mental health careers through community outreach to high school students.

We must be diligent and effective mentors to medical students; mentorship is a powerful catalyst for career decision-making.

We need to make psychiatry clerkships exciting, to show off the best of what our specialty has to offer, and to cultivate sustained interest among our students in the brain and its psychiatric disorders.

We need to highlight the momentous advances in knowledge, biology, and treatments that now characterize our psychiatric profession. We need to advocate for more of these accomplishments.

We must be public stigma-busters! (Our patients need us to do this, too.)

And there is more to do:

Collaborate. In delivering psychiatric health care, we need to expand our effectiveness to achieve more collaboration, greater extension of effect, and broader outreach. Collaborative care has come of age as a delivery model; it should be embraced more broadly. We need to continue our efforts to bridge the many sister mental health disciplines—psychology, nursing, social work, counseling—that collectively provide mental health care.

Unite. Given the inadequate workforce numbers and enormous need, we will diminish ourselves by “guild infighting” and, consequently, weaken our legislative advocacy and leverage. We need to embrace and support all medical specialties and have them support us as well. We need to grow closer to primary care and support this specialty as the true front line of mental health. We also need to bridge the gap between addiction medicine and psychiatry, especially given the high level of addiction comorbidity in many psychiatric disorders.

Foster innovation. The deficit of psychiatric workers might be buffered by innovations in how we leverage our expertise. Telepsychiatry, for example, is clearly advancing, and brings psychiatry to remote areas where psychiatrists are scarce. Mobile health also has great potential for mental health. As one of us (H.A.N.) highlighted recently,³ as genetics become more molecular, what has been the potential of clinically applicable pharmacogenomics might become reality. Psychiatry needs to make progress toward personalized medicine because the disorders we treat are extremely heterogeneous in their etiology, phenomenology, treatment response, and outcomes.

The appeal of working with mind and brain

The extent to which we can convey unfettered optimism about the role of psychiatry in medicine and the relentless progress in neurobiological research, together, will go a long way toward attracting the best and brightest newly minted physicians to our specialty. The brain is the last frontier in medicine; psychiatry is intimately tethered to its unfolding complexity. With millennials placing a higher premium on work–life issues, the enviable balance and quality of life of a psychiatric career might now be particularly opportune, enhancing the quantity and quality of professionals that we can attract to psychiatry.
 

The dilemma of a diminishing workforce pool might seem more the province of medical school deans, psychiatry department chairs, and psychiatry residency training directors, but our ability to recruit and retain psychiatrists is, in reality, everyone’s concern—including hospitals, clinics, and, especially, patients and their families. Even without knowledge of the specialty or any numerical appraisal, for example, it is common knowledge that we have a dire shortage of child and adolescent and geriatric psychiatrists—a topic of widespread interest and great consequence for access to mental health care.

Tracking a decline

The very title of a recent provocative paper¹ in Health Affairs says it all: “Population of US practicing psychiatrists declined 2003-13, which may help explain poor access to mental health care.” In an elegant analysis, the authors expose (1) a 10% decline in the number of psychiatrists for every 100,000 people and (2) wide regional variability in the availability of psychiatrists. In stark contrast, the number of neurologists increased by >15% and the primary care workforce remained stable, with a 1.3% increase in the number of physicians, over the same 10 years.

At the beginning of the psychiatry workforce pipeline, the number of medical students who choose psychiatry remains both small (typically, slightly more than 4% of graduating students) and remarkably stable over time. Wilbanks et al,² in a thoughtful analysis of the 2011 to 2013 Medical School Graduation Questionnaire of the Association of American Medical Colleges, affirm and, in part, explain this consistent pattern. They note that the 4 most important considerations among students who select psychiatry are:

• personality fit
• specialty content
• work–life balance
• role model influences.

Some of these considerations also overlap with those of students in other specialties; the authors also note that older medical students and women are more likely to choose psychiatry.

Here is what we must do to erase the shortage

It does appear that, despite scientific advances in brain and behavior, expanding therapeutic options, and unique patient interactions that, taken together, should make a career in psychiatry exciting and appealing, there are simply not enough of us to meet the population’s mental health needs. This is a serious problem. It is our professional obligation—all of us—that we take on this shortage and develop solutions to it.

At its zenith, only about 7% of medical students chose psychiatry. We need to proactively prime the pump for our specialty by encouraging more observerships and promoting mental health careers through community outreach to high school students.

We must be diligent and effective mentors to medical students; mentorship is a powerful catalyst for career decision-making.

We need to make psychiatry clerkships exciting, to show off the best of what our specialty has to offer, and to cultivate sustained interest among our students in the brain and its psychiatric disorders.

We need to highlight the momentous advances in knowledge, biology, and treatments that now characterize our psychiatric profession. We need to advocate for more of these accomplishments.

We must be public stigma-busters! (Our patients need us to do this, too.)

And there is more to do:

Collaborate. In delivering psychiatric health care, we need to expand our effectiveness to achieve more collaboration, greater extension of effect, and broader outreach. Collaborative care has come of age as a delivery model; it should be embraced more broadly. We need to continue our efforts to bridge the many sister mental health disciplines—psychology, nursing, social work, counseling—that collectively provide mental health care.

Unite. Given the inadequate workforce numbers and enormous need, we will diminish ourselves by “guild infighting” and, consequently, weaken our legislative advocacy and leverage. We need to embrace and support all medical specialties and have them support us as well. We need to grow closer to primary care and support this specialty as the true front line of mental health. We also need to bridge the gap between addiction medicine and psychiatry, especially given the high level of addiction comorbidity in many psychiatric disorders.

Foster innovation. The deficit of psychiatric workers might be buffered by innovations in how we leverage our expertise. Telepsychiatry, for example, is clearly advancing, and brings psychiatry to remote areas where psychiatrists are scarce. Mobile health also has great potential for mental health. As one of us (H.A.N.) highlighted recently,³ as genetics become more molecular, what has been the potential of clinically applicable pharmacogenomics might become reality. Psychiatry needs to make progress toward personalized medicine because the disorders we treat are extremely heterogeneous in their etiology, phenomenology, treatment response, and outcomes.

The appeal of working with mind and brain

The extent to which we can convey unfettered optimism about the role of psychiatry in medicine and the relentless progress in neurobiological research, together, will go a long way toward attracting the best and brightest newly minted physicians to our specialty. The brain is the last frontier in medicine; psychiatry is intimately tethered to its unfolding complexity. With millennials placing a higher premium on work–life issues, the enviable balance and quality of life of a psychiatric career might now be particularly opportune, enhancing the quantity and quality of professionals that we can attract to psychiatry.
 

The dilemma of a diminishing workforce pool might seem more the province of medical school deans, psychiatry department chairs, and psychiatry residency training directors, but our ability to recruit and retain psychiatrists is, in reality, everyone’s concern—including hospitals, clinics, and, especially, patients and their families. Even without knowledge of the specialty or any numerical appraisal, for example, it is common knowledge that we have a dire shortage of child and adolescent and geriatric psychiatrists—a topic of widespread interest and great consequence for access to mental health care.

Tracking a decline

The very title of a recent provocative paper¹ in Health Affairs says it all: “Population of US practicing psychiatrists declined 2003-13, which may help explain poor access to mental health care.” In an elegant analysis, the authors expose (1) a 10% decline in the number of psychiatrists for every 100,000 people and (2) wide regional variability in the availability of psychiatrists. In stark contrast, the number of neurologists increased by >15% and the primary care workforce remained stable, with a 1.3% increase in the number of physicians, over the same 10 years.

At the beginning of the psychiatry workforce pipeline, the number of medical students who choose psychiatry remains both small (typically, slightly more than 4% of graduating students) and remarkably stable over time. Wilbanks et al,² in a thoughtful analysis of the 2011 to 2013 Medical School Graduation Questionnaire of the Association of American Medical Colleges, affirm and, in part, explain this consistent pattern. They note that the 4 most important considerations among students who select psychiatry are:

• personality fit
• specialty content
• work–life balance
• role model influences.

Some of these considerations also overlap with those of students in other specialties; the authors also note that older medical students and women are more likely to choose psychiatry.

Here is what we must do to erase the shortage

It does appear that, despite scientific advances in brain and behavior, expanding therapeutic options, and unique patient interactions that, taken together, should make a career in psychiatry exciting and appealing, there are simply not enough of us to meet the population’s mental health needs. This is a serious problem. It is our professional obligation—all of us—that we take on this shortage and develop solutions to it.

At its zenith, only about 7% of medical students chose psychiatry. We need to proactively prime the pump for our specialty by encouraging more observerships and promoting mental health careers through community outreach to high school students.

We must be diligent and effective mentors to medical students; mentorship is a powerful catalyst for career decision-making.

We need to make psychiatry clerkships exciting, to show off the best of what our specialty has to offer, and to cultivate sustained interest among our students in the brain and its psychiatric disorders.

We need to highlight the momentous advances in knowledge, biology, and treatments that now characterize our psychiatric profession. We need to advocate for more of these accomplishments.

We must be public stigma-busters! (Our patients need us to do this, too.)

And there is more to do:

Collaborate. In delivering psychiatric health care, we need to expand our effectiveness to achieve more collaboration, greater extension of effect, and broader outreach. Collaborative care has come of age as a delivery model; it should be embraced more broadly. We need to continue our efforts to bridge the many sister mental health disciplines—psychology, nursing, social work, counseling—that collectively provide mental health care.

Unite. Given the inadequate workforce numbers and enormous need, we will diminish ourselves by “guild infighting” and, consequently, weaken our legislative advocacy and leverage. We need to embrace and support all medical specialties and have them support us as well. We need to grow closer to primary care and support this specialty as the true front line of mental health. We also need to bridge the gap between addiction medicine and psychiatry, especially given the high level of addiction comorbidity in many psychiatric disorders.

Foster innovation. The deficit of psychiatric workers might be buffered by innovations in how we leverage our expertise. Telepsychiatry, for example, is clearly advancing, and brings psychiatry to remote areas where psychiatrists are scarce. Mobile health also has great potential for mental health. As one of us (H.A.N.) highlighted recently,³ as genetics become more molecular, what has been the potential of clinically applicable pharmacogenomics might become reality. Psychiatry needs to make progress toward personalized medicine because the disorders we treat are extremely heterogeneous in their etiology, phenomenology, treatment response, and outcomes.

The appeal of working with mind and brain

The extent to which we can convey unfettered optimism about the role of psychiatry in medicine and the relentless progress in neurobiological research, together, will go a long way toward attracting the best and brightest newly minted physicians to our specialty. The brain is the last frontier in medicine; psychiatry is intimately tethered to its unfolding complexity. With millennials placing a higher premium on work–life issues, the enviable balance and quality of life of a psychiatric career might now be particularly opportune, enhancing the quantity and quality of professionals that we can attract to psychiatry.
 

But many of our own questions await an answer. The fact is that psychiatrists have serious, nagging questions—in every cortical fold of their collective brain—about patients’ welfare, psychiatric practice, and professional matters. Their questions about frustrations of daily practice deserve an honest and convincing response, yet go begging—expressed so well in songwriter Bob Dylan’s lyric, “The answer is blowin’ in the wind.”

What follows are long-standing “Why?” questions whose answers are still blowin’ in the wind. (Dylan didn’t specify which wind is blowin’, so I’ve provided the names of 22 atmospheric movements of air molecules in the Box. Take your pick!)

Why is a jail OK for the mentally ill but an asylum is not? Why is it necessary to put armed guards in charge of psychiatric patients instead of a multi­disciplinary team of psychiatrists, primary care providers, nurses, social workers, psychologists, and pharmacists? Why has a brain disease, such as psychosis or bipolar disorder, become a punishable felony instead of a treatable illness?

Why did the system of mental health care degenerate to the point that a severely depressed or suicidal, or acutely psychotic, patient can be hospitalized for only 4 or 5 days, then must be discharged before her (his) illness has been fully controlled? Why do health care insurers exhibit that atrocious combination of maximum greed and minimal compassion?

