Henry A. Nasrallah, MD

The vast majority of psychiatrists and psychiatric nurse practitioners in the United States are aware of the following facts:

• The unhealthy lifestyle of persons with chronic psychotic disorders (sedentary living, smoking, poor diet) is conducive to weight gain, metabolic disorders, high cardiovascular risk, and premature mortality. ¹
• Second-generation antipsychotics (SGAs) are associated with metabolic dysregulation, including obesity, diabetes, dyslipidemia, and hypertension.²
• The dramatic increase in diabetes, diabetic ketoacidosis, and death in the late 1990s and early 2000s prompted the FDA in August 2003 to apply a class warning to the labels of all SGAs and require that practitioners monitor metabolic parameters in patients receiving SGAs, before and after initiating therapy.³
• The consensus statement published by the American Psychiatric Association (APA) and American Diabetes Association (ADA) in February 2004 reviewed the metabolic side-effects literature of SGAs and included guidelines for monitoring the metabolic status of patients at baseline and after initiating treatment, including family history of metabolic disorders, body mass index, waist circumference, blood pressure, fasting glucose, and fasting lipids.^4,5
• The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study⁶ confirmed the APA/ADA findings and indicated that 43% of 1,460 outpatients with schizophrenia met criteria for metabolic syndrome⁷ when they enrolled in the study and the prevalence of metabolic syndrome increased over the duration of the study.⁸
• The CATIE study also reported that a substantial proportion of patients with schizophrenia had no access to primary care and never received standard treatment for hyperlipidemia, hypertension, and diabetes,⁹ prompting an angry Current Psychiatry editorial.¹⁰

And now for the grim facts. It is simply shocking that many practitioners are not monitoring the metabolic status of their patients consistently or at all. A recent systematic review and meta-analysis of 48 published studies showed that clinicians who prescribed antipsychotics are not abiding by guidelines to monitor metabolic risk in their seriously ill psychotic patients.¹¹ The inconsistent monitoring was evident not only in the United States but also in Canada, the United Kingdom, Australia, and Spain. Thirty-nine of those studies were conducted on the pattern of monitoring before any guidelines were published and 9 were conducted after monitoring guidelines were published. All of them were equally dismal in their findings.

The most urgent question is why aren’t practitioners monitoring vulnerable, seriously mentally ill patients to protect them from potential iatrogenic harm? If we don’t do it, who will? Wouldn’t we be outraged if a family member was not receiving standard clinical monitoring for a serious medical condition? The language that the FDA inserted in SGA labels specifically states that intervention is required if hyperglycemia emerges during monitoring, including treatment or switch to a metabolically more benign antipsychotic agent. How can an intervention be implemented if the monitoring is not done in a timely manner?

Persons suffering from psychotic disorders such as schizophrenia are compromised mentally and physically. They rely on us to give them proper treatment and follow-up, driven by evidence as well as compassion and commitment. Our guiding principle is to treat while doing no harm. The potential benefit of antipsychotic pharmacotherapy is widely accepted and the potential harm also is well recognized; published guidelines help protect patients via early detection of metabolic dysregulation. There is absolutely no excuse for failing to provide patients who need antipsychotics with consistent, guideline-based monitoring. No excuses. None.

The vast majority of psychiatrists and psychiatric nurse practitioners in the United States are aware of the following facts:

• The unhealthy lifestyle of persons with chronic psychotic disorders (sedentary living, smoking, poor diet) is conducive to weight gain, metabolic disorders, high cardiovascular risk, and premature mortality. ¹
• Second-generation antipsychotics (SGAs) are associated with metabolic dysregulation, including obesity, diabetes, dyslipidemia, and hypertension.²
• The dramatic increase in diabetes, diabetic ketoacidosis, and death in the late 1990s and early 2000s prompted the FDA in August 2003 to apply a class warning to the labels of all SGAs and require that practitioners monitor metabolic parameters in patients receiving SGAs, before and after initiating therapy.³
• The consensus statement published by the American Psychiatric Association (APA) and American Diabetes Association (ADA) in February 2004 reviewed the metabolic side-effects literature of SGAs and included guidelines for monitoring the metabolic status of patients at baseline and after initiating treatment, including family history of metabolic disorders, body mass index, waist circumference, blood pressure, fasting glucose, and fasting lipids.^4,5
• The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study⁶ confirmed the APA/ADA findings and indicated that 43% of 1,460 outpatients with schizophrenia met criteria for metabolic syndrome⁷ when they enrolled in the study and the prevalence of metabolic syndrome increased over the duration of the study.⁸
• The CATIE study also reported that a substantial proportion of patients with schizophrenia had no access to primary care and never received standard treatment for hyperlipidemia, hypertension, and diabetes,⁹ prompting an angry Current Psychiatry editorial.¹⁰

And now for the grim facts. It is simply shocking that many practitioners are not monitoring the metabolic status of their patients consistently or at all. A recent systematic review and meta-analysis of 48 published studies showed that clinicians who prescribed antipsychotics are not abiding by guidelines to monitor metabolic risk in their seriously ill psychotic patients.¹¹ The inconsistent monitoring was evident not only in the United States but also in Canada, the United Kingdom, Australia, and Spain. Thirty-nine of those studies were conducted on the pattern of monitoring before any guidelines were published and 9 were conducted after monitoring guidelines were published. All of them were equally dismal in their findings.

The most urgent question is why aren’t practitioners monitoring vulnerable, seriously mentally ill patients to protect them from potential iatrogenic harm? If we don’t do it, who will? Wouldn’t we be outraged if a family member was not receiving standard clinical monitoring for a serious medical condition? The language that the FDA inserted in SGA labels specifically states that intervention is required if hyperglycemia emerges during monitoring, including treatment or switch to a metabolically more benign antipsychotic agent. How can an intervention be implemented if the monitoring is not done in a timely manner?

Persons suffering from psychotic disorders such as schizophrenia are compromised mentally and physically. They rely on us to give them proper treatment and follow-up, driven by evidence as well as compassion and commitment. Our guiding principle is to treat while doing no harm. The potential benefit of antipsychotic pharmacotherapy is widely accepted and the potential harm also is well recognized; published guidelines help protect patients via early detection of metabolic dysregulation. There is absolutely no excuse for failing to provide patients who need antipsychotics with consistent, guideline-based monitoring. No excuses. None.

The vast majority of psychiatrists and psychiatric nurse practitioners in the United States are aware of the following facts:

• The unhealthy lifestyle of persons with chronic psychotic disorders (sedentary living, smoking, poor diet) is conducive to weight gain, metabolic disorders, high cardiovascular risk, and premature mortality. ¹
• Second-generation antipsychotics (SGAs) are associated with metabolic dysregulation, including obesity, diabetes, dyslipidemia, and hypertension.²
• The dramatic increase in diabetes, diabetic ketoacidosis, and death in the late 1990s and early 2000s prompted the FDA in August 2003 to apply a class warning to the labels of all SGAs and require that practitioners monitor metabolic parameters in patients receiving SGAs, before and after initiating therapy.³
• The consensus statement published by the American Psychiatric Association (APA) and American Diabetes Association (ADA) in February 2004 reviewed the metabolic side-effects literature of SGAs and included guidelines for monitoring the metabolic status of patients at baseline and after initiating treatment, including family history of metabolic disorders, body mass index, waist circumference, blood pressure, fasting glucose, and fasting lipids.^4,5
• The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study⁶ confirmed the APA/ADA findings and indicated that 43% of 1,460 outpatients with schizophrenia met criteria for metabolic syndrome⁷ when they enrolled in the study and the prevalence of metabolic syndrome increased over the duration of the study.⁸
• The CATIE study also reported that a substantial proportion of patients with schizophrenia had no access to primary care and never received standard treatment for hyperlipidemia, hypertension, and diabetes,⁹ prompting an angry Current Psychiatry editorial.¹⁰

And now for the grim facts. It is simply shocking that many practitioners are not monitoring the metabolic status of their patients consistently or at all. A recent systematic review and meta-analysis of 48 published studies showed that clinicians who prescribed antipsychotics are not abiding by guidelines to monitor metabolic risk in their seriously ill psychotic patients.¹¹ The inconsistent monitoring was evident not only in the United States but also in Canada, the United Kingdom, Australia, and Spain. Thirty-nine of those studies were conducted on the pattern of monitoring before any guidelines were published and 9 were conducted after monitoring guidelines were published. All of them were equally dismal in their findings.

The most urgent question is why aren’t practitioners monitoring vulnerable, seriously mentally ill patients to protect them from potential iatrogenic harm? If we don’t do it, who will? Wouldn’t we be outraged if a family member was not receiving standard clinical monitoring for a serious medical condition? The language that the FDA inserted in SGA labels specifically states that intervention is required if hyperglycemia emerges during monitoring, including treatment or switch to a metabolically more benign antipsychotic agent. How can an intervention be implemented if the monitoring is not done in a timely manner?

