Abstract
Antipsychotic drugs are one of the largest types of prescribed drugs. However, antipsychotic-induced weight gain (AIWG) is a major problem for the patients. AIWG increases cardiovascular and cerebrovascular morbidity and mortality, and reduces quality of life and drug compliance. To characterize changes in gene expression related to AIWG, we sequenced total messenger RNA from the blood samples of two groups of schizophrenia patients before and after 3 months of treatment with antipsychotics. The “weight gain” group was defined by an increase of body mass index (BMI) >1.5 points (18 patients; median BMI increase = 2.69) and the “no weight gain” group was defined by a change of BMI between <1.0 and >−1.0 points (18 patients; median BMI increase = 0.26). We found 115 genes with significant differential expression in the weight gain group before and after medication and 156 in the no weight gain group before and after medication. The weight gain group was significantly enriched with genes related to “obesity” and “BMI” (Fisher; p = 0.0002 and 0.01, respectively) according to the Gene Reference into Function (GeneRIF) database. In the no weight gain group, the enrichment was much smaller (Fisher; p = 0.02 and 0.79). This study is a first step toward detecting genetic factors that cause AIWG and to generating prediction tests in future studies with larger data sets.
Highlights
Antipsychotic drugs are widely used to treat mental health problems including schizophrenia,[1,2] bipolar disorder, depression, dementia, and autism among other clinical conditions.[3,4,5] They are one of the most prescribed and costly groups of drugs in clinical practice.[6]
It is known that antipsychotics induce weight gain[10] and that genetic factors play a major role in this weight gain.[8,26]
Excluding the genes altered by medication in the no weight gain group, we characterized 82 genes with expression significantly altered by antipsychotics only in the weight gain group (Fig. 1)
Summary
Antipsychotic drugs are widely used to treat mental health problems including schizophrenia,[1,2] bipolar disorder, depression, dementia, and autism among other clinical conditions.[3,4,5] They are one of the most prescribed and costly groups of drugs in clinical practice.[6]. We sequenced the transcriptome of two cohorts of first-episode schizophrenia patients before and after 3 months of treatment with antipsychotics (Table 1). The transcriptomes of each group were analyzed independently to define the genes with significant differential expression before and after medication using the program Deseq.[20] The first cohort, or the “weight gain” group, included 18 individuals who gained more than 1.5 points of BMI after the treatment. The second cohort, the “no weight gain” group, included 18 individuals with a change in BMI after the treatment between 1.0 and −1.0 points
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