Molecular genetics of bipolar disorder.

Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202-4887, USA.
Genes Brain and Behavior (Impact Factor: 3.51). 03/2006; 5(1):85-95. DOI: 10.1111/j.1601-183X.2005.00138.x
Source: PubMed

ABSTRACT Bipolar disorder (BPD) is an often devastating illness characterized by extreme mood dysregulation. Although family, twin and adoption studies consistently indicate a strong genetic component, specific genes that contribute to the illness remain unclear. This study gives an overview of linkage studies of BPD, concluding that the regions with the best evidence for linkage include areas on chromosomes 2p, 4p, 4q, 6q, 8q, 11p, 12q, 13q, 16p, 16q, 18p, 18q, 21q, 22q and Xq. Association studies are summarized, which support a possible role for numerous candidate genes in BPD including COMT, DAT, HTR4, DRD4, DRD2, HTR2A, 5-HTT, the G72/G30 complex, DISC1, P2RX7, MAOA and BDNF. Animal models related to bipolar illness are also reviewed, with special attention paid to those with clear genetic implications. We conclude with suggestions for strategies that may help clarify the genetic bases of this complex illness.

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    ABSTRACT: Background 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).Methods 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.ResultsTwenty-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).Conclusions There is no compelling evidence to supportVal66Met polymorphism in BDNF gene playing an important role in the susceptibility to BPD across different ethnicities.
    BMC Psychiatry 12/2014; 14(1):5. DOI:10.1186/s12888-014-0366-9 · 2.24 Impact Factor
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    ABSTRACT: Background: Genetic factors may encourage or even cause the occurrence of mood disorders such as anxiety and/or depression. However, despite the significant amount of work and sophisticated technology is not fully elucidated which genes or regions of nuclear or mitochondrial DNA, or which types of genetic changes, alone or in combination, can represent reliable genetic markers of anxiety and/or depression. Objective: To identify whether there are genetic changes that can cause depression or anxiety and if there are genetic markers that can be used to detect these changes. Methods: A systematic review of 01.012004 to 0328 2014 was held by VHL (Virtual Health Library). The search was performed with the descriptors "anxiety", "depression", "mutation" and "genetic markers". The selected articles were indexed in MEDLINE. The information pertinent to the study was selected, categorized and analyzed. Of the 374 articles found, 29 met the eligibility criteria. Results: FMR1 gene polymorphisms, dopaminergic (DAT, DRD, COMT), serotonin (5-HTTLPR, HTR1A, EITR2A), interleukins, MCR1, HCN (potassium channel), neurorregulinas, GABAergic (GABA, GAD, DBI) DBI, GABA (Gabra) receptors and GAD genes (GAD1, GAD2) appear to contribute to generate condition of depression or anxiety like. Mutations in mitochonclrial DNA in 124pb allele of D252944 in oil 1 and 2 loci of chromosomes 4 and 7, respectively, and the chromosomes 8p, 17p and 15q appear to be associated with the origin of depression or anxiety. Conclusion: Some studies show only associations with one of the disorders, mainly anxiety. Few have shown association with both simultaneously. Other studies showed specific association of gender, or even specific ethnic groups, It was noticed, controversies over certain markers. Interesting results were observed in combination of changes, especially in cases of SNPs, indicating that perhaps this is the most appropriate way to find reliable markers.
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    Proceedings of the National Academy of Sciences 10/2014; 111(44). DOI:10.1073/pnas.1417294111 · 9.81 Impact Factor