Persons suffering from psychotic disorders such as schizophrenia are compromised mentally and physically. They rely on us to give them proper treatment and follow-up, driven by evidence as well as compassion and commitment. Our guiding principle is to treat while doing no harm. The potential benefit of antipsychotic pharmacotherapy is widely accepted and the potential harm also is well recognized; published guidelines help protect patients via early detection of metabolic dysregulation. There is absolutely no excuse for failing to provide patients who need antipsychotics with consistent, guideline-based monitoring. No excuses. None.

Beneath the current haze of the election buzz, a national anticipatory panic is building up because of the looming “fiscal cliff,” when massive government budget cuts are expected to have grave ramifications and bleak economic and existential repercussions.

Individuals from all political affiliations are frantically demanding that lawmakers do something to avoid a disastrous plunge into chaos for government institutions.

Paradoxically and inexplicably, nothing is being done so far to circumvent this impending doom scenario. A sword of Damocles is hanging over the nation, held, as the legend goes, at the pommel by a single hair of a horse’s tail!

I often feel that’s also what is happening in psychiatry. We are facing not 1, but multiple serious and disruptive challenges, crises, and threats to our profession and our patients. It evokes a grim image of multiple Damocles’ swords hanging over us. We do not seem to be doing anything tangible to avoid these dangerous and injurious swords. I quietly fear that living in imminent danger has become the “new normal” for psychiatry. That’s actually a euphemism for “massive denial.” We all seem to be going on with our lives as if we are not heading to our own version of a “fiscal cliff.” The apathy, inaction, and lack of a sense of urgency by “organized psychiatry” are astonishing, given the critical need for urgent action.

Consider the following swords of Damocles hanging over psychiatry:

• Down-to-the-bone budget cuts in public psychiatry with inadequate resources in community mental health and public hospitals.
• Severe bed shortages: psychiatry has dropped from the most overbedded medical specialty in the 1960s to the most underbedded one, with devastating adverse effects on acutely ill patients who need inpatient treatment.
• Unabating incarceration and criminalization of seriously mentally ill patients as a substitute for hospitalization or care at residential facilities.
• A chronic shortage of psychiatrists, which is fueling the argument by some mental health professions with no medical or advanced nursing background that they should be permitted to “acquire” prescription privileges, as if prescribing is a skill independent from the extensive training of 4 years of medical school plus 4 years of psychiatric training. The consequences for disabled patients will be low-quality, even dangerous care.
• The low rate of medical students choosing psychiatry as a career. The shortage of psychiatrists will worsen if attrition from retirement or mortality is not offset by substantial annual infusions of newly minted psychiatrists.
• The deplorably short life span of patients with severe mental illness—25 years less than non-mentally ill individuals—mainly attributable to excess cardiovascular risk and lack of access to adequate primary care as part of community mental health management.
• An anemic pipeline of psychiatric residents choosing careers as teachers or researchers. Huge student loans and lack of mentorship are only some of the reasons residents select clinical work over academic careers.
• Withdrawal of several major pharmaceutical companies from research and development to discover new psychiatric drugs. It would be more judicious to engage and partner with them instead of demonizing them simply because they are the only entities that design, develop, test, and produce psychiatric medications. The unmet needs in psychiatry are enormous, especially because 80% of DSM-IV-TR psychiatric disorders have no FDA-approved medication.
• A lack of coalescence and cohesiveness of psychiatrists in the United States. We have fragmented into small organizations and factions, speaking with several faint voices instead of one powerful voice. Other disciplines are far better organized and can lobby more effectively for their causes.
• A lack of participation by psychiatrists in their professional organizations and low support for political action committees to navigate the agenda of psychiatry at the local, state, and national levels. The image and influence of psychiatry can be bolstered only by ongoing member donations and the reverse will occur without consistent member support.
• The persistent stigma of mental illness that continues to haunt our patients, inhibits treatment-seeking, and undermines treatment adherence. Despite magnificent advances in the medical basis of mental disorders, psychiatric illnesses are not regarded with the same acceptance and understanding as other medical disorders.
• A frustrating lag in translating the veritable explosion in basic neuroscience discoveries into clinical applications for diagnosis or therapeutics. Psychiatry could benefit greatly if a sufficient number of well-funded translational researchers get involved. A partnership between the National Institute of Mental Health (NIMH)and the pharmaceutical industry can expedite this translation, but has yet to happen.

This list of “dangling swords” may appear daunting and overwhelming but if we shed our apathy and unite, we can parry their threats and emerge stronger. I do not claim to have the answers but I do have an abiding faith in the collective wisdom and abilities of my fellow psychiatrists, if they decide to mobilize. The root of our “fiscal cliff” is our chronic inaction, passivity, and lack of cohesiveness and a passionate pursuit of our shared goals. We better wake up and act soon before these Damocles’ swords start falling and inflicting their exquisite pain.

Beneath the current haze of the election buzz, a national anticipatory panic is building up because of the looming “fiscal cliff,” when massive government budget cuts are expected to have grave ramifications and bleak economic and existential repercussions.

Individuals from all political affiliations are frantically demanding that lawmakers do something to avoid a disastrous plunge into chaos for government institutions.

Paradoxically and inexplicably, nothing is being done so far to circumvent this impending doom scenario. A sword of Damocles is hanging over the nation, held, as the legend goes, at the pommel by a single hair of a horse’s tail!

I often feel that’s also what is happening in psychiatry. We are facing not 1, but multiple serious and disruptive challenges, crises, and threats to our profession and our patients. It evokes a grim image of multiple Damocles’ swords hanging over us. We do not seem to be doing anything tangible to avoid these dangerous and injurious swords. I quietly fear that living in imminent danger has become the “new normal” for psychiatry. That’s actually a euphemism for “massive denial.” We all seem to be going on with our lives as if we are not heading to our own version of a “fiscal cliff.” The apathy, inaction, and lack of a sense of urgency by “organized psychiatry” are astonishing, given the critical need for urgent action.

Consider the following swords of Damocles hanging over psychiatry:

• Down-to-the-bone budget cuts in public psychiatry with inadequate resources in community mental health and public hospitals.
• Severe bed shortages: psychiatry has dropped from the most overbedded medical specialty in the 1960s to the most underbedded one, with devastating adverse effects on acutely ill patients who need inpatient treatment.
• Unabating incarceration and criminalization of seriously mentally ill patients as a substitute for hospitalization or care at residential facilities.
• A chronic shortage of psychiatrists, which is fueling the argument by some mental health professions with no medical or advanced nursing background that they should be permitted to “acquire” prescription privileges, as if prescribing is a skill independent from the extensive training of 4 years of medical school plus 4 years of psychiatric training. The consequences for disabled patients will be low-quality, even dangerous care.
• The low rate of medical students choosing psychiatry as a career. The shortage of psychiatrists will worsen if attrition from retirement or mortality is not offset by substantial annual infusions of newly minted psychiatrists.
• The deplorably short life span of patients with severe mental illness—25 years less than non-mentally ill individuals—mainly attributable to excess cardiovascular risk and lack of access to adequate primary care as part of community mental health management.
• An anemic pipeline of psychiatric residents choosing careers as teachers or researchers. Huge student loans and lack of mentorship are only some of the reasons residents select clinical work over academic careers.
• Withdrawal of several major pharmaceutical companies from research and development to discover new psychiatric drugs. It would be more judicious to engage and partner with them instead of demonizing them simply because they are the only entities that design, develop, test, and produce psychiatric medications. The unmet needs in psychiatry are enormous, especially because 80% of DSM-IV-TR psychiatric disorders have no FDA-approved medication.
• A lack of coalescence and cohesiveness of psychiatrists in the United States. We have fragmented into small organizations and factions, speaking with several faint voices instead of one powerful voice. Other disciplines are far better organized and can lobby more effectively for their causes.
• A lack of participation by psychiatrists in their professional organizations and low support for political action committees to navigate the agenda of psychiatry at the local, state, and national levels. The image and influence of psychiatry can be bolstered only by ongoing member donations and the reverse will occur without consistent member support.
• The persistent stigma of mental illness that continues to haunt our patients, inhibits treatment-seeking, and undermines treatment adherence. Despite magnificent advances in the medical basis of mental disorders, psychiatric illnesses are not regarded with the same acceptance and understanding as other medical disorders.
• A frustrating lag in translating the veritable explosion in basic neuroscience discoveries into clinical applications for diagnosis or therapeutics. Psychiatry could benefit greatly if a sufficient number of well-funded translational researchers get involved. A partnership between the National Institute of Mental Health (NIMH)and the pharmaceutical industry can expedite this translation, but has yet to happen.

