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.A multiplex PCR technique designed using Sequenom SpectroDESIGNER software was employed by inputting a sequence containing 100 bp of flanking sequence on either side of the COMT Val158Met polymorphism. The SNP was then grouped into multiplexes so that the extended product would not overlap in mass with any other oligonucleotide present in the reaction mix, and where no primer-primer, primer-product, or nonspecific interactions would occur. The PCR was carried out in 384-well reaction plates in a volume of 5 μl using 10 ng genomic or whole-genome amplified DNA. All subsequent steps, up until the reaction, were spotted onto the SpectroCHIP and carried out in the same reaction plate. After PCR, any unincorporated dNTPs from the PCR were removed from the reaction by digestion with Shrimp alkaline phosphatase. dNTPs were removed so that they could not play any role in the extension of the oligonucleotide at the SNP site. The extension reaction was then carried out in the presence of the extension oligonucleotide and a termination mix containing mass-modified dideoxynucleotides which extended the oligonucleotide over the SNP site with one base. Before spotting onto the SpectroCHIP, the reaction was cleaned by incubation with a cation-exchange resin which removed any salts present.
The extension product was then spotted onto a 384-well spectroCHIP before being flown in the MALDI-TOF mass spectrometer. Data were collected, in real time,cannabis grow lights using SpectroTYPER Analyzer 3.3.0.15, SpectraAQUIRE 3.3.1.1 and SpectroCALLER 3.3.0.14 algorithms. All genotyping was performed by an accredited commercial laboratory .All statistical tests and procedures were conducted using SPSS 10.0 . Univariate comparisons across the three COMT genotypes were performed using one-way analysis of variance for continuous and chi-squared tests for categorical variables. In cases, where data violated normality assumptions medians were calculated and nonparametric tests performed. To examine the main and explore the interaction effects of executive functioning and COMT on sexual risk behaviors, hierarchical multiple linear regressions in accord with Barron and Kenny’s approach were conducted for each of the seven sexual risk behaviors under study. Prior to running each analysis, the executive functioning variable was centered and the COMT genotype contrast coded to reduce problems resulting from multi-collinearity . In addition, interaction terms were created by multiplying COMT genotype by the centered executive functioning variable. Next, multiple linear regressions were used to examine potential confounders based on univariate genotype comparisons described above. These confounders included: ethnicity, METH status, HIV status and age at first intercourse. We also included BDI scores based on inclusion of this measure in recent work testing a similar hypothesis. Results showed that METH status, HIV status, and age at first intercourse accounted for a significant unique variance for all sexual behaviors under investigation . Thus to control for these potential confounding effects, the residuals derived from each of the sexual behavior models were used as the dependent variables for all subsequent regression models. The centered executive functioning variable and COMT genotype as well as the new interaction term were then entered as independent variables into seven individual hierarchical multiple regression models using the residuals described above as the dependent variable. For models in which a significant interaction was observed, a final round of regressions were conducted stratified by COMT genotype to determine the nature of the interaction between executive functioning and COMT on the particular sexual risk behavior.
Due to the exploratory nature of the interaction analysis we selected a relaxed alpha threshold alpha < .10 to reduce Type II errors, albeit the traditional alpha threshold of .05 was used for all.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, 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,cannabis grow tent 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. Post-hoc analysis within our sample showed no significant difference in recall deficit by COMT genotype, albeit there did appear to be a trend = 2.89; P = .058 in which carriers of the Val/Val genotype had greater deficits than that of Val/Met and Met/Met genotypes . 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.These interruptions are a result of both widespread closure of services deemed nonessential in order to reduce social interactions and slow the spread of the novel coronavirus that causes COVID-19, and voluntary avoidance of situations perceived to be high risk for contracting COVID-19. These non-pharmaceutical interventions reduced the incidence of COVID-19 , allowing time for the development of effective vaccines and preventing potentially tens of thousands of deaths. However, interventions also led to substantial disruption of health and healthcare services , possibly at the expense of the health of people who relied on this medical care.