title: Genetic predictor of working memory and prefrontal function in women with HIV.
abstract: The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p < 0.05). A significant serostatus by genotype interaction (p < 0.01) revealed that, among Val/Val, but not Met allele carriers, HIV-infected women performed significantly worse than HIV-uninfected controls across N-back conditions (p < 0.01). Analogous to behavioral findings, a serostatus by genotype interaction revealed that HIV-infected Val/Val carriers showed significantly greater prefrontal activation compared with HIV-uninfected Val/Val carriers (p < 0.01). Conversely, HIV-uninfected Met allele carriers demonstrated significantly greater prefrontal activation compared with HIV-infected Met allele carriers. Findings suggest that the combination of HIV infection and the Val/Val COMT genotype leads to working memory deficits and altered prefrontal function in HIV-infected individuals.
authors.affiliation: Department of Neurology, Albert Einstein College of Medicine, 1165 Morris Park Ave., New York, NY, 10461, USA, erin.sundermann@einstein.yu.edu.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Sundermann
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bishop
authors.forename: Leah H
authors.initials: LH
authors.lastname: Rubin
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Little
authors.forename: Vanessa J
authors.initials: VJ
authors.lastname: Meyer
authors.forename: Eileen
authors.initials: E
authors.lastname: Martin
authors.forename: Kathleen
authors.initials: K
authors.lastname: Weber
authors.forename: Mardge
authors.initials: M
authors.lastname: Cohen
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Maki
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D056344:Executive Function; D005260:Female; D015870:Gene Expression; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology* / Q000821:virology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008570:Memory, Short-Term; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000503:physiopathology* / Q000821:virology; D012703:Serotyping
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase