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Background: Identifying suicidal risk based on clinical assessment is challenging. Suicidal ideation fluctuates, can be downplayed or denied, and seems stigmatizing if divulged. In contrast, vitality is foundational to subjectivity in being immediately conscious before reflection. Including its assessment may improve detection of suicidal risk compared to relying on suicidal ideation alone. We hypothesized that objective motility measures would be associated with vitality and enhance assessment of suicidal risk., Methods: We evaluated 83 adult-psychiatric outpatients with a DSM-5 bipolar (BD) or major depressive disorder (MDD): BD-I (n = 48), BD-II (20), and MDD (15) during a major depressive episode. They were actigraphically monitored continuously over 3 weekdays and self-rated their subjective states at regular intervals. We applied cosinor analysis to actigraphic data and analyzed associations of subjective psychopathology measures with circadian activity parameters., Results: Actigraphic circadian mesor, amplitude, day- and nighttime activity were lower with BD versus MDD. Self-rated vitality (wish-to-live) was significantly lower, self-rated suicidality (wish-to-die) was higher, and their difference was lower, with BD versus MDD. There were no other significant diagnostic differences in actigraphic sleep parameters or in self-rated depression, dysphoria, or anxiety. By linear regression, the difference between vitality and passive suicidal ideation was strongly positively correlated with mesor (p < 0.0001), daytime activity (p < 0.0001), and amplitude (p = 0.001)., Conclusions: Higher circadian activity measures reflected enhanced levels of subjective vitality and were associated with lesser suicidal ideation. Current suicidal-risk assessment might usefully include monitoring of motility and vitality in addition to examining negative affects and suicidal thinking., (© 2023 S. Karger AG, Basel.)

