The positive association between antipsychotic-induced weight gain and therapeutic response: New biotypes of schizophrenia

•Co-occurrence of weight gain and efficacy may belong to a special biotype.•The study established three new biotypes, TR+nonAIWG, TR+AIWG and nonTR+nonAIWG.•Clinical and genetic data revealed the shared mechanism between AIWG and TR.•Clinicians should pay attention to the “thin” patients with higher obesity risk. Co-occurrence of antipsychotic-induced weight gain (AIWG) and therapeutic response (TR) did exist in clinic but was rarely studied. This study aims to identify potential TR/ AIWG biotypes and explore the clinical, genetic and neuroimaging features. This study enrolled 3030 patients to identify potential TR/AIWG biotypes and explore the clinical, genetic and neuroimaging features. We found three biotypes: TR+nonAIWG (46.91%), TR+AIWG (18.82%), and nonTR+nonAIWG (34.27%). TR+AIWG showed lower weight and lipid level at baseline, but higher changing rate, and higher genetic risk of obesity than TR+nonAIWG and nonTR+nonAIWG. GWAS identified ADIPOQ gene related to TR+AIWG biotypes and top-ranked loci enriched in one-carbon metabolic process, which related to both schizophrenia and metabolic dysfunction. Genetically predicted TR+AIWG was associated with higher odds of diabetes (OR=1.05). The left supplementary motor area was significantly negatively correlated with PRS of obesity. The distinguishing ability with multi-omics data to identify TR+AIWG reached 0.787. In a word, the “thin” patients with a higher risk of obesity are the target population of early intervention.