COMT polymorphisms as predictors of cognitive dysfunction during manic and mixed episodes in bipolar I disorder.
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.
Mood Disorders Unit GRUDA, Department and Institute of Psychiatry, School of Medicine, University of São Paulo, Brazil. mgss@usp.br
Márcio Gerhardt
MG
Soeiro-de-Souza
Rodrigo
R
Machado-Vieira
Danielle
D
Soares Bio
Carolina Martins
CM
Do Prado
Ricardo Alberto
RA
Moreno
D000328:Adult; D000483:Alleles; D001288:Attention; D001714:Bipolar Disorder / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D056344:Executive Function; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D008568:Memory; D009483:Neuropsychological Tests; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000378:metabolism
D002394:Catechol O-Methyltransferase; D004298:Dopamine