Background: Research findings on factors associated with onset-age (OA) with bipolar (BD) and major depressive disorders (MDD) have been inconsistent, but often indicate greater morbidity following early OA., Methods: We considered factors associated with OA in 1033 carefully evaluated, systematically followed mood disorder subjects with DSM-5 BD (n = 505) or MDD (n = 528), comparing rates of descriptive and clinical characteristics following early (age <18), intermediate (18-40), or later onset (≥40 years), as well as regressing selected measures versus OA. Exposure time (years ill) was matched among these subgroups., Results: As hypothesized, many features were associated with early OA: familial psychiatric illness, including BD, greater maternal age, early sexual abuse, nondepressive first episodes, co-occurring ADHD, suicide attempts and violent suicidal behavior, abuse of alcohol or drugs, smoking, and unemployment. Other features increased consistently with later OA: %-time-depressed (in BD and MDD, women and men), as well as depressions/year and intake ratings of depression, educational levels, co-occurring medical disorders, rates of marriage and number of children., Conclusions: OA averaged 7.5 years earlier in BD versus MDD (30.7 vs. 38.2). Some OA-associated measures may reflect maturation. Associations with family history and suicidal risk with earlier OA were expected; increases of time-depressed in both BD and MDD with later OA were not. We conclude that associations of OA with later morbidity are complex and not unidirectional but may be clinically useful., (© 2022 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Objectives: To clarify the clinical features preceding the onset of bipolar disorder (BD) has become a public health priority for the prevention of high morbidity and mortality. BD remains frequently under- or misdiagnosed, and under- or mistreated, often for years., Methods: We assessed the predictive value of precursors and prodromes of BD. We assessed precursors of first-lifetime manic or hypomanic episodes with/without mixed features in retrospective and prospective studies. The task force evaluated and summarized separately assessments of familial risk, premorbid personality traits, retrospective, and prospective studies., Results: Cyclothymic features, a family history of BD, retrospectively reported attenuated manic symptoms, prospectively identified subthreshold symptoms of hypomania, recurrence of depression, panic anxiety and psychotic features, have been identified as clinical precursors of BD. The prodromal symptoms like [hypo]mania often appears to be long enough to encourage early identification and timely intervention., Conclusions: The predictive value of any risk factor identified remains largely unknown. Prospective controlled studies are urgently needed for prevention and effective treatment., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Bizarre delusions (BizD) are not specific to schizophrenia (SZ) and can be found in other psychotic disorders. However, to date, there are no studies investigating socio-demographic and clinical characteristics associated with BizD across the psychosis spectrum. In this study 819 subjects with a diagnosis of SZ (n = 250), schizoaffective disorder (SZA) (n = 228) and bipolar I disorder (BD) (n = 341) were included. Patients with history of BizD and with no BizD were compared with respect to socidemographic and clinical variables, and predictors of BizD were explored. Patients with BizD were less educated, less likely to be married, had higher Positive and Negative Syndrome Scale (PANSS) negative scores and lower Young Mania Rating Scale scores. Younger age, SZ and SZA diagnoses, higher PANSS positive scores, presence of reference delusions, tactile and olfactory hallucinations were predictors. Our results indicate that BizD are associated with higher illness severity, lower functionality and specific set of symptoms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Early course in contemporary, clinically treated, nonaffective psychotic disorders other than schizophrenia remains incompletely defined., Methods: We prospectively, repeatedly, and systematically assessed 114 patients hospitalized for a first episode of DSM-IV-TR nonaffective psychotic illness for ≥ 2 years (1989-1996) using structured (Structured Clinical Interview for DSM-III-R, Patient Edition; Clinical Global Impressions scale; Scale for the Assessment of Negative Symptoms; Scale for the Assessment of Positive Symptoms; and the expanded version of the Brief Psychiatric Rating Scale) and unstructured (best-estimate procedure, life charting) naturalistic follow-up procedures and survival analysis., Results: Duration of untreated psychosis (22 ± 38 months) was longest with schizophrenia. Within 2 years, syndromal remission sustained for ≥ 8 weeks (recovery) was attained by 75 subjects (65.8%); median latency to syndromal recovery was 9.4 (95% CI, 5.7-13.3) weeks and was shorter with cycloid features, initial diagnosis of brief psychosis or schizophreniform disorder, and shorter initial hospitalization. Functional recovery within 2 years was achieved by 28 of 68 subjects (41.2%), more often without initial mood-psychomotor instability or homicidal ideation. New episodes occurred in 52 of 114 subjects (45.6%) and were more likely with less affective flattening, younger age, and white race. Median time to new episodes (43.7 [27.9-70.6] weeks) was earlier with initial first-rank auditory hallucinations, substance abuse, and functional nonrecovery. Diagnosis changed to other nonaffective, schizoaffective, or affective disorders within 2 years in 62 of 108 cases (57.4%)., Conclusions: Three-quarters of patients presenting in first lifetime, nonaffective psychotic episodes achieved recovery within 2 years, but only 41% returned to baseline functioning, and nearly half experienced new episodes. Patients with schizophrenia had the longest duration of untreated psychosis. A majority changed diagnosis, indicating instability of some DSM psychotic-disorder diagnoses., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Objective: To evaluate the presence of affective signs and symptoms as precursors of bipolar disorder in prospective studies, including assessment of their prevalence, duration, and predictive value., Data Sources: We followed PRISMA guidelines to search PubMed, CINAHL, PsycINFO, EMBASE, SCOPUS, and ISI Web of Science databases to May 31, 2013, using the terms bipolar disorder AND (antecedent* OR predict* OR prodrom* OR prospect*) AND (diagnosis OR development). Hand searching of identified reports led to additional relevant references., Study Selection: We included only English-language articles containing (1) prospective, longitudinal studies with at least 2 structured clinical assessments (intake and follow-up); (2) no previous DSM-III or DSM-IV diagnoses of bipolar I or bipolar II; and (3) diagnostic outcome of bipolar I or bipolar II. Studies of subjects at familial risk of bipolar disorder were excluded, as these have been reviewed elsewhere., Data Extraction: We tabulated details of study design, outcomes, precursors, and predictive value. Only studies reporting a positive predictive association were included., Results: In 26 published reports meeting selection criteria, methods varied widely in terms of design, duration of follow-up, ages, and populations investigated. Despite such heterogeneity in methods, findings were notably consistent. Precursors of bipolar disorder include mood lability, subsyndromal and major depression, subsyndromal hypomanic symptoms with or without major depression, cyclothymia and bipolar not otherwise specified, major depression with psychotic features, and other psychotic disorders. Bipolar disorder was also predicted by juvenile onset of major depression as well as frequency and loading of hypomanic or depressive symptoms., Conclusions: Despite the limitations of published reports, prospectively identified precursors of bipolar disorder typically arose years prior to syndromal onset, often with significant early morbidity and disability. Prospectively identified precursors of bipolar disorder are generally consistent with findings in retrospective and family-risk studies. Combining precursors and other risk factors may increase predictive value, support earlier diagnosis, improve treatment, and limit disability in bipolar disorder., (© Copyright 2015 Physicians Postgraduate Press, Inc.)

