COMT Val158Met Polymorphism, Executive Dysfunction, and Sexual Risk Behavior in the Context of HIV Infection and Methamphetamine Dependence

Catechol-O-methyltransferease (COMT) metabolizes prefrontal cortex dopamine (DA), a neurotransmitter involved in executive behavior; the Val158Met genotype has been linked to executive dysfunction, which might increase sexual risk behaviors favoring HIV transmission. Main and interaction effects of COMT genotype and executive functioning on sexual risk behavior were examined. 192 sexually active nonmonogamous men completed a sexual behavior questionnaire, executive functioning tests, and were genotyped using blood-derived DNA. Main effects for executive dysfunction but not COMT on number of sexual partners were observed. A COMT x executive dysfunction interaction was found for number of sexual partners and insertive anal sex, significant for carriers of the Met/Met and to a lesser extent Val/Met genotypes but not Val/Val carriers. In the context of HIV and methamphetamine dependence, dopaminergic overactivity in prefrontal cortex conferred by the Met/Met genotype appears to result in a liability for executive dysfunction and potentially associated risky sexual behavior

COMT Val158Met Polymorphism, Executive Dysfunction, and Sexual Risk Behavior in the Context of HIV Infection and Methamphetamine Dependence.

Catechol-O-methyltransferease (COMT) metabolizes prefrontal cortex dopamine (DA), a neurotransmitter involved in executive behavior; the Val158Met genotype has been linked to executive dysfunction, which might increase sexual risk behaviors favoring HIV transmission. Main and interaction effects of COMT genotype and executive functioning on sexual risk behavior were examined. 192 sexually active nonmonogamous men completed a sexual behavior questionnaire, executive functioning tests, and were genotyped using blood-derived DNA. Main effects for executive dysfunction but not COMT on number of sexual partners were observed. A COMT x executive dysfunction interaction was found for number of sexual partners and insertive anal sex, significant for carriers of the Met/Met and to a lesser extent Val/Met genotypes but not Val/Val carriers. In the context of HIV and methamphetamine dependence, dopaminergic overactivity in prefrontal cortex conferred by the Met/Met genotype appears to result in a liability for executive dysfunction and potentially associated risky sexual behavior

Is gender dysphoria dysphoric? Elevated depression and anxiety in gender dysphoric and non-dysphoric homosexual and bisexual men in an HIV sample.