Why does a completely unjustified and hurtful stigma continue to plague mental brain disorders, patients who suffer from them, mental health professionals, and the very discipline of psychiatry?

Why do otherwise intelligent people show compassion toward people with a brain disorder such as stroke, Parkinson’s disease, multiple sclerosis, myasthenia gravis, or migraine, but express aversion and even disdain for psychiatric brain disorders such as schizophrenia, depression, obsessive-compulsive disorder, and panic disorder?

And why does this prejudice persist despite advances in psychiatric neuroscience that have used neurogenetics, neuroimaging, and molecular studies to establish, without a doubt, the neurobiological basis of all psychiatric disorders.

Why are there still no objective diagnostic criteria for psychiatric disorders? Why do we persist in using defining symptoms that have been volunteered by patients—symptoms that can be subject to distortion or malingering? Why aren’t the hundreds of established biomarkers being incorporated into the diagnostic formulation, to lessen subjectivity and improve reliability and validity?

Why is off-label prescribing, the judicious clinical repurposing of psychotropic medications, criticized and panned, even though there are no approved drugs for 88.5% psychiatric diagnoses?¹ Why allow insurers to refuse to pay for a medication that can help a patient, just because the patient has not been given the “official” diagnosis for which the FDA approved that drug?

And why doesn’t the FDA solve this problem by revising its requirements that registration trials for new medications test their efficacy for a single symptom, rather than a diagnosis comprising multiple symptoms?

Why do people not accept the fact that all drugs have benefits and risks, and that it is impossible to have pure efficacy without side effects? Why empower lawyers to make clinical care adversarial? Why do lawyers refrain from suing oncologists or manufacturers of life-saving chemotherapy drugs because of terrible adverse effects, but pounce on other medications that might cause a serious side effect in a tiny percentage of patients that is clearly spelled out in the package insert?

Why do people demonize the pharmaceutical industry far more than other industries? No other entity discovers and develops life-saving medications.

Why don’t people realize that, without medications, massive numbers of patients would be hospitalized and the death rate would rise? Why can’t people weigh risks and benefits of having a pharmaceutical industry, just as they assess the risk-benefit ratio of everything in life?

Should the government impose a massive ($1 or $2 trillion) tax hike to establish infrastructure for drug research and development, for the benefit of psychiatry and all other medical specialties?

Why is there a severe shortage of psychiatrists but a glut of lawyers? Why doesn’t society rationally deploy its resources to meet urgent social needs and priorities? And why do lawyers bill us for every minute we talk to them, while we field telephone calls and e-mail messages from patients without compensation?

Why did the FDA allow the pharmaceutical industry to develop direct-to-consumer advertising? Why do they not realize how that decision has complicated the doctor–patient relationship, and how it preempts physicians’ evidence-based decision-making by encouraging consumers to demand a drug that they saw on television—a contorted version of prescribing by proxy?

Why (speaking of prescribing without a license), do politicians pass laws allowing people who do not have required medical training to take a short-cut to becoming a prescriber? Why not mandate that politicians, and their families, receive medical care exclusively from unqualified practitioners on whom they bestow prescribing privileges without requisite comprehensive medical training?Why do some psychiatrists resist changing their practice patterns despite continuous advances that update the care they provide? Why do reports of exciting therapeutic breakthroughs, published in top-tier journals, go unread by so many practitioners? Why do they say they are too busy to read journals or peruse PubMed?

Why don’t people realize that today’s research is tomorrow’s treatment? That research is not a luxury but an ongoing necessity? Why don’t more freshly minted, young psychiatrists pursue a career in research to accelerate the pace of progress about the biological causes and treatments of serious psychiatric disorders? Why aren’t there more incentives to grow the next generation of psychiatric discoverers and Nobel laureates? Why don’t clinicians support research by referring patients to clinical trials of medications or to National Institutes of Health-funded investigations of the neurobiology of psychiatric disorders?

Are these just rhetorical questions?
Some might sound that way. But they are not. These questions are brewing inside the hearts and minds of many psychiatrists, although only a few seem determined to relentlessly seek answers on which medical science and society can act.

We should collectively pose these “why” questions and not accept long-winded, hollow answers. We need to foster the winds of change—not resign ourselves to winds in which answers blow about but, ultimately, disappear.

But many of our own questions await an answer. The fact is that psychiatrists have serious, nagging questions—in every cortical fold of their collective brain—about patients’ welfare, psychiatric practice, and professional matters. Their questions about frustrations of daily practice deserve an honest and convincing response, yet go begging—expressed so well in songwriter Bob Dylan’s lyric, “The answer is blowin’ in the wind.”

What follows are long-standing “Why?” questions whose answers are still blowin’ in the wind. (Dylan didn’t specify which wind is blowin’, so I’ve provided the names of 22 atmospheric movements of air molecules in the Box. Take your pick!)

Why is a jail OK for the mentally ill but an asylum is not? Why is it necessary to put armed guards in charge of psychiatric patients instead of a multi­disciplinary team of psychiatrists, primary care providers, nurses, social workers, psychologists, and pharmacists? Why has a brain disease, such as psychosis or bipolar disorder, become a punishable felony instead of a treatable illness?

Why did the system of mental health care degenerate to the point that a severely depressed or suicidal, or acutely psychotic, patient can be hospitalized for only 4 or 5 days, then must be discharged before her (his) illness has been fully controlled? Why do health care insurers exhibit that atrocious combination of maximum greed and minimal compassion?

Why does a completely unjustified and hurtful stigma continue to plague mental brain disorders, patients who suffer from them, mental health professionals, and the very discipline of psychiatry?

Why do otherwise intelligent people show compassion toward people with a brain disorder such as stroke, Parkinson’s disease, multiple sclerosis, myasthenia gravis, or migraine, but express aversion and even disdain for psychiatric brain disorders such as schizophrenia, depression, obsessive-compulsive disorder, and panic disorder?

And why does this prejudice persist despite advances in psychiatric neuroscience that have used neurogenetics, neuroimaging, and molecular studies to establish, without a doubt, the neurobiological basis of all psychiatric disorders.

Why are there still no objective diagnostic criteria for psychiatric disorders? Why do we persist in using defining symptoms that have been volunteered by patients—symptoms that can be subject to distortion or malingering? Why aren’t the hundreds of established biomarkers being incorporated into the diagnostic formulation, to lessen subjectivity and improve reliability and validity?

Why is off-label prescribing, the judicious clinical repurposing of psychotropic medications, criticized and panned, even though there are no approved drugs for 88.5% psychiatric diagnoses?¹ Why allow insurers to refuse to pay for a medication that can help a patient, just because the patient has not been given the “official” diagnosis for which the FDA approved that drug?

And why doesn’t the FDA solve this problem by revising its requirements that registration trials for new medications test their efficacy for a single symptom, rather than a diagnosis comprising multiple symptoms?

Why do people not accept the fact that all drugs have benefits and risks, and that it is impossible to have pure efficacy without side effects? Why empower lawyers to make clinical care adversarial? Why do lawyers refrain from suing oncologists or manufacturers of life-saving chemotherapy drugs because of terrible adverse effects, but pounce on other medications that might cause a serious side effect in a tiny percentage of patients that is clearly spelled out in the package insert?

Why do people demonize the pharmaceutical industry far more than other industries? No other entity discovers and develops life-saving medications.

Why don’t people realize that, without medications, massive numbers of patients would be hospitalized and the death rate would rise? Why can’t people weigh risks and benefits of having a pharmaceutical industry, just as they assess the risk-benefit ratio of everything in life?

Should the government impose a massive ($1 or $2 trillion) tax hike to establish infrastructure for drug research and development, for the benefit of psychiatry and all other medical specialties?

Why is there a severe shortage of psychiatrists but a glut of lawyers? Why doesn’t society rationally deploy its resources to meet urgent social needs and priorities? And why do lawyers bill us for every minute we talk to them, while we field telephone calls and e-mail messages from patients without compensation?

Why did the FDA allow the pharmaceutical industry to develop direct-to-consumer advertising? Why do they not realize how that decision has complicated the doctor–patient relationship, and how it preempts physicians’ evidence-based decision-making by encouraging consumers to demand a drug that they saw on television—a contorted version of prescribing by proxy?

Why (speaking of prescribing without a license), do politicians pass laws allowing people who do not have required medical training to take a short-cut to becoming a prescriber? Why not mandate that politicians, and their families, receive medical care exclusively from unqualified practitioners on whom they bestow prescribing privileges without requisite comprehensive medical training?Why do some psychiatrists resist changing their practice patterns despite continuous advances that update the care they provide? Why do reports of exciting therapeutic breakthroughs, published in top-tier journals, go unread by so many practitioners? Why do they say they are too busy to read journals or peruse PubMed?

Why don’t people realize that today’s research is tomorrow’s treatment? That research is not a luxury but an ongoing necessity? Why don’t more freshly minted, young psychiatrists pursue a career in research to accelerate the pace of progress about the biological causes and treatments of serious psychiatric disorders? Why aren’t there more incentives to grow the next generation of psychiatric discoverers and Nobel laureates? Why don’t clinicians support research by referring patients to clinical trials of medications or to National Institutes of Health-funded investigations of the neurobiology of psychiatric disorders?

Are these just rhetorical questions?
Some might sound that way. But they are not. These questions are brewing inside the hearts and minds of many psychiatrists, although only a few seem determined to relentlessly seek answers on which medical science and society can act.

We should collectively pose these “why” questions and not accept long-winded, hollow answers. We need to foster the winds of change—not resign ourselves to winds in which answers blow about but, ultimately, disappear.

But many of our own questions await an answer. The fact is that psychiatrists have serious, nagging questions—in every cortical fold of their collective brain—about patients’ welfare, psychiatric practice, and professional matters. Their questions about frustrations of daily practice deserve an honest and convincing response, yet go begging—expressed so well in songwriter Bob Dylan’s lyric, “The answer is blowin’ in the wind.”

What follows are long-standing “Why?” questions whose answers are still blowin’ in the wind. (Dylan didn’t specify which wind is blowin’, so I’ve provided the names of 22 atmospheric movements of air molecules in the Box. Take your pick!)

Why is a jail OK for the mentally ill but an asylum is not? Why is it necessary to put armed guards in charge of psychiatric patients instead of a multi­disciplinary team of psychiatrists, primary care providers, nurses, social workers, psychologists, and pharmacists? Why has a brain disease, such as psychosis or bipolar disorder, become a punishable felony instead of a treatable illness?

Why did the system of mental health care degenerate to the point that a severely depressed or suicidal, or acutely psychotic, patient can be hospitalized for only 4 or 5 days, then must be discharged before her (his) illness has been fully controlled? Why do health care insurers exhibit that atrocious combination of maximum greed and minimal compassion?

Why does a completely unjustified and hurtful stigma continue to plague mental brain disorders, patients who suffer from them, mental health professionals, and the very discipline of psychiatry?

Why do otherwise intelligent people show compassion toward people with a brain disorder such as stroke, Parkinson’s disease, multiple sclerosis, myasthenia gravis, or migraine, but express aversion and even disdain for psychiatric brain disorders such as schizophrenia, depression, obsessive-compulsive disorder, and panic disorder?

And why does this prejudice persist despite advances in psychiatric neuroscience that have used neurogenetics, neuroimaging, and molecular studies to establish, without a doubt, the neurobiological basis of all psychiatric disorders.

Why are there still no objective diagnostic criteria for psychiatric disorders? Why do we persist in using defining symptoms that have been volunteered by patients—symptoms that can be subject to distortion or malingering? Why aren’t the hundreds of established biomarkers being incorporated into the diagnostic formulation, to lessen subjectivity and improve reliability and validity?

Why is off-label prescribing, the judicious clinical repurposing of psychotropic medications, criticized and panned, even though there are no approved drugs for 88.5% psychiatric diagnoses?¹ Why allow insurers to refuse to pay for a medication that can help a patient, just because the patient has not been given the “official” diagnosis for which the FDA approved that drug?