This list of “dangling swords” may appear daunting and overwhelming but if we shed our apathy and unite, we can parry their threats and emerge stronger. I do not claim to have the answers but I do have an abiding faith in the collective wisdom and abilities of my fellow psychiatrists, if they decide to mobilize. The root of our “fiscal cliff” is our chronic inaction, passivity, and lack of cohesiveness and a passionate pursuit of our shared goals. We better wake up and act soon before these Damocles’ swords start falling and inflicting their exquisite pain.

Beneath the current haze of the election buzz, a national anticipatory panic is building up because of the looming “fiscal cliff,” when massive government budget cuts are expected to have grave ramifications and bleak economic and existential repercussions.

Individuals from all political affiliations are frantically demanding that lawmakers do something to avoid a disastrous plunge into chaos for government institutions.

Paradoxically and inexplicably, nothing is being done so far to circumvent this impending doom scenario. A sword of Damocles is hanging over the nation, held, as the legend goes, at the pommel by a single hair of a horse’s tail!

I often feel that’s also what is happening in psychiatry. We are facing not 1, but multiple serious and disruptive challenges, crises, and threats to our profession and our patients. It evokes a grim image of multiple Damocles’ swords hanging over us. We do not seem to be doing anything tangible to avoid these dangerous and injurious swords. I quietly fear that living in imminent danger has become the “new normal” for psychiatry. That’s actually a euphemism for “massive denial.” We all seem to be going on with our lives as if we are not heading to our own version of a “fiscal cliff.” The apathy, inaction, and lack of a sense of urgency by “organized psychiatry” are astonishing, given the critical need for urgent action.

Consider the following swords of Damocles hanging over psychiatry:

• Down-to-the-bone budget cuts in public psychiatry with inadequate resources in community mental health and public hospitals.
• Severe bed shortages: psychiatry has dropped from the most overbedded medical specialty in the 1960s to the most underbedded one, with devastating adverse effects on acutely ill patients who need inpatient treatment.
• Unabating incarceration and criminalization of seriously mentally ill patients as a substitute for hospitalization or care at residential facilities.
• A chronic shortage of psychiatrists, which is fueling the argument by some mental health professions with no medical or advanced nursing background that they should be permitted to “acquire” prescription privileges, as if prescribing is a skill independent from the extensive training of 4 years of medical school plus 4 years of psychiatric training. The consequences for disabled patients will be low-quality, even dangerous care.
• The low rate of medical students choosing psychiatry as a career. The shortage of psychiatrists will worsen if attrition from retirement or mortality is not offset by substantial annual infusions of newly minted psychiatrists.
• The deplorably short life span of patients with severe mental illness—25 years less than non-mentally ill individuals—mainly attributable to excess cardiovascular risk and lack of access to adequate primary care as part of community mental health management.
• An anemic pipeline of psychiatric residents choosing careers as teachers or researchers. Huge student loans and lack of mentorship are only some of the reasons residents select clinical work over academic careers.
• Withdrawal of several major pharmaceutical companies from research and development to discover new psychiatric drugs. It would be more judicious to engage and partner with them instead of demonizing them simply because they are the only entities that design, develop, test, and produce psychiatric medications. The unmet needs in psychiatry are enormous, especially because 80% of DSM-IV-TR psychiatric disorders have no FDA-approved medication.
• A lack of coalescence and cohesiveness of psychiatrists in the United States. We have fragmented into small organizations and factions, speaking with several faint voices instead of one powerful voice. Other disciplines are far better organized and can lobby more effectively for their causes.
• A lack of participation by psychiatrists in their professional organizations and low support for political action committees to navigate the agenda of psychiatry at the local, state, and national levels. The image and influence of psychiatry can be bolstered only by ongoing member donations and the reverse will occur without consistent member support.
• The persistent stigma of mental illness that continues to haunt our patients, inhibits treatment-seeking, and undermines treatment adherence. Despite magnificent advances in the medical basis of mental disorders, psychiatric illnesses are not regarded with the same acceptance and understanding as other medical disorders.
• A frustrating lag in translating the veritable explosion in basic neuroscience discoveries into clinical applications for diagnosis or therapeutics. Psychiatry could benefit greatly if a sufficient number of well-funded translational researchers get involved. A partnership between the National Institute of Mental Health (NIMH)and the pharmaceutical industry can expedite this translation, but has yet to happen.

This list of “dangling swords” may appear daunting and overwhelming but if we shed our apathy and unite, we can parry their threats and emerge stronger. I do not claim to have the answers but I do have an abiding faith in the collective wisdom and abilities of my fellow psychiatrists, if they decide to mobilize. The root of our “fiscal cliff” is our chronic inaction, passivity, and lack of cohesiveness and a passionate pursuit of our shared goals. We better wake up and act soon before these Damocles’ swords start falling and inflicting their exquisite pain.

I have always regarded the French saying “plus ça change, plus c’est la même chose” (the more things change, the more they are the same) to be a quote for the ages. Nowhere is this truism more evident than in the fluctuations in incarceration of individuals with serious mental illness (SMI) in the United States and persecution of real and faux patients in certain regimes around the world.

A truly jarring 2010 report by E. Fuller Torrey et al¹ revealed the shocking deterioration and regression of the United States mental health system. In 2010, the percentage of persons with SMI in jails and prisons ballooned to the same as it was 170 years ago! The deplorable mistreatment of the mentally ill in 1840, due to pervasive ignorance, prompted legendary reformer Dorothea Dix to launch her historic campaign for a more humane (asylum-based) treatment of persons afflicted with severe mental disorders. How troubling it is that the iconic Dorothea Dix Hospital in Raleigh, NC was shuttered earlier this year! Built on >2,300 acres and eventually growing to 282 buildings (in 1974), housing approximately 3,000 patients cared for by >6,000 employees on 3 around-the-clock shifts, this institution was a revered symbol of the transition from unjust criminalization to humane medical treatment of the SMI population. All other states eventually established similar medical institutions to house, protect, and care for the severely mentally ill, even though no effective treatments were available until the serendipitous discovery that an anesthetic adjunctive agent, a phenothiazine called chlorpromazine, could miraculously suppress delusions, hallucinations, and bizarre behavior.

Throughout the 20^th century, while patients with SMI in the United States were hospitalized instead of incarcerated, several despotic regimes abused the mentally ill or misused psychiatric institutions as proxies for prisons. The malevolent and criminal Nazi regime determined that mentally ill or mentally challenged individuals were “unworthy to live” and turned many psychiatric institutions into “killing centers” to “euthanize” persons with SMI with lethal injections, and later with carbon monoxide. Some psychiatrists and clergy raised objections but they were ignored or suppressed.

The totalitarian Soviet Union was notorious for abusing psychiatry by “diagnosing” political dissenters as “schizophrenic” and incarcerating them for life in psychiatric hospitals, which eventually were transformed into political prisons for those protesting the dictatorship of the Soviet regime. Other communist countries adopted a similar approach to silence dissenters and some reportedly still are doing this today. Regrettably, a regressive event took place in America, a paragon of freedom and social justice in the world. In 1983, 6.4% of prison inmates had SMI. This proportion almost tripled to 16% in 2010 and continues to grow steadily. This tragic deterioration is embodied in the following statistics from Torrey et al¹: today there are 300% more patients with SMI in jails and prisons than in hospitals around the United States. Some states have truly scandalous figures: in Arizona and Nevada, there are 10 times more patients with SMI in prisons and jails than in hospitals!

There also is an alarming, even dangerous, shortage of psychiatric beds in the United States. Psychiatrists and other mental health professionals are painfully aware of how many inpatient units have closed in cities and towns across the country: In 1955, there was 1 psychiatric bed for every 300 citizens. In 2010, the ratio had fallen drastically to 1 bed for every 3,000 Americans. To make things worse, in most states most remaining beds are filled by court-ordered patients and are, in fact, not available for new patients.

Sadly, as was the case in 1840, the United States now incarcerates the majority of its seriously mentally ill citizens. So much has changed in the United States over the past 2 centuries, yet for patients with SMI, things are practically the same as in a medically primitive era of our past. How can we allow this virulent plague of widespread incarceration and criminalization that has afflicted the sickest and most vulnerable psychiatric patients, who are being denied the compassion and medical management that they deserve? When will we unite and strongly demand and lobby for a more just treatment of persons with psychiatric disorders and scream that they are medical conditions, not criminal cases? Why do we, mental health professionals, remain silent and go on with our daily work, implicitly accepting the awful status quo? Isn’t incarcerating, instead of hospitalizing, the truly mentally ill just as immoral and deplorable as forcibly hospitalizing mentally healthy political dissenters in the Soviet Union? Why was there universal condemnation of human rights violations by the Soviet dictatorship but a deafening silence about widespread incarceration of medically disabled persons in the land of the free? Why aren’t we adopting policies to expedite and facilitate psychiatric treatment, ensure adherence, and promote remission in those who suffer their first psychotic or manic episode? Why are we building more jails and prisons instead of therapeutic communities?

