1. Prodromal Phases Preceding First-Major Episodes of Bipolar-I Disorder: Prediction of Later Illness Salvatore P, a,b,c Khalsa HMK, a Vazquez G, b Tohen M, d Maggini C, b,c Baldessarini RJ a a.Department of Psychiatry, Harvard Medical School & McLean Hospital, Belmont MA; b.International Consortium for Bipolar and Psychotic Disorders Research, McLean Hospital, Belmont MA; c. Section of Psychiatry, Department of Neuroscience,University of Parma, Italy; d. Department of Psychiatry, University of Texas Health Sciences Center, San Antonio, TX. ———————————————————————————————————————————————————————————————————————————————————————————————————————— Background: Prodomes and other early symptoms often precede development of fully expressed major psychiatric disorders. They have been much better studied in early schizophrenia than in bipolar-I disorder (BPD), although we have found that illnesses following manic versus other presentations differ markedly. Identification of precursor phenomena may lead to earlier clinical identification of persons at risk, inform prognosis, and guide earlier interventions and planning of long- term treatment. Methods: We carried out a comprehensive review of all available clinical documents to develop descriptions of 32 categories and timing of prodromal psychopathological characteristics in 263 subjects eventually diagnosed with DSM-IV BPD, and followed prospectively, systematically for several years from first hospitalizations for manic, or other DSM-IV (mixed, depressive, or psychotic) episodes in the McLean-Harvard International First-Episode Project. Figure. Most-prevalent phenomena in different prodromal stages* Results: Patient-subjects were divided into those with Manic (n=150) vs. Other (mixed, depressive, psychotic; n=113) first major episodes. Early-prodrome onset was 2.7 yrs younger in patients with later non-manic onsets (Other=17.0, Manic=19.7 yrs). Most prevalent prodromal phenomena were: major depression (MDD), substance-abuse, generalized anxiety-somatization (GAD), impulse-dyscontrol, mood lability-cyclothymia, dysphoric and unstable mixed states, psychotic perplexity, as well as suicide attempts and being sexually abused (Fig.). Manic first-episodes followed shorter latency from initial prodomes to first-episodes. In addition to depressive and fluctuating affective states, Other BPD patients were more likely to experience early shyness or introversion, and schizo-obsessive tendencies, as well as passivity feelings, depersonalization-derealization, and attentional disturbances. At intermediate prodromal presentations Other BPD subjects had more substance-abuse and major depression than later Manic cases. During late prodromes Other onset patients had more anergic-depressive states, sleep & eating disturbances, and greater functional decline (Table 1). By logistic multivariate regression modeling, patients with Manic onset-episodes more likely had depressive states during intermediate prodromes, whereas Other-onset cases had younger early-prodrome onset, longer latency from initial to intermediate prodromes, more early unstable mixed and dysphoric states, as well as perceptual disturbances, perplexity, and other prepsychotic experiences (Table 2). Conclusions: Early prodromal antecedents in BPD may help to predict dissimilar diagnostic subtypes known to have different courses, outcomes and treatment requirements—long before fully expressed clinical syndromes emerge. 114 [Support : NARSAD, Anderson Foundation, McLean Donors] *Figure includes phenomena with at least 10% prevalence at each of three stages.