And why doesn’t the FDA solve this problem by revising its requirements that registration trials for new medications test their efficacy for a single symptom, rather than a diagnosis comprising multiple symptoms?

Why do people not accept the fact that all drugs have benefits and risks, and that it is impossible to have pure efficacy without side effects? Why empower lawyers to make clinical care adversarial? Why do lawyers refrain from suing oncologists or manufacturers of life-saving chemotherapy drugs because of terrible adverse effects, but pounce on other medications that might cause a serious side effect in a tiny percentage of patients that is clearly spelled out in the package insert?

Why do people demonize the pharmaceutical industry far more than other industries? No other entity discovers and develops life-saving medications.

Why don’t people realize that, without medications, massive numbers of patients would be hospitalized and the death rate would rise? Why can’t people weigh risks and benefits of having a pharmaceutical industry, just as they assess the risk-benefit ratio of everything in life?

Should the government impose a massive ($1 or $2 trillion) tax hike to establish infrastructure for drug research and development, for the benefit of psychiatry and all other medical specialties?

Why is there a severe shortage of psychiatrists but a glut of lawyers? Why doesn’t society rationally deploy its resources to meet urgent social needs and priorities? And why do lawyers bill us for every minute we talk to them, while we field telephone calls and e-mail messages from patients without compensation?

Why did the FDA allow the pharmaceutical industry to develop direct-to-consumer advertising? Why do they not realize how that decision has complicated the doctor–patient relationship, and how it preempts physicians’ evidence-based decision-making by encouraging consumers to demand a drug that they saw on television—a contorted version of prescribing by proxy?

Why (speaking of prescribing without a license), do politicians pass laws allowing people who do not have required medical training to take a short-cut to becoming a prescriber? Why not mandate that politicians, and their families, receive medical care exclusively from unqualified practitioners on whom they bestow prescribing privileges without requisite comprehensive medical training?Why do some psychiatrists resist changing their practice patterns despite continuous advances that update the care they provide? Why do reports of exciting therapeutic breakthroughs, published in top-tier journals, go unread by so many practitioners? Why do they say they are too busy to read journals or peruse PubMed?

Why don’t people realize that today’s research is tomorrow’s treatment? That research is not a luxury but an ongoing necessity? Why don’t more freshly minted, young psychiatrists pursue a career in research to accelerate the pace of progress about the biological causes and treatments of serious psychiatric disorders? Why aren’t there more incentives to grow the next generation of psychiatric discoverers and Nobel laureates? Why don’t clinicians support research by referring patients to clinical trials of medications or to National Institutes of Health-funded investigations of the neurobiology of psychiatric disorders?

Are these just rhetorical questions?
Some might sound that way. But they are not. These questions are brewing inside the hearts and minds of many psychiatrists, although only a few seem determined to relentlessly seek answers on which medical science and society can act.

We should collectively pose these “why” questions and not accept long-winded, hollow answers. We need to foster the winds of change—not resign ourselves to winds in which answers blow about but, ultimately, disappear.

A day in the psychiatry clinic? No—just scenes from that high-stakes festival of intense human competitiveness gone awry: the current presidential election. Alas, we have no FDA-approved treatments for any of these unusual political behaviors.

More stunning is how blind some loyal voters are to the flaws of their candidate of choice. They seem to be joyfully intoxicated by sharing the unusual beliefs of the candidate, in a cultish folie en masse of epidemic proportion.

Other (rational) voters are stunned and jarred by what they see and hear; they appear to be in need of Rx: an intellectual antiemetic.

The rise of uber-narcissism
A certain amount of narcissism is, understandably, necessary to run for the nation’s highest office and to believe, against all odds, that winning is certain despite microscopic favorability in the polls. In this election cycle, the cup of narcissism has run over; yet, to adoring fans, narcissism only adds a wondrous halo to their candidate.

The history of the United States is rife with similar behavior by elected officials, including our revered Founding Fathers.¹ But today’s psychiatrists, witnessing this national charade, are perplexed and question the rationality of the national psyche. Established rules for seeking the Presidency have been demolished and the show goes on as if heightened narcissism is the new normal in human behavior.

Giving voice to my colleagues’ consternation
Here are a few thoughts that might cross the mind of psychiatrists as they watch, with a frown and pursed lips, this unconventional election cycle:

From a psychoanalytic perspective, the id has left the ego in its dust, and the super-ego went home to hide.

When boorishness trumps civility, hillaryous consequences ensue.

The gullibility of voters deserves serious scientific study. Jeste and Harris² reviewed the evidence for a neurobiology of wisdom; The National Institutes of Health should fund research into how some voters believe the candidate of their choice will provide them with everything they wish. The chicken in every pot expands to 100 in every pot, and money grows on trees (at least on 1% of the forest!).

From an evolutionary standpoint, survival of the fittest has become survival of the most bombastic.

The zeitgeist reflects an electorate that oscillates agonizingly from surprise to anger to cynicism to disgust.

The traditional internal conflict (studied by political scientists) of choosing between 2 reasonably meritorious candidates has been transformed into a conflict over whether to vote at all.

This is the least nuanced presidential campaign—ever.

All decision-making in politics is unconscious, political scientist Jon A. Krosnick proposed. In this election, however, candidates’ enunciations are so overt that it’s hard to believe there’s anything left in the unconscious. Freud spoke of the “primary process” arising from the unconscious; he definitely was not referring to the primary process we experienced during this election cycle.

From a neuropsychiatric perspective, the limbic system has kicked the cortex in the metaphorical derrière in this election campaign.

Unabashed display of character flaws, personal shortcomings, and biases prove that anyone can run for president in a democracy, and that some voters will display a flight of reason and vote for a flawed candidate.

Even an inept demagogue can be misperceived as a savior by followers. Some voters could use a few sessions of insight-oriented therapy or cognitive-behavioral therapy for their unrealistic expectations.

It is dizzying, mentally, to watch candidates’ verbal acrobatics as they try to pass several litmus tests to satisfy disparate demands of sundry constituencies and mendaciously flip-flop on many issues—ignoring the fact that everything they have said was recorded or videotaped. Intellectual transvestism is a political sin, and sinners abound.

Oh, for a Jenner, Pasteur, or Sabin to discover vaccines for the intellect
Writing this editorial has been therapeutic. It feels good to ventilate about this bizarre election process that has the nation in its grip. I would feel much better if neuroscientists would develop and license vaccines that would broadly inoculate candidates against demagoguery, dishonesty, and pandering and voters against mind-boggling gullibility.

That would make elections so boring. But also so on-label….

A day in the psychiatry clinic? No—just scenes from that high-stakes festival of intense human competitiveness gone awry: the current presidential election. Alas, we have no FDA-approved treatments for any of these unusual political behaviors.

More stunning is how blind some loyal voters are to the flaws of their candidate of choice. They seem to be joyfully intoxicated by sharing the unusual beliefs of the candidate, in a cultish folie en masse of epidemic proportion.

Other (rational) voters are stunned and jarred by what they see and hear; they appear to be in need of Rx: an intellectual antiemetic.

The rise of uber-narcissism
A certain amount of narcissism is, understandably, necessary to run for the nation’s highest office and to believe, against all odds, that winning is certain despite microscopic favorability in the polls. In this election cycle, the cup of narcissism has run over; yet, to adoring fans, narcissism only adds a wondrous halo to their candidate.

The history of the United States is rife with similar behavior by elected officials, including our revered Founding Fathers.¹ But today’s psychiatrists, witnessing this national charade, are perplexed and question the rationality of the national psyche. Established rules for seeking the Presidency have been demolished and the show goes on as if heightened narcissism is the new normal in human behavior.

Giving voice to my colleagues’ consternation
Here are a few thoughts that might cross the mind of psychiatrists as they watch, with a frown and pursed lips, this unconventional election cycle:

From a psychoanalytic perspective, the id has left the ego in its dust, and the super-ego went home to hide.

When boorishness trumps civility, hillaryous consequences ensue.

The gullibility of voters deserves serious scientific study. Jeste and Harris² reviewed the evidence for a neurobiology of wisdom; The National Institutes of Health should fund research into how some voters believe the candidate of their choice will provide them with everything they wish. The chicken in every pot expands to 100 in every pot, and money grows on trees (at least on 1% of the forest!).

From an evolutionary standpoint, survival of the fittest has become survival of the most bombastic.

The zeitgeist reflects an electorate that oscillates agonizingly from surprise to anger to cynicism to disgust.

The traditional internal conflict (studied by political scientists) of choosing between 2 reasonably meritorious candidates has been transformed into a conflict over whether to vote at all.

This is the least nuanced presidential campaign—ever.

All decision-making in politics is unconscious, political scientist Jon A. Krosnick proposed. In this election, however, candidates’ enunciations are so overt that it’s hard to believe there’s anything left in the unconscious. Freud spoke of the “primary process” arising from the unconscious; he definitely was not referring to the primary process we experienced during this election cycle.

From a neuropsychiatric perspective, the limbic system has kicked the cortex in the metaphorical derrière in this election campaign.

Unabashed display of character flaws, personal shortcomings, and biases prove that anyone can run for president in a democracy, and that some voters will display a flight of reason and vote for a flawed candidate.

Even an inept demagogue can be misperceived as a savior by followers. Some voters could use a few sessions of insight-oriented therapy or cognitive-behavioral therapy for their unrealistic expectations.

It is dizzying, mentally, to watch candidates’ verbal acrobatics as they try to pass several litmus tests to satisfy disparate demands of sundry constituencies and mendaciously flip-flop on many issues—ignoring the fact that everything they have said was recorded or videotaped. Intellectual transvestism is a political sin, and sinners abound.

Oh, for a Jenner, Pasteur, or Sabin to discover vaccines for the intellect
Writing this editorial has been therapeutic. It feels good to ventilate about this bizarre election process that has the nation in its grip. I would feel much better if neuroscientists would develop and license vaccines that would broadly inoculate candidates against demagoguery, dishonesty, and pandering and voters against mind-boggling gullibility.

That would make elections so boring. But also so on-label….

A day in the psychiatry clinic? No—just scenes from that high-stakes festival of intense human competitiveness gone awry: the current presidential election. Alas, we have no FDA-approved treatments for any of these unusual political behaviors.

More stunning is how blind some loyal voters are to the flaws of their candidate of choice. They seem to be joyfully intoxicated by sharing the unusual beliefs of the candidate, in a cultish folie en masse of epidemic proportion.

Other (rational) voters are stunned and jarred by what they see and hear; they appear to be in need of Rx: an intellectual antiemetic.

The rise of uber-narcissism
A certain amount of narcissism is, understandably, necessary to run for the nation’s highest office and to believe, against all odds, that winning is certain despite microscopic favorability in the polls. In this election cycle, the cup of narcissism has run over; yet, to adoring fans, narcissism only adds a wondrous halo to their candidate.

The history of the United States is rife with similar behavior by elected officials, including our revered Founding Fathers.¹ But today’s psychiatrists, witnessing this national charade, are perplexed and question the rationality of the national psyche. Established rules for seeking the Presidency have been demolished and the show goes on as if heightened narcissism is the new normal in human behavior.

Giving voice to my colleagues’ consternation
Here are a few thoughts that might cross the mind of psychiatrists as they watch, with a frown and pursed lips, this unconventional election cycle:

From a psychoanalytic perspective, the id has left the ego in its dust, and the super-ego went home to hide.

When boorishness trumps civility, hillaryous consequences ensue.

The gullibility of voters deserves serious scientific study. Jeste and Harris² reviewed the evidence for a neurobiology of wisdom; The National Institutes of Health should fund research into how some voters believe the candidate of their choice will provide them with everything they wish. The chicken in every pot expands to 100 in every pot, and money grows on trees (at least on 1% of the forest!).

From an evolutionary standpoint, survival of the fittest has become survival of the most bombastic.

The zeitgeist reflects an electorate that oscillates agonizingly from surprise to anger to cynicism to disgust.