Although things have changed a lot in the United States since 1840, if a modern day Dorothea Dix does not emerge, then in many ways they will remain the same. And that’s a real shame.

I have always regarded the French saying “plus ça change, plus c’est la même chose” (the more things change, the more they are the same) to be a quote for the ages. Nowhere is this truism more evident than in the fluctuations in incarceration of individuals with serious mental illness (SMI) in the United States and persecution of real and faux patients in certain regimes around the world.

A truly jarring 2010 report by E. Fuller Torrey et al¹ revealed the shocking deterioration and regression of the United States mental health system. In 2010, the percentage of persons with SMI in jails and prisons ballooned to the same as it was 170 years ago! The deplorable mistreatment of the mentally ill in 1840, due to pervasive ignorance, prompted legendary reformer Dorothea Dix to launch her historic campaign for a more humane (asylum-based) treatment of persons afflicted with severe mental disorders. How troubling it is that the iconic Dorothea Dix Hospital in Raleigh, NC was shuttered earlier this year! Built on >2,300 acres and eventually growing to 282 buildings (in 1974), housing approximately 3,000 patients cared for by >6,000 employees on 3 around-the-clock shifts, this institution was a revered symbol of the transition from unjust criminalization to humane medical treatment of the SMI population. All other states eventually established similar medical institutions to house, protect, and care for the severely mentally ill, even though no effective treatments were available until the serendipitous discovery that an anesthetic adjunctive agent, a phenothiazine called chlorpromazine, could miraculously suppress delusions, hallucinations, and bizarre behavior.

Throughout the 20^th century, while patients with SMI in the United States were hospitalized instead of incarcerated, several despotic regimes abused the mentally ill or misused psychiatric institutions as proxies for prisons. The malevolent and criminal Nazi regime determined that mentally ill or mentally challenged individuals were “unworthy to live” and turned many psychiatric institutions into “killing centers” to “euthanize” persons with SMI with lethal injections, and later with carbon monoxide. Some psychiatrists and clergy raised objections but they were ignored or suppressed.

The totalitarian Soviet Union was notorious for abusing psychiatry by “diagnosing” political dissenters as “schizophrenic” and incarcerating them for life in psychiatric hospitals, which eventually were transformed into political prisons for those protesting the dictatorship of the Soviet regime. Other communist countries adopted a similar approach to silence dissenters and some reportedly still are doing this today. Regrettably, a regressive event took place in America, a paragon of freedom and social justice in the world. In 1983, 6.4% of prison inmates had SMI. This proportion almost tripled to 16% in 2010 and continues to grow steadily. This tragic deterioration is embodied in the following statistics from Torrey et al¹: today there are 300% more patients with SMI in jails and prisons than in hospitals around the United States. Some states have truly scandalous figures: in Arizona and Nevada, there are 10 times more patients with SMI in prisons and jails than in hospitals!

There also is an alarming, even dangerous, shortage of psychiatric beds in the United States. Psychiatrists and other mental health professionals are painfully aware of how many inpatient units have closed in cities and towns across the country: In 1955, there was 1 psychiatric bed for every 300 citizens. In 2010, the ratio had fallen drastically to 1 bed for every 3,000 Americans. To make things worse, in most states most remaining beds are filled by court-ordered patients and are, in fact, not available for new patients.

Sadly, as was the case in 1840, the United States now incarcerates the majority of its seriously mentally ill citizens. So much has changed in the United States over the past 2 centuries, yet for patients with SMI, things are practically the same as in a medically primitive era of our past. How can we allow this virulent plague of widespread incarceration and criminalization that has afflicted the sickest and most vulnerable psychiatric patients, who are being denied the compassion and medical management that they deserve? When will we unite and strongly demand and lobby for a more just treatment of persons with psychiatric disorders and scream that they are medical conditions, not criminal cases? Why do we, mental health professionals, remain silent and go on with our daily work, implicitly accepting the awful status quo? Isn’t incarcerating, instead of hospitalizing, the truly mentally ill just as immoral and deplorable as forcibly hospitalizing mentally healthy political dissenters in the Soviet Union? Why was there universal condemnation of human rights violations by the Soviet dictatorship but a deafening silence about widespread incarceration of medically disabled persons in the land of the free? Why aren’t we adopting policies to expedite and facilitate psychiatric treatment, ensure adherence, and promote remission in those who suffer their first psychotic or manic episode? Why are we building more jails and prisons instead of therapeutic communities?

Although things have changed a lot in the United States since 1840, if a modern day Dorothea Dix does not emerge, then in many ways they will remain the same. And that’s a real shame.

I have always regarded the French saying “plus ça change, plus c’est la même chose” (the more things change, the more they are the same) to be a quote for the ages. Nowhere is this truism more evident than in the fluctuations in incarceration of individuals with serious mental illness (SMI) in the United States and persecution of real and faux patients in certain regimes around the world.

A truly jarring 2010 report by E. Fuller Torrey et al¹ revealed the shocking deterioration and regression of the United States mental health system. In 2010, the percentage of persons with SMI in jails and prisons ballooned to the same as it was 170 years ago! The deplorable mistreatment of the mentally ill in 1840, due to pervasive ignorance, prompted legendary reformer Dorothea Dix to launch her historic campaign for a more humane (asylum-based) treatment of persons afflicted with severe mental disorders. How troubling it is that the iconic Dorothea Dix Hospital in Raleigh, NC was shuttered earlier this year! Built on >2,300 acres and eventually growing to 282 buildings (in 1974), housing approximately 3,000 patients cared for by >6,000 employees on 3 around-the-clock shifts, this institution was a revered symbol of the transition from unjust criminalization to humane medical treatment of the SMI population. All other states eventually established similar medical institutions to house, protect, and care for the severely mentally ill, even though no effective treatments were available until the serendipitous discovery that an anesthetic adjunctive agent, a phenothiazine called chlorpromazine, could miraculously suppress delusions, hallucinations, and bizarre behavior.

Throughout the 20^th century, while patients with SMI in the United States were hospitalized instead of incarcerated, several despotic regimes abused the mentally ill or misused psychiatric institutions as proxies for prisons. The malevolent and criminal Nazi regime determined that mentally ill or mentally challenged individuals were “unworthy to live” and turned many psychiatric institutions into “killing centers” to “euthanize” persons with SMI with lethal injections, and later with carbon monoxide. Some psychiatrists and clergy raised objections but they were ignored or suppressed.

The totalitarian Soviet Union was notorious for abusing psychiatry by “diagnosing” political dissenters as “schizophrenic” and incarcerating them for life in psychiatric hospitals, which eventually were transformed into political prisons for those protesting the dictatorship of the Soviet regime. Other communist countries adopted a similar approach to silence dissenters and some reportedly still are doing this today. Regrettably, a regressive event took place in America, a paragon of freedom and social justice in the world. In 1983, 6.4% of prison inmates had SMI. This proportion almost tripled to 16% in 2010 and continues to grow steadily. This tragic deterioration is embodied in the following statistics from Torrey et al¹: today there are 300% more patients with SMI in jails and prisons than in hospitals around the United States. Some states have truly scandalous figures: in Arizona and Nevada, there are 10 times more patients with SMI in prisons and jails than in hospitals!

There also is an alarming, even dangerous, shortage of psychiatric beds in the United States. Psychiatrists and other mental health professionals are painfully aware of how many inpatient units have closed in cities and towns across the country: In 1955, there was 1 psychiatric bed for every 300 citizens. In 2010, the ratio had fallen drastically to 1 bed for every 3,000 Americans. To make things worse, in most states most remaining beds are filled by court-ordered patients and are, in fact, not available for new patients.

Sadly, as was the case in 1840, the United States now incarcerates the majority of its seriously mentally ill citizens. So much has changed in the United States over the past 2 centuries, yet for patients with SMI, things are practically the same as in a medically primitive era of our past. How can we allow this virulent plague of widespread incarceration and criminalization that has afflicted the sickest and most vulnerable psychiatric patients, who are being denied the compassion and medical management that they deserve? When will we unite and strongly demand and lobby for a more just treatment of persons with psychiatric disorders and scream that they are medical conditions, not criminal cases? Why do we, mental health professionals, remain silent and go on with our daily work, implicitly accepting the awful status quo? Isn’t incarcerating, instead of hospitalizing, the truly mentally ill just as immoral and deplorable as forcibly hospitalizing mentally healthy political dissenters in the Soviet Union? Why was there universal condemnation of human rights violations by the Soviet dictatorship but a deafening silence about widespread incarceration of medically disabled persons in the land of the free? Why aren’t we adopting policies to expedite and facilitate psychiatric treatment, ensure adherence, and promote remission in those who suffer their first psychotic or manic episode? Why are we building more jails and prisons instead of therapeutic communities?

Although things have changed a lot in the United States since 1840, if a modern day Dorothea Dix does not emerge, then in many ways they will remain the same. And that’s a real shame.

On July 20 of every year, I recall the transcendent wonder I felt on that day in 1969 when the entire world and I were glued to our television sets, witnessing one of the greatest achievements in the history of the human race: American astronauts landing on the moon and beaming pictures of their extraordinary celestial expedition to the billions of earthlings sitting on the edge of their seats.

Every year on July 20, I ponder the supreme and brilliant abilities of the human brain that transformed walking on the moon from an absurd fantasy to a thrilling reality. After becoming a psychiatrist, trained to observe everything through the prism of mind and brain, the moon landing represented the zenith achievement of the divinely evolved human neocortex, especially the prefrontal lobe of President John F. Kennedy, who established that lofty goal, and the advanced brains of thousands of NASA scientists and engineers, who set out to fulfill that towering expectation in less than a decade. That’s why every year on July 20, my abiding faith in the limitless capacities of the human brain to do great things is confirmed and reinforced.

However, this year was different as July 20 took on a much darker meaning. The tragic shooting in Aurora, CO that killed 12 people and wounded 58 others—perpetrated by the bizarre machinations of a graduate school student who had been receiving psychiatric treatment when he suddenly dropped out—rudely reminded me how, like the moon, the human brain has a dark side. A healthy brain that can envision, plan, and execute a magnificent moon landing is capable, when perturbed, of carrying out a dreadfully heinous crime. So henceforth, July 20 always will remind me of the zenith vs nadir dichotomy of the human mind potential in health and disease.

As a longtime academic psychiatrist, I have repeatedly witnessed the tragic disability my patients suffer when the frontal lobe—the most advanced component of their brains— becomes seriously impaired, rendering them dysfunctional. Unless driven by an intense delusion or command hallucinations, patients with schizophrenia rarely commit a murder. However, the media often has linked psychosis with violent crime, whether in movies¹ or in news reporting, which has led to public misconception that every person suffering from psychosis is a potential mass murderer. The truth is that the vast majority of murders are committed by nonpsychotic criminals with severe antisocial traits.

Because of the shocking killings in Aurora, July 20 may become an annual reminder that perpetuates the unfair and ignorant notion that mental illness always is associated with horrendous crimes. That would further darken the discriminatory stigma of mental illness and may foster a hatred of and aversion to mentally ill individuals, the vast majority of whom are law-abiding citizens. Even the legally mandated “not guilty by reason of insanity” defense is being described as a spurious “excuse” and is under assault, which may lead to death sentences for medically ill persons whose actions are triggered by a severe brain pathology that impairs judgment and distorts reality testing of what is right or wrong.

The devastated families of the victims also are very much on my mind. For them, July 20 will become a dark anniversary of how their loved ones—most of whom were in the prime of life—lost theirs lives while watching a movie called The Dark Knight Rises. Their annual grief on July 20 will for many years reopen the deep wounds inflicted on their souls.

In the future, on July 20 I will no longer be merely inspired by the human brain’s potential for achievements. I now also will remember the potential for despicable and murderous actions when a sickened human brain and its convoluted mind go terribly awry. As an academic investigator dedicated to finding a cure for schizophrenia and related disorders, I regard the tragic events in Aurora on July 20, 2012 as another call to escalate the commitment of researchers to restore normalcy to the blighted brains of those afflicted by this cruel disease, or, better yet, to ultimately discover how to prevent schizophrenia from developing. Only then will the darkness of severe mental illness finally ebb and vanish.

Editor's Note: This editorial was written before Neil Armstrong, the first man to walk on the moon, died on August 25, 2012.

On July 20 of every year, I recall the transcendent wonder I felt on that day in 1969 when the entire world and I were glued to our television sets, witnessing one of the greatest achievements in the history of the human race: American astronauts landing on the moon and beaming pictures of their extraordinary celestial expedition to the billions of earthlings sitting on the edge of their seats.

Every year on July 20, I ponder the supreme and brilliant abilities of the human brain that transformed walking on the moon from an absurd fantasy to a thrilling reality. After becoming a psychiatrist, trained to observe everything through the prism of mind and brain, the moon landing represented the zenith achievement of the divinely evolved human neocortex, especially the prefrontal lobe of President John F. Kennedy, who established that lofty goal, and the advanced brains of thousands of NASA scientists and engineers, who set out to fulfill that towering expectation in less than a decade. That’s why every year on July 20, my abiding faith in the limitless capacities of the human brain to do great things is confirmed and reinforced.

However, this year was different as July 20 took on a much darker meaning. The tragic shooting in Aurora, CO that killed 12 people and wounded 58 others—perpetrated by the bizarre machinations of a graduate school student who had been receiving psychiatric treatment when he suddenly dropped out—rudely reminded me how, like the moon, the human brain has a dark side. A healthy brain that can envision, plan, and execute a magnificent moon landing is capable, when perturbed, of carrying out a dreadfully heinous crime. So henceforth, July 20 always will remind me of the zenith vs nadir dichotomy of the human mind potential in health and disease.

As a longtime academic psychiatrist, I have repeatedly witnessed the tragic disability my patients suffer when the frontal lobe—the most advanced component of their brains— becomes seriously impaired, rendering them dysfunctional. Unless driven by an intense delusion or command hallucinations, patients with schizophrenia rarely commit a murder. However, the media often has linked psychosis with violent crime, whether in movies¹ or in news reporting, which has led to public misconception that every person suffering from psychosis is a potential mass murderer. The truth is that the vast majority of murders are committed by nonpsychotic criminals with severe antisocial traits.

Because of the shocking killings in Aurora, July 20 may become an annual reminder that perpetuates the unfair and ignorant notion that mental illness always is associated with horrendous crimes. That would further darken the discriminatory stigma of mental illness and may foster a hatred of and aversion to mentally ill individuals, the vast majority of whom are law-abiding citizens. Even the legally mandated “not guilty by reason of insanity” defense is being described as a spurious “excuse” and is under assault, which may lead to death sentences for medically ill persons whose actions are triggered by a severe brain pathology that impairs judgment and distorts reality testing of what is right or wrong.

The devastated families of the victims also are very much on my mind. For them, July 20 will become a dark anniversary of how their loved ones—most of whom were in the prime of life—lost theirs lives while watching a movie called The Dark Knight Rises. Their annual grief on July 20 will for many years reopen the deep wounds inflicted on their souls.

In the future, on July 20 I will no longer be merely inspired by the human brain’s potential for achievements. I now also will remember the potential for despicable and murderous actions when a sickened human brain and its convoluted mind go terribly awry. As an academic investigator dedicated to finding a cure for schizophrenia and related disorders, I regard the tragic events in Aurora on July 20, 2012 as another call to escalate the commitment of researchers to restore normalcy to the blighted brains of those afflicted by this cruel disease, or, better yet, to ultimately discover how to prevent schizophrenia from developing. Only then will the darkness of severe mental illness finally ebb and vanish.

Editor's Note: This editorial was written before Neil Armstrong, the first man to walk on the moon, died on August 25, 2012.

On July 20 of every year, I recall the transcendent wonder I felt on that day in 1969 when the entire world and I were glued to our television sets, witnessing one of the greatest achievements in the history of the human race: American astronauts landing on the moon and beaming pictures of their extraordinary celestial expedition to the billions of earthlings sitting on the edge of their seats.

Every year on July 20, I ponder the supreme and brilliant abilities of the human brain that transformed walking on the moon from an absurd fantasy to a thrilling reality. After becoming a psychiatrist, trained to observe everything through the prism of mind and brain, the moon landing represented the zenith achievement of the divinely evolved human neocortex, especially the prefrontal lobe of President John F. Kennedy, who established that lofty goal, and the advanced brains of thousands of NASA scientists and engineers, who set out to fulfill that towering expectation in less than a decade. That’s why every year on July 20, my abiding faith in the limitless capacities of the human brain to do great things is confirmed and reinforced.

