Antecedents of manic versus other first psychotic episodes in 263 bipolar I disorder patients.

OBJECTIVE: As initial episode type can predict later morbidity in bipolar disorder, we tested the hypothesis that clinical antecedents might predict initial episode types. METHOD: We studied 263 first-episode, adult, DSM-IV-TR type I bipolar disorder (BD-I) subjects within the McLean-Harvard-International First-Episode Project. Based on blinded assessments of antecedents from SCID examinations and clinical records, we compared first lifetime manic vs. other (mixed, depressive, or non-affective) major psychotic episodes. RESULTS: We identified 32 antecedents arising at early, intermediate or later times, starting 12.3±10.7 years prior to first lifetime major psychotic episodes. Based on multivariate modeling, antecedents associated significantly and independently with other (n=113) more than manic (n=150) first lifetime major psychotic episodes ranked by odds ratio: more early attentional disturbances, more late depression, more early perplexity, more detoxification, more early unstable mixed affects, more antidepressants, more early dysphoria, more intermediate depression, more early impulsivity, more late anhedonia, longer early-to-intermediate intervals, more intermediate substance abuse, more family history of major depression, and younger at earliest antecedents. Antecedents selectively preceding manic more than other first psychotic episodes included more late behavioral problems and more risk of familial BD-I. CONCLUSION: Clinical antecedents in adult, BD-I patients, beginning a decade before first major episodes and progressing through sequential stages were dissimilar in manic vs. other first psychotic episodes.

Episode cycles with increasing recurrences in first-episode bipolar-I disorder patients.

BACKGROUND: Preliminary review of a century of studies of the course of manic-depressive syndromes produced 40 reports, of which approximately one-third report evidence of shortening wellness intervals or cycle-lengths with more recurrences, and two-thirds did not. METHODS: We evaluated inter-episode intervals (cycle-length) in 128 clinically-treated, DSM-IV bipolar-I disorder patients followed prospectively and systematically over 5.7 years, with 6.5 episodes/person. RESULTS: As expected, cycle-length varied inversely with total cycle-count/person; however, multivariate linear regression found only longer initial hospitalization and fewer total cycles to be associated with cycle-length, whereas cycle-number (1, 2, 3, etc.), sex, intake-age, and first-episode polarity were not. Regression of within-subject cycle-length versus cycle-number yielded individual slope-functions with pseudo-random distribution (28% fell within ±1 month/cycle of the null [zero-slope]). Mean duration of early and late euthymic intervals (cycles 2 vs. 5) in patients with matched recurrence-counts was nearly identical. CONCLUSIONS: The course of bipolar-I disorder from onset was largely random or chaotic over nearly 6 years from onset. Only a minority of patients showed either cycle-acceleration or slowing, without changes in wellness intervals. The findings may be influenced by treatment-effects, but seem to indicate that most current bipolar-I disorder patients are unlikely to show progressive shortening of recurrence-cycles.

Predominant recurrence polarity among 928 adult international bipolar I disorder patients.

OBJECTIVE: To test the hypothesis that patients with bipolar disorder (BPD) differ demographically and clinically within subgroups based on the predominant-polarity of major recurrences. METHOD: We tested factors for association with predominantly (≥2 : 1) depressive vs. mania-like episodes with 928 DSM-IV type-I BPD subjects from five international sites. RESULTS: Factors preliminarily associated with predominant-depression included: electroconvulsive treatment, longer latency-to-BPD diagnosis, first episode depressive or mixed, more suicide attempts, more Axis-II comorbidity, ever having mixed-states, ever married, and female sex. Predominant-mania was associated with: initial manic or psychotic episodes, more drug abuse, more education, and more family psychiatric history. Of the 47.3% of subjects without polarity-predominance, risks for all factors considered were intermediate. Expanding the definition of polarity-predominance to ≥51% added little, but shifting mixed-states to 'predominant-depression' increased risk of suicidal acts from 2.4- to 4.5-fold excess over predominant-mania-hypomania, and suicidal risk was associated continuously with increasing proportions of depressive or mixed episodes. CONCLUSION: Subtyping by predominant-polarity yielded predictive associations, including the polarity of first episodes and risk of suicide attempts. Such subtyping may contribute to improve planning of clinical care and to biological studies of BPD.

Psychopathology factors in first-episode affective and non-affective psychotic disorders.

BACKGROUND: Since the onset, prevalence, and course of specific psychopathological features rarely have been analyzed simultaneously from the start of dissimilar psychotic illnesses, we compared symptom-clusters in first-episode DSM-IV affective and non-affective psychotic disorders. METHODS: Subjects (N=377) from the McLean-Harvard First Episode Project hospitalized for first-lifetime primary psychotic illnesses were followed prospectively for 2 years to verify stable DSM-IV diagnoses. We ascertained initial symptoms from baseline SCID and clinical assessments, applying AMDP and Bonn psychopathology schemes systematically to describe a broad range of features. Final consensus diagnoses were based on intake and follow-up SCID assessments, family interviews, and medical records. Factor-analytic methods defined first-episode symptom-clusters (Factors), and multiple-regression modeling related identified factors to initial DSM-IV diagnoses and to later categories (affective, non-affective, or schizoaffective disorders). RESULTS: Psychopathological features were accommodated by four factors: I represented mania with psychosis; II a mixed depressive-agitated state; III an excited-hallucinatory-delusional state; IV a disorganized-catatonic-autistic state. Each factor was associated with characteristic prodromal symptoms. Factors I and III associated with DSM-IV mania, II with major depression or bipolar mixed-state, III negatively with delusional disorder, IV with major depression and negatively with mania. Factors I and II predicted later affective diagnoses; absence of Factor I features predicted non-affective diagnoses, and no Factor predicted later schizoaffective diagnoses. CONCLUSION: The findings contribute to descriptive categorizations of psychopathology from onset of dissimilar psychotic illnesses. This approach was effective in identifying and subtyping affective psychotic disorders early in their clinical evolution, but non-affective and schizoaffective conditions appear to be more complex and unstable.