Background: Early phases and suspected precursor states of bipolar disorder are not well characterized. We evaluate the prevalence, duration, clinical features and predictive value of non-affective psychopathology as clinical risk factors for bipolar disorder in prospective studies., Methods: We screened PubMed, CINAHL, PsycINFO, Embase, SCOPUS, and ISI-Web of Science databases from inception up to January 31, 2014, following PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and searched: bipolar disorder AND [antecedent⁎ OR predict⁎ OR prodrom⁎ OR prospect⁎ OR risk⁎] AND [diagnosis OR development]. We included only English language reports on prospective, longitudinal studies with two structured clinical assessments (intake and follow-up); no DSM intake diagnosis of bipolar-I or -II; diagnostic outcome was bipolar-I or -II. Details of study design, risk factors, and predictive value were tabulated., Results: We found 16 published reports meeting selection criteria, with varying study design. Despite heterogeneity in methods, findings across studies were consistent. Clinical risk factors of bipolar disorder were early-onset panic attacks and disorder, separation anxiety and generalized anxiety disorders, conduct symptoms and disorder, ADHD, impulsivity and criminal behavior., Limitations: Since risk factors identified in some prospective studies are predictive of other conditions besides bipolar disorder, these preliminary findings require replication, and their sensitivity, specificity and predictive value need to be assessed., Conclusions: Clinical risk factors for bipolar disorder typically arise years prior to syndromal onset, include anxiety and behavioral disorders with unclear sensitivity and specificity. Prospectively identified clinical risk factors for bipolar disorder are consistent with retrospective and family-risk studies. Combining clinical risk factors with precursors and family-risk may improve early identification and timely and appropriate treatment of bipolar disorder., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: Early assessment can guide accurate diagnosis, prognosis, and treatment-planning for patients with major mental illnesses. Longitudinal studies in psychotic depression from onset are rare, encouraging the present study., Method: We followed 56 DSM-IV MDD patients with psychotic features prospectively and systematically to assess course and predictors of operationally-defined syndromal remission, syndromal recovery, symptomatic remission, functional recovery, and new episodes, and to evaluate diagnostic stability., Results: Among 49/56 cases followed for ≥2 years, 59% retained the initial diagnosis and most achieved syndromal remission (86%) and recovery (84%); 58% remitted symptomatically, and only 35% (17/49) recovered functionally. Syndromal recovery was earlier following subacute onset, lower initial depression scores, and lack of moodincongruent psychotic features. Within 2 years, 45% (22/49) experienced new episodes - earlier with younger onset and higher CGI scores. DSM diagnosis changed in 41%, to bipolar (33%), or schizoaffective disorders (12%), which followed early mania-like or schizophrenia-like features, respectively., Conclusions: Within 2 years of first-hospitalizations, 41% of patients initially diagnosed with psychotic-depression met criteria for DSM-IV bipolar or schizoaffective disorders. Of the 59% retaining the initial diagnosis for 2 years, nearly half experienced new episodes, 42% remained symptomatic, and two-thirds failed to regain their own prior functional status., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Major depression occurs at high prevalence in the general population, often starts in juvenile years, recurs over a lifetime, and is strongly associated with disability and suicide. Searches for biological markers in depression may have been hindered by assuming that depression is a unitary and relatively homogeneous disorder, mainly of mood, rather than addressing particular, clinically crucial features or diagnostic subtypes. Many studies have implicated quantitative alterations of motility rhythms in depressed human subjects. Since a candidate feature of great public-health significance is the unusually high risk of suicidal behavior in depressive disorders, we studied correlations between a measure (vulnerability index [VI]) derived from multi-scale characteristics of daily-motility rhythms in depressed subjects (n = 36) monitored with noninvasive, wrist-worn, electronic actigraphs and their self-assessed level of suicidal thinking operationalized as a wish to die. Patient-subjects had a stable clinical diagnosis of bipolar-I, bipolar-II, or unipolar major depression (n = 12 of each type). VI was associated inversely with suicidal thinking (r = -0.61 with all subjects and r = -0.73 with bipolar disorder subjects; both p<0.0001) and distinguished patients with bipolar versus unipolar major depression with a sensitivity of 91.7% and a specificity of 79.2%. VI may be a useful biomarker of characteristic features of major depression, contribute to differentiating bipolar and unipolar depression, and help to detect risk of suicide. An objective biomarker of suicide-risk could be advantageous when patients are unwilling or unable to share suicidal thinking with clinicians.

Largely unknown in Anglophonic medicine, eighteenth-century Spanish physician-scholar Andrés Piquer-Arrufat was early to coin a name (affectio melancholico-maníaca, or "melancholic-manic illness") for the syndrome that emerged much later as manic-depressive illness and then bipolar disorder. He considered it a single, independent diagnostic entity, distinct from mania and melancholia, with varying manifestations over time. Piquer recognized mixed states, seasonality, and rapid cycling, and hypothesized "mental or cerebral damage" as underlying the disorder. His formulations evolved from clinical observations of patients over time, including his detailed longitudinal clinical description of Spanish King Ferdinand VI (1759), and as presented in his own medical textbook (1764). Piquer anticipated the often cited nineteenth-century works of Jean Falret and Jules Baillarger in Paris, and later, Emil Kraepelin in Heidelberg, by more than a century., (© 2011 President and Fellows of Harvard College)

Scale invariance is a feature of complex biological systems, and abnormality of multi-scale behaviour may serve as an indicator of pathology. The hypothalamic suprachiasmatic nucleus (SCN) is a major node in central neural networks responsible for regulating multi-scale behaviour in measures of human locomotor activity. SCN also is implicated in the pathophysiology of bipolar disorder (BD) or manic-depressive illness, a severe, episodic disorder of mood, cognition and behaviour. Here, we investigated scaling behaviour in actigraphically recorded human motility data for potential indicators of BD, particularly its manic phase. A proposed index of scaling behaviour (Vulnerability Index [VI]) derived from such data distinguished between: [i] healthy subjects at high versus low risk of mood disorders; [ii] currently clinically stable BD patients versus matched controls; and [iii] among clinical states in BD patients.