Although most cases of HIV infection in North America have been acquired sexually, only a few sex researchers have applied their unique perspectives and skills to the AIDS epidemic, and few mainstream psychiatrists and psychologists have addressed the sexual aspects of the disease. That is, there has been little cross-fertilization of ideas between the psychiatric research community and the sex research community. The present report is an attempt to introduce what might be called a traditional sexological perspective into a mainstream psychiatric research program on HIV disease and neuropsychology, with results that may be pertinent to questions of interest to a broad range of scientists and clinicians. The HIV Neurobehavioral Research Center (HNRC) is a large, federally funded interdisciplinary research project affiliated with the Department of Psychiatry at the University of California, San Diego. Its basic mission is to investigate the natural history and prevalence of the neuropsychological sequelae of HIV infection, with attention given to neurology, psychiatry, virology, medicine, brain imaging, and other disciplines. A central concern of the HNRC is the assessment of rates of psychiatric morbidity such as depression and anxiety. We have found that the levels of depression and anxiety in our homosexual subjects, whether HIV positive or HIV negative, are substantially higher than those found in representative general population samples. For example, our homosexual populations (HIV-positive and HIV-negative) had lifetime frequencies of major depression (diagnosed by the Diagnostic Interview Schedule for DSM- III of 31-32% (N = 135), compared to 9% in 22 HIV-negative heterosexual controls (Atkinson et al., 1989). Similar findings have been presented from other investigators of AIDS-related homosexual samples (Hays et al., 1990; Perry et al., 1990; Viney et al., 1991; Williams et at., 1991), although the finding is not universal. Of course, AIDS is a life-threatening disease arguably capable of triggering depression in and of itself. It could do so indirectly through the conscious recognition of one's increased likelihood of mortality due to the disease, or directly via hypothesized effects on neurotransmitters or other forms of CNS morbidity. However, some of the studies that found high levels of depression in HIV-related samples of homosexual men reported that the history of depression predated the AIDS epidemic (Atkinson et al., 1988; Joseph et al., 1990; Williams et at., 1991). Accordingly, the higher levels of depression now observed can probably not be explained merely as the result of the undoubted pressures caused by this epidemic. Although it might in theory be expected that homosexuals living in a hostile society may experience depression as a reaction to the social stigma attached to their orientation, in fact there is little if any documentation of such an increased level of rigorously diagnosed depression from nonclinical samples studied before the AIDS epidemic (Saghir and Robins, 1973; Gonsiorek, 1991). We found two reports of higher depression from this period, but these studies did not assess depression with a clinical interview or standardized questionnaire. One found higher depression among homosexual men (compared with the general population) in samples from three different countries (Weinberg and Williams, 1974, p. 152), and higher levels among effeminate homosexual men than among those who were not effeminate (p. 172). Although this result corresponds well to those we report presently, that study's measure of depression was the subjects' responses to an item asking if they "felt they were happy" persons. The other study used subjects' answers to seven questions likewise not previously standardized (e.g., how frequently did they feel life was worthwhile, experience hurt feelings, etc.: Bell and Weinberg, 1978, pp. 200-201). Even the latter study found that levels of depression were not elevated among the male homosexuals who were in monogamous relationships or who were "functional" (i.e., uncoupled but functioning successfully in the gay world). One notable study from this period which used more rigorous psychiatric methodology found no difference in levels of depression by sexual orientation (Saghir and Robins, 1973, pp. 113- 118). Accordingly, it is important to ascertain which aspects of sexual orientation are associated with depression in homosexual populations, if any. Given the unfortunate history of the classification of homosexuality per se as a disease, it is worthwhile to study depression in this population without presupposing that it is a reflection of an underlying pathology but might instead be a response to environmental circumstances or even an intermittent aspect of otherwise normal personality in certain personality types. One of the few psychological traits that has been shown, in both retrospective and prospective studies, to be both statistically and substantively significant when differentiating and contrasting the average backgrounds of heterosexual and homosexual men has been termed childhood gender nonconformity (CGN) by some authors (Bell and Weinberg, 1978), childhood femininity by others (Green, 1974, 1987; Freund et al., 1974), and gender dysphoria in the DSM-III-R. Such behaviors are far from universal in the histories of homosexual men in Western societies, but they are not uncommon, and they are apparently much less common among men who identify themselves as heterosexual. One questionnaire used to assess such behavior is the Freund Feminine Gender Identity questionnaire (FGI; Freund et al., 1974, 1977). We have observed a mild correlation between homosexual men's scores on the FGI and their interest in receptive anal intercourse (Weinrich et al., 1992). (Note that we did not assume a priori that sex-role nonconformity such as that measured by the FGI must necessarily be related to variability in sexual orientation or preferences for particular erotosexual roles; we observed that a moderate correlation existed.) This correlation alone should alert AIDS researchers that CGN may be a personality variable that contributed to HIV exposure (before the era of safer sex), which might in turn suggest that HIV-related samples are likely to have a higher proportion of high-CGN men than more widely representative samples. And it should alert researchers that CGN could be important to study whenever sexual orientation is investigated. Logically speaking, a desire to be a member of the opposite sex (whether in adulthood or childhood) is not necessarily dysphoric. Anyone expressing a desire to change an important facet of their life might be suspected of being dysphoric about their current circumstances, but whether this presumed dysphoria actually exists, can be detected by our measurement instruments, and ever reaches the level of clinical depression are empirical questions. Accordingly, we thought it important to assess the extent to which CGN, as measured by FGI, is in fact associated with dysphoria and to that extent might account for some of the differences in depression observed between heterosexual and homosexual male samples. Note that one of the early papers on the FGI found that homosexual psychiatric patients scored higher on the FGI than did a group of homosexual nonpatients (Freund et al., 1977, p. 512). If it is indeed the case that the previously cited samples of homosexual men from before the AIDS epidemic show no evidence of clinically depressed mood, but most samples of HIV-positives and HIV- negatives report high levels of a lifetime diagnosis of major depression perhaps dating from before the epidemic, then we face some troubling and intriguing questions. Are sample selection biases before and after the advent of AIDS so different that they could account for such a striking difference in findings about depression? This is counterintuitive, albeit possible. Are homosexual men who are currently depressed by the HIV health crisis likely to retroactively distort their accounts of lifetime depression? This would challenge well-validated clinical interviewing instruments. Societal pressures and stigmatization attached to homosexuality might account for a proportion of the elevated lifetime rates of major depression, but there seems to be little evidence that this stigmatization is higher now than it was when the previous studies were conducted (indeed, it seems likely that just the opposite would be the case, given the progress made in struggles for gay rights). However, individual developmental factors, which are now just becoming measurable, may add to our understanding of this process. The purpose of the present paper is to see whether anxiety, depression, and their related symptoms might be illuminated by measuring CGN within a homosexual and bisexual sample. Our specific hypothesis is that men with high FGI scores would show elevated average levels of anxiety and depression. If confirmed, this hypothesis would predict that samples of homosexual men varying in average CGN could easily have different average levels of syndromic depression and/or depressed or anxious symptoms (all of which would have predated the AIDS epidemic). If there were reason to expect that AIDS-related samples of homosexual men would be skewed toward individuals of higher CGN, then this hypothesis would receive additional support

Cluster Analysis of the Klein Sexual Orientation Grid in Clinical and Nonclinical Samples: When Bisexuality Is Not Bisexuality

<div><p>A cluster analysis of the Klein Sexual Orientation Grid (KSOG) in three samples (Internet-recruited men and women; HIV study men) resulted in objectively determined 4- or 5-cluster classifications (such as “bi-heterosexual” or “bi-bisexual”). Group means and standard deviations on the KSOG's 21 items revealed that overtly erotic items (sexual fantasies, sexual behavior, sexual attraction) and self-identification items were more uniform within groups than social items (emotional preference, socialize with, lifestyle) were