The traditional internal conflict (studied by political scientists) of choosing between 2 reasonably meritorious candidates has been transformed into a conflict over whether to vote at all.

This is the least nuanced presidential campaign—ever.

All decision-making in politics is unconscious, political scientist Jon A. Krosnick proposed. In this election, however, candidates’ enunciations are so overt that it’s hard to believe there’s anything left in the unconscious. Freud spoke of the “primary process” arising from the unconscious; he definitely was not referring to the primary process we experienced during this election cycle.

From a neuropsychiatric perspective, the limbic system has kicked the cortex in the metaphorical derrière in this election campaign.

Unabashed display of character flaws, personal shortcomings, and biases prove that anyone can run for president in a democracy, and that some voters will display a flight of reason and vote for a flawed candidate.

Even an inept demagogue can be misperceived as a savior by followers. Some voters could use a few sessions of insight-oriented therapy or cognitive-behavioral therapy for their unrealistic expectations.

It is dizzying, mentally, to watch candidates’ verbal acrobatics as they try to pass several litmus tests to satisfy disparate demands of sundry constituencies and mendaciously flip-flop on many issues—ignoring the fact that everything they have said was recorded or videotaped. Intellectual transvestism is a political sin, and sinners abound.

Oh, for a Jenner, Pasteur, or Sabin to discover vaccines for the intellect
Writing this editorial has been therapeutic. It feels good to ventilate about this bizarre election process that has the nation in its grip. I would feel much better if neuroscientists would develop and license vaccines that would broadly inoculate candidates against demagoguery, dishonesty, and pandering and voters against mind-boggling gullibility.

That would make elections so boring. But also so on-label….

What if this increase had occurred in cardiovascular disease or cancer (both on the decline, in fact, thanks to the intense attention they receive)? I think there would have been a public outcry, followed by demands by Congress that the National Institutes of Health and the CDC address this catastrophic rise immediately. And billions of dollars would then be earmarked to prevent these 2 diseases. 

How sad that society has “forgotten” that mental illness has deadly consequences, often leading to suicide (42,773 deaths in 2014 alone²—the second most common cause among people age 15 to 25³)! Hundreds of thousands of people attempt suicide every year, and those who do not lose their life often end up injured or maimed. Millions who suffer depression, bipolar disorder, schizophrenia, anxiety, posttraumatic stress disorder, or a substance use disorder are at high risk of suicide, and many never receive the timely intervention that might save their life.

Our national blind spot
It is poignant that the CDC report was released in spring: The rate of suicide is highest in April and May, when the light-dark cycle is reversed. This springtime peak runs contrary to the common belief that the rate of suicide is highest during winter months. The Annual Meeting of the American Psychiatric Association convenes in May, such that, ironically, thousands of psychiatrists are away from their office exactly when their patients might need them most

Lack of attention to the high risk of suicide among all ages and both sexes is emblematic of society’s inexplicable neglect of the needs of the mentally ill. That neglect is fueled, and exacerbated, by the destructive stigma attached to brain disorders that display psychiatric symptoms. As a neuropsychiatrist, I label this neglect societal anosognosia—the same as the lack of insight seen in patients with acute schizophrenia, who are unaware of how impaired they are and insist that they are not sick. (Anosognosia also occurs in stroke patients who deny that their limb is paralyzed and insist that all is well.)

Loss of insight can have serious consequences for patients who lose the ability to monitor and evaluate their physical and mental health. Just as patients with anosognosia think they do not need help, a society that fails to attend to the mental illness of its citizens endangers their overall health and welfare.

From neglect of mental illness many hazards arise
Tens of millions of Americans suffer from mental illness, according to the National Institute of Mental Health-sponsored Epidemiologic Catchment Area Study.⁴ The last thing these people can afford is societal anosognosia, which deprives them of necessary and timely access to psychiatric care.

Societal anosognosia is associated with numerous hazards for persons with mental illness, including:

• Lack of compassion, which is readily available for people with a medical ailment (broken bones, cardiovascular disease, cancer).
• Lack of adequate, affordable health insurance and financial support, compared with what is available for non-psychiatric disorders.
• Shortage of publicly funded programs and mental health practitioners to provide prevention and intervention for those who consider ending their life during an episode of depression, psychosis, stress, or a panic attack.
• Allowing the stigma to continue unabated. Why are there strict laws about hate crimes, but not about stigma? Why does society continue to portray depression and anxiety as a personal weakness or failure, while patients with Parkinson’s disease or multiple sclerosis who have motor weakness are not stigmatized for their physical deficits?
• Transforming the seriously mentally ill into felons by arresting and jailing them because of erratic behavior—instead of hospitalizing them for the medical care they need. The trans­institutionalization of the mentally ill—from state hospitals to prisons—is one of the most shameful consequences of societal anosognosia, burdening our patients with the dual stigma of being a criminal and mentally ill.
• Turning a blind eye to abuses by insurance companies. More appalling is the perpetuation of restricted health coverage despite the passage of parity laws! Why are sensory and motor disorders of brain lesions covered fully, while the thought, emotional, and behavior disorders of the brain covered only partially?
• Consent laws that restrict psychiatrists from medicating acutely psychotic or depressed patients unless they consent—but no laws that restrict a cardiologist from immediately treating an unconscious heart attack patient who cannot consent, or an obtunded stroke patient who cannot communicate? The duration of untreated psychosis or depression has been shown repeatedly to have deleterious effects on brain tissue and functional outcomes, yet treatment of an acutely ill psychiatric patient is often delayed until a court order is obtained. When was the last time a court order was needed to treat an acute myocardial infarction?
• Failure to recognize that premature mortality (by approximately 25 years) is a devastating consequence of mental illness, whether from suicide or cardiometabolic risk factors due to smoking, substance use (often used to self-medicate because proper treatment is lacking), poor diet, and sedentary living.
• Failure to provide basic primary care to people with severe mental illness, and the much lower use of life-saving diagnostic and treatment procedures offered to these patients, compared with non-psychiatric patients.
• Inadequate funding for research on psychiatric disorders, compared with other medical disorders—even though direct and indirect costs of mental illness to society (hundreds of billions of dollars a year) far exceed costs of most medical disorders.
• Severe shortage of rehabilitation programs for the mentally ill, compared with many other medical disorders. Why does paralysis of the mind receive far less support than paralysis of the legs or arms? 

The rising suicide rate reflects poorly on us
Societal anosognosia is a global scourge, affecting many underdeveloped countries. Why do developed nations, like ours, have the same blind spot for mental illness? Might ignorance and discrimination be universal?

The tragic rise in the rate of death by suicide in men and women, among all age groups, year after year, is stunningly incongruent when juxtaposed against the elimination of smallpox and other communicable diseases through a concerted societal effort to support scientific advances in vaccine development. Societal anosognosia appears to be selective: We have comprehensive insight about diseases of the body but not diseases of the mind.

The essence and soul of a society are the collective minds of its citizens, not their bodies. Societal anosognosia is a serious dysfunction of its mind, and a rising suicide rate is a symptom of that pathological dysfunction.

What if this increase had occurred in cardiovascular disease or cancer (both on the decline, in fact, thanks to the intense attention they receive)? I think there would have been a public outcry, followed by demands by Congress that the National Institutes of Health and the CDC address this catastrophic rise immediately. And billions of dollars would then be earmarked to prevent these 2 diseases. 

How sad that society has “forgotten” that mental illness has deadly consequences, often leading to suicide (42,773 deaths in 2014 alone²—the second most common cause among people age 15 to 25³)! Hundreds of thousands of people attempt suicide every year, and those who do not lose their life often end up injured or maimed. Millions who suffer depression, bipolar disorder, schizophrenia, anxiety, posttraumatic stress disorder, or a substance use disorder are at high risk of suicide, and many never receive the timely intervention that might save their life.

Our national blind spot
It is poignant that the CDC report was released in spring: The rate of suicide is highest in April and May, when the light-dark cycle is reversed. This springtime peak runs contrary to the common belief that the rate of suicide is highest during winter months. The Annual Meeting of the American Psychiatric Association convenes in May, such that, ironically, thousands of psychiatrists are away from their office exactly when their patients might need them most

Lack of attention to the high risk of suicide among all ages and both sexes is emblematic of society’s inexplicable neglect of the needs of the mentally ill. That neglect is fueled, and exacerbated, by the destructive stigma attached to brain disorders that display psychiatric symptoms. As a neuropsychiatrist, I label this neglect societal anosognosia—the same as the lack of insight seen in patients with acute schizophrenia, who are unaware of how impaired they are and insist that they are not sick. (Anosognosia also occurs in stroke patients who deny that their limb is paralyzed and insist that all is well.)

Loss of insight can have serious consequences for patients who lose the ability to monitor and evaluate their physical and mental health. Just as patients with anosognosia think they do not need help, a society that fails to attend to the mental illness of its citizens endangers their overall health and welfare.

From neglect of mental illness many hazards arise
Tens of millions of Americans suffer from mental illness, according to the National Institute of Mental Health-sponsored Epidemiologic Catchment Area Study.⁴ The last thing these people can afford is societal anosognosia, which deprives them of necessary and timely access to psychiatric care.

Societal anosognosia is associated with numerous hazards for persons with mental illness, including:

• Lack of compassion, which is readily available for people with a medical ailment (broken bones, cardiovascular disease, cancer).
• Lack of adequate, affordable health insurance and financial support, compared with what is available for non-psychiatric disorders.
• Shortage of publicly funded programs and mental health practitioners to provide prevention and intervention for those who consider ending their life during an episode of depression, psychosis, stress, or a panic attack.
• Allowing the stigma to continue unabated. Why are there strict laws about hate crimes, but not about stigma? Why does society continue to portray depression and anxiety as a personal weakness or failure, while patients with Parkinson’s disease or multiple sclerosis who have motor weakness are not stigmatized for their physical deficits?
• Transforming the seriously mentally ill into felons by arresting and jailing them because of erratic behavior—instead of hospitalizing them for the medical care they need. The trans­institutionalization of the mentally ill—from state hospitals to prisons—is one of the most shameful consequences of societal anosognosia, burdening our patients with the dual stigma of being a criminal and mentally ill.
• Turning a blind eye to abuses by insurance companies. More appalling is the perpetuation of restricted health coverage despite the passage of parity laws! Why are sensory and motor disorders of brain lesions covered fully, while the thought, emotional, and behavior disorders of the brain covered only partially?
• Consent laws that restrict psychiatrists from medicating acutely psychotic or depressed patients unless they consent—but no laws that restrict a cardiologist from immediately treating an unconscious heart attack patient who cannot consent, or an obtunded stroke patient who cannot communicate? The duration of untreated psychosis or depression has been shown repeatedly to have deleterious effects on brain tissue and functional outcomes, yet treatment of an acutely ill psychiatric patient is often delayed until a court order is obtained. When was the last time a court order was needed to treat an acute myocardial infarction?
• Failure to recognize that premature mortality (by approximately 25 years) is a devastating consequence of mental illness, whether from suicide or cardiometabolic risk factors due to smoking, substance use (often used to self-medicate because proper treatment is lacking), poor diet, and sedentary living.
• Failure to provide basic primary care to people with severe mental illness, and the much lower use of life-saving diagnostic and treatment procedures offered to these patients, compared with non-psychiatric patients.
• Inadequate funding for research on psychiatric disorders, compared with other medical disorders—even though direct and indirect costs of mental illness to society (hundreds of billions of dollars a year) far exceed costs of most medical disorders.
• Severe shortage of rehabilitation programs for the mentally ill, compared with many other medical disorders. Why does paralysis of the mind receive far less support than paralysis of the legs or arms? 

The rising suicide rate reflects poorly on us
Societal anosognosia is a global scourge, affecting many underdeveloped countries. Why do developed nations, like ours, have the same blind spot for mental illness? Might ignorance and discrimination be universal?

The tragic rise in the rate of death by suicide in men and women, among all age groups, year after year, is stunningly incongruent when juxtaposed against the elimination of smallpox and other communicable diseases through a concerted societal effort to support scientific advances in vaccine development. Societal anosognosia appears to be selective: We have comprehensive insight about diseases of the body but not diseases of the mind.

The essence and soul of a society are the collective minds of its citizens, not their bodies. Societal anosognosia is a serious dysfunction of its mind, and a rising suicide rate is a symptom of that pathological dysfunction.

What if this increase had occurred in cardiovascular disease or cancer (both on the decline, in fact, thanks to the intense attention they receive)? I think there would have been a public outcry, followed by demands by Congress that the National Institutes of Health and the CDC address this catastrophic rise immediately. And billions of dollars would then be earmarked to prevent these 2 diseases. 

How sad that society has “forgotten” that mental illness has deadly consequences, often leading to suicide (42,773 deaths in 2014 alone²—the second most common cause among people age 15 to 25³)! Hundreds of thousands of people attempt suicide every year, and those who do not lose their life often end up injured or maimed. Millions who suffer depression, bipolar disorder, schizophrenia, anxiety, posttraumatic stress disorder, or a substance use disorder are at high risk of suicide, and many never receive the timely intervention that might save their life.

Our national blind spot
It is poignant that the CDC report was released in spring: The rate of suicide is highest in April and May, when the light-dark cycle is reversed. This springtime peak runs contrary to the common belief that the rate of suicide is highest during winter months. The Annual Meeting of the American Psychiatric Association convenes in May, such that, ironically, thousands of psychiatrists are away from their office exactly when their patients might need them most

Lack of attention to the high risk of suicide among all ages and both sexes is emblematic of society’s inexplicable neglect of the needs of the mentally ill. That neglect is fueled, and exacerbated, by the destructive stigma attached to brain disorders that display psychiatric symptoms. As a neuropsychiatrist, I label this neglect societal anosognosia—the same as the lack of insight seen in patients with acute schizophrenia, who are unaware of how impaired they are and insist that they are not sick. (Anosognosia also occurs in stroke patients who deny that their limb is paralyzed and insist that all is well.)

Loss of insight can have serious consequences for patients who lose the ability to monitor and evaluate their physical and mental health. Just as patients with anosognosia think they do not need help, a society that fails to attend to the mental illness of its citizens endangers their overall health and welfare.

From neglect of mental illness many hazards arise
Tens of millions of Americans suffer from mental illness, according to the National Institute of Mental Health-sponsored Epidemiologic Catchment Area Study.⁴ The last thing these people can afford is societal anosognosia, which deprives them of necessary and timely access to psychiatric care.

Societal anosognosia is associated with numerous hazards for persons with mental illness, including:

• Lack of compassion, which is readily available for people with a medical ailment (broken bones, cardiovascular disease, cancer).
• Lack of adequate, affordable health insurance and financial support, compared with what is available for non-psychiatric disorders.
• Shortage of publicly funded programs and mental health practitioners to provide prevention and intervention for those who consider ending their life during an episode of depression, psychosis, stress, or a panic attack.
• Allowing the stigma to continue unabated. Why are there strict laws about hate crimes, but not about stigma? Why does society continue to portray depression and anxiety as a personal weakness or failure, while patients with Parkinson’s disease or multiple sclerosis who have motor weakness are not stigmatized for their physical deficits?
• Transforming the seriously mentally ill into felons by arresting and jailing them because of erratic behavior—instead of hospitalizing them for the medical care they need. The trans­institutionalization of the mentally ill—from state hospitals to prisons—is one of the most shameful consequences of societal anosognosia, burdening our patients with the dual stigma of being a criminal and mentally ill.
• Turning a blind eye to abuses by insurance companies. More appalling is the perpetuation of restricted health coverage despite the passage of parity laws! Why are sensory and motor disorders of brain lesions covered fully, while the thought, emotional, and behavior disorders of the brain covered only partially?
• Consent laws that restrict psychiatrists from medicating acutely psychotic or depressed patients unless they consent—but no laws that restrict a cardiologist from immediately treating an unconscious heart attack patient who cannot consent, or an obtunded stroke patient who cannot communicate? The duration of untreated psychosis or depression has been shown repeatedly to have deleterious effects on brain tissue and functional outcomes, yet treatment of an acutely ill psychiatric patient is often delayed until a court order is obtained. When was the last time a court order was needed to treat an acute myocardial infarction?
• Failure to recognize that premature mortality (by approximately 25 years) is a devastating consequence of mental illness, whether from suicide or cardiometabolic risk factors due to smoking, substance use (often used to self-medicate because proper treatment is lacking), poor diet, and sedentary living.
• Failure to provide basic primary care to people with severe mental illness, and the much lower use of life-saving diagnostic and treatment procedures offered to these patients, compared with non-psychiatric patients.
• Inadequate funding for research on psychiatric disorders, compared with other medical disorders—even though direct and indirect costs of mental illness to society (hundreds of billions of dollars a year) far exceed costs of most medical disorders.
• Severe shortage of rehabilitation programs for the mentally ill, compared with many other medical disorders. Why does paralysis of the mind receive far less support than paralysis of the legs or arms? 

The rising suicide rate reflects poorly on us
Societal anosognosia is a global scourge, affecting many underdeveloped countries. Why do developed nations, like ours, have the same blind spot for mental illness? Might ignorance and discrimination be universal?

The tragic rise in the rate of death by suicide in men and women, among all age groups, year after year, is stunningly incongruent when juxtaposed against the elimination of smallpox and other communicable diseases through a concerted societal effort to support scientific advances in vaccine development. Societal anosognosia appears to be selective: We have comprehensive insight about diseases of the body but not diseases of the mind.

The essence and soul of a society are the collective minds of its citizens, not their bodies. Societal anosognosia is a serious dysfunction of its mind, and a rising suicide rate is a symptom of that pathological dysfunction.

Unprecedented collaboration among 900 genetics investigators across 40 countries led to creation of the highly productive Psychiatric Genomics Consortium (PGC), which is analyzing 400,000 individual DNA samples.¹ The Consortium has an open-source approach, with data freely available to all who are interested.^a

The PGC recently published the results of a large Genome Wide Association Study (GWAS) of 36,989 people with schizophrenia and 113,075 controls. Investigators discovered 108 genetic loci (each containing as many as 26 genes), adding up to 341 protein-coding risk genes for schizophrenia, distributed across all 23 chromosomes.² One of these risk genes, on chromosome 6, is in the major histocompatibility complex and has the strongest association with schizophrenia (P = 10^–31). This finding provides insight that schizophrenia might be related to immune dysfunction, supported by evidence for neuro-inflammation and elevated pro-inflammatory biomarkers in this syndrome.³

In addition to heritable risk genes, the PGC has found many copy number variants (CNVs) and rare de novo mutations that are found significantly more often (10-fold or greater) in schizophrenia. But, as reflected by the 50% concordance rate for schizophrenia in monozygotic twins, non-genetic pathways to schizophrenia obviously exist; this is especially so through adverse events during pregnancy, which can disrupt brain development in a manner similar to disruption caused by risk genes, CNVs, and mutations.

The most exciting consequence of these breakthroughs?These genetic discoveries have great implications for novel drug development for the hundreds of biological subtypes of schizophrenia. At latest count, 23,345 genes that code for proteins, the building blocks of the body, are found in the human set of 23 chromosomes.² Approximately 7,000 of those genes are druggable and can open the way to developing new agents. In fact, identifying potential targets for pharmacotherapeutic intervention is the major goal of conducting a GWAS.⁴

What it means to be ‘druggable.’ Two conditions must be met for a gene to be druggable: First, it must code for a protein with folds that can interact with chemical compounds; second, that protein must be associated with a human disease.⁵ A drug that interacts with several target proteins (eg, kinases, proteases, transporters, enzymes) is considered promiscuous. After such a drug is found to have efficacy in 1 disease, it can be repurposed for treating other diseases. Such repositioning of an already approved drug for other conditions could save the pharmaceutical industry an enormous amount of time and billions of research and development dollars in developing new drugs for psychiatric illnesses that might have been used to treat various other medical conditions.

To exploit the principle of re-purposing, Lencz and Malhotra² examined the 341 coding genes associated with schizophrenia, to determine whether available drugs interact with the proteins produced by some of those genes. They identified 40 druggable genes (11.7% of the 341) and reported that:

• 27 coding genes (7.92% of the 341) are drug targets⁶
• 20 of the 40 druggable genes are already approved by the FDA to treat a range of medical disorders, including glaucoma, epilepsy, hypertension, angina, irritable bowel syndrome, incontinence, smoking cessation, nausea, hypertension, prostate cancer, type 2 diabetes mellitus, pulmonary fibrosis, and acute promyelocytic leukemia; in addition, some genes act as a diuretic or an nonsteroidal anti-inflammatory drug
• another 20 druggable genes are not approved for use but are in clinical trials for disorders such as Alzheimer’s disease, heart failure, neuropathic pain, depression, cancer, immune-supported acne psoriasis, and myeloma.

The opportunity to repurpose some of those promiscuous drugs for various medical indications for the treatment of schizophrenia is exciting, and presents Pandora’s box of new mechanisms of action.⁷ It is intriguing how therapeutic mechanisms for a wide range of unrelated medical conditions may have commonality with the neurobiological underpinnings of a serious brain disorder such as schizophrenia.

Journey from genome to clinicPsychiatrists should be heartened by this translational research into the pharmacotherapeutic promise of emerging genetic advances. The parched terrain of psychopharmacology—the result of a drought of truly innovative medications for serious psychiatric brain disorders—soon may be drenched by a shower of translational discoveries from druggable genes.⁸ An auspicious scientific journey, from the genome to the clinic, has begun in earnest.

That is great news for our patients, and uplifting to us as well. Breakthroughs to cure intractable and persistent psychiatric brain disorders will not only vanquish disability and restore functioning, but also will be a powerful, long-awaited antidote to the virulent stigma of mental illness.

^aAvailable at http://pgc.unc.edu/downloads.

Unprecedented collaboration among 900 genetics investigators across 40 countries led to creation of the highly productive Psychiatric Genomics Consortium (PGC), which is analyzing 400,000 individual DNA samples.¹ The Consortium has an open-source approach, with data freely available to all who are interested.^a

The PGC recently published the results of a large Genome Wide Association Study (GWAS) of 36,989 people with schizophrenia and 113,075 controls. Investigators discovered 108 genetic loci (each containing as many as 26 genes), adding up to 341 protein-coding risk genes for schizophrenia, distributed across all 23 chromosomes.² One of these risk genes, on chromosome 6, is in the major histocompatibility complex and has the strongest association with schizophrenia (P = 10^–31). This finding provides insight that schizophrenia might be related to immune dysfunction, supported by evidence for neuro-inflammation and elevated pro-inflammatory biomarkers in this syndrome.³

In addition to heritable risk genes, the PGC has found many copy number variants (CNVs) and rare de novo mutations that are found significantly more often (10-fold or greater) in schizophrenia. But, as reflected by the 50% concordance rate for schizophrenia in monozygotic twins, non-genetic pathways to schizophrenia obviously exist; this is especially so through adverse events during pregnancy, which can disrupt brain development in a manner similar to disruption caused by risk genes, CNVs, and mutations.

The most exciting consequence of these breakthroughs?These genetic discoveries have great implications for novel drug development for the hundreds of biological subtypes of schizophrenia. At latest count, 23,345 genes that code for proteins, the building blocks of the body, are found in the human set of 23 chromosomes.² Approximately 7,000 of those genes are druggable and can open the way to developing new agents. In fact, identifying potential targets for pharmacotherapeutic intervention is the major goal of conducting a GWAS.⁴

What it means to be ‘druggable.’ Two conditions must be met for a gene to be druggable: First, it must code for a protein with folds that can interact with chemical compounds; second, that protein must be associated with a human disease.⁵ A drug that interacts with several target proteins (eg, kinases, proteases, transporters, enzymes) is considered promiscuous. After such a drug is found to have efficacy in 1 disease, it can be repurposed for treating other diseases. Such repositioning of an already approved drug for other conditions could save the pharmaceutical industry an enormous amount of time and billions of research and development dollars in developing new drugs for psychiatric illnesses that might have been used to treat various other medical conditions.

To exploit the principle of re-purposing, Lencz and Malhotra² examined the 341 coding genes associated with schizophrenia, to determine whether available drugs interact with the proteins produced by some of those genes. They identified 40 druggable genes (11.7% of the 341) and reported that:

• 27 coding genes (7.92% of the 341) are drug targets⁶
• 20 of the 40 druggable genes are already approved by the FDA to treat a range of medical disorders, including glaucoma, epilepsy, hypertension, angina, irritable bowel syndrome, incontinence, smoking cessation, nausea, hypertension, prostate cancer, type 2 diabetes mellitus, pulmonary fibrosis, and acute promyelocytic leukemia; in addition, some genes act as a diuretic or an nonsteroidal anti-inflammatory drug
• another 20 druggable genes are not approved for use but are in clinical trials for disorders such as Alzheimer’s disease, heart failure, neuropathic pain, depression, cancer, immune-supported acne psoriasis, and myeloma.

The opportunity to repurpose some of those promiscuous drugs for various medical indications for the treatment of schizophrenia is exciting, and presents Pandora’s box of new mechanisms of action.⁷ It is intriguing how therapeutic mechanisms for a wide range of unrelated medical conditions may have commonality with the neurobiological underpinnings of a serious brain disorder such as schizophrenia.

Journey from genome to clinicPsychiatrists should be heartened by this translational research into the pharmacotherapeutic promise of emerging genetic advances. The parched terrain of psychopharmacology—the result of a drought of truly innovative medications for serious psychiatric brain disorders—soon may be drenched by a shower of translational discoveries from druggable genes.⁸ An auspicious scientific journey, from the genome to the clinic, has begun in earnest.

That is great news for our patients, and uplifting to us as well. Breakthroughs to cure intractable and persistent psychiatric brain disorders will not only vanquish disability and restore functioning, but also will be a powerful, long-awaited antidote to the virulent stigma of mental illness.

^aAvailable at http://pgc.unc.edu/downloads.

Unprecedented collaboration among 900 genetics investigators across 40 countries led to creation of the highly productive Psychiatric Genomics Consortium (PGC), which is analyzing 400,000 individual DNA samples.¹ The Consortium has an open-source approach, with data freely available to all who are interested.^a

The PGC recently published the results of a large Genome Wide Association Study (GWAS) of 36,989 people with schizophrenia and 113,075 controls. Investigators discovered 108 genetic loci (each containing as many as 26 genes), adding up to 341 protein-coding risk genes for schizophrenia, distributed across all 23 chromosomes.² One of these risk genes, on chromosome 6, is in the major histocompatibility complex and has the strongest association with schizophrenia (P = 10^–31). This finding provides insight that schizophrenia might be related to immune dysfunction, supported by evidence for neuro-inflammation and elevated pro-inflammatory biomarkers in this syndrome.³

In addition to heritable risk genes, the PGC has found many copy number variants (CNVs) and rare de novo mutations that are found significantly more often (10-fold or greater) in schizophrenia. But, as reflected by the 50% concordance rate for schizophrenia in monozygotic twins, non-genetic pathways to schizophrenia obviously exist; this is especially so through adverse events during pregnancy, which can disrupt brain development in a manner similar to disruption caused by risk genes, CNVs, and mutations.

The most exciting consequence of these breakthroughs?These genetic discoveries have great implications for novel drug development for the hundreds of biological subtypes of schizophrenia. At latest count, 23,345 genes that code for proteins, the building blocks of the body, are found in the human set of 23 chromosomes.² Approximately 7,000 of those genes are druggable and can open the way to developing new agents. In fact, identifying potential targets for pharmacotherapeutic intervention is the major goal of conducting a GWAS.⁴

What it means to be ‘druggable.’ Two conditions must be met for a gene to be druggable: First, it must code for a protein with folds that can interact with chemical compounds; second, that protein must be associated with a human disease.⁵ A drug that interacts with several target proteins (eg, kinases, proteases, transporters, enzymes) is considered promiscuous. After such a drug is found to have efficacy in 1 disease, it can be repurposed for treating other diseases. Such repositioning of an already approved drug for other conditions could save the pharmaceutical industry an enormous amount of time and billions of research and development dollars in developing new drugs for psychiatric illnesses that might have been used to treat various other medical conditions.

To exploit the principle of re-purposing, Lencz and Malhotra² examined the 341 coding genes associated with schizophrenia, to determine whether available drugs interact with the proteins produced by some of those genes. They identified 40 druggable genes (11.7% of the 341) and reported that:

• 27 coding genes (7.92% of the 341) are drug targets⁶
• 20 of the 40 druggable genes are already approved by the FDA to treat a range of medical disorders, including glaucoma, epilepsy, hypertension, angina, irritable bowel syndrome, incontinence, smoking cessation, nausea, hypertension, prostate cancer, type 2 diabetes mellitus, pulmonary fibrosis, and acute promyelocytic leukemia; in addition, some genes act as a diuretic or an nonsteroidal anti-inflammatory drug
• another 20 druggable genes are not approved for use but are in clinical trials for disorders such as Alzheimer’s disease, heart failure, neuropathic pain, depression, cancer, immune-supported acne psoriasis, and myeloma.

The opportunity to repurpose some of those promiscuous drugs for various medical indications for the treatment of schizophrenia is exciting, and presents Pandora’s box of new mechanisms of action.⁷ It is intriguing how therapeutic mechanisms for a wide range of unrelated medical conditions may have commonality with the neurobiological underpinnings of a serious brain disorder such as schizophrenia.

Journey from genome to clinicPsychiatrists should be heartened by this translational research into the pharmacotherapeutic promise of emerging genetic advances. The parched terrain of psychopharmacology—the result of a drought of truly innovative medications for serious psychiatric brain disorders—soon may be drenched by a shower of translational discoveries from druggable genes.⁸ An auspicious scientific journey, from the genome to the clinic, has begun in earnest.

That is great news for our patients, and uplifting to us as well. Breakthroughs to cure intractable and persistent psychiatric brain disorders will not only vanquish disability and restore functioning, but also will be a powerful, long-awaited antidote to the virulent stigma of mental illness.

^aAvailable at http://pgc.unc.edu/downloads.

That expression is a residue of the absurd belief during the Middle Ages that mental illness is caused by evil spirits—that justified burning the afflicted person at the stake. (Remember Joan of Arc?)

This ignorant, even maliciously unscientific, portrayal of psychiatric symptoms is an appalling disservice to all our patients who struggle with a potentially disabling neuropsychiatric disorder. Regrettably, some religious entities still propagate the fallacy of possession by an evil spirit and call for exorcism of bizarre behaviors sometimes associated with psychosis.¹ What is really needed is an exorcism of unscientific and harmful misconceptions that mental illness is the nefarious work of Beelzebub or Lucifer.

Strange manifestations beget weird explanations
I can understand how ignorance about the neurologic basis of unusual delusions and behavior can trigger absurd religious explanations for their cause. Sometimes, brain pathology can have strange clinical manifestations that are beyond the ken of the average layperson, which invites metaphysical, religious, or philosophical explanation. Here are examples of neuropsychiatric symptoms in the category of “very unusual” that might summon a demonic malfeasance.

Delusion of possession or alien control. Some people complain of being possessed²; delusional people who have a strong religious background might believe they are possessed by Satan himself. Some of my patients with psychotic depression believe this, expressing great guilt and anguish about being doomed to go to Hell.

Alternately, patients with schizophrenia often think they are under the control of an “alien force” that shapes their behavior, feelings, and thoughts (a Schneiderian first-rank symptom). In a 2012 editorial, I proposed that this “alien intruder” is the unintegrated right hemispheric consciousness,³ and that disintegration of the 200 million inter-hemispheric white matter fibers of the corpus callosum might be the cause of the loss of integration of the right hemisphere into the dominant left hemisphere.

Some people attribute external control on their lives to a government agency, a foreign country, or a spiteful neighbor; others believe it is the work of evil spirits. Whereas the foundation of the delusion is brain pathology, the content of the delusion is colored by the affected person’s cultural and religious background.

Apotemnophilia. A neurologic disorder that manifests in a bizarre clinical symptom that invites faulty explanation: A person demands amputation of a leg because “it doesn’t belong to my body.”⁴ The cause of this strange and confusing disorder has been misinterpreted as a paraphilia, a desire by the affected person to achieve greater sexual satisfaction by having a stump. It was first reported in the September/October 1972 issue of the magazine Penthouse, where it was described as the motivation to heighten one’s sexual appeal because stumps can be sexually exciting to their partners.

It took many years of neurologic research to demonstrate that apotemnophilia is caused by pathology in the parietal lobe, where the physical representation of the body is located. Incomplete neurodevelopment of the parietal lobe can cause a person to fail to recognize a leg as a “legitimate” part of his body, and he (she) then desperately seeks amputation of the so-called alien limb (see the description of xenomelia below) that is attached to his body.

When an affected person is asked to delineate the borders of an alien limb, he draws a line on the skin at the precise border between the alien limb and the rest of his body—where the amputation should take place. Requests for surgical amputation were adamantly denied when the disorder was thought to be a weird sexual practice, but elective amputation in the context of neuropsychopathology is seriously debated now—and has, in fact, been reported.⁵ The term “body impaired integrity disorder” has been proposed, but neurologists consider the disorder an example of xenomelia.

Xenomelia (‘alien limb syndrome’). An odd neurologic disorder produced by brain pathology, in which a person has a sense of estrangement about 1 or more limbs.⁵ The disorder can be caused by a neurologic lesion such as tumor, Creutzfeldt-Jakob disease, hereditary diffuse leukoencephalopathy, demyelinating disease, progressive dementia, corpus callosotomy, intracerebral hemorrhage, or thalamic degeneration.⁶

So-called “alien hand syndrome,” or asomatognosia, is a widely recognized example of xenomelia, and is associated with medial frontal lobe damage.

Another variant of xenomelia is somatoparaphrenia, unawareness of a part of one’s body.⁷

Cotard syndrome. A nihilistic delusion of the nonexistence or dissolution of a body part; in extreme form, the delusion of being dead or nonexistent.⁸ The syndrome sometimes occurs in the setting of severe depression. Research has shown an association with atrophy of the insula,⁹ which is responsible for internal proprioception (interoception).

Delusional misidentification syndrome. A set of neuropsychiatric conditions in which a person misidentifies people, places, objects, or events¹⁰:

• Capgras syndrome (one perceives a familiar person as an imposter)
• Fregoli syndrome (one perceives that a familiar person is repeatedly disguised to change appearance)
• intermetamorphosis (one perceives that a person changes his external appearance and personality or identity)
• lycanthropy (one delusionally misidentifies one’s self as an animal—eg, a wolf, rabbit, or snake, and behaves accordingly)
• Ekbom syndrome (delusional belief of being infested with parasites )
• delusion of hermaphroditism (one has merged in the same body with another person of the opposite sex)
• delusion of sexual transformation (one has changed to the opposite sex)
• delusion of being the Antichrist.

Delusional misidentification syndrome can develop after the onset of focal or diffuse brain pathology, such as right hemispheric stroke, multiple sclerosis, hyperparathyroidism, traumatic brain injury, dementia, and schizophrenia. In several studies, researchers have reported an increased risk of violence in delusional misidentification syndromes.¹¹

Neurological, not diabolical!
A disruption in brain anatomy, neurodevelopment, or circuitry/interconnectivity can produce odd beliefs and bizarre behavior that might prompt a lay observer to believe that a demon or an evil spirt is responsible for the incomprehensible symptoms. I have one response to the “blame-the-devil” proponents: It’s the brain pathology, stupid!

That expression is a residue of the absurd belief during the Middle Ages that mental illness is caused by evil spirits—that justified burning the afflicted person at the stake. (Remember Joan of Arc?)

