Mechanisms Underlying the Comorbidity of Schizophrenia and Type 2 Diabetes Mellitus

Yutaka Mizuki, Shinji Sakamoto, Yuko Okahisa, Yuji Yada, Nozomu Hashimoto, Manabu Takaki, Norihito Yamada

Research output: Contribution to journalReview articlepeer-review

24 Citations (Scopus)


The mortality rate of patients with schizophrenia is high, and life expectancy is shorter by 10 to 20 years. Metabolic abnormalities including type 2 diabetes mellitus (T2DM) are among the main reasons. The prevalence of T2DM in patients with schizophrenia may be epidemiologically frequent because antipsychotics induce weight gain as a side effect and the cognitive dysfunction of patients with schizophrenia relates to a disordered lifestyle, poor diet, and low socioeconomic status. Apart from these common risk factors and risk factors unique to schizophrenia, accumulating evidence suggests the existence of common susceptibility genes between schizophrenia and T2DM. Functional proteins translated from common genetic susceptibility genes are known to regulate neuronal development in the brain and insulin in the pancreas through several common cascades. In this review, we discuss common susceptibility genes, functional cascades, and the relationship between schizophrenia and T2DM. Many genetic and epidemiological studies have reliably associated the comorbidity of schizophrenia and T2DM, and it is probably safe to think that common cascades and mechanisms suspected from common genes' functions are related to the onset of both schizophrenia and T2DM. On the other hand, even when genetic analyses are performed on a relatively large number of comorbid patients, the results are sometimes inconsistent, and susceptibility genes may carry only a low or moderate risk. We anticipate future directions in this field.

Original languageEnglish
Pages (from-to)367-382
Number of pages16
JournalInternational Journal of Neuropsychopharmacology
Issue number5
Publication statusPublished - May 1 2021


  • ARHGEF11
  • Akt/GSK3β
  • DISC1
  • Wnt/β-catenin
  • kalirin

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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