Laura J. Fochtmann

Trauma Exposure and Posttraumatic Stress Disorder in Psychosis: Findings From a First-Admission Cohort

This study examined the lifetime prevalence of trauma exposure and posttraumatic stress disorder (PTSD) and their demographic, diagnostic, and trauma-related correlates in a clinical cohort of 426 patients with a first psychiatric admission for psychosis. The prevalence of trauma exposure was 68.5%. Female gender and substance abuse were risk factors for trauma exposure. The prevalence of PTSD was 14.3% in the full sample and 26.5% in those with trauma exposure. PTSD was less prevalent in patients with bipolar disorder and schizophrenia and was twice as common in women. Other significant risk factors were younger age and trauma exposure that was repeated and ongoing or that involved childhood victimization. The findings highlight the importance of systematically ascertaining trauma histories in patients with psychotic disorders.

Diagnostic shifts during the decade following first admission for psychosis.

OBJECTIVE Diagnostic shifts have been prospectively examined in the short term, but the long-term stability of diagnoses has rarely been evaluated. The authors examined diagnostic shifts over a 10-year follow-up period. METHOD A cohort of 470 first-admission patients with psychotic disorders was systematically assessed at baseline and at 6-month, 2-year, and 10-year follow-ups. Longitudinal best-estimate consensus diagnoses were formulated after each assessment. RESULTS At baseline, the diagnostic distribution was 29.6% schizophrenia spectrum disorders, 21.1% bipolar disorder with psychotic features, 17.0% major depression with psychotic features, 2.4% substance-induced psychosis, and 27.9% other psychoses. At year 10, the distribution changed to 49.8%, 24.0%, 11.1%, 7.0%, and 8.1%, respectively. Overall, diagnoses were changed for 50.7% of study participants at some point during the study. Most participants who were initially diagnosed with schizophrenia or bipolar disorder retained the diagnosis at year 10 (89.2% and 77.8%, respectively). However, 32.0% of participants (N=98) originally given a non-schizophrenia diagnosis had gradually shifted to a schizophrenia diagnosis by year 10. The second largest shift was to bipolar disorder (10.7% of those not given this diagnosis at baseline). Changes in the clinical picture explained many diagnostic shifts. In particular, poorer functioning and greater negative and psychotic symptom ratings predicted a subsequent shift to schizophrenia. Better functioning and lower negative and depressive symptom ratings predicted the shift to bipolar disorder. CONCLUSIONS First-admission patients with psychotic disorders run the risk of being misclassified at early stages in the illness course, including more than 2 years after first hospitalization. Diagnosis should be reassessed at all follow-up points.

Schizophrenia in the Internalizing-Externalizing Framework: A Third Dimension?

BACKGROUND Prior studies of common disorders in community-dwelling adults identified internalizing and externalizing spectra of mental illness. We investigated the placement of schizophrenia and schizotypal personality disorder in this framework and tested the validity of the resulting organization in a clinical population. METHODS The data came from the Suffolk County Mental Health Project cohort (N = 628), which consists of first-admission patients with psychosis recruited from inpatient units throughout Suffolk County, NY (72% response rate). The sample was reassessed multiple times over the following 10 years. Complete diagnostic data were available for 469 participants. Mental health professionals diagnosed 11 target conditions based on semistructured clinical interviews, review of medical records, and reports of significant others. Two validators were included: family history of schizophrenia and 10-year illness course. RESULTS Confirmatory factor analysis revealed that the The Diagnostic and Statistical Manual of Mental Disorders-IV grouping of conditions fit the data poorly. The best alternative classification consisted of three clusters: internalizing, externalizing, and schizophrenic. Both validators supported the coherence and distinctiveness of the schizophrenic cluster. CONCLUSIONS We replicated internalizing and externalizing spectra in a clinical population, identified a schizophrenic spectrum, and provided initial evidence of its validity. These findings suggest that schizotypal personality disorder may be better placed with schizophrenia, antisocial conditions with substance use disorders, and major depression with anxiety disorders.

