Copyright 2008 Iberoamerican Network for Bipolar Disorder. All rights reserved.
Article selection
by Mauricio Tohen, Flávio kapczinski, Michael Berk and Eduard Vieta
October selection
Mauricio Tohen
Flávio Kapczinski
Michael Berk
Eduard Vieta
Geller B, Tillman R, Bolhofner K, Zimerman B. Child bipolar I disorder: prospective continuity with adult bipolar I disorder; characteristics of second and third episodes; predictors of 8-year outcome.
Arch Gen Psychiatry
. 2008 Oct;65(10):1125-33.
CONTEXT: Child bipolar I disorder (BP-I) is a contentious diagnosis. OBJECTIVE: To investigate continuity of child and adult BP-I and characteristics of later episodes. DESIGN: Inception cohort longitudinal study. Prospective, blinded, controlled, consecutive new case ascertainment. SETTING: University medical school research unit. Subjects There were 115 children, enrolled from 1995 through 1998, aged 11.1 (SD, 2.6) years with first episode DSM-IV BP-I, mixed or manic phase, with 1 or both cardinal symptoms (elation or grandiosity) and score of 60 or less on the Children's Global Assessment Scale (CGAS). All DSM-IV severity and duration criteria were fulfilled. Separate interviews were conducted of parents about their children and of children about themselves. MAIN OUTCOME MEASURES: Washington University in St Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS); Psychosocial Schedule for School Age Children-Revised; CGAS. RESULTS: Retention was 93.9% (n = 108) for completing assessments at every one of the 9 follow-up visits. Subjects spent 60.2% of weeks with any mood episodes and 39.6% of weeks with mania episodes, during 8-year follow-up. During follow-up, 87.8% recovered from mania, but 73.3% relapsed to mania. Even accounting for family psychopathology, low maternal warmth predicted relapse to mania, and more weeks ill with manic episodes was predicted by low maternal warmth and younger baseline age. Largely similar to first episodes, second and third episodes of mania were characterized by psychosis, daily (ultradian) cycling, and long duration (55.2 and 40.0 weeks, respectively), but significantly shorter than first episodes. At 8-year follow-up, 54 subjects were 18.0 years or older. Among subjects 18.0 years or older, 44.4% had manic episodes and 35.2% had substance use disorders. CONCLUSIONS: In grown-up subjects with child BP-I, the 44.4% frequency of manic episodes was 13 to 44 times higher than population prevalences, strongly supporting continuity. The rate of substance use disorders in grown-up child BP-I was similar to that in adult BP-I.
Kauer-Sant'anna M, Kapczinski F, Andreazza AC, Bond DJ, Lam RW, Trevor Young L, Yatham LN. Brain-derived neurotrophic factor and inflammatory markers in patients with early- vs. late-stage bipolar disorder.
Int J Neuropsychopharmacol
. 2008 Sep 4:1-12.
Bipolar I disorder (BD) has a poorer longer-term outcome than previously thought, with persistent cognitive impairment and functional decline. The neurobiological underpinnings that might underlie these changes remain unknown. Changes in brain-derived neurotrophic factor (BDNF) levels and cytokines are potential candidates. The aim of this study was to examine both cytokine and BDNF levels and their relationship in BD patients in the early and late stages of the disorder. We measured serum BDNF, TNF- were increased in the early stages of BD, compared to controls. While TNF- showed a significant increase at the later stage. Failure of inflammatory defences in the late stage of the disorder may account for reduction in BDNF and continued elevations in cytokines; thus these may have the potential to serve as markers of illness progression in BD.
Kato T. Molecular neurobiology of bipolar disorder: a disease of 'mood-stabilizing neurons'?
Trends Neurosci
. 2008 Oct;31(10):495-503.
Although the role of a genetic factor is established in bipolar disorder, causative genes or robust genetic risk factors have not been identified. Increased incidence of subcortical hyperintensity, altered calcium levels in cells derived from patients and neuroprotective effects of mood stabilizers suggest vulnerability or impaired resilience of neurons in bipolar disorder. Mitochondrial dysfunction or impaired endoplasmic reticulum stress response is suggested to play a role in the neurons' vulnerability. Progressive loss or dysfunction of 'mood-stabilizing neurons' might account for the characteristic course of the illness. The important next step in the neurobiological study of bipolar disorder is identification of the neural systems that are responsible for this disorder.
Vieta E, T'joen C, McQuade RD, Carson WH Jr, Marcus RN, Sanchez R, Owen R, Nameche L., Efficacy of adjunctive aripiprazole to either valproate or lithium in bipolar mania patients partially nonresponsive to valproate/lithium monotherapy: a placebo-controlled study. Am J Psychiatry. 2008 Oct;165(10):1316-25.
OBJECTIVE: The authors evaluated the efficacy and safety of adjunctive aripiprazole in bipolar I patients with mania partially nonresponsive to lithium/valproate monotherapy. METHOD: This multicenter, randomized, placebo-controlled study included outpatients experiencing a manic or mixed episode (with or without psychotic features). Patients with partial nonresponse to lithium/valproate monotherapy (defined as a Young Mania Rating Scale total score >/=16 at the end of phases 1 and 2, with a decrease of </=25% between phases) with target serum concentrations of lithium (0.6-1.0 mmol/liter) or valproate (50-125 mug/ml) were randomly assigned in a 2:1 ratio to adjunctive aripiprazole (N=253; 15 or 30 mg/day) or placebo (N=131) for 6 weeks. RESULTS: Mean improvement from baseline in Young Mania Rating Scale total score at week 6 (primary endpoint) was significantly greater with aripiprazole (-13.3) than with placebo (-10.7). Significant improvements in Young Mania Rating Scale total score with aripiprazole versus placebo occurred from week 1 onward. In addition, the mean improvement in Clinical Global Impression Bipolar Version (CGI-BP) severity of illness (mania) score from baseline to week 6 was significantly greater with aripiprazole (-1.9) than with placebo (-1.6). Discontinuation rates due to adverse events were higher with aripiprazole than with placebo (9% versus 5%, respectively). Akathisia was the most frequently reported extrapyramidal symptom-related adverse event and occurred significantly more frequently among those receiving aripiprazole (18.6%) than among those receiving placebo (5.4%). There were no significant differences between treatments in weight change from baseline to week 6 (+0.55 kg and +0.23 kg for aripiprazole and placebo, respectively; last observation carried forward). CONCLUSIONS: Adjunctive aripiprazole therapy showed significant improvements in mania symptoms as early as week 1 and demonstrated a tolerability profile similar to that of monotherapy studies.
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