Neuroplasticity, Neurotransmission and Brain-Related Genes in Major Depression and Bipolar Disorder: Focus on Treatment Outcomes in an Asiatic Sample

Abstract

IntroductionMood disorders are common and disabling disorders. Despite the availability of over 100 psychotropic compounds, only one-third of patients benefit from first-line treatments. Over the past 20years, many studies have focused on the biological factors modulating disease risk and response to treatments, but with still inconclusive data. In order to improve our current knowledge, in this study, we investigated the role of a set of genes involved in different pathways (neurotransmission, neuroplasticity, circadian rhythms, transcription factors, signal transduction and cellular metabolism) in the treatment outcome of major depressive disorder (MDD) and bipolar disorder (BD) after naturalistic pharmacological treatment.MethodsTotals of 242 MDD, 132 BD patients and 326 healthy controls of Asian ethnicity (Koreans) were genotyped for polymorphisms within 19 genes. Response and remission after 6-8weeks of treatment with antidepressants and mood stabilizers were evaluated. In secondary analyses, genetic associations with disease risk and some disease-associated features (age of onset, suicide attempt and psychotic BD) were also tested.ResultsNone of the variants within the investigated genes was significantly associated with treatment outcomes. Some marginal association (uncorrected p<0.01) was observed for HTR2A, BDNF, CHL1, RORA and HOMER1 SNPs. In secondary analyses, HTR2A (rs643627, p=0.002) and CHL1 (rs4003413, p=0.002) were found associated with risk for BD, HOMER1 (rs6872497, p=0.002) with lifetime history of suicide attempt in patients, and RORA with early onset and presence of psychotic features in BD. Marginal results were also observed for ST8SIA2 and COMT.DiscussionDespite limitations linked to multiple testing on small samples, methodological shortcomings and small significance of the findings, this study may support the involvement of some candidate genes in the outcomes of treatments for mood disorders, as well as in BD risk and other disease features.