Given the aforementioned paucity of research in the current literature addressing the contribution of genetic and neurocognitive factors on sexual risk behavior, the primary aim of this study was to examine the main effects of executive functioning as well as the main effects of the COMT Val.Met polymorphism on sexual risk behavior among a ethnically diverse population of men with and without METH dependence and/or HIV infection. Within this aim, we hypothesized that the highly active COMT Val/Val genotype and its putatively associated deficits in executive functioning would be independently associated with sexual risk behaviors. In addition, as a result of previously mentioned research that has demonstrated an association between COMT genotype and executive functioning we also explored the potential interaction effects of COMT and executive dysfunction on sexual risk behavior.Participants were volunteers evaluated at the HIV Neurobehavioral Research Center at the University of California in San Diego as part of a cohort study focused on central nervous system effects of HIV and methamphetamine. The current study comprised 192 sexually active non-monogamous men with and without methamphetamine dependence and/or HIV infection . Men were classified as nonmonogamous if they stated they had “no current partner” at time of assessment. Monogamous men were excluded because unsafe sexual behavior within a monogamous relationship is less risky than in non-monogamous relationships. All participants underwent a comprehensive characterization procedure that included collection of demographic, neuromedical,hydroponic shelf system psychiatric as well as neuropsychiatric information.
HIV serological status was determined by enzyme linked immunosorbent assays plus a confirmatory test. Lifetime METH dependence was determined by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders Version IV . However, participants were not actively using other substances, with the exception of cannabis and alcohol. Potential participants were excluded if they met lifetime dependence criteria for other drugs, unless the dependence was judged to be remote and episodic in nature by a doctoral level clinician. Alcohol dependence within the last year was also an exclusion criterion. All participants were seronegative for hepatitis C infection. Additional information for each participant was collected as it relates to current depressed mood as well as lifetime diagnosis of Major Depression Disorder and/or Bipolar Disorder I or II. Current depressed mood was assessed utilizing the Beck Depression Inventory-I and MDD and Bipolar Disorder were ascertained using the SCID-IV. Information was also collected to determine lifetime dependence on sedatives, cannabis, opioids, cocaine,hallucinogens, and alcohol, using the SCID-IV. For METH+ participants, additional information was collected regarding age at first use, years of use, and days since last use of METH; whereas for HIV+ participants, HIV RNA plasma copies was ascertained as part of a larger neuromedical evaluation. All participants gave written consent prior to enrollment and all procedures were approved by the Human Research Protection Program of the University of California, San Diego and San Diego State University.Executive functioning was determined as part of a larger comprehensive battery of tests covering seven ability domains . The executive functioning domain deficit score, of particular focus in this study, was made up of perseverative responses on the Wisconsin Card Sorting Test; errors on the Halstead Category Test, which measures abstraction and cognitive flexibility; and time to complete the Trail Making Test part B, reflecting ability to switch and maintain attention between ongoing sequences.
Raw scores for each of these component tests were converted to demographically-adjusted T-scores , including adjustments for age, education, gender, and ethnicity as available for each test. The demographically adjusted T-scores for each test were then converted into deficit scores, which reflect degree of impairment by setting performances within the normal range at zero with a range from 0 to 5 . Finally, the individual deficit scores were averaged to derive the domain deficit score, which reflects the severity of executive functioning deficit. Previous work has demonstrated that deficit scores achieve good diagnostic agreement with classifications made by blind clinical ratings. All neurocognitive testing and scoring was performed by trained psychometrists blinded to participants’ genotypes.To our knowledge this study is the first to examine main effects as well as explore the interaction effects of COMT genotype and executive functioning on sexual risk behavior. Our main findings suggest significant executive dysfunction main effects for number of sexual partners as well as frequency of oral sex and condom use. In addition, results of our exploratory interaction analyses provide evidence that COMT genotype and executive dysfunction interact in models of number of sexual partners, condom use, insertive and receptive anal sex, as well as oral sex. Stratified analyses further suggest that the strength of these associations is dependent on the number of Met alleles the individual was carrying, with the exception of oral sex in which Val/Val was the informative genotype. Our significant executive dysfunction main effects for sexual risk behaviors are discordant with the only other study, to our knowledge, that has examined the association between executive dysfunction and sexual risk behavior. In that study, no association was found between executivedys function and sexual risk behavior among an African American sample of men and women poly-substance abusers with and without HIV infection.