The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia.

anagement of behavioral disturbances Mand psychosis associated with dementia is a clinical and, in some cases, a medicolegal and ethical challenge for clinicians, caregivers, and health care settings. These medications are associated with multiple adverse outcomes, including serious adverse effects, such as increased risk for cerebrovascular events and mortality. At the same time, clinicians feel pressure from caregivers, acute inpatient staff, and long-term care settings to safely manage psychotic and aggressive behaviors in this population. The incidence and prevalence of dementia and associated behavioral disturbances in the adult population is on the rise. There is a lack of consistent practices and guidance to manage these behaviors as well as an upto-date review of the existing effectiveness literature, and these are much needed. Thus, the recent publication of the American Psychiatric Associations (APAs) practice guidelines on the use of antipsychotics to treat agitation or psychosis in patients with dementia comes at a most opportune time. Practice guidelines are unique in that they have the potential to positively impact behavior of practicing clinicians. They are also likely to be used as standard of care by insurance companies and in lawsuits or other litigation. It is thus important that practice guidelines provide a thorough, balanced, accurate, and current review of available treatments based on medical and scientific literature. The APAs most recent practice guideline on antipsychotic treatment in patients with dementia appears to have done just that. The practice guideline is organized into two main sections. The first section is broken up into four main categories: an introduction and overview of the guidelines, the guidelines themselves and how they were implemented based on current evidence in literature, quality measurement considerations, and the guideline development process. The second section is an appendix that provides a comprehensive review of available evidence and the results of expert opinion survey data. The authors also included a list of acronyms and abbreviations used in the guidelines, glossary of terms, list

Time to remission and relapse after the first hospital admission in severe bipolar disorder.

BackgroundFew studies of the time to remission and first relapse in severe bipolar disorder have been based on epidemiologically defined samples or have examined patient characteristics and time-varying indicators of medication use simultaneously. Using a cohort from the Suffolk County Mental Health Project, we describe these temporal patterns and their relationships with childhood, illness, and treatment characteristics.MethodA multi-facility cohort of 123 first-admission inpatients with DSM-IV bipolar disorder with psychotic features was followed for 4 years. Dates of the first complete remission (lasting at least 2 months), subsequent relapses, and use of antimanic (AM),antipsychotic (AP), and antidepressant (AD) medications were recorded. Childhood and illness characteristics were ascertained at baseline using standard instruments.ResultsBy the 4-year point, 83.7% had achieved a full remission, with 42.3% remitting within 3 months, 63.4% within 6 months, and 74.8% within 1 year. Overall, younger age of onset, history of childhood psychopathology, and higher Brief Psychiatric Rating Scale (BPRS) anxiety/depression scores were significantly associated with longer time to remission. Discontinuing AM, AP and AD (compared to never using) and taking AP and AD (compared to never using) were significantly associated with remission in the multivariate analysis. Of the 103 participants with complete remission, 61.2% suffered a relapse; 24.3 % relapsed within 6 months of remission, and 35.9% within a year. Overall, 32.5% of the 123 participants had a single episode followed by full remission. Childhood internalizing-type problems, higher BPRS anxiety/depression and Hamilton depression scores, and an admission episode not involving mania, but not patterns of medication use, were associated with shorter time to relapse.ConclusionBy 4-year follow-up, the majority of severely ill bipolar patients had remitted from their initial episode, but more than half subsequently relapsed. Illness characteristics, especially depressive symptoms, and medication treatment were associated with the early course, although medication use after remission was not associated with relapse.

Caffeine augmentation of electroconvulsive seizures.

Caffeine has been used clinically to increase seizure length in electroconvulsive treatment (ECT). The present study was designed to establish an animal model of caffeine-augmented seizures for further study of mechanisms and effects of pharmacological manipulation of seizure length. Increasing doses of caffeine (0–200 mg/kg, IP) were given before electroconvulsive stimulation (ECS) in rats and resulting seizure lengths were quantified by timing of classical tonic-clonic convulsive movements. With this paradigm, caffeine led to a dose-dependent increase in seizure duration. This proconvulsant action of caffeine was detectable within 1 min after dosing, persisted for at least 230 min and was reversible. The results suggest that seizure length is a practicable measure in pharmacological modification of electroconvulsive seizures. They also suggest that pharmacologically-modified ECS can be modeled effectively in animals.

