Background and importance Psychotropic induced weight gain (PIWG) may lead to an increased risk of cardiovascular diseases, metabolic disorders and, ultimately, treatment discontinuation. Identification of the genetic makeup at risk for PIWG could characterise subjects at risk for this possible severe side effect and help move a step forward in the direction of personalised treatment in psychiatry.

Aim and objectives The hypothesis tested in the study was that PIWG might be genetically driven. Analysis of the complete molecular pathways may grant sufficient power to tackle the biologic variance of PIWG.

Material and methods A genetic sample from the CATIE trial (n=765; 556 men, mean age 40.93±11.03 years) treated with diverse antipsychotic drugs was investigated. A molecular pathway analysis was conducted in an R environment for the identification of the molecular pathways enriched in variations associated with PIWG.

Results The developmental biology molecular pathway was found to be significantly (p adj=0.018) enriched in genetic variations significantly (p<0.01) associated with PIWG. A total of 18 genes were identified and discussed. The developmental biology molecular pathway was involved in the regulation of β cell development, and the transcriptional regulation of white adipocyte differentiation. Interestingly, this finding was a result of a hypothesis free approach.

Conclusion and relevance The results correlate with previous evidence and are consistent with our earlier results in the STAR*D sample. Furthermore, the involvement of β cell development and transcriptional regulation of white adipocyte differentiation pathways stress the relevance of peripheral tissue rearrangement, rather than increased food intake, in the biologic modifications that follow psychotropic treatment and may lead to PIWG. Further research is warranted.

References and/or acknowledgements No conflict of interest.