In view of previous conflicting findings, this meta-analysis was performed to comprehensively determine the overall strength of associations between brain-derived neurotrophic factor (BDNF) genetic polymorphism Val66Met and susceptibility to bipolar disorders (BPD). Literatures published and cited in Pubmed and Wanfang Data was searched with terms of ‘Val66Met’, ‘G196A’, ‘rs6265’, ‘BDNF’, ‘association’, and ‘bipolar disorder’ up to March 2014. All original case–control association studies were meta-analyzed with a pooled OR to estimate the risk and 95% confidence interval (CI) to reflect the magnitude of variance. Twenty-one case–control association studies met our criteria for the meta-analysis. Overall, there was no significant difference in allelic distribution of Val66Met polymorphism between patients and controls with a pooled OR = 1.03 (95% CI 0.98, 1.08) although there was a trend towards association between Val66Met polymorphism and BPD in Caucasians with an OR of 1.08 (95% CI 1.00, 1.16). However, subgroup analyses showed that there was a significant association of Val allele with decreased disease susceptibility for bipolar disorder type II with a pooled OR of 0.88 (95% CI 0.78, 0.99). There is no compelling evidence to supportVal66Met polymorphism in BDNF gene playing an important role in the susceptibility to BPD across different ethnicities.

Introduction: Antipsychotic-induced weight gain (WG) and metabolic abnormalities are major concerns. This review was untaken to answer if there is a weight-neutral second-generation antipsychotic for bipolar disorder (BPD). Areas covered: English-language literature in MEDLINE was searched with the keywords of antipsychotic/second-generation antipsychotic or generic/brand name of second-generation antipsychotic, and BPD/mania/depression or bipolar maintenance, and safety/tolerability or WG/weight increase, and randomized, placebo-controlled trial. Difference between an antipsychotic monotherapy and placebo in absolute weight gain (AWG) and/or ≥ 7% (WG in three phases of BPD was compared based on the data from original publications. The number needed to treat to harm was used for the comparison of ≥ 7% WG. Among antipsychotics with short-term (mania and/or bipolar depression) and long-term (maintenance) studies, olanzapine, asenapine, quetiapine, risperidone had significant WG compared to placebo in both short-term and long-term trials. Aripiprazole did not cause significant WG compared to placebo in short-term studies, but caused significant WG in long-term studies. Paliperidone-ER-induced WG was significant in a mania study as measured with AWG, and ziprasidone caused significant WG in a mania study measured with ≥ 7% WG. Expert commentary: These data suggest that it is unlikely there is a weight-neutral second-generation antipsychotic in BPD.