However, three major methodological differences may explain our discordant findings. First, Gonzalez et al. estimated sexual risk behavior in the past 6 months compared to our window of 12 months and also utilized a composite score rather than individual sexual risk behaviors as their dependent variable. Second, executive dysfunction was assessed using the Iowa Gambling Task, delayed non-matching to sample paradigm, and Stroop task-reaction time version which, respectively, measure decision-making, working memory, and response inhibition. Although these tests are well justified, other components of executive functioning such as perseveration, cognitive sequencing, and concept formation which were assessed in the current study, were not examined. Third and finally, regression models were adjusted for sensation seeking, a factor shown in previous research to be associated with sexual risk behavior; however, in the current study sensation seeking data was not available and was not adjusted for. Thus, future work examining the association between executive dysfunction and sexual risk behaviors are warranted; particularly research utilizing larger samples with diverse measures of executive functioning and models adjusting for sensation seeking and other personality covariates. Novel to the current study,cannabis drying racks commercial we demonstrated several genotype by endophenotype interactions for sexual risk behaviors. A relaxed significance criterion produced significant interactions for number of sexual partners, condom use, insertive and receptive anal sex, as well as oral sex. These interactions collectively advocate for further investigation of genotypeendophenotype interactions for sexual risk behavior. However, due to the exploratory nature of these interactions our discussion will be confined to interactions observed for number of sexual partners, frequency of insertive anal sex and condom use, as interactions observed in these models met the traditional significance criterion . We observed both a main and interaction effect for number of sexual partners, albeit only within the model including the composite executive functioning deficit score. In this model we found that among carriers of the Met allele , a positive association between executive functioning deficit and number of sexual partners was present. Thus, among Met allele carriers those with greater deficit scores reported greater number of sexual partners; whereas among Val/Val carriers this association was not significant. Similar to results for number of sexual partners, stratified analysis showed that among carriers of the Met/Met but not Val/Met or Val/Val genotype an positive association between executive dysfunction and frequency of insertive anal sex was present, although only statistically significant for models including the Trails B test. Thus, individuals with lower T-scores on Trails B reported greater frequency of insertive anal sex only if they were carriers of the Met/Met genotype. Finally, the strongest interaction observed was between COMT and the Halstead Category Test for frequency of condom use. Contrary to the expected association, results suggest a negative association among carriers of the Met/Met genotype in which lower T-scores on the Category Test was associated with an increased frequency of condom use. This unexpected finding may be a result of several factors. First, the psychometric properties of the questionnaire used to measure sexual risk behaviors in our study have not been reported and thus measurement error may be influencing our reported associations.
Although there is no agreed upon “gold-standard” for measuring sexual risk behavior, recommendations from a review of 56 sexual risk behavior measures in the literature have been developed and future studies should be encouraged to adopt these measurement strategies to improve accuracy of sexual risk behavior characterization. Second, recall deficits may result in sexual risk behavior reporting errors. This is particularly a concern when measuring sexual risk behavior retrospectively over large spans of time as was done in the current study. Thus, it is possible that recall deficits within the Val/Val group biased our findings toward those in the Met/Met group and should be interpreted with caution. Finally and most speculative, harm reduction campaigns have long aimed to increase condom use within both HIV-infected and METH using populations and our finding may be an artifact of their success. Collectively, these findings provide a preliminary model of differential susceptibility to sexual risk behavior via executive dysfunction, dependent on COMT genotype, particularly the Met/Met genotype . Although the role of the Met/Met genotype is contrary to our hypothesis, our findings, when placed in the context of previous research are informative. Recent research has linked the COMT Met/Met genotype to novelty seeking behavior in healthy and methamphetamine using populations. In addition, work by Gonzalez et al. on executive functioning and sexual risk behavior demonstrated that sensation seeking was independently associated with sexual risk, particularly among HIV-seropositive individuals. Thus, it appears that individuals with the Met/Met genotype may have a lower tolerance for monotony and may seek and participate in higher risk behaviors such as METH use or unprotected sex. Furthermore, work by our group and others have suggested that possession of the Met allele enhances executive functioning in healthy controls;however, this neuroprotective effect is significantly reduced among individuals exposed to methamphetamine. Thus, it is probable that in our sample, of which approximately half were methamphetamine dependent, the putative protective effect of the Met/Met genotype is diminished and propensity to sexual risk behavior enhanced. It is apparent that the associations between COMT, executive dysfunction, and sexual risk behavior are highly complex and context dependent. The current study provides preliminary evidence of these complex relationships and advocates for larger investigations that improve upon and consider several of the limitations that have been presented. Future work should also attempt to address independent and interaction effects of other putative polymorphisms particularly those involved in dopamine synthesis , metabolism , and reception . In addition, future transdisciplinary work that combines genetic and neurocognitive factors with psychosocial factors will provide valuable insights and elucidate a clearer picture of sexual risk behavior. Completion of such work in combination with the current as well as others previous work will further our understanding of the genotypic and endophenotypic factors involved in the phenotypic expression of sexual risk behaviors and potentially assist with risk identification, prevention, and treatment efforts in the future.Due to the advent of antiretroviral therapy in the mid-1990s, HIV is now considered a chronic medical condition rather than a devastating terminal illness. Currently, over 50% of PWH in the United States are over the age of 50, with aging trends projected to continue . As such, researching aging with HIV is critical to better understand the impact of HIV on the aging process and how it may differ from the general population. Aging with HIV is associated with an increased risk of HIV-associated neurocognitive disorders , the current research term to describe neurocognitive impairments associated with HIV disease, with some evidence of accelerated brain aging . Given the potentially compounding effects of HIV and aging on the brain, the rapidly growing population of aging PWH may be at increased risk for Alzheimer’s disease and its precursor, amnestic mild cognitive impairment . As such, there is an urgent public health need to identify clinical tools to accurately identify older PWH on the AD trajectory and understand biological mechanisms that may put PWH at higher risk of aMCI/AD.