Background: Mixed-states of bipolar disorders (BPD) may predict worse future illness and more depressive than manic morbidity, challenging a tendency to conflate mixed-states and mania., Methods: Patients (N=247) were followed-up systematically for 24 months following hospitalization for initial major episodes of DSM-IV type-I BPD and scored for weekly interval morbidity-types., Results: Overall morbidity during follow-up was 1.6-times greater following mixed (n=97) versus manic (n=150) first-episodes of BPD (60.0 vs. 37.8%-of-weeks; p<0.0001). Patients with initial mixed-states had a nearly 12-fold later excess of mixed-states, 6.5-times more major depression, and 69% more dysthymia during follow-up than those presenting in mania. In contrast, manic first-episodes were followed by over 10-times more mania, 6-times more hypomania, and 35% more psychotic illness., Limitations: Estimates of longitudinal morbidity may be inaccurate, and ongoing treatment may distort them., Conclusions: Based on detailed, prospective assessments among first-episode BPD patients, those presenting in mixed-states were more ill, and much more likely to experience mixed, depressive and dysthymic morbidity during follow-up, versus much more mania, hypomania, and perhaps more psychosis following mania. The findings support two markedly dissimilar subtypes of BPD, and call for more explicit therapeutic studies of mixed-states., (Copyright 2010 Elsevier B.V. All rights reserved.)

Objectives: To test the hypotheses that: (i) depressive-dysthymic-dysphoric (D-type) morbidity is more prevalent than manic-hypomanic-psychotic (M-type) morbidity even from first episodes of bipolar I disorder (BPD-I) and despite treatment; (ii) initial presentations predict later morbidity; (iii) morbidity varies internationally; and (iv) early and later morbidity are similar., Methods: We followed SCID-based, DSM-IV BPD-I patients (n = 303) systematically and prospectively for two years to estimate the percent of weeks in specific morbid states from first lifetime major episodes., Results: Total morbidity accounted for 44% of the first two years, and D-type exceeded M-type illnesses by 2.1-fold (30%/14%) among morbidities ranking: mixed states (major + minor) >or= dysthymia >or= mania >or= major depression > hypomania > psychosis. In 164 cases, morbidities at 0.5-2.5 and 2.5-4.5 years were very similar. Depressive or mixed initial episodes predicted a 3.6-fold excess of D-type morbidity, and initial M-type episodes predicted a 7.1-fold excess of M-type morbidity over two years. Morbidity in European (EU) sites was nearly half that in the U.S., and 22% greater overall among men than women. In five comparable studies, illness accounted for 54% of follow-up time, and the ratio of D/M morbidity averaged 3.0., Conclusions: In accord with four midcourse studies, morbidity from BPD-I onset, despite treatment by community standards, averaged 44%, was 68% D-type morbidity, and was strongly predicted by first-episode polarity. Lower morbidity in EU than U.S. sites may reflect differences in healthcare or social systems.

Objectives: Since bipolar disorder (BPD) patients have high rates of comorbid substance abuse, and the temporal relationships involved are unclear, we evaluated the sequencing of specific substance use and affective morbidity., Methods: Prospective follow-up (4.7 years) of 166 first-episode DSM-IV type I BPD patients with reliable, standardized assessments provided data for longitudinal analysis of temporal distribution of alcohol and cannabis use versus manic or depressive episodes or symptoms, using generalized estimating equation regression modeling., Results: By quarters, cannabis use selectively and strongly preceded and coincided with mania/hypomania, and alcohol use preceded or coincided with depression, whereas substance use was unassociated with mood states in preceding quarters., Conclusions: These preliminary findings suggest potentially predictive temporal associations, in which the abuse of cannabis or alcohol anticipated or corresponded with, but did not follow, affective morbidity, including selective association of cannabis with mania and alcohol with depression.

Objectives: Most physiological indicators of bipolar disorder (BPD) reflect current acute illness, and rarely have proved to be state-independent. Activity rhythms are highly abnormal in acute phases of BPD; we compared circadian activity rhythms in BPD I patients during ill and recovered states to those of normal controls to test the hypothesis that some abnormalities may persist., Methods: We compared 36 adult DSM-IV BPD I patients during acute mania or mixed states, and during full and sustained clinical recovery, to 32 healthy controls of similar age and sex distribution, using wrist-worn, piezoelectric actigraphic monitoring for 72 h and computed cosinor analysis of circadian activity rhythms., Results: We verified expected major differences between manic or mixed-state BPD I patients and matched normal controls, including phase advances averaging 2.1 h in ill BPD I patients and 1.8 h in recovered patients. Moreover, recovered BPD patients differed highly significantly from controls in several measures, including acrophase advance, higher percentage of nocturnal sleep, and lower average daily activity (mesor). Actigraphic measures among recovered BPD patients were independent of ratings of mania (on the Young Mania Rating Scale), depression (on the Hamilton Depression Rating Scale), or rating-scale scored subjective distress, as well as the type and dose of concurrent psychotropic medication., Conclusions: These findings suggest that abnormal activity rhythms, including sustained phase advances, may represent enduring (trait) characteristics of BPD patients even during clinical recovery. If verified, such indices may be useful in supporting diagnoses and as an objective phenotype for genetic or other biological studies.

