Sex differences in gene expression related to antipsychotic induced weight gain

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.

Molecular signature of extracellular matrix pathology in schizophrenia

“…Antipsychotics, lithium and VPA have all been reported to impact ECM molecules in rodent and human studies. In many cases, the effects of these drugs are opposite to changes observed in subjects with SZ, suggesting that these treatments may achieve therapeutic efficacy in part by correcting for changes in ECM molecules (Ruso‐Julve et al., 2019; Sainz et al., 2019; Yukawa et al., 2018). For example, expression of ADAMTS2, which was upregulated across all brain regions examined in our study, was increased in peripheral blood samples from subjects with SZ, and decreased following antipsychotic treatment (Ruso‐Julve et al., 2019; Sainz et al., 2019).…”

Progress in Genetic Polymorphisms Related to Lipid Disturbances Induced by Atypical Antipsychotic Drugs

“…Evidence has shown worse lipid metabolic dysfunction in female schizophrenia patients due to antipsychotics (Castellani et al, 2019). Sex differences were also found in gene expression associated with antipsychotic induced weight gain (Sainz et al, 2019). Younger age has been reported to be a risk of greater antipsychotic-related weight gain (Maayan and Correll, 2010;Greil et al, 2013).…”

BDNF Val66Met Polymorphism, the Allele-Specific Analysis by qRT-PCR - a Novel Protocol

“…Our results showed that amongst the genes expressing constant patterns (stability) in the human muscle regardless of sex and physiological conditions, the most stable one is the gene of hypoxanthine phosphoribosyl transferase ( HPRT1 ). The establishment of a tissue-specific reference gene can help discriminate both distinctive characteristics, and genetic-based changes in cell functioning among different physiological conditions 36 , 37 , 38 , 39 ; 40 . Precision in the determination of a gene of reference for comparative analysis of the expression of specific proteins is crucial to enable the assessment of factors that are expressed in low quantities in tissue.…”