COMT polymorphisms as predictors of cognitive dysfunction during manic and mixed episodes in bipolar I disorder

Bipolar Disord. 2012 Aug;14(5):554-64. doi: 10.1111/j.1399-5618.2012.01030.x. Epub 2012 Jun 19.

Abstract

Objective: The dopaminergic system plays an important role in the prefrontal cortex (PFC) and is believed to mediate cognitive dysfunction (CD) in bipolar disorder (BD). The enzyme catechol-O-methyltransferase (COMT) is involved in the catabolism of dopamine in the PFC, and an association between COMT single nucleotide polymorphisms (SNPs) and BD has been reported. COMT SNPs have also been associated with executive and working memory performance in healthy subjects, patients with schizophrenia, and euthymic BD patients. The objective of this study was to investigate the association between COMT SNPs and acute CD during BD mood episodes.

Methods: Seventy-two symptomatic, medication-free subjects with bipolar I disorder (BD-I) and 76 healthy controls were evaluated using neuropsychological tests, and genotyped for COMT SNPs rs4680 and rs165599.

Results: Patients undergoing mania and mixed episodes carrying the COMT allele G had better performance on executive function, memory, verbal fluency, and intelligence tests. Moreover, an interaction was detected between the COMT allele G and the Young Mania Rating Scale in BD CD.

Conclusions: Allele G from COMT SNPs rs4680 and rs165599 may represent reliable state-dependent predictors of global CD during manic and mixed episodes in BD. Further studies in larger samples are necessary to confirm these findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Attention
  • Bipolar Disorder / complications
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / metabolism
  • Case-Control Studies
  • Catechol O-Methyltransferase / genetics*
  • Catechol O-Methyltransferase / metabolism
  • Cognition Disorders / etiology
  • Cognition Disorders / genetics*
  • Cognition Disorders / metabolism
  • Dopamine / metabolism
  • Executive Function
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Intelligence Tests
  • Male
  • Memory
  • Neuropsychological Tests
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Prefrontal Cortex / metabolism

Substances

  • Catechol O-Methyltransferase
  • Dopamine