The catechol O-methyltransferase Val158Met polymorphism and herpes simplex virus type 1 infection are risk factors for cognitive impairment in bipolar disorder: additive gene-environmental effects in a complex human psychiatric disorder.
BACKGROUND
Bipolar disorder is associated with deficits in cognitive functioning. The etiology of cognitive impairment in bipolar disorder may relate to both genetic and environmental factors. A valine/methionine polymorphism of the catechol O-methyltransferase gene at amino acid 158 (COMT Val158Met polymorphism) has been identified as a risk factor for cognitive impairment in schizophrenia. Serological evidence of infection with herpes simplex virus type 1 (HSV-1) has also been identified as a risk factor for cognitive impairment in bipolar disorder.


METHODS
We used Taqman technology to measure COMT Val158Met alleles in 107 individuals with bipolar disorder and in 95 controls. We also measured antibodies to HSV-1 in sera obtained from the same individuals. Cognitive functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status and the Letter-Number Sequencing Test. The effects of the COMT Val158Met polymorphism and antibodies to HSV-1 on cognitive functioning were analyzed with multinomial logistic regressions.


RESULTS
The COMT Val158Val genotype and serological evidence of infection with HSV-1 are independent risk factors for cognitive impairment in individuals with bipolar disorder, particularly in the domains of immediate and delayed memory. Individuals with bipolar disorder with the COMT158 Val/Val genotype and serological evidence of HSV-1 infection were more than 85 times more likely to be in the lowest quintile of cognitive functioning when compared with the highest quintile when controlling for potential confounding variables such as symptom severity and education. Control individuals did not display this association.


CONCLUSIONS
Both the COMT Val158Met polymorphism and serological evidence of HSV-1 infection affect cognitive functioning in individuals with bipolar disorder.
Stanley Research Center, Sheppard Pratt Health System, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Faith B
FB
Dickerson
John J
JJ
Boronow
Cassie
C
Stallings
Andrea E
AE
Origoni
Sara
S
Cole
Flora
F
Leister
Bogdana
B
Krivogorsky
Robert H
RH
Yolken
D000328:Adult; D001714:Bipolar Disorder / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000821:virology; D017931:DNA Primers / Q000235:genetics; D003710:Demography; D004777:Environment; D005260:Female; D005838:Genotype; D006561:Herpes Simplex / Q000150:complications* / Q000453:epidemiology; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics
D017931:DNA Primers; D002394:Catechol O-Methyltransferase