Background: Risks of life-threatening behaviors are high among bipolar disorder (BPD) patients, but early rates and associated risk factors for suicides and accidents remain ill-defined., Methods: We assessed 216 DSM-IV BP-I patients prospectively for 4.2 years from first-lifetime hospitalization, using ordinal logistic-regression to estimate risks and associated demographic and clinical factors among risk-groups with: [1] no suicidal ideation, acts, or accidents, [2] suicidal ideation only, [3] suicides and attempts, [4] accidents, and [5] both suicidal acts and accidents., Results: Suicidal thoughts or acts were identified in 127/216 subjects/4.2 years (14%/year), including suicidal ideation in 88 (9.7%/year), and acts in 39 (4.3%/year: 38 attempts [17.6%/year], 1 suicide [0.11%/year]); 87% of acts occurred within a year of a first-episode. Life-threatening accidents occurred in 20 cases (2.2%/year) with a mean latency of 3.8 years, including 12 with suicidal ideation or attempts (60% co-occurrence of accidents and suicidality); alcohol was implicated in 25% of accidents. The 53 cases of violent behaviors (5.84%/year) included a fatal car-wreck and a suicide, for a mortality risk of 0.22%/year (2/216/4.2 years). Suicidality was associated with initial mixed-state, proportion of follow-up weeks in mixed-states or depression, and prior suicide attempts; accidents were associated selectively with initial mania or psychosis, later mania or hypomania, and alcohol abuse. Violent acts also were associated with use of more psychotropic medicines/person, and with use of antipsychotics or sedative-anxiolytics., Limitations: Treatment was clinical and uncontrolled, illness relatively severe, and statistical power limited., Conclusions: Early in BP-I disorder, risks of suicidal acts and accidents were high, inter-related, and associated with particular types of initial and later morbidity, suggesting some predictability and potential for preventive intervention.

Emil Kraepelin proposed to separate psychiatric disorders with psychotic features into two major categories, dementia praecox (later schizophrenia) and manic-depressive insanity (later bipolar disorder and major depression). Over the past century, there have been many efforts to categorize conditions that do not fit readily in either group. These conditions include many cases of acute psychotic illnesses of limited duration, with recovery between recurrences. For some of these conditions, Karl Kleist proposed the term cycloid psychosis: acute features were psychotic, as in schizophrenia, but the course was episodic, as in manic-depression. His concept was later elaborated by Karl Leonhard and Carlo Perris, and validated by modern studies. Leonhard described three overlapping cycloid subtypes (anxiety-beatific, excited-inhibited confusional, and hyperkinetic-akinetic motility dysfunction forms); Perris proposed a more unitary syndrome with operational diagnostic criteria; and recent investigators have considered relatively affective versus thought-disordered subtypes. The cycloid concept is not explicitly included in standard international diagnostic schemes, but both DSM-IV and ICD-10 have broad categories for acute, recurrent psychotic disorders, whose validity remains insecure. We present two cases of probable cycloid psychosis, review the history of the concept, and propose that it be reconsidered as a clinically useful category whose validity and utility for prognosis and treatment can be further tested.

Background: Aripiprazole is the first dopamine D2 receptor partial-agonist approved for treatment of schizophrenia. Its apparently benign adverse-effect profile encourages broader use in other disorders, especially to limit weight gain associated with other antipsychotic or antimanic agents. We considered the first 6 months of experience with aripiprazole in psychiatric inpatients with a range of disorders., Methods: We analyzed data obtained from medical records of patients treated with aripiprazole who were hospitalized at McLean Hospital (for 19 +/- 18 days) between December 2002 and June 2003 to evaluate dosing, tolerability, and clinical effects of this new agent in patients diagnosed with DSM-IV psychotic, major affective, or other disorders., Results: Out of a sample of 2766 adult inpatients (65.5% women), 142 were given aripiprazole (mean final daily dose, 16.1 +/- 6.2 mg, 0.20 +/- 0.09 mg/kg body weight) for major affective disorders (52%), primary psychotic disorders (40%), and dementia (8%). CGI ratings improved by 20% on average. Adverse effects were infrequent (15.5%), were three times more likely among women, and most often involved moderate behavioral activation or nausea, with no new episodes of mania. Of the patients who were given aripiprazole, 83% continued it at discharge. Many patients were obese when they were admitted, and obesity was associated with relatively low mg/kg doses of aripiprazole., Conclusions: Aripiprazole was used in a range of disorders and was generally well tolerated. Adverse effects may reflect its unique dopamine partial-agonist activity. Since aripiprazole is likely to be considered for obese patients, body weight should be considered in establishing adequate doses. Controlled trials of this antipsychotic agent in disorders other than schizophrenia are needed.

Objective: This study clarified the early characteristics of substance use disorders in patients with first-episode bipolar I disorder., Method: The authors evaluated substance use disorders, associated factors, and clinical course, prospectively, in the first 2 years of DSM-IV bipolar I disorder with standardized methods., Results: Baseline substance use disorder was found in 33% (37 of 112) of the patients at baseline and in 39% at 24 months. Anxiety disorders were more frequent in the patients with than without substance use disorder (30% and 13%, respectively). Associations of alcohol dependence with depressive symptoms and cannabis dependence with manic symptoms were suggested. Patients using two or more substances had worse outcomes., Conclusions: Since substance use disorders were frequent from the beginning of bipolar I disorder and were associated with anxiety disorders and poor outcome, early interventions for substance use disorder and anxiety might improve later outcome.

