MIR218 polygenic risk score is associated with cognitive function and neurochemical metabolites among patients with depressed bipolar disorders

J Affect Disord. 2025 Feb 15:371:104-112. doi: 10.1016/j.jad.2024.11.046. Epub 2024 Nov 17.

Abstract

Backgrounds: Evidence from animal and population studies has consistently revealed that microRNA 218 (MIR218) is involved in susceptibility to depression and cognitive functions. Nevertheless, few studies have evaluated the association between MIR218 and clinical features in patients with depressed bipolar disorder (BD).

Methods: A total of 66 patients with depressed BD and 49 healthy controls (HCs) were recruited for this study. MIR218 polygenic risk score (PRS) was used to assess the addictive effects of the MIR218 regulated genes. We compared the MIR218 PRS between patients with depressed BD and HCs to investigate whether it can be used to predict the risk of BD, and further explored the association between MIR218 PRS and cognitive performance as well as neurochemical metabolites among depressed BD.

Results: We found that there was a significant difference in MIR218 PRS between patients with depressed BD and HCs. The correlation analysis indicated that MIR218 PRS was negative associated with the number of disease onset (r = -0.311, P = 0.033) and choline (Cho)/creatine (Cr) in right thalamus (r = -0.285, P = 0.021). Additionally, as supported by previous findings, patients with lower MIR218 PRS presented more domains of impaired cognitive function than those with higher scores.

Conclusion: These findings suggested MIR218 PRS might be useful in differentiating patients with depressed BD from HCs. Moreover, depressed BD with lower MIR218 PRS showed more pronounced cognitive impairment than those with higher scores, which may be associated with disease recurrence and Cho metabolism in right thalamus.

Keywords: Bipolar disorder; Cognitive function; MicroRNA-218; Polygenic risk score; Proton magnetic resonance spectroscopy.

MeSH terms

  • Adult
  • Bipolar Disorder* / genetics
  • Bipolar Disorder* / metabolism
  • Case-Control Studies
  • Choline / metabolism
  • Cognition / physiology
  • Cognitive Dysfunction / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genetic Risk Score
  • Humans
  • Male
  • MicroRNAs* / genetics
  • Middle Aged
  • Multifactorial Inheritance*
  • Thalamus / metabolism

Substances

  • MicroRNAs
  • Choline