Abstract
Antipsychotics are crucial for the treatment of schizophrenia and contribute to weight gain in psychosis, particularly during early phases. Antipsychotic Induced Weight Gain (AIWG) might contribute to reduce the quality of life, drug compliance and to increase mortality. To characterize sex differences of gene expression related to AIWG, we sequenced total mRNA from blood samples of schizophrenia patients, before and after 3 months of antipsychotic-treatment. We analyzed schizophrenia patients according to their sex (38 males and 39 females) and their BMI increase after medication, characterizing the differential gene expression before and after medication. Individuals in each group were categorized in patients who gain weight and those whose do not gain weight. The “weight gain” groups included patients with an increase of body mass index (BMI) > 1.0 points (27 males and 23 females with a median BMI increase of 2.68 and 2.32 respectively). The “no weight gain” groups included patients with a change of BMI between < 1.0 and > -1.0 points (11 males and 16 females with a median BMI increase of 0.21 and 0.16 respectively). The males had 331 genes with significant differential expression in the weight gain group and 24 genes in the no weight gain group. The females had 119 genes with significant differential expression in the weight gain group and 75 genes in the no weight gain group. Both weight gain groups were significantly enriched with “obesity” genes (Fisher; p = 1.1E-09 and p = 0.0001 respectively), according to the Gene Reference into Function (GeneRIF) database.In conclusion, we characterized genes with differential expression associated to AIWG that are specific to males, to females and common to both sexes. These genes are good candidates to depict the biological processes involved in AIWG and provide additional evidence of the genetic links between weight gain and the immune system.
Highlights
Antipsychotic medications are the keystone for the treatment of schizophrenia and other psychotic disorders
When we analyzed for the string “body mass index (BMI)”, we found 15 genes or 5.1% of the annotated genes while we expect 2.8% (Fisher; p = 0.03)
It is well known that antipsychotics induce weight gain[29] and that genetic factors play a major role in this weight gain.[7]
Summary
Antipsychotic medications are the keystone for the treatment of schizophrenia and other psychotic disorders Antipsychotic-induced weight gain (AIWG) is a major management problem for clinicians, given that obesity and overweight have a strong negative impact in health[9]. Given that that AIWG has a strong genetic component[19], we analyzed the transcriptome expression changes related to weight gain caused by antipsychotics. To obtain information about the genetics behind the sex differences, we analyzed independently males and females comparing individuals with weight gain and without it. The “no weight gain” groups included 11 males and 16 females with a change on BMI after medication lower than 1.0 points and higher than -1.0 points. The transcriptomes of the four different groups were analyzed independently to define genes with significant differential expression before and after medication in the male and female weight and no weight gain groups using the program Deseq[20]. Age BMI before medication BMI after medication BMI increase Triglycerides before medication (mmol/L) Triglycerides after medication (mmol/L) Cholesterol before medication (mg/dl) Cholesterol after medication (mg/dl)
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