Background: The syndrome of manic-depressive insanity (MDI), as conceptualized by Emil Kraepelin a century ago, with later refinements, continues to dominate research and clinical practice with mood disorder patients. Current understanding of Kraepelin's views by Anglophones is heavily influenced by the late, highly developed, MDI concept represented in the 1921 partial English translation of the last complete edition of his textbook, the product of gradual development over several decades., Method: We reviewed all nine editions and revisions of Kraepelin's Textbook (1883-1926) and other writings by him to document the evolution of his views of MDI, and characterized salient developments within biographical and historical contexts., Results: We found support for the traditional impression that Kraepelin's clinical perception of similarities of various forms of periodic psychiatric disorders marked by fundamental dysregulation of excitation and inhibition of thought and behavior, as well as of mood--as distinct from chronic psychotic illnesses--encouraged his broad, mature concept of MDI. However, our findings indicate a complex evolution of Kraepelin's MDI concept in the 1880s and 1890s, his use of more creative and less empirical clinical methods than traditionally believed, and his considerable personal uncertainty about making clear distinctions among MDI, dementia praecox, intermediate conditions, and paranoid disorders--an uncertainty that persisted to the end of his career in the 1920s., Conclusions: Kraepelin responded to a compelling international need for diagnostic order in nineteenth-century psychiatry, and effectively promoted his diagnostic proposals with a widely used and influential textbook. Though his methods were less empirical than is usually realized, his legacy includes analysis of large clinical samples to describe psychopathology and illness-course, along with efforts to define psychobiologically coherent and clinically differentiable entities, as steps toward defining psychiatric syndromes. Modern international "neo-Kraepelinian" enthusiasm for descriptive, criterion-based diagnosis should be tempered by Kraepelin's own appreciation of the tentative and uncertain nature of psychiatric nosology, particularly in classifying illnesses with both affective and psychotic features.

Since the classic descriptions of the course of bipolar and recurrent depressive forms of manic-depressive illness by Emil Kraepelin a century ago, it has been considered a truism that the rate of cycling increases, and wellness intervals shorten, with rising counts of recurrences, particularly early in the natural history of the illness. Less well known is that the analysis of this phenomenon is vulnerable to a computational artifact first described by Eliot Slater, based on his reanalysis of data from manic-depressive patients first evaluated by Kraepelin at the Munich Psychiatric Institute. Slater realized that there is an increasingly disproportionate representation of faster-cycling patients in sub-samples involving higher cycle-counts in pooled samples of subjects. More accurate results require analyzing illness-course either within individuals, or in groups matched for episode-counts. This artifact is pervasive in the older and modern research literature, but still not widely recognized. Since Slater's 1938 report in German is not well known, we provide an abbreviated English translation with commentary and additional reanalysis to highlight the phenomenon that might be termed 'Slater's Fallacy'.

Objective: Since improved prediction of illness course early in bipolar disorder is required to guide treatment planning, the authors evaluated recovery, first recurrence, and new illness onset following first hospitalization for mania., Method: Bipolar disorder patients (N=166) were followed 2-4 years after their first hospitalization for a manic or mixed episode to assess timing and predictors of outcomes. Three aspects of recovery were measured: syndromal (DSM-IV criteria for disorder no longer met), symptomatic (Young Mania Rating Scale score /=8 weeks), switching (onset of new dissimilar illness before recovery), relapse (new episode of mania within 8 weeks of syndromal recovery), and recurrence (new episode postremission) were also assessed., Results: By 2 years, most subjects achieved syndromal recovery (98%, with 50% achieving recovery by 5.4 weeks); 72% achieved symptomatic recovery. Factors associated with a shorter time to syndromal recovery for 50% of the subjects were female sex, shorter index hospitalization, and lower initial depression ratings. Only 43% achieved functional recovery; these subjects were more often older and had shorter index hospitalizations. Within 2 years of syndromal recovery, 40% experienced a new episode of mania (20%) or depression (20%), and 19% switched phases without recovery. Predictors of mania recurrence were initial mood-congruent psychosis, lower premorbid occupational status, and initial manic presentation. Predictors of depression onset were higher occupational status, initial mixed presentation, and any comorbidity. Antidepressant treatment was marginally related to longer time to recovery and earlier relapse., Conclusions: Within 2-4 years of first lifetime hospitalization for mania, all but 2% of patients experienced syndromal recovery, but 28% remained symptomatic, only 43% achieved functional recovery, and 57% switched or had new illness episodes. Risks of new manic and depressive episodes were similar but were predicted by contrasting factors.

Objective: The authors compared the new extended-release and standard preparations of divalproex sodium., Method: Twelve patients with DSM-IV bipolar disorder or schizoaffective disorder who were clinically stable while taking the standard form of divalproex participated in the study. These patients were given a single daily dose of the extended-release preparation of divalproex in an open 6-week trial. Clinical symptoms and adverse effects were rated weekly. Doses were adjusted to maintain steady serum valproate concentrations., Results: The medication change was associated with negligible changes in clinical status and tolerability. To maintain serum drug levels, however, 21% higher doses of the extended-release preparation were required., Conclusions: Use of extended-release divalproex once a day was as well tolerated as the standard preparation, with no change in efficacy within 6 weeks, but the daily dose needed to maintain stable serum valproic acid concentration was 21% higher.

