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.
Bibliographical noteFunding Information:
Erin Sundermann, Pauline M. Maki, Jeffrey R. Bishop, and Deborah M. Little are responsible for study concept and design. Erin Sundermann, Vanessa Meyer, Deborah M. Little, and Kathleen Weber are responsible for data acquisition. Jeffrey R. Bishop is responsible for genotyping. Erin Sundermann, Vanessa Meyer, Deborah M. Little, and Pauline M. Maki are responsible for MRI data analysis. Leah H. Rubin, Erin Sundermann, Pauline M. Maki, and Jeffrey R. Bishop are responsible for statistical analysis and interpretation. Erin Sundermann is responsible for initial manuscript preparation. All authors provided critical revision of manuscript for important intellectual content and approved the final manuscript. Erin Sundermann’s participation was funded by the National Institute of Mental Health (NIMH 1F31MH083537-01), the Mt. Sinai Institute for NeuroAIDS Disparities (2009-01946), and the Alice Dan Dissertation Research Award. V. Meyer’s effort on this project was supported by the National Institute on Drug Abuse (1F31DA028573). Leah Rubin’s participation was supported by grant number 1K01MH098798-01 from the NIMH and K12HD055892 from the National Institute of Child Health and Human Development (NICHD), and the National Institutes of Health Office of Research on Women’s Health (ORWH). Dr. Bishop’s participation was funded by grant number K08MH083888 from the NIMH. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health, University of Illinois at Chicago, Baylor Scott and White Health, Texas A&M University Health Sciences College of Medicine, Rush University Medical Center or The Core Center at Stroger Hospital of Cook County. The Women’s Interagency HIV Study (WIHS) is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the National Institute of Child Health and Human Development (UO1-HD-32632). The study is co-funded by the National Cancer Institute, the National Institute on Drug Abuse, the National Institute on Deafness and Other Communication Disorders, and the NIMH. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). Study investigators received training, mentorship, and guidance in the execution and interpretation of this study from the Chicago Developmental Center for AIDS Research (D-CFAR), an NIH-funded program (P30 AI08251), which is supported by the following NIH institutes and centers (NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NCCAM). Results of this study were presented as a poster at the 2013 Human Brain Mapping Annual Meeting in Seattle, WA.
© 2014, Journal of NeuroVirology, Inc.
- COMT genotype
- Prefrontal function
- Single-nucleotide polymorphism (SNP)
- Working memory