However, this year was different as July 20 took on a much darker meaning. The tragic shooting in Aurora, CO that killed 12 people and wounded 58 others—perpetrated by the bizarre machinations of a graduate school student who had been receiving psychiatric treatment when he suddenly dropped out—rudely reminded me how, like the moon, the human brain has a dark side. A healthy brain that can envision, plan, and execute a magnificent moon landing is capable, when perturbed, of carrying out a dreadfully heinous crime. So henceforth, July 20 always will remind me of the zenith vs nadir dichotomy of the human mind potential in health and disease.

As a longtime academic psychiatrist, I have repeatedly witnessed the tragic disability my patients suffer when the frontal lobe—the most advanced component of their brains— becomes seriously impaired, rendering them dysfunctional. Unless driven by an intense delusion or command hallucinations, patients with schizophrenia rarely commit a murder. However, the media often has linked psychosis with violent crime, whether in movies¹ or in news reporting, which has led to public misconception that every person suffering from psychosis is a potential mass murderer. The truth is that the vast majority of murders are committed by nonpsychotic criminals with severe antisocial traits.

Because of the shocking killings in Aurora, July 20 may become an annual reminder that perpetuates the unfair and ignorant notion that mental illness always is associated with horrendous crimes. That would further darken the discriminatory stigma of mental illness and may foster a hatred of and aversion to mentally ill individuals, the vast majority of whom are law-abiding citizens. Even the legally mandated “not guilty by reason of insanity” defense is being described as a spurious “excuse” and is under assault, which may lead to death sentences for medically ill persons whose actions are triggered by a severe brain pathology that impairs judgment and distorts reality testing of what is right or wrong.

The devastated families of the victims also are very much on my mind. For them, July 20 will become a dark anniversary of how their loved ones—most of whom were in the prime of life—lost theirs lives while watching a movie called The Dark Knight Rises. Their annual grief on July 20 will for many years reopen the deep wounds inflicted on their souls.

In the future, on July 20 I will no longer be merely inspired by the human brain’s potential for achievements. I now also will remember the potential for despicable and murderous actions when a sickened human brain and its convoluted mind go terribly awry. As an academic investigator dedicated to finding a cure for schizophrenia and related disorders, I regard the tragic events in Aurora on July 20, 2012 as another call to escalate the commitment of researchers to restore normalcy to the blighted brains of those afflicted by this cruel disease, or, better yet, to ultimately discover how to prevent schizophrenia from developing. Only then will the darkness of severe mental illness finally ebb and vanish.

Editor's Note: This editorial was written before Neil Armstrong, the first man to walk on the moon, died on August 25, 2012.

Psychiatrists recognize that schizophrenia is a disorder in which the highest mental functions, such as thought, language, emotions, conation, and cognition, are drastically disrupted. However, the most serious impairment in schizophrenia is a global malfunction in self-integration and personal identity that includes a deficit in self-recognition.

This distorted sense of self leads persons with schizophrenia to fail to recognize what is or is not part of their own mind, which can produce clinical symptoms of schizophrenia, including bizarre delusions, hallucinations, thought disorder, social deficits, and information processing.¹

Just as intact physical proprioception enables a healthy person to be continuously aware of where his body and its parts are located in space, allowing sensory-motor integration, mental proprioception enables one to be fully aware of his identity and self-boundaries, and that his thoughts and actions are generated from within his own sphere of consciousness, not from an external source. In schizophrenia, the coherent sense of self is shattered and fragmented, a frightening experience patients describe after emerging from psychosis.² A person affected by schizophrenia feels lost, as if his “self no longer belong[s]” to him. He feels alienated from his “real self” and refers to himself in the third person. He feels “disconnected, disintegrated, and diminished,” with a sense of “emptiness, a painful void of existence,” of being disembodied with no clear demarcation between self and others.²

Not surprisingly, false beliefs (delusions) and perceptual aberrations (hallucinations) emerge from a fragmented sense of self. Patients fail to recognize that their actions, thoughts, or feelings are initiated from within the self, leading to delusions of passivity and being controlled by an outside force. One’s impulses are misperceived as being imposed by an alien. One’s thoughts, fantasies, and memories become external hallucinations instead of internal recollections. It is not surprising that depersonalization and derealization are common in schizophrenia and in the prodrome stage. Phencyclidine and ketamine, which can produce schizophrenia-like psychoses, are known to trigger dissociative phenomena and a loss of a coherent sense of self.

What causes the disintegration of the mind (self) in schizophrenia? The leading neurobiologic explanation is well-documented white matter pathology.³ Numerous studies have demonstrated that the myelinated axons and fibers that connect various brain regions are abnormal in patients with schizophrenia. The evidence for the breakdown of white matter—and, consequently, brain connectedness and integration—includes several lines of evidence, such as: a) in vivo neuroimaging studies using diffusion tensor imaging (DTI) that show abnormal water mobility in the myelin; b) genetic aberrations in myelin genes; c) postmortem evidence of reduced oligodendrocytes, the glial cells that manufacture myelin; and d) biochemical markers such as the calcium-binding protein S100B, which is released by compromised glial cells.³

Therefore, it is reasonable to think that the disruption of the sense of self and its proprioception may be due to the extensive disconnectivity of brain regions caused by myelin pathology.⁴ However, grey matter abnormality also may play a role in loss of mental proprioceptive functions, which causes a failure to properly recognize one’s self. The inferior parietal cortex, which controls body image, concept of self, sensory integration, and executive function, has been reported to be structurally impaired in patients with schizophrenia.⁵ Damage to the parietal cortex can alter awareness in healthy persons that they are initiating a voluntary action as they do it.⁶ Furthermore, refractory auditory hallucinations can be suppressed with repetitive transcranial magnetic stimulation (rTMS) or with transcranial direct current stimulation (tDCS) over the left parietotemporal area.⁷

More than 25 years ago, I published a hypothesis⁸ postulating that the delusions of passivity and external control may be caused by an abnormality in the corpus callosum—the largest white matter bundle in the brain, comprised of approximately 200 million myelinated fibers connecting homologous regions in the left and right cerebral hemispheres. I proposed that failed inter- hemispheric connectivity across the corpus callosum would disrupt the unified sense of self that integrates the 2 hemispheres, each of which has its own sphere of consciousness, producing hallucinations and delusions of alien control. The discovery of multiple white matter abnormalities over the past decade and acceptance of disconnectivity in schizophrenia confirms the model I proposed in 1985 as a possible mechanism for schizophrenia.⁹

Finally, it is interesting that DSM-IV-TR does not contain any reference to self disorder or fragmentation in schizophrenia, and diagnostic criteria do not include any reference to loss of self-identity in schizophrenia despite the extensive literature. The term “self” does not even appear in the index. Perhaps now is an opportune time to incorporate this new knowledge in DSM-5 and even consider a new name for schizophrenia. How about “self-proprioception disorder”?

Psychiatrists recognize that schizophrenia is a disorder in which the highest mental functions, such as thought, language, emotions, conation, and cognition, are drastically disrupted. However, the most serious impairment in schizophrenia is a global malfunction in self-integration and personal identity that includes a deficit in self-recognition.

This distorted sense of self leads persons with schizophrenia to fail to recognize what is or is not part of their own mind, which can produce clinical symptoms of schizophrenia, including bizarre delusions, hallucinations, thought disorder, social deficits, and information processing.¹

Just as intact physical proprioception enables a healthy person to be continuously aware of where his body and its parts are located in space, allowing sensory-motor integration, mental proprioception enables one to be fully aware of his identity and self-boundaries, and that his thoughts and actions are generated from within his own sphere of consciousness, not from an external source. In schizophrenia, the coherent sense of self is shattered and fragmented, a frightening experience patients describe after emerging from psychosis.² A person affected by schizophrenia feels lost, as if his “self no longer belong[s]” to him. He feels alienated from his “real self” and refers to himself in the third person. He feels “disconnected, disintegrated, and diminished,” with a sense of “emptiness, a painful void of existence,” of being disembodied with no clear demarcation between self and others.²

Not surprisingly, false beliefs (delusions) and perceptual aberrations (hallucinations) emerge from a fragmented sense of self. Patients fail to recognize that their actions, thoughts, or feelings are initiated from within the self, leading to delusions of passivity and being controlled by an outside force. One’s impulses are misperceived as being imposed by an alien. One’s thoughts, fantasies, and memories become external hallucinations instead of internal recollections. It is not surprising that depersonalization and derealization are common in schizophrenia and in the prodrome stage. Phencyclidine and ketamine, which can produce schizophrenia-like psychoses, are known to trigger dissociative phenomena and a loss of a coherent sense of self.

What causes the disintegration of the mind (self) in schizophrenia? The leading neurobiologic explanation is well-documented white matter pathology.³ Numerous studies have demonstrated that the myelinated axons and fibers that connect various brain regions are abnormal in patients with schizophrenia. The evidence for the breakdown of white matter—and, consequently, brain connectedness and integration—includes several lines of evidence, such as: a) in vivo neuroimaging studies using diffusion tensor imaging (DTI) that show abnormal water mobility in the myelin; b) genetic aberrations in myelin genes; c) postmortem evidence of reduced oligodendrocytes, the glial cells that manufacture myelin; and d) biochemical markers such as the calcium-binding protein S100B, which is released by compromised glial cells.³

Therefore, it is reasonable to think that the disruption of the sense of self and its proprioception may be due to the extensive disconnectivity of brain regions caused by myelin pathology.⁴ However, grey matter abnormality also may play a role in loss of mental proprioceptive functions, which causes a failure to properly recognize one’s self. The inferior parietal cortex, which controls body image, concept of self, sensory integration, and executive function, has been reported to be structurally impaired in patients with schizophrenia.⁵ Damage to the parietal cortex can alter awareness in healthy persons that they are initiating a voluntary action as they do it.⁶ Furthermore, refractory auditory hallucinations can be suppressed with repetitive transcranial magnetic stimulation (rTMS) or with transcranial direct current stimulation (tDCS) over the left parietotemporal area.⁷

More than 25 years ago, I published a hypothesis⁸ postulating that the delusions of passivity and external control may be caused by an abnormality in the corpus callosum—the largest white matter bundle in the brain, comprised of approximately 200 million myelinated fibers connecting homologous regions in the left and right cerebral hemispheres. I proposed that failed inter- hemispheric connectivity across the corpus callosum would disrupt the unified sense of self that integrates the 2 hemispheres, each of which has its own sphere of consciousness, producing hallucinations and delusions of alien control. The discovery of multiple white matter abnormalities over the past decade and acceptance of disconnectivity in schizophrenia confirms the model I proposed in 1985 as a possible mechanism for schizophrenia.⁹

Finally, it is interesting that DSM-IV-TR does not contain any reference to self disorder or fragmentation in schizophrenia, and diagnostic criteria do not include any reference to loss of self-identity in schizophrenia despite the extensive literature. The term “self” does not even appear in the index. Perhaps now is an opportune time to incorporate this new knowledge in DSM-5 and even consider a new name for schizophrenia. How about “self-proprioception disorder”?

Psychiatrists recognize that schizophrenia is a disorder in which the highest mental functions, such as thought, language, emotions, conation, and cognition, are drastically disrupted. However, the most serious impairment in schizophrenia is a global malfunction in self-integration and personal identity that includes a deficit in self-recognition.

This distorted sense of self leads persons with schizophrenia to fail to recognize what is or is not part of their own mind, which can produce clinical symptoms of schizophrenia, including bizarre delusions, hallucinations, thought disorder, social deficits, and information processing.¹

Just as intact physical proprioception enables a healthy person to be continuously aware of where his body and its parts are located in space, allowing sensory-motor integration, mental proprioception enables one to be fully aware of his identity and self-boundaries, and that his thoughts and actions are generated from within his own sphere of consciousness, not from an external source. In schizophrenia, the coherent sense of self is shattered and fragmented, a frightening experience patients describe after emerging from psychosis.² A person affected by schizophrenia feels lost, as if his “self no longer belong[s]” to him. He feels alienated from his “real self” and refers to himself in the third person. He feels “disconnected, disintegrated, and diminished,” with a sense of “emptiness, a painful void of existence,” of being disembodied with no clear demarcation between self and others.²

Not surprisingly, false beliefs (delusions) and perceptual aberrations (hallucinations) emerge from a fragmented sense of self. Patients fail to recognize that their actions, thoughts, or feelings are initiated from within the self, leading to delusions of passivity and being controlled by an outside force. One’s impulses are misperceived as being imposed by an alien. One’s thoughts, fantasies, and memories become external hallucinations instead of internal recollections. It is not surprising that depersonalization and derealization are common in schizophrenia and in the prodrome stage. Phencyclidine and ketamine, which can produce schizophrenia-like psychoses, are known to trigger dissociative phenomena and a loss of a coherent sense of self.

What causes the disintegration of the mind (self) in schizophrenia? The leading neurobiologic explanation is well-documented white matter pathology.³ Numerous studies have demonstrated that the myelinated axons and fibers that connect various brain regions are abnormal in patients with schizophrenia. The evidence for the breakdown of white matter—and, consequently, brain connectedness and integration—includes several lines of evidence, such as: a) in vivo neuroimaging studies using diffusion tensor imaging (DTI) that show abnormal water mobility in the myelin; b) genetic aberrations in myelin genes; c) postmortem evidence of reduced oligodendrocytes, the glial cells that manufacture myelin; and d) biochemical markers such as the calcium-binding protein S100B, which is released by compromised glial cells.³

Therefore, it is reasonable to think that the disruption of the sense of self and its proprioception may be due to the extensive disconnectivity of brain regions caused by myelin pathology.⁴ However, grey matter abnormality also may play a role in loss of mental proprioceptive functions, which causes a failure to properly recognize one’s self. The inferior parietal cortex, which controls body image, concept of self, sensory integration, and executive function, has been reported to be structurally impaired in patients with schizophrenia.⁵ Damage to the parietal cortex can alter awareness in healthy persons that they are initiating a voluntary action as they do it.⁶ Furthermore, refractory auditory hallucinations can be suppressed with repetitive transcranial magnetic stimulation (rTMS) or with transcranial direct current stimulation (tDCS) over the left parietotemporal area.⁷

More than 25 years ago, I published a hypothesis⁸ postulating that the delusions of passivity and external control may be caused by an abnormality in the corpus callosum—the largest white matter bundle in the brain, comprised of approximately 200 million myelinated fibers connecting homologous regions in the left and right cerebral hemispheres. I proposed that failed inter- hemispheric connectivity across the corpus callosum would disrupt the unified sense of self that integrates the 2 hemispheres, each of which has its own sphere of consciousness, producing hallucinations and delusions of alien control. The discovery of multiple white matter abnormalities over the past decade and acceptance of disconnectivity in schizophrenia confirms the model I proposed in 1985 as a possible mechanism for schizophrenia.⁹

Finally, it is interesting that DSM-IV-TR does not contain any reference to self disorder or fragmentation in schizophrenia, and diagnostic criteria do not include any reference to loss of self-identity in schizophrenia despite the extensive literature. The term “self” does not even appear in the index. Perhaps now is an opportune time to incorporate this new knowledge in DSM-5 and even consider a new name for schizophrenia. How about “self-proprioception disorder”?

For many scientists and clinicians, serendipity is a welcome blessing. It can result in the fortuitous discovery of a new treatment for a previously untreatable illness. In psychiatry, there are several examples, including chlorpromazine for psychosis and monoamine oxidase inhibitors and tricyclics for depression. But serendipity also can have a downside. It can skew and misdirect research efforts into one direction to the exclusion of others, which can be a curse in the pursuit of scientific truth.

For example, consider major depressive disorder (MDD), which is a major public health challenge with enormous direct and indirect costs to society. MDD is the most disabling medical disorder not just in psychiatry, but in the entire field of medicine (psychiatry claims 3 other disorders in the top 5: schizophrenia, bipolar disorder, and alcohol abuse).¹ In the United States, 8% to 10% of the population—children, adolescents, adults, and geriatric patients—suffer from depression at some point in their lives, and many will attempt suicide or die from self-inflicted injury if their depression is left untreated.² In the United States, 34,000 persons die each year from suicide³; most of them have MDD.⁴

Despite the gravity of depression’s disabling effects, MDD treatment barely has budged from the entrenched model constructed around increasing the availability of ≥1 monoamines—serotonin, norepinephrine, and dopamine—in the brain. For the past 5 decades, researchers have not deviated from the therapeutic dogma spawned by serendipity. Yet the efficacy of antidepressants from tricyclics to selective serotonin reuptake inhibitors to serotonin-norepinephrine reuptake inhibitors has been less than stellar, with remission in a few patients, partial response in others, and treatment resistance in many.

This is not surprising given that depression is a diverse syndrome, a heterogeneous gamut of disorders with variable pathogenesis but a shared clinical phenotype. So why did the pharmaceutical industry continue to develop drugs that inhibit the reuptake of one monoamine or another instead of innovating and developing novel agents with diverse mechanisms of action? Powerful inertia of the serendipitously discovered older antidepressants has persisted, without the benefit of new, “out-of-the-monoamine-box” innovative discovery based on emerging pathophysiologic research in mood disorders.

Things finally may be changing. Basic neuroscience and animal models have generated a wealth of new mechanisms and pathways that seem to work in animal models of depression, such as learned helplessness and social defeat.⁵ The old mold of monoamine reuptake inhibition soon may be replaced by a plethora of alternatives that may transform the landscape of depression treatment.