Karl Ludwig Kahlbaum (1828-1899) spent most of his professional career as director of a private psychiatric sanatorium in Germany. He remains influential for introducing his "clinical method" (based on considering the course of an illness as well as the signs and symptoms) of differential diagnosis of specific psychiatric syndromes and urging abandonment of the more unitary views of psychotic disorders favored by the leading German academic theorists of his time. Kahlbaum's approach to nosology, detailed in an 1863 monograph and other works, strongly influenced Kraepelin's views. However, remarkably few of the important writings of this keen clinical observer are available in English translation. His seminal lecture-essay "On Cyclic Insanity" [Uber cyklisches Irresein] of 1882 is translated into English here for the first time, with comments about its place in the history of the evolution of the concept of bipolar disorder, including its position as a link between Falret's folie circulaire and Kraepelin's manic-depressive insanity.

Wilhelm Weygandt's Uber die Mischzustände des manisch-depressiven Irreseins (On the Mixed States of Manic-Depressive Insanity) describes and conceptualizes mixed states of mood, behavior, and thinking commonly found in manic-depressive disorders. These ideas emerged from Weygandt's service in the 1890s at the Psychiatric Clinic of the University of Heidelberg, directed by Emil Kraepelin. In the sixth (1899) edition of Kraepelin's influential textbook, the concept of manic-depressive illnesses underwent a fundamental shift from a complex group of syndromal subtypes to a single integrated disorder, widely known from the 1921 English translation of the eighth (1920) edition. In the 1899 edition, Kraepelin acknowledged Weygandt for a new section on mixed manic-depressive states within the new integrated view of manic-depressive disorder. We provide biographical notes on Weygandt, a little-known but historically important figure, as well as the first English translation of his monograph and interpretive summaries of his findings. We also consider whether Weygandt's important insight that the same person could be both manic and depressed not only at different times but even at the same time served as an important stimulus to Kraepelin's unified manic-depressive disorder concept, which survives as bipolar disorder a century later.

Background: Study aims were to analyze psychopathological details of prodromes leading to first-lifetime psychotic episodes and apply them to improve prediction of final diagnoses.Methods: Comprehensive records of subjects with final diagnoses of bipolar I (BD-I; n = 216), schizoaffective (SzAffD; n = 71), or psychotic major-depressive (MDD; n = 42) disorders in the Harvard-McLean First-Psychotic Episode Project were analyzed to identify psychopathological details of prodromes leading to first-lifetime episodes with psychotic features and their ability to predict final diagnoses tested with multivariable logistic regression modeling.Results: While held blind to final diagnoses, we identified 84 distinct psychopathological characteristics of prodromes to first-psychotic episodes, including perceptual disturbances, affective symptoms, sleep disturbances, onset rate, and duration. Prevalence of 19 factors appeared to differ among final diagnoses, and were tested with multivariable regression modeling. Significantly and independently more associated with final diagnoses of MDD than BD-I were 7 features: suicidal ideation, somatic delusions, anorexia, lack of insomnia, older presenting age, depressive symptoms, and lack of impulsivity; 9 others were associated more with later SzAffD than MDD or BD-I: lack of insomnia, homicidal behavior, lack of excitement, visual hallucinations, command hallucinations, longer prodrome, male sex, responding to internal stimuli, and younger age at presentation.Limitations: Historical-retrospective and prospective assessments may have misidentified some prodromal features, and subjects with final psychotic-MDD diagnosis were relatively few.Conclusions: Psychopathological features identified during prodromes leading to first-episodes with psychotic features predicted and distinguished among final diagnoses of MDD, BD-I, and SzAffD. The findings add to growing impressions that early psychopathology has value in predicting final diagnoses of major affective and schizoaffective disorders. [ABSTRACT FROM AUTHOR]

Many efforts have been made to develop coherent and clinically useful categories of depressive illness, especially to facilitate prediction of morbidity and guide treatment-response. They include proposals to resurrect the ancient concept of melancholia, as a form of severe depression with particular symptomatic and proposed psychobiological characteristics. However, modern research is inconsistent in supporting differences between melancholic and nonmelancholic depression. In our recent study of over 3200 patient-subjects with DSM-5 major depressive episodes with/without melancholic characteristics, and matched for illness severity, prevalence of melancholic features was 35.2% with remarkably few clinical and demographic differences between melancholic and nonmelancholic subjects. Also, our systematic review of trials comparing melancholic and nonmelancholic subjects found little difference in responses to antidepressant treatments. These findings indicate that the concept of melancholia may have limited value for clinical prediction and treatment-selection. Overlap of symptoms in melancholic and nonmelancholic depression, based on DSM criteria, may limit distinction of melancholia; alternative definitions can be sought, and psychomotor retardation is a particularly strong differentiating feature. For now, however, melancholia seems best considered a state-dependent depression-type strongly associated with greater symptomatic severity, rather than a distinct syndrome. Its DSM-5 current status as a depression-type specifier seems appropriate, and it may be a logical target for genetic and other biomedical studies. [ABSTRACT FROM AUTHOR]

The article discusses a study which evaluated psychotic patients in the McLean-Harvard International First Episode Project. Results showed that diagnoses remained stable in 77.6% of patients. Most changed diagnoses were to schizoaffective disorder, bipolar I disorder and schizophrenia. Diagnostic change was linked with nonaffective psychosis and auditory hallucinations. It is concluded that diagnostic changes involved emergence of affective symptoms and predicted by premorbid factors.

