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Atypical antipsychotics and some other psychotropic drugs such as valproate, lithium or mirtazapine are known to induce several metabolic complications. However there is an inter-individual variability in developing metabolic features which may be explained by clinical and genetic factors.
To determine whether weight gain and/or appetite change after one month are predictors for a weight gain after 3 and 12 months of treatment.
A longitudinal clinical and pharmacogenetic study is presently ongoing in the Department of Psychiatry-CHUV. Several clinical data have been recorded over one year following the introduction of psychotropic treatment. 406 patients with weight at baseline, after one month and with at least a third weight measure during the first year of treatment were included in the present study.
Using Receiver Operating Characteristic (ROC) analyses, an initial weight increase of 5% was found to be a good predictor for a consequent weight gain at 3 months (ROCAUC=77) and one year (ROCAUC=68). By using a generalized linear mixed model corrected by several confounders, this weight change of 5% was found to be significantly associated (p-value<0.0001) with an important weight change (10 to 20% increase from baseline value) over one year. Appetite was not found to be good a predictor of weight gain over one year.
An initial weight gain of 5% during the first month following an introduction of atypical antipsychotics, lithium, valproate and/or mirtazapine is a predictor for further weight gain and should be a warning sign to introduce weight lowering strategies.
Weight gain and obesity are serious problems associated with psychiatric diseases, in which psychotropic treatments play an important role. The CREB-regulated transcription coactivator 3 (CRTC3) gene was linked to energy balance in animal models, and in humans CRTC3 rs8033595 polymorphism was associated with obesity markers only in Mexican-Americans, a population with a high prevalence of obesity.
To determine whether polymorphisms within the CRTC3 gene are associated with adiposity markers in Caucasian psychiatric patients, a population with also a high prevalence of obesity.
The association of the CRTC3 rs8033595 and 2 other selected CRTC3 polymorphisms (rs3743401 and rs3902286) was investigated in three independent groups of Caucasian psychiatric patients taking weight gain-inducing psychotropic drugs such as atypical antipsychotics, lithium and valproate (n1=168, n2=188, and n3=448). Body mass index (BMI) was chosen as a marker for obesity. Generalized Additive Mixed Model (GAMM) was used to test the association of CRTC3 polymorphisms with BMI.
Obesity prevalence was high in the three psychiatric populations (n1:40%, n2:28% and n3:19%). The three CRTC3 polymorphisms did not deviate from Hardy-Weinberg equilibrium and the minor allelic frequency (MAF) was 44%, 25% and 19% for CRTC3 rs8033595, rs3743401 and rs3902286, respectively. None of the CRTC3 polymorphisms were found to be associated with BMI in any of the three psychiatric samples and when analyzing the combined samples together.
CRTC3 polymorphisms seem not to have an influence on adiposity markers (BMI) in Caucasian psychiatric patients receiving drugs inducing weight gain.
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