Boundaries of Schizoaffective Disorder: Revisiting Kraepelin

IMPORTANCE Established nosology identifies schizoaffective disorder as a distinct category with boundaries separating it from mood disorders with psychosis and from schizophrenia. Alternative models argue for a single boundary distinguishing mood disorders with psychosis from schizophrenia (kraepelinian dichotomy) or a continuous spectrum from affective to nonaffective psychosis. OBJECTIVE To identify natural boundaries within psychotic disorders by evaluating associations between symptom course and long-term outcome. DESIGN, SETTING, AND PARTICIPANTS The Suffolk County Mental Health Project cohort consists of first-admission patients with psychosis recruited from all inpatient units of Suffolk County, New York (72% response rate). In an inception cohort design, participants were monitored closely for 4 years after admission, and their symptom course was charted for 526 individuals; 10-year outcome was obtained for 413. MAIN OUTCOMES AND MEASURES Global Assessment of Functioning (GAF) and other consensus ratings of study psychiatrists. RESULTS We used nonlinear modeling (locally weighted scatterplot smoothing and spline regression) to examine links between 4-year symptom variables (ratio of nonaffective psychosis to mood disturbance, duration of mania/hypomania, depression, and psychosis) and 10-year outcomes. Nonaffective psychosis ratio exhibited a sharp discontinuity-10 days or more of psychosis outside mood episodes predicted an 11-point decrement in GAF-consistent with the kraepelinian dichotomy. Duration of mania/hypomania showed 2 discontinuities demarcating 3 groups: mania absent, episodic mania, and chronic mania (manic/hypomanic >1 year). The episodic group had a better outcome compared with the mania absent and chronic mania groups (12-point and 8-point difference on GAF). Duration of depression and psychosis had linear associations with worse outcome. CONCLUSIONS AND RELEVANCE Our data support the kraepelinian dichotomy, although the study requires replication. A boundary between schizoaffective disorder and schizophrenia was not observed, which casts further doubt on schizoaffective diagnosis. Co-occurring schizophrenia and mood disorder may be better coded as separate diagnoses, an approach that could simplify diagnosis, improve its reliability, and align it with the natural taxonomy.

Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10−8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.

Remission and relapse after the first hospital admission in psychotic depression: a 4-year naturalistic follow-up

BACKGROUND Few studies have examined the course of illness among severely depressed patients ascertained at first hospitalization. Using data from the Suffolk County Mental Health Project (SCMHP), we investigated the times to and predictors of the first full remission and the first relapse during a 4-year period in a first-admission cohort with major depressive disorder (MDD) with psychotic features. METHOD The cohort included 87 county-wide, first-admission patients with a longitudinal consensus diagnosis of MDD with psychotic features who were systematically followed over a 4-year period. We examined the associations of background, clinical and treatment factors, and time-varying indices of antidepressant (AD) and antipsychotic (AP) medication use to time to remission and relapse using Cox regression. RESULTS By the 4-year follow-up, 60 respondents (69.0%) had achieved a period of full remission (median time of 22 weeks among remitters and 54 weeks in the full sample). In the multivariable analysis, longer time to remission was associated with longer latency between initial episode and hospitalization, lower pre-hospital Global Assessment of Functioning (GAF) score, and lack of insurance, but not use of medication. Twenty-six remitters (43.3%) relapsed (median time of 50 weeks among those who relapsed and 192 weeks among all remitters). None of the risk factors or time-varying medication variables was significantly associated with time to relapse. CONCLUSION Only two-thirds of the sample had at least one full remission by 4 years, and almost half of them subsequently relapsed. Poorer pre-hospital resources predicted remission but not relapse. Medication use over the follow-up was not associated with remission or relapse.

Genetic Approaches to the Neurobiology of Electroconvulsive Therapy

Although electroconvulsive therapy effectively treats severe psychiatric disorders, its neurobiologic mechanisms are not fully understood. Also unclear is the basis for variability in seizure threshold and duration among patients. We used multiple strains of rats and mice to test for genetic variation in the properties of seizures induced by electroconvulsive shock (ECS). We specifically measured seizure duration, sensitivity to proconvulsant actions of caffeine, and relative refractoriness to postictal induction of further seizures, all of which showed significant interstrain variability. In addition, tonic-clonic seizure durations correlated with rates of immediate mortality, suggesting variations in underlying levels of cellular excitability across strains. By using quantitative autoradiography to relate these findings to neurobiologic mechanisms, we found significant correlations between hippocampal A1-receptor binding, cortical and striatal N-methyl-D-aspartate (NMDA)-receptor binding, and the modification of seizure duration by caffeine. These studies suggest that heritable factors modulate the neurobiologic determinants of electrically induced seizures. Furthermore, they suggest that genetic factors may contribute to clinically observed variability in seizure thresholds. Finally, the data provide a basis for future molecular genetic approaches to link ECS-induced changes in seizure properties to relevant transmitter systems.