Mood disorders and 5-HTR2A genetic variants – the moderator effect of inflammation on expression of affective polarity phenotype

Abstract Background Although repeatedly confirmed, the molecular nature of gene-environment (GxE) interactions has rarely been investigated in the clinical context of mood disorders. This study assesses the relationship between HTR2A genetic variants and the modulatory effect of inflammation in a co...

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Main Authors: Maja Pantovic-Stefanovic, Jelena Karanovic, Vladimir Jurisic, Bojana Dunjic-Kostic, Milica Nesic, Sara Dodic, Marta Gostiljac, Marija Puric, Dusanka Savic Pavicevic, Maja Ivkovic
Format: Article
Language:English
Published: BMC 2024-10-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-024-06207-y
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Summary:Abstract Background Although repeatedly confirmed, the molecular nature of gene-environment (GxE) interactions has rarely been investigated in the clinical context of mood disorders. This study assesses the relationship between HTR2A genetic variants and the modulatory effect of inflammation in a collective cohort of patients with major depressive disorder (MDD) and bipolar disorder (BD), as a unified group with two distinct phenotypes. Methods The study included 138 patients with acute mood episodes (BD = 83; MDD = 55). HTR2A rs6313 and rs6314 genotyping was performed while measuring platelet-derived indicators of inflammation (platelet count (PLT), mean platelet volume (MPV), plateletcrit, and platelet distribution width) and the MPV/PLT ratio. Results The HTR2A rs6313 variant is a significant predictor of the polarity phenotype in mood disorders, with the MPV/PLT ratio moderating this relationship, but only under low-inflammatory conditions. In more pronounced inflammatory states, genetic influences lose their predictive role. Conclusions To our knowledge, this is the first study to investigate the complex interplay between platelet-derived indicators of inflammation and HTR2A variants in the context of mood disorders. Without pro-inflammatory conditions, mood disorders seem to be more genetically determined. Under pro-inflammatory conditions, phenotypic presentation is less dependent on genetic factors. GxE interactions in mood disorders are multifaceted, context-dependent and relevant for assessing their clinical presentation and course.
ISSN:1471-244X