Higher schizotypy predicts better metabolic profile in unaffected siblings of patients with schizophrenia

E. Cem Atbasoglu*, Guvem Gumus-Akay, Sinan Guloksuz, Meram Can Saka, Alp Ucok, Koksal Alptekin, Sevim Gullu, Jim van Os

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Rationale: Type 2 diabetes (T2D) is more frequent in schizophrenia (Sz) than in the general population. This association is partly accounted for by shared susceptibility genetic variants. Objective: We tested the hypotheses that a genetic predisposition to Sz would be associated with higher likelihood of insulin resistance (IR), and that IR would be predicted by subthreshold psychosis phenotypes. Methods: Unaffected siblings of Sz patients (n = 101) were compared with a nonclinical sample (n = 305) in terms of IR, schizotypy (SzTy), and a behavioural experiment of “jumping to conclusions”. The measures, respectively, were the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Structured Interview for Schizotypy-Revised (SIS-R), and the Beads Task (BT). The likelihood of IR was examined in multiple regression models that included sociodemographic, metabolic, and cognitive parameters alongside group status, SIS-R scores, and BT performance. Results: Insulin resistance was less frequent in siblings (31.7%) compared to controls (43.3%) (p < 0.05), and negatively associated with SzTy, as compared among the tertile groups for the latter (p < 0.001). The regression model that examined all relevant parameters included the tSzTy tertiles, TG and HDL-C levels, and BMI, as significant predictors of IR. Lack of IR was predicted by the highest as compared to the lowest SzTy tertile [OR (95%CI): 0.43 (0.21–0.85), p = 0.015]. Conclusion: Higher dopaminergic activity may contribute to both schizotypal features and a favourable metabolic profile in the same individual. This is compatible with dopamine’s regulatory role in glucose metabolism via indirect central actions and a direct action on pancreatic insulin secretion. The relationship between dopaminergic activity and metabolic profile in Sz must be examined in longitudinal studies with younger unaffected siblings.

Original languageEnglish
Pages (from-to)1029-1039
Number of pages11
Issue number4
Publication statusPublished - 1 Apr 2018


  • Dopamine
  • Genetics
  • Insulin resistance
  • Schizophrenia
  • Schizotypy
  • Type 2 diabetes mellitus


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