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 20 years, 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 6–8 weeks 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.Electronic supplementary materialThe online version of this article (10.1007/s12325-018-0781-2) contains supplementary material, which is available to authorized users.

Benchmarking post-GWAS analysis tools in major depression: Challenges and implications

“…The overlap between eGenes and pGenes from PICS and TORUS fine-mapping was very small, with 3 genes in total. Among them, KTN1 has also been associated with MD ( Dall’Aglio et al, 2021 ) and ESYT2 is involved in neurodevelopmental pathways and may be associated with suicidal behaviour trends in MDD although more research is needed ( Calabrò et al, 2018 ). eGenes from PICS+CLPP were functionally enriched with miRNAs.…”

Genetic neuroimaging of bipolar disorder: a systematic 2017–2020 update

“…The hippocampus is a stress-sensitive area, and here Homer1 proteins functionally interact with metabotropic mGluR5 glutamate receptors to control glutamate-dependent behaviours. The evidence for the involvement of the Homer1 rs7713917 polymorphism in BD derives from just one study (Benedetti et al, 2018), while other studies showed only a general reduction of Homer1 expression in post-mortem PFC of patients with BD and schizophrenia (Zimmerman et al, 2020) or no association of eight HOMER1 SNPs with BD in an underpowered study (Calabrò et al, 2018).…”

Genetic Polymorphisms rs643627 in Serotonin Receptor Gene (5-HTR2A) with Schizophrenia

“…Many factors may contribute to these inconsistent results.SCZ has been linked to genetic and environment factors.HT2A gene was reported to beassociated with more than one mental disorder (obsessive-compulsive disorder, schizophrenia, bipolar disorder and major depressive disorders) [28].The rs643627 within 5-HTR2Agene was also reported to be associated with psychiatric disorder, bipolar disorder and major depressive disorders [19].…”