This ignorant, even maliciously unscientific, portrayal of psychiatric symptoms is an appalling disservice to all our patients who struggle with a potentially disabling neuropsychiatric disorder. Regrettably, some religious entities still propagate the fallacy of possession by an evil spirit and call for exorcism of bizarre behaviors sometimes associated with psychosis.¹ What is really needed is an exorcism of unscientific and harmful misconceptions that mental illness is the nefarious work of Beelzebub or Lucifer.

Strange manifestations beget weird explanations
I can understand how ignorance about the neurologic basis of unusual delusions and behavior can trigger absurd religious explanations for their cause. Sometimes, brain pathology can have strange clinical manifestations that are beyond the ken of the average layperson, which invites metaphysical, religious, or philosophical explanation. Here are examples of neuropsychiatric symptoms in the category of “very unusual” that might summon a demonic malfeasance.

Delusion of possession or alien control. Some people complain of being possessed²; delusional people who have a strong religious background might believe they are possessed by Satan himself. Some of my patients with psychotic depression believe this, expressing great guilt and anguish about being doomed to go to Hell.

Alternately, patients with schizophrenia often think they are under the control of an “alien force” that shapes their behavior, feelings, and thoughts (a Schneiderian first-rank symptom). In a 2012 editorial, I proposed that this “alien intruder” is the unintegrated right hemispheric consciousness,³ and that disintegration of the 200 million inter-hemispheric white matter fibers of the corpus callosum might be the cause of the loss of integration of the right hemisphere into the dominant left hemisphere.

Some people attribute external control on their lives to a government agency, a foreign country, or a spiteful neighbor; others believe it is the work of evil spirits. Whereas the foundation of the delusion is brain pathology, the content of the delusion is colored by the affected person’s cultural and religious background.

Apotemnophilia. A neurologic disorder that manifests in a bizarre clinical symptom that invites faulty explanation: A person demands amputation of a leg because “it doesn’t belong to my body.”⁴ The cause of this strange and confusing disorder has been misinterpreted as a paraphilia, a desire by the affected person to achieve greater sexual satisfaction by having a stump. It was first reported in the September/October 1972 issue of the magazine Penthouse, where it was described as the motivation to heighten one’s sexual appeal because stumps can be sexually exciting to their partners.

It took many years of neurologic research to demonstrate that apotemnophilia is caused by pathology in the parietal lobe, where the physical representation of the body is located. Incomplete neurodevelopment of the parietal lobe can cause a person to fail to recognize a leg as a “legitimate” part of his body, and he (she) then desperately seeks amputation of the so-called alien limb (see the description of xenomelia below) that is attached to his body.

When an affected person is asked to delineate the borders of an alien limb, he draws a line on the skin at the precise border between the alien limb and the rest of his body—where the amputation should take place. Requests for surgical amputation were adamantly denied when the disorder was thought to be a weird sexual practice, but elective amputation in the context of neuropsychopathology is seriously debated now—and has, in fact, been reported.⁵ The term “body impaired integrity disorder” has been proposed, but neurologists consider the disorder an example of xenomelia.

Xenomelia (‘alien limb syndrome’). An odd neurologic disorder produced by brain pathology, in which a person has a sense of estrangement about 1 or more limbs.⁵ The disorder can be caused by a neurologic lesion such as tumor, Creutzfeldt-Jakob disease, hereditary diffuse leukoencephalopathy, demyelinating disease, progressive dementia, corpus callosotomy, intracerebral hemorrhage, or thalamic degeneration.⁶

So-called “alien hand syndrome,” or asomatognosia, is a widely recognized example of xenomelia, and is associated with medial frontal lobe damage.

Another variant of xenomelia is somatoparaphrenia, unawareness of a part of one’s body.⁷

Cotard syndrome. A nihilistic delusion of the nonexistence or dissolution of a body part; in extreme form, the delusion of being dead or nonexistent.⁸ The syndrome sometimes occurs in the setting of severe depression. Research has shown an association with atrophy of the insula,⁹ which is responsible for internal proprioception (interoception).

Delusional misidentification syndrome. A set of neuropsychiatric conditions in which a person misidentifies people, places, objects, or events¹⁰:

• Capgras syndrome (one perceives a familiar person as an imposter)
• Fregoli syndrome (one perceives that a familiar person is repeatedly disguised to change appearance)
• intermetamorphosis (one perceives that a person changes his external appearance and personality or identity)
• lycanthropy (one delusionally misidentifies one’s self as an animal—eg, a wolf, rabbit, or snake, and behaves accordingly)
• Ekbom syndrome (delusional belief of being infested with parasites )
• delusion of hermaphroditism (one has merged in the same body with another person of the opposite sex)
• delusion of sexual transformation (one has changed to the opposite sex)
• delusion of being the Antichrist.

Delusional misidentification syndrome can develop after the onset of focal or diffuse brain pathology, such as right hemispheric stroke, multiple sclerosis, hyperparathyroidism, traumatic brain injury, dementia, and schizophrenia. In several studies, researchers have reported an increased risk of violence in delusional misidentification syndromes.¹¹

Neurological, not diabolical!
A disruption in brain anatomy, neurodevelopment, or circuitry/interconnectivity can produce odd beliefs and bizarre behavior that might prompt a lay observer to believe that a demon or an evil spirt is responsible for the incomprehensible symptoms. I have one response to the “blame-the-devil” proponents: It’s the brain pathology, stupid!

That expression is a residue of the absurd belief during the Middle Ages that mental illness is caused by evil spirits—that justified burning the afflicted person at the stake. (Remember Joan of Arc?)

This ignorant, even maliciously unscientific, portrayal of psychiatric symptoms is an appalling disservice to all our patients who struggle with a potentially disabling neuropsychiatric disorder. Regrettably, some religious entities still propagate the fallacy of possession by an evil spirit and call for exorcism of bizarre behaviors sometimes associated with psychosis.¹ What is really needed is an exorcism of unscientific and harmful misconceptions that mental illness is the nefarious work of Beelzebub or Lucifer.

Strange manifestations beget weird explanations
I can understand how ignorance about the neurologic basis of unusual delusions and behavior can trigger absurd religious explanations for their cause. Sometimes, brain pathology can have strange clinical manifestations that are beyond the ken of the average layperson, which invites metaphysical, religious, or philosophical explanation. Here are examples of neuropsychiatric symptoms in the category of “very unusual” that might summon a demonic malfeasance.

Delusion of possession or alien control. Some people complain of being possessed²; delusional people who have a strong religious background might believe they are possessed by Satan himself. Some of my patients with psychotic depression believe this, expressing great guilt and anguish about being doomed to go to Hell.

Alternately, patients with schizophrenia often think they are under the control of an “alien force” that shapes their behavior, feelings, and thoughts (a Schneiderian first-rank symptom). In a 2012 editorial, I proposed that this “alien intruder” is the unintegrated right hemispheric consciousness,³ and that disintegration of the 200 million inter-hemispheric white matter fibers of the corpus callosum might be the cause of the loss of integration of the right hemisphere into the dominant left hemisphere.

Some people attribute external control on their lives to a government agency, a foreign country, or a spiteful neighbor; others believe it is the work of evil spirits. Whereas the foundation of the delusion is brain pathology, the content of the delusion is colored by the affected person’s cultural and religious background.

Apotemnophilia. A neurologic disorder that manifests in a bizarre clinical symptom that invites faulty explanation: A person demands amputation of a leg because “it doesn’t belong to my body.”⁴ The cause of this strange and confusing disorder has been misinterpreted as a paraphilia, a desire by the affected person to achieve greater sexual satisfaction by having a stump. It was first reported in the September/October 1972 issue of the magazine Penthouse, where it was described as the motivation to heighten one’s sexual appeal because stumps can be sexually exciting to their partners.

It took many years of neurologic research to demonstrate that apotemnophilia is caused by pathology in the parietal lobe, where the physical representation of the body is located. Incomplete neurodevelopment of the parietal lobe can cause a person to fail to recognize a leg as a “legitimate” part of his body, and he (she) then desperately seeks amputation of the so-called alien limb (see the description of xenomelia below) that is attached to his body.

When an affected person is asked to delineate the borders of an alien limb, he draws a line on the skin at the precise border between the alien limb and the rest of his body—where the amputation should take place. Requests for surgical amputation were adamantly denied when the disorder was thought to be a weird sexual practice, but elective amputation in the context of neuropsychopathology is seriously debated now—and has, in fact, been reported.⁵ The term “body impaired integrity disorder” has been proposed, but neurologists consider the disorder an example of xenomelia.

Xenomelia (‘alien limb syndrome’). An odd neurologic disorder produced by brain pathology, in which a person has a sense of estrangement about 1 or more limbs.⁵ The disorder can be caused by a neurologic lesion such as tumor, Creutzfeldt-Jakob disease, hereditary diffuse leukoencephalopathy, demyelinating disease, progressive dementia, corpus callosotomy, intracerebral hemorrhage, or thalamic degeneration.⁶

So-called “alien hand syndrome,” or asomatognosia, is a widely recognized example of xenomelia, and is associated with medial frontal lobe damage.

Another variant of xenomelia is somatoparaphrenia, unawareness of a part of one’s body.⁷

Cotard syndrome. A nihilistic delusion of the nonexistence or dissolution of a body part; in extreme form, the delusion of being dead or nonexistent.⁸ The syndrome sometimes occurs in the setting of severe depression. Research has shown an association with atrophy of the insula,⁹ which is responsible for internal proprioception (interoception).

Delusional misidentification syndrome. A set of neuropsychiatric conditions in which a person misidentifies people, places, objects, or events¹⁰:

• Capgras syndrome (one perceives a familiar person as an imposter)
• Fregoli syndrome (one perceives that a familiar person is repeatedly disguised to change appearance)
• intermetamorphosis (one perceives that a person changes his external appearance and personality or identity)
• lycanthropy (one delusionally misidentifies one’s self as an animal—eg, a wolf, rabbit, or snake, and behaves accordingly)
• Ekbom syndrome (delusional belief of being infested with parasites )
• delusion of hermaphroditism (one has merged in the same body with another person of the opposite sex)
• delusion of sexual transformation (one has changed to the opposite sex)
• delusion of being the Antichrist.

Delusional misidentification syndrome can develop after the onset of focal or diffuse brain pathology, such as right hemispheric stroke, multiple sclerosis, hyperparathyroidism, traumatic brain injury, dementia, and schizophrenia. In several studies, researchers have reported an increased risk of violence in delusional misidentification syndromes.¹¹

Neurological, not diabolical!
A disruption in brain anatomy, neurodevelopment, or circuitry/interconnectivity can produce odd beliefs and bizarre behavior that might prompt a lay observer to believe that a demon or an evil spirt is responsible for the incomprehensible symptoms. I have one response to the “blame-the-devil” proponents: It’s the brain pathology, stupid!

Such decisions can be made at any time, but the dawn of a year is a powerful signal of a new beginning—another lease on life, a potential turning point. Imbedded in those resolutions is a subliminal sense of urgency to correct one’s long-neglected shortcomings as the calendar ruthlessly points to inevitable aging and the relentless march of time.

A psychiatric perspective
For psychiatrists, New Year’s resolutions transcend the (often ephemeral) impulse to go on a diet or buy a membership at the local gym. We have a unique perspective on the challenges that our patients face every day as they cope with the complex demands of life despite their anxiety, depression, or psychosis.

We are aware of the many unmet needs in managing complex neuropsychiatric brain disorders and the major challenges of erasing the burdensome stigma that engulfs our patients and the practice of psychiatry itself—despite its noble mission of repairing fractured brains, mending tortured souls, and restoring peace of mind and wellness. We are proud of our clinical and scientific accomplishments but are painfully cognizant of our limitations and the huge chasm between what we know and what we will eventually know once the brain reveals its glorious mysteries through neuroscientific research.

