Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and...

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Cognitive impairment is a key characteristic of schizophrenia, often linked to dopamine system dysfunction in the prefrontal cortex.
• Single nucleotide polymorphisms (SNPs) in the catechol-O-methyltransferase (COMT) gene, particularly rs4680, are hypothesized to influence this relationship.

Purpose of the Study:

• To investigate the association of three COMT gene SNPs (rs737865, rs165599, and rs4680) with schizophrenia.
• To determine the impact of these COMT SNPs on working memory performance in individuals with schizophrenia and healthy controls.

Main Methods:

• Genetic association analyses were conducted on 212 individuals with schizophrenia and 257 healthy controls.
• Working memory was assessed using the Visual Working Memory (VWM) Task, Keep Track Task, and Letter Memory Task in a subset of participants (133 schizophrenics, 93 HCs).

Main Results:

• The rs737865 SNP showed a significant association, with the GG genotype being protective and the GA haplotype (rs4680/rs165599) conferring risk for schizophrenia.
• COMT rs4680 AA and rs737865 AA genotypes were associated with lower scores on the Keep Track Task.
• rs165599 demonstrated opposing effects on VWM and Keep Track task performance between patients and controls, with AA carriers performing lowest among controls but highest among patients.

Conclusions:

• The findings support the hypothesis that COMT gene polymorphisms are associated with schizophrenia.
• COMT polymorphisms appear to modulate cognitive performance, specifically working memory, in both individuals with schizophrenia and healthy controls.