Emerging therapeutic targets

Consider the following novel mechanisms that may become the basis for creating entirely new antidepressants in the foreseeable future, by design, not by serendipity:

• corticotropin-releasing factor (CRF) and glucocorticoids
• neurokinin system
• brain derived neurotropic factor (BDNF) and other neurotropins, such as fibroblast growth factor (FGF) or vascular endothelial growth factor (VEGF)
• phosphodiesterase inhibitors
• glutamate pathway modulators
• hypothalamic feeding peptides
• circadian gene products
• other evolving antidepressants

It is heartening to psychiatrists and their chronically depressed patients that many novel mechanisms and therapeutic targets have emerged, thanks to intensive research, not serendipity and happenstance. Although that’s uplifting news, the sobering downside is the lack of sufficient resources to expedite translational research. We need far more funding than what is available, and several pharmaceutical companies have dismantled their psychiatry research infrastructure and laid off thousands of scientists. This may be the time when strong philanthropic support may have to come to the rescue of this worthy cause, similar to how the Bill & Melinda Gates Foundation has focused on eradicating malaria. If only a multi-billionaire would adopt depression research as his or her pet charity with the goal of discovering several effective new treatments for the most disabling medical disorder in the world. What a fantastic legacy that would be.

Serendipity is out, intensive (and expensive!) brain research is in! Calling all enlightened billionaires…

For many scientists and clinicians, serendipity is a welcome blessing. It can result in the fortuitous discovery of a new treatment for a previously untreatable illness. In psychiatry, there are several examples, including chlorpromazine for psychosis and monoamine oxidase inhibitors and tricyclics for depression. But serendipity also can have a downside. It can skew and misdirect research efforts into one direction to the exclusion of others, which can be a curse in the pursuit of scientific truth.

For example, consider major depressive disorder (MDD), which is a major public health challenge with enormous direct and indirect costs to society. MDD is the most disabling medical disorder not just in psychiatry, but in the entire field of medicine (psychiatry claims 3 other disorders in the top 5: schizophrenia, bipolar disorder, and alcohol abuse).¹ In the United States, 8% to 10% of the population—children, adolescents, adults, and geriatric patients—suffer from depression at some point in their lives, and many will attempt suicide or die from self-inflicted injury if their depression is left untreated.² In the United States, 34,000 persons die each year from suicide³; most of them have MDD.⁴

Despite the gravity of depression’s disabling effects, MDD treatment barely has budged from the entrenched model constructed around increasing the availability of ≥1 monoamines—serotonin, norepinephrine, and dopamine—in the brain. For the past 5 decades, researchers have not deviated from the therapeutic dogma spawned by serendipity. Yet the efficacy of antidepressants from tricyclics to selective serotonin reuptake inhibitors to serotonin-norepinephrine reuptake inhibitors has been less than stellar, with remission in a few patients, partial response in others, and treatment resistance in many.

This is not surprising given that depression is a diverse syndrome, a heterogeneous gamut of disorders with variable pathogenesis but a shared clinical phenotype. So why did the pharmaceutical industry continue to develop drugs that inhibit the reuptake of one monoamine or another instead of innovating and developing novel agents with diverse mechanisms of action? Powerful inertia of the serendipitously discovered older antidepressants has persisted, without the benefit of new, “out-of-the-monoamine-box” innovative discovery based on emerging pathophysiologic research in mood disorders.

Things finally may be changing. Basic neuroscience and animal models have generated a wealth of new mechanisms and pathways that seem to work in animal models of depression, such as learned helplessness and social defeat.⁵ The old mold of monoamine reuptake inhibition soon may be replaced by a plethora of alternatives that may transform the landscape of depression treatment.

Emerging therapeutic targets

Consider the following novel mechanisms that may become the basis for creating entirely new antidepressants in the foreseeable future, by design, not by serendipity:

• corticotropin-releasing factor (CRF) and glucocorticoids
• neurokinin system
• brain derived neurotropic factor (BDNF) and other neurotropins, such as fibroblast growth factor (FGF) or vascular endothelial growth factor (VEGF)
• phosphodiesterase inhibitors
• glutamate pathway modulators
• hypothalamic feeding peptides
• circadian gene products
• other evolving antidepressants

It is heartening to psychiatrists and their chronically depressed patients that many novel mechanisms and therapeutic targets have emerged, thanks to intensive research, not serendipity and happenstance. Although that’s uplifting news, the sobering downside is the lack of sufficient resources to expedite translational research. We need far more funding than what is available, and several pharmaceutical companies have dismantled their psychiatry research infrastructure and laid off thousands of scientists. This may be the time when strong philanthropic support may have to come to the rescue of this worthy cause, similar to how the Bill & Melinda Gates Foundation has focused on eradicating malaria. If only a multi-billionaire would adopt depression research as his or her pet charity with the goal of discovering several effective new treatments for the most disabling medical disorder in the world. What a fantastic legacy that would be.

Serendipity is out, intensive (and expensive!) brain research is in! Calling all enlightened billionaires…

For many scientists and clinicians, serendipity is a welcome blessing. It can result in the fortuitous discovery of a new treatment for a previously untreatable illness. In psychiatry, there are several examples, including chlorpromazine for psychosis and monoamine oxidase inhibitors and tricyclics for depression. But serendipity also can have a downside. It can skew and misdirect research efforts into one direction to the exclusion of others, which can be a curse in the pursuit of scientific truth.

For example, consider major depressive disorder (MDD), which is a major public health challenge with enormous direct and indirect costs to society. MDD is the most disabling medical disorder not just in psychiatry, but in the entire field of medicine (psychiatry claims 3 other disorders in the top 5: schizophrenia, bipolar disorder, and alcohol abuse).¹ In the United States, 8% to 10% of the population—children, adolescents, adults, and geriatric patients—suffer from depression at some point in their lives, and many will attempt suicide or die from self-inflicted injury if their depression is left untreated.² In the United States, 34,000 persons die each year from suicide³; most of them have MDD.⁴

Despite the gravity of depression’s disabling effects, MDD treatment barely has budged from the entrenched model constructed around increasing the availability of ≥1 monoamines—serotonin, norepinephrine, and dopamine—in the brain. For the past 5 decades, researchers have not deviated from the therapeutic dogma spawned by serendipity. Yet the efficacy of antidepressants from tricyclics to selective serotonin reuptake inhibitors to serotonin-norepinephrine reuptake inhibitors has been less than stellar, with remission in a few patients, partial response in others, and treatment resistance in many.

This is not surprising given that depression is a diverse syndrome, a heterogeneous gamut of disorders with variable pathogenesis but a shared clinical phenotype. So why did the pharmaceutical industry continue to develop drugs that inhibit the reuptake of one monoamine or another instead of innovating and developing novel agents with diverse mechanisms of action? Powerful inertia of the serendipitously discovered older antidepressants has persisted, without the benefit of new, “out-of-the-monoamine-box” innovative discovery based on emerging pathophysiologic research in mood disorders.

Things finally may be changing. Basic neuroscience and animal models have generated a wealth of new mechanisms and pathways that seem to work in animal models of depression, such as learned helplessness and social defeat.⁵ The old mold of monoamine reuptake inhibition soon may be replaced by a plethora of alternatives that may transform the landscape of depression treatment.

Emerging therapeutic targets

Consider the following novel mechanisms that may become the basis for creating entirely new antidepressants in the foreseeable future, by design, not by serendipity:

• corticotropin-releasing factor (CRF) and glucocorticoids
• neurokinin system
• brain derived neurotropic factor (BDNF) and other neurotropins, such as fibroblast growth factor (FGF) or vascular endothelial growth factor (VEGF)
• phosphodiesterase inhibitors
• glutamate pathway modulators
• hypothalamic feeding peptides
• circadian gene products
• other evolving antidepressants

It is heartening to psychiatrists and their chronically depressed patients that many novel mechanisms and therapeutic targets have emerged, thanks to intensive research, not serendipity and happenstance. Although that’s uplifting news, the sobering downside is the lack of sufficient resources to expedite translational research. We need far more funding than what is available, and several pharmaceutical companies have dismantled their psychiatry research infrastructure and laid off thousands of scientists. This may be the time when strong philanthropic support may have to come to the rescue of this worthy cause, similar to how the Bill & Melinda Gates Foundation has focused on eradicating malaria. If only a multi-billionaire would adopt depression research as his or her pet charity with the goal of discovering several effective new treatments for the most disabling medical disorder in the world. What a fantastic legacy that would be.

Serendipity is out, intensive (and expensive!) brain research is in! Calling all enlightened billionaires…