Personality Disorders as a Basis for Discharge and Denial of Benefits in the Military: Logical or Abusive?

The US Department of Defense specifically states that intellectual disability and personality disorders are not diseases for compensation purposes, and disabilities from them may not be service connected absent a superimposed mental disorder. In addition, the diagnosis of a personality disorder led to the discharge of 31,000 troops during the years 2001 to 2010. I review the history of these developments, and how the Diagnostic and Statistical Manual of Mental Disorders enabled these actions.

Whither Research Domain Criteria?

In 2010, the National Institute of Mental Health launched the Research Diagnostic Criteria (RDoC) as a research framework aimed at advancing research into the etiology of mental disorders, the development of clinically actionable biomarkers, and the eventual development of precision medications. The foundation of RDoC in that first phase rested in the assumption that mental disorders are brain disorders that originate in aberrant neural circuitry, and that therapeutic advances could flow from alterations in that circuitry. RDoC proposed a matrix of psychological constructs with seven levels of analysis ranging from the cell to self-report, but with neural circuitry at the center.

The nature of bradykinesia in schizophrenia treated with antipsychotics.

Recognizing drug-induced parkinsonian bradykinesia in psychosis patients can be challenging due to overlapping presentation with psychomotor slowing associated with depression, negative symptoms, or cognitive disturbances. In this study, we apply prior findings on the pathophysiology of bradykinesia in Parkinson's disease to gain an understanding of motor slowing in psychosis patients. Handwriting movements from 57 healthy participants and 70 psychosis patients were recorded on a digitizing tablet.

Neural circuitry and precision medicines for mental disorders: are they compatible?

Given the failure of psychiatry to develop clinically useful biomarkers for psychiatric disorders, and the concomitant failure to develop significant advances in diagnosis and treatment, the National Institute of Mental Health (NIMH) in 2010 launched the Research Domain Criteria (RDoC), a framework for research based on the assumption that mental disorders are disorders of identifiable brain neural circuits, with neural circuitry at the center of units of analysis ranging from genes, molecules, and cells to behavior, self-reports, and paradigms. These were to be integrated with five validated dimensional psychological constructs such as negative and positive valence systems. Four years later, the NIMH stated that the ultimate goal of RDoC is precision medicine for psychiatry, with the assumption that precision medications will normalize dysfunctional neural circuits.

Social inequality, scientific inequality, and the future of mental illness.

Background: Despite five decades of increasingly elegant studies aimed at advancing the pathophysiology and treatment of mental illness, the results have not met expectations. Diagnoses are still based on observation, the clinical history, and an outmoded diagnostic system that stresses the historic goal of disease specificity. Psychotropic drugs are still based on molecular targets developed decades ago, with no increase in efficacy.

A quantitative measure of handwriting dysfluency for assessing tardive dyskinesia.

Tardive dyskinesia (TD) is a movement disorder commonly associated with chronic exposure to antidopaminergic medications, which may be in some cases disfiguring and socially disabling. The consensus from a growing body of research on the incidence and prevalence of TD in the modern era of antipsychotics indicates that this disorder has not disappeared continues to challenge the effective management of psychotic symptoms in patients with schizophrenia. A fundamental component in an effective strategy for managing TD is its reliable and accurate assessment.

The death of specificity in psychiatry: cheers or tears?

During the past five decades, psychiatry has pursued two goals, one being specificity of diagnosis and treatment, and the other a series of all-inclusive diagnostic manuals that paradoxically emphasized the absence of definite boundaries between disorders, and the absence of definite boundaries between disorders and normality (although normality was never defined). Leaders in the field continue to emphasize that diagnoses must be validated by the pathogenesis, course, and response to treatment of specific disorders. However, many current genetic and family studies have failed to support the concept of diagnostic specificity, as has the current use of psychotropic agents, which are now being prescribed with little regard for diagnosis.

Psychopharmacology: a house divided.

Background: Psychopharmacology and psychiatry during the past 50 years have focused on the specificity model in which it is assumed that psychiatric disorders are specific entities which should respond to drugs with specific mechanisms of action. However, the validity of this model has been challenged by the approval of multiple drugs for the same disorder, as well as the approval of single agents for a variety of disorders which have little in common. As an example of this unacknowledged paradigm shift, I will examine the foundation for using antipsychotics in the treatment of depression.

Handwriting movement kinematics for quantifying extrapyramidal side effects in patients treated with atypical antipsychotics.

Ongoing monitoring of neuroleptic-induced extrapyramidal side effects (EPS) is important to maximize treatment outcome, improve medication adherence and reduce re-hospitalization. Traditional approaches for assessing EPS such as Parkinsonism, tardive akathisia, or dyskinesia rely upon clinical ratings. However, these observer-based EPS severity ratings can be unreliable and are subject to examiner bias.

Handwriting movement analyses for monitoring drug-induced motor side effects in schizophrenia patients treated with risperidone.

