A functional magnetic resonance imaging study of cortical asymmetry in bipolar disorder

Objectives: Individuals with bipolar disorder (BPD) exhibit motor, perceptual, and cognitive disturbances involving predominantly right hemisphere dysfunction. This asymmetry has been used to advance the hypothesis that the pathogenesis of bipolar disorder may be related to disturbances of the right cerebral hemisphere. We employed functional magnetic resonance imaging to examine hemispheric asymmetries in manic and depressed BPD. A secondary goal of the Study was to examine effects of psychotropic medications on blood Volume changes in the motor cortices. Methods: We studied 18 right-handed BPD and 13 right-handed normal healthy comparison subjects. Blood oxygen level dependent (BOLD) responses in the primary motor area (M1) and Supplementary motor area (SMA) of both hemispheres were elicited during reaction time (RT) tasks. Results: Healthy subjects activated the SMA in a reciprocal fashion with significantly greater activity in the left SMA for right hand trials and the right SMA for left hand trials. Depressed BPD subjects failed to show this normal reciprocity indicating a failure to Suppress unwanted activity in the ipsilateral right SMA, whereas manic BPD subjects failed to suppress unwanted ipsilateral SMA activity in both hemispheres. Manic and depressed BPD subjects exhibited greater activity in the left primary motor area suggesting increased cortical excitability. BPD subjects treated with antipsychotics or mood-stabilizing medications exhibited longer RTs, lower BOLD responses in M1 and SMA, and a loss of normal hemispheric asymmetry in the SMA than untreated subjects. Conclusions: The presence of a right hemisphere disturbance in BPD is consistent with the hypothesis that the right hemisphere may be dominant in mood regulation. The presence of both left and right hemisphere disturbances in mania may explain the coexisting psychotic and affective symptoms observed in this condition

Neurobiologia do transtorno de humor bipolar e tomada de decisão na abordagem psicofarmacológica

O Transtorno do Humor Bipolar (THB) caracteriza-se por oscilações do humor que causam prejuízos significativos no âmbito biopsicossocial. O interesse da comunidade científica por este transtorno vem aumentando nos últimos cinco anos em função de sua crescente prevalência associada ao refinamento diagnóstico, à ampliação do arsenal terapêutico e ao conhecimento dos avanços nas pesquisas da neurobiologia do transtorno. A presente revisão aborda questões diagnosticas e terapêuticas aplicadas à neurobiologia dos THB, relacionando-as diretamente à terapêutica dos quadros de mania, hipomania, estados mistos, depressão bipolar e ciclagem rápida, da infância à idade adulta. São revisados criticamente importantes estudos realizados com diferentes fármacos potencialmente eficazes como estabilizadores do humor, nos diversos subdiagnósticos do THB. São analisados fármacos, tais como o lítio, anticonvulsivantes, antipsicóticos, benzodiazepínicos, bloqueadores dos canais de cálcio e hormônio tireoideo, bem como as possíveis bases biológicas para seus efeitos terapêuticos. Em síntese, este trabalho aborda os avanços da psicofarmacologia cuja eficácia é comprovada nos subtipos do THB, procurando relacioná-los com a neurobiologia deste transtorno.Bipolar Disorder (BD) is characterized by mood swings that cause significant impairment in social, occupational, or other areas of functioning. During the last years, new insights have been provided in the diagnosis, etiology, neurobiological basis and treatment of bipolar disorder. This paper emphasizes recent studies related to some diagnostic and therapeutic aspects during manic episode, hypomanic, mixed episode, bipolar depression and rapid cycling, in children, adolescents and adults. Studies using proposed mood stabilizers, which present adequate metodological basis, including double–blind, controlled studies and which presented a significant number of patients were included and critically evaluated in this revision. Drugs such as the lithium, anticonvulsants, antipsychotics, benzodiazepines, calcium channels blockers and thyroid augmentation are proposed to be effective in certain diagnostic profiles. The possible biological bases for these drugs therapeutic effects are also revised. In summary, this article focuses on recent and important psychopharmacological progresses on the treatment of BD subtypes. Furthermore, the revision presents possible biological basis to explain the therapeutic profile of these drugs

Depressão resistente a tratamento: uma revisão das estratégias farmacológicas de potencialização de antidepressivos Treatment-resistant depression: review of pharmacologic antidepressant strategies

OBJETIVO: Fazer uma revisão sobre oito estratégias farmacológicas de potencialização de antidepressivos na DRT. MÉTODOS: Fez-se um levantamento bibliográfico de 1990 até janeiro de 2006, nas bases eletrônicas de busca Medline, LILACS e da Biblioteca Cochrane, utilizando-se os termos de busca treatment, resistant, refractory e depression e os descritores depression, drug resistance e augmentation, incluindo apenas ensaios controlados duplo-cegos. Foi consultada a referência dos artigos para obtenção de ensaios realizados em data anterior a 1990 e artigos originais de valor histórico. RESULTADOS: Foram encontrados 17 estudos duplo-cegos com o lítio, seis com o hormônio tireoidiano, dois com a buspirona, seis com o pindolol, um com a carbamazepina, dois com a lamotrigina e quatro com a olanzapina. Foram favoráveis à potencialização 41,2% dos ensaios com lítio; 60% daqueles com hormônio tireoidiano e antidepressivos tricíclicos e nenhum com hormônio tireoidiano e inibidores seletivos da recaptação da serotonina (ISRS); 50% dos com pindolol; 100% dos ensaios com carbamazepina e 40% daqueles com olanzapina. Nenhum dos estudos com a buspirona foi favorável. No único estudo com lamotrigina não houve eficácia de tratamento na avaliação pelo critério principal, mas superioridade ao placebo em critérios secundários. CONCLUSÃO: Na DRT há evidência de eficácia apenas em relação ao lítio na potencialização de várias classes de antidepressivos e ao hormônio tireoidiano na potencialização de tricíclicos. A olanzapina foi razoavelmente estudada e sua eficácia não foi estabelecida. Os poucos estudos realizados com a buspirona e o pindolol não comprovaram sua eficácia. A carbamazepina foi muito pouco estudada, e a lamotrigina ainda não foi adequadamente avaliada.<br>OBJECTIVE: The aim of this study is to review eight pharmacologic antidepressant augmentation strategies in TRD. METHODS: Database search on Medline, LILACS and Cochrane Library, from 1990 to June 2006 using the words treatment, resistant, refractory, depression and the medical subject headings depression, drug resistance and augmentation. Double-blind controlled trials and reviews were included. We also consulted reference of the articles in order to obtain studies and original articles of historical value from before 1990. RESULTS: There were 17 double-blind trials with lithium, six with thyroid hormone, two with buspirone, six with pindolol one with carbamazepine, two with lamotrigine and four with olanzapine. Forty-one percent of the trials with lithium, 60% of those with thyroid hormone and tricyclics, 0% of the ones with thyroid hormone and selective serotonin reuptake inhibitors (SSRI), 50% of those with pindolol, 100% of those with carbamazepine and 40% of the ones with olanzapine were favorable. No trials with buspirone were favorable. The only trial with lamotrigine did not show efficacy using the main outcome measures. Otherwise, there was superiority over placebo on secondary measures. CONCLUSION: Only lithium and thyroid hormone showed efficacy as antidepressant augmentation strategies for TRD. Olanzapine was reasonably studied and did not prove its efficacy. There were just a few studies on buspirone and pindolol and they were not favorable to them. Carbamazepine was studied very little. Lamotrigine was not adequately evaluated