Background The empirical use of combinations of antipsychotic agents appears to be increasing with little research support for the relative efficacy, safety or cost-effectiveness of this practice. Such treatment was evaluated in hospitalized psychiatric patients. Methods Samples of consecutive inpatients treated with ≥ 2 (‘polytherapy’) vs 1 antipsychotic (‘monotherapy’) were matched on age, sex, diagnosis and admission clinical ratings, and these groups were compared on total daily chlorpromazine-equivalent doses, days in hospital, and changes in clinical ratings between admission and discharge. Results The study sample included 69 polytherapy and 115 well-matched monotherapy subjects. Despite matching for initial CGI and GAF ratings, polytherapy was associated with high PANSS subscale scores of positive symptoms among affective psychosis, and relatively greater PANSS subscale ratings of excitement-agitation among patients diagnosed with schizophrenia. Estimated clinical improvement during hospitalization was similar among poly- and monotherapy patients, but total daily CPZ-eq doses at discharge averaged twice-greater with polytherapy, and hospitalization lasted 1.5 times longer. Conclusions Antipsychotic polytherapy as well as the types of agents combined may reflect clinician responses to particular symptom patterns. The value of specific combinations of antipsychotic agents and their comparison with monotherapies requires specific, prospective, randomized and well-controlled trials that consider matching on clinical characteristics and truly comparable doses across regimens. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: The authors compared the new extended-release and standard preparations of divalproex sodium. Method: Twelve patients with DSM-IV bipolar disorder or schizoaffective disorder who were clinically stable while taking the standard form of divalproex participated in the study. These patients were given a single daily dose of the extended-release preparation of divalproex in an open 6-week trial. Clinical symptoms and adverse effects were rated weekly. Doses were adjusted to maintain steady serum valproate concentrations. Results: The medication change was associated with negligible changes in clinical status and tolerability. To maintain serum drug levels, however, 21% higher doses of the extended-release preparation were required. Conclusions: Use of extended-release divalproex once a day was as well tolerated as the standard preparation, with no change in efficacy within 6 weeks, but the daily dose needed to maintain stable serum valproic acid concentration was 21% higher. [ABSTRACT FROM AUTHOR]

Dado que el trastorno bipolar inicial requiere un pronóstico más certero del curso de la enfermedad para orientar la planificación terapéutica, los autores evaluaron el restablecimiento clínico, la primera recurrencia y el comienzo de una nueva enfermedad después de una primera hospitalización por manía. Método: Un colectivo de pacientes con trastorno bipolar(n = 166) fue seguido durante 2-4 años después de su primera hospitalización por un episodio maníaco o mixto, con el objetivo de evaluar el desarrollo temporal y los factores pronóstico de su evolución clínica. Se determinaron tres índices de mejoría clínica: el aspecto sindrómico (incumplimiento de los criterios del trastorno según el DSM-IV),el aspecto sintomático (puntuación <5 en la Escala de Manía de Young y s 8 en la Escala de Depresión de Hamilton) y el aspecto funcional (recuperación de la situación residencial y profesional premorbida). También se evaluaron los índices de remisión (recuperación sindrómica mantenida durante > 8 semanas), el cambio de polaridad (inicio da una enfermedad designo contrario que precede a la recuperación), la recaída (un nuevo episodio de manía antes de transcurridas 8 semanas de la recuperación sindromica) y la recurrencia (un nuevo episodio después de la remisión). Resultados: Al cabo de 2 años, la mayoría de los individuos había alcanzado la plena recuperación sindrómica (el 98 % había alcanzado el 50 % la recuperación a las 5,4 semanas), y el 72 %, una mejoría sintomática. Los factores relacionados con un menor tiempo de recuperación sindrómica fueron, para el 50 % de los individuos, el sexo femenino, una hospitalización de referencia más corta y unas puntuaciones iniciales de depresión más bajas. Sólo el 43% alcanzó la recuperación funcional; estos individuos tendieron a ser mayores, y las hospitalizaciones de referencia, más cortas. Antes de transcurridos 2 años de la recuperación sindrómica, el 40 % había experimentado un nuevo episodio de manía (20 %) o depresión (20 %), mientras que el 19% había cambiado de polaridad sin experimentar una mejoría. Los factores que pronosticaron la recurrencia de la manía fueron una psicosis inicial congruente con el estado anímico, una situación profesional premorbida más baja y la presentación inicial de un cuadro maníaco. Los factores que pronosticaron el inicio de un cuadro depresivo fueron una situación profesional más alta, la presentación inicial de un cuadro mixto y cualquier comorbilidad. El tratamiento antidepresivo se relacionó, mínimamente, con un tiempo de recuperación más largo y una recaída más rápida. Conclusiones: A los 2-4 años de la primera hospitalización por manía experimentada a lo largo de la vida todos, excepto el 2 % de los pacientes, experimentaron una recuperación sindrómica, si bien el 28 % permaneció sintomático, solo el 43 % alcanzó la plena recuperación funcional y el 57% cambió de polaridad o presentó episodios nuevos de la enfermedad. El riesgo de desarrollar nuevos episodios maniacos o depresivos fue similar, aunque los factores pronóstico fueron de signo contrario. [ABSTRACT FROM PUBLISHER]