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HIV-related cognitive impairment shows bi-directional association with dopamine receptor DRD1 and DRD2 polymorphisms in substance-dependent and substance-independent populations

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Abstract

It has been postulated that drugs of abuse act synergistically with HIV, leading to increased neurotoxicity and neurocognitive impairment. The CNS impacts of HIV and drug use converge on the mesocorticolimbic dopamine (DA) system, which contains two main receptor subtypes: dopamine receptors 1 (DRD1) and 2 (DRD2). DRD1 and DRD2 have been linked to substance dependence; whether they predict HIV-associated neurocognitive disorder (HAND) is unclear. Using an advanced-stage HIV+ population, we sought to determine if drug dependence impacts the contribution of DA receptor polymorphisms on neurocognition. We observed that both DRD1 and DRD2 polymorphisms were associated with opiate and cocaine dependence (P < 0.05) in Caucasian subjects, but not African-American individuals. Using linear regression analysis, we examined the polymorphisms for associations with neuropsychological performance in global and cognitive domain T-scores (Motor, Processing Speed, Verbal Fluency, Learning, Memory, Executive Functioning, Working Memory) while controlling for opiate and cocaine dependency. In the Motor domain, we observed an association for two DRD2 polymorphisms (P < 0.05) in Caucasian subjects. The effects differed for substance dependence groups as the direction of the correlations with DRD2 were opposite to what was seen in subjects without these dependencies. In African-American subjects, associations were observed in nearly every domain, and again, the direction of the correlation differed between substance-dependent and substance-independent groups. We conclude that studies to examine genetic risk for HAND must carefully account for substance dependence patterns when assaying dopaminergic systems, as the neurobiological substrates of cognition in HIV populations may vary with tonic alterations secondary to chronic substance exposures.

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Acknowledgments

This work was funded by grants from the National Institutes on Drug Abuse, T32DA007135 (MMJ) and R01DA015446 (YLH); the National Institute of Mental Health, R25MH080663 (MMJ, SM) and U01MH083501 (SM); and the NIH UL1RR029887 (MSSM CTSA).

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Departments of Neurology, The Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1065, New York, NY, 10029, USA

    Michelle M. Jacobs, Jacinta Murray, Desiree A. Byrd & Susan Morgello

  2. Departments of Psychiatry, The Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1065, New York, NY, 10029, USA

    Desiree A. Byrd & Yasmin L. Hurd

  3. Departments of Neuroscience, The Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Yasmin L. Hurd & Susan Morgello

  4. Departments of Pathology, The Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Susan Morgello

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  1. Michelle M. Jacobs
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Correspondence to Michelle M. Jacobs.

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Jacobs, M.M., Murray, J., Byrd, D.A. et al. HIV-related cognitive impairment shows bi-directional association with dopamine receptor DRD1 and DRD2 polymorphisms in substance-dependent and substance-independent populations. J. Neurovirol. 19, 495–504 (2013). https://doi.org/10.1007/s13365-013-0204-8

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