What can you resolve?
Here is my proposed list of pragmatic resolutions that most psychiatrists would regard as part of a perpetual to-do list—a must-do bucket of cherished goals and brave new horizons to bring complete mental health for our patients and immeasurable gratification for us, who dream of cures for brain disorders that trigger various ailments of the mind.

• Practice like a physician to emphasize the medical foundation of psychiatry: Always check on a patient’s physical health, and monitor his (her) cardiometabolic status. Wear the symbolic white coat that often enhances the physician−patient relationship.
• Dedicate a significant percentage of your practice to the sickest patients. There are enough non-physician mental health professionals to handle the walking wounded and worried well.
• Advocate relentlessly throughout your sphere of influence, and publicly, for true parity between psychiatric and non-mental medical disorders—not only for insurance coverage but for overall societal acceptance and compassion as well.
• Lobby vigorously for hospitalization instead of imprisonment of the seriously mentally ill because psychosis is a brain disease, not a criminal offense.
• Adopt evidence-based psychiatric practice whenever possible to achieve the best outcomes. Judiciously implement off-label practices, however, if no evidence-based treatments exist for a suffering patient.
• Avoid senseless and irrational polypharmacy but do not hesitate to use rational, beneficial combination therapy.
• Provide 1 hour a week of pro bono psychiatric work for the indigent and underserved. The rewards of giving what amounts to 1 week a year are immeasurably more gratifying than a few more dollars in your bank account.
• Resist calling an ill person a ‘client’ or ‘consumer’—at least until oncologists and cardiologists start doing so. Refuse to give up your medical identify in the many de-medicalized mental health clinics.
• Never let a patient leave your office without some psychotherapy, even as part of a 15-minute med-check.
• Stay current and on the cutting edge of evolving psychiatric practice by logging into PubMed every day (even briefly) to read a few abstracts of the latest studies related to patients you saw that day.
• Think like a neurologist by identifying the neural circuits of psychiatric symptoms. Act like a cardiologist by doing everything medically possible to prevent recurrence of psychotic, manic, or depressive episodes because they damage brain tissue just as a myocardial infarction damages the heart.
• Support research with words, money, and passion. Psychiatric neuroscientific breakthroughs generate superior treatments, erase stigma, and advance the quality of life for patients. Donate annually to the researchers of your choice, at the medical school where you were trained, or at a nonprofit research institute.
• Make time to write for publication, annually, at least 1 case report or a letter to the editor about observations from your practice. You can contribute immensely to the discovery process by sharing novel clinical insights.
• Never give up on any patient or set expectations too low, regardless of the diagnosis or severity of illness. Giving up destroys hope and ushers in despondency. Get a second opinion if you run out of options for a patient.
• Always set remission followed by recovery as the therapeutic goal for every patient. Let the patient know this and ask him (her) commit to that goal with you.
• Be genuinely proud to be a psychiatrist. You assess and rectify disorders of the mind, the most complex and magical product of the human brain that determines who we are and how we think, emote, communicate, verbalize, empathize, love, hate, remember, plan, problem-solve, and, of course, make resolutions.

Back to diet and exercise—for our patients and for us!
It’s OK to include, among your New Year’s resolutions, a pledge to strongly encourage patients to diet and exercise. Given the tendency of many of them to gain weight and die prematurely as a consequence of obesity-related cardiometabolic risk factors, you should urge them to eat healthy and exercise every time you see them, not only on New Year’s Day.

Such decisions can be made at any time, but the dawn of a year is a powerful signal of a new beginning—another lease on life, a potential turning point. Imbedded in those resolutions is a subliminal sense of urgency to correct one’s long-neglected shortcomings as the calendar ruthlessly points to inevitable aging and the relentless march of time.

A psychiatric perspective
For psychiatrists, New Year’s resolutions transcend the (often ephemeral) impulse to go on a diet or buy a membership at the local gym. We have a unique perspective on the challenges that our patients face every day as they cope with the complex demands of life despite their anxiety, depression, or psychosis.

We are aware of the many unmet needs in managing complex neuropsychiatric brain disorders and the major challenges of erasing the burdensome stigma that engulfs our patients and the practice of psychiatry itself—despite its noble mission of repairing fractured brains, mending tortured souls, and restoring peace of mind and wellness. We are proud of our clinical and scientific accomplishments but are painfully cognizant of our limitations and the huge chasm between what we know and what we will eventually know once the brain reveals its glorious mysteries through neuroscientific research.

What can you resolve?
Here is my proposed list of pragmatic resolutions that most psychiatrists would regard as part of a perpetual to-do list—a must-do bucket of cherished goals and brave new horizons to bring complete mental health for our patients and immeasurable gratification for us, who dream of cures for brain disorders that trigger various ailments of the mind.

• Practice like a physician to emphasize the medical foundation of psychiatry: Always check on a patient’s physical health, and monitor his (her) cardiometabolic status. Wear the symbolic white coat that often enhances the physician−patient relationship.
• Dedicate a significant percentage of your practice to the sickest patients. There are enough non-physician mental health professionals to handle the walking wounded and worried well.
• Advocate relentlessly throughout your sphere of influence, and publicly, for true parity between psychiatric and non-mental medical disorders—not only for insurance coverage but for overall societal acceptance and compassion as well.
• Lobby vigorously for hospitalization instead of imprisonment of the seriously mentally ill because psychosis is a brain disease, not a criminal offense.
• Adopt evidence-based psychiatric practice whenever possible to achieve the best outcomes. Judiciously implement off-label practices, however, if no evidence-based treatments exist for a suffering patient.
• Avoid senseless and irrational polypharmacy but do not hesitate to use rational, beneficial combination therapy.
• Provide 1 hour a week of pro bono psychiatric work for the indigent and underserved. The rewards of giving what amounts to 1 week a year are immeasurably more gratifying than a few more dollars in your bank account.
• Resist calling an ill person a ‘client’ or ‘consumer’—at least until oncologists and cardiologists start doing so. Refuse to give up your medical identify in the many de-medicalized mental health clinics.
• Never let a patient leave your office without some psychotherapy, even as part of a 15-minute med-check.
• Stay current and on the cutting edge of evolving psychiatric practice by logging into PubMed every day (even briefly) to read a few abstracts of the latest studies related to patients you saw that day.
• Think like a neurologist by identifying the neural circuits of psychiatric symptoms. Act like a cardiologist by doing everything medically possible to prevent recurrence of psychotic, manic, or depressive episodes because they damage brain tissue just as a myocardial infarction damages the heart.
• Support research with words, money, and passion. Psychiatric neuroscientific breakthroughs generate superior treatments, erase stigma, and advance the quality of life for patients. Donate annually to the researchers of your choice, at the medical school where you were trained, or at a nonprofit research institute.
• Make time to write for publication, annually, at least 1 case report or a letter to the editor about observations from your practice. You can contribute immensely to the discovery process by sharing novel clinical insights.
• Never give up on any patient or set expectations too low, regardless of the diagnosis or severity of illness. Giving up destroys hope and ushers in despondency. Get a second opinion if you run out of options for a patient.
• Always set remission followed by recovery as the therapeutic goal for every patient. Let the patient know this and ask him (her) commit to that goal with you.
• Be genuinely proud to be a psychiatrist. You assess and rectify disorders of the mind, the most complex and magical product of the human brain that determines who we are and how we think, emote, communicate, verbalize, empathize, love, hate, remember, plan, problem-solve, and, of course, make resolutions.

Back to diet and exercise—for our patients and for us!
It’s OK to include, among your New Year’s resolutions, a pledge to strongly encourage patients to diet and exercise. Given the tendency of many of them to gain weight and die prematurely as a consequence of obesity-related cardiometabolic risk factors, you should urge them to eat healthy and exercise every time you see them, not only on New Year’s Day.

Such decisions can be made at any time, but the dawn of a year is a powerful signal of a new beginning—another lease on life, a potential turning point. Imbedded in those resolutions is a subliminal sense of urgency to correct one’s long-neglected shortcomings as the calendar ruthlessly points to inevitable aging and the relentless march of time.

A psychiatric perspective
For psychiatrists, New Year’s resolutions transcend the (often ephemeral) impulse to go on a diet or buy a membership at the local gym. We have a unique perspective on the challenges that our patients face every day as they cope with the complex demands of life despite their anxiety, depression, or psychosis.

We are aware of the many unmet needs in managing complex neuropsychiatric brain disorders and the major challenges of erasing the burdensome stigma that engulfs our patients and the practice of psychiatry itself—despite its noble mission of repairing fractured brains, mending tortured souls, and restoring peace of mind and wellness. We are proud of our clinical and scientific accomplishments but are painfully cognizant of our limitations and the huge chasm between what we know and what we will eventually know once the brain reveals its glorious mysteries through neuroscientific research.

What can you resolve?
Here is my proposed list of pragmatic resolutions that most psychiatrists would regard as part of a perpetual to-do list—a must-do bucket of cherished goals and brave new horizons to bring complete mental health for our patients and immeasurable gratification for us, who dream of cures for brain disorders that trigger various ailments of the mind.

• Practice like a physician to emphasize the medical foundation of psychiatry: Always check on a patient’s physical health, and monitor his (her) cardiometabolic status. Wear the symbolic white coat that often enhances the physician−patient relationship.
• Dedicate a significant percentage of your practice to the sickest patients. There are enough non-physician mental health professionals to handle the walking wounded and worried well.
• Advocate relentlessly throughout your sphere of influence, and publicly, for true parity between psychiatric and non-mental medical disorders—not only for insurance coverage but for overall societal acceptance and compassion as well.
• Lobby vigorously for hospitalization instead of imprisonment of the seriously mentally ill because psychosis is a brain disease, not a criminal offense.
• Adopt evidence-based psychiatric practice whenever possible to achieve the best outcomes. Judiciously implement off-label practices, however, if no evidence-based treatments exist for a suffering patient.
• Avoid senseless and irrational polypharmacy but do not hesitate to use rational, beneficial combination therapy.
• Provide 1 hour a week of pro bono psychiatric work for the indigent and underserved. The rewards of giving what amounts to 1 week a year are immeasurably more gratifying than a few more dollars in your bank account.
• Resist calling an ill person a ‘client’ or ‘consumer’—at least until oncologists and cardiologists start doing so. Refuse to give up your medical identify in the many de-medicalized mental health clinics.
• Never let a patient leave your office without some psychotherapy, even as part of a 15-minute med-check.
• Stay current and on the cutting edge of evolving psychiatric practice by logging into PubMed every day (even briefly) to read a few abstracts of the latest studies related to patients you saw that day.
• Think like a neurologist by identifying the neural circuits of psychiatric symptoms. Act like a cardiologist by doing everything medically possible to prevent recurrence of psychotic, manic, or depressive episodes because they damage brain tissue just as a myocardial infarction damages the heart.
• Support research with words, money, and passion. Psychiatric neuroscientific breakthroughs generate superior treatments, erase stigma, and advance the quality of life for patients. Donate annually to the researchers of your choice, at the medical school where you were trained, or at a nonprofit research institute.
• Make time to write for publication, annually, at least 1 case report or a letter to the editor about observations from your practice. You can contribute immensely to the discovery process by sharing novel clinical insights.
• Never give up on any patient or set expectations too low, regardless of the diagnosis or severity of illness. Giving up destroys hope and ushers in despondency. Get a second opinion if you run out of options for a patient.
• Always set remission followed by recovery as the therapeutic goal for every patient. Let the patient know this and ask him (her) commit to that goal with you.
• Be genuinely proud to be a psychiatrist. You assess and rectify disorders of the mind, the most complex and magical product of the human brain that determines who we are and how we think, emote, communicate, verbalize, empathize, love, hate, remember, plan, problem-solve, and, of course, make resolutions.

Back to diet and exercise—for our patients and for us!
It’s OK to include, among your New Year’s resolutions, a pledge to strongly encourage patients to diet and exercise. Given the tendency of many of them to gain weight and die prematurely as a consequence of obesity-related cardiometabolic risk factors, you should urge them to eat healthy and exercise every time you see them, not only on New Year’s Day.