Epidemiologic studies indicate that nearly 60% of schizophrenia (SZ) patients treated with conventional antipsychotic drugs develop extrapyramidal side effects (EPS) such as parkinsonism and tardive dyskinesia. Although the prevalence of EPS has decreased due to the newer antipsychotics, EPS continue to limit the effectiveness of these medicines. Ongoing monitoring of EPS is likely to improve treatment outcome or compliance and reduce the frequency of re-hospitalization.

Personalized medicine: boon or budget-buster?

While the development of personalized or molecular medicine is a laudable goal, there remain multiple barriers to its implementation. For example, little is known about the functions of noncoding regions of DNA, as well as the interplay of drug response, environmental factors, and the patient's genetic profile. In addition, there is a constant influx of new information on genetic factors such as epigenetic variation that could further complicate the development of medications based on the genetic profile, as well as the cost of profiling.

Mortality and tardive dyskinesia: long-term study using the US National Death Index.

Background: Whether the development of tardive dyskinesia leads to an increase in mortality is still unclear.

Aims: To explore the relationship between tardive dyskinesia and mortality over a 10-year period, using the National Death Index.

Method: Death certificates were obtained from the National Death Index on 1621 people repeatedly assessed for tardive dyskinesia by trained raters.

Predictors of neuroleptic-induced dyskinesia and parkinsonism: the influence of measurement methods and definitions.

The accurate and objective measurement of abnormal, involuntary movements remains highly desirable, whether the movements are secondary to pharmacotherapy or an expression of the primary illness. In a previous study, we found that the prevalence of tardive dyskinesia in a sample of 100 subjects ranged from 28% when using the Abnormal Involuntary Movement Scale (AIMS) or the Dyskinesia Identification Scale, Condensed User Version (DISCUS) to 62% using an instrumental measurement (IM) of peripheral dyskinesia. The goal of this study was to examine the relationship between various risk factors for tardive dyskinesia as predictor variables, and the AIMS, DISCUS, and IMs of dyskinesia, tremor, and velocity of motor movement as dependent variables.

Antipsychotic-associated neuronal changes in the brain: toxic, therapeutic, or irrelevant to the long-term outcome of schizophrenia?

The increasingly wide-spread use of antipsychotics in both adults and children calls for a detailed examination of antipsychotic-associated neuronal changes in the brain, and whether these changes are toxic, therapeutic, or perhaps irrelevant to the outcome of major psychiatric disorders, especially schizophrenia. In this review we will examine the extensive evidence demonstrating both acute and longer-term antipsychotic-associated neurotoxicity and neuroplasticity, as well as the more specific cellular changes that appear to underlie these phenomena. These include changes in proteins affecting cell survival, impairment of the mitochondrial respiratory chain, increases in DNA fragmentation, injury to dendritic microtubules, increases in dopamine-generated reactive oxygen species, changes in cell morphology, and rapid induction of apoptosis.

Ziprasidone-associated mania: a review and report of 2 additional cases.

Although mania was not reported as an adverse event in the pivotal trials of ziprasidone, there have been 7 reports of ziprasidone-induced mania in 12 patients. We now report 2 additional cases wherein the introduction of ziprasidone resulted in new-onset manic episodes. In 1 case, the patient required hospitalization and lost his job.

Regional induction of CYP1A1 in rat liver following treatment with mixtures of PCB 126 and PCB 153.

Liver enzyme induction has been shown previously to be regional with clear borders between induced and uninduced regions in vivo, and cells either fully induced or not induced in vitro. The current study examined this phenomenon in vivo by evaluating enzyme induction after exposure to PCB 126 and PCB 153 in female Fisher 344 (F344) and male Sprague-Dawley (SD) rats. IHC revealed a regional induction of CYP1A1 after exposure to PCB 126, apparent in the centrilobular region at lower doses and progressing to panlobular with higher doses.

Clinical rating scales and instruments: how do they compare in assessing abnormal, involuntary movements?

Objective: Recent studies have shown that quantitative instrumental measurements are more sensitive than clinical rating scales to subclinical dyskinesia and parkinsonism. We therefore hypothesized that an instrumental assessment would be more sensitive to the presence of dyskinetic and parkinsonian movements than the Abnormal Involuntary Movement Scale (AIMS), the Dyskinesia Identification Scale, Condensed User Version (DISCUS), and the Simpson-Angus Scale (SAS). We also hypothesized that the DISCUS, by virtue of its more detailed protocol, would be more sensitive than the AIMS.

Imipramine-associated hyperpigmentation.

Objective: To inform clinicians of the potential for severe and persistent facial hyperpigmentation with the long-term use of imipramine.

Case Summary: A 65-year-old white male veteran with a history of paranoid schizophrenia was referred to the psychiatry service by a dentist who thought that the patient was both cyanotic and psychotic. The history and biopsy results indicated the possibility of imipramine-associated hyperpigmentation, only the second reported case in a male patient.