Enriched developmental biology molecular pathways impact on antipsychotics-induced weight gain

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Psychotropic-induced weight gain (PIWG) may lead to increased risk for cardiovasculardiseases, metabolic disorders and treatment discontinuation. PIWG may be genetically driven. The analysis of complete molecular pathways may grant suffcient power to tackle the biologic variance of PIWG. Such identifcation would help to move a step forward in the direction of personalized treatment in psychiatry. A genetic sample from the CATIE trial (n = 765; M = 556, mean age = 40.93 ± 11.03) treated with diverse antipsychotic drugs was investigated. A molecular pathway analysis was conducted for the identifcation of the molecular pathways enriched in variations associated with PIWG. The developmental biology molecular pathway was signifcantly (P.adj = 0.018) enriched in genetic variations signifcantly (P < 0.01) associated with PIWG. A total of 18 genes were identifed and discussed. The developmental biology molecular pathway is involved in the regulation of β-cell development, and the transcriptional regulation of white adipocyte differentiation. Results from the current contribution correlate with previous evidence and it is consistent with our earlier result on the STAR*D sample. Furthermore, the involvement of the β-cell development and the transcriptional regulation of white adipocyte differentiation pathways stress the relevance of the peripheral tissue rearrangement, rather than increased food intake, in the biologic modifcations that follow psychotropic treatment and may lead to PIWG. Further research is warranted.

Original languageEnglish
JournalPharmacogenetics and Genomics
Pages (from-to)9-20
Number of pages12
Publication statusPublished - 2020

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