Insight gained from genome-wide interaction and enrichment analysis on weight gain during citalopram treatment

Abstract

IntroductionWeight gain is a side effect of pharmacological antidepressant treatments, causing a poorer compliance, increasing the risk of metabolic syndrome and periods of untreated disease.ObjectivesThe ability to precisely prescribe pharmacological treatments based on personal genetic makeups would increase the quality of the current antidepressant treatments.AimsThe molecular pathways enriched during citalopram induced weight gain are identified.Methods643 depressed citalopram treated individuals with available clinical and genome-wide genetic information were investigated in the present contribution in order to identify the molecular pathways that holds the key to weight gain. Statistics were conducted in R environment (Bioconductor and Reactome packages), ANOVA and MANCOVA served when appropriate. Plink was used for genetic analysis in a linux environment.ResultsOne hundred and eleven individuals had their weight increased after treatment with citalopram. The axon guidance (P. adjust = 0.005) and the developmental biology pathway (P. adjust = 0.01) were found to be enriched in genetic variations associated with weight gain.ConclusionsThe development biology pathway includes molecular cascades involved in the regulation of beta-cell development, and the transcriptional regulation of white adipocyte differentiation. A number of variations were harboured by genes whose products are involved in the synthesis of collagen (COL4A3, COL5A1 and ITGA1), activity of the thyroid-hormones (NCOR1 and NCOR2), energy metabolism (ADIPOQ, PPARGC1A) and myogenic differentiation (CDON). A molecular pathway analysis conducted in a sample of depressed patients identifies new candidate genes whose future investigation may grant relevant insights in the molecular events that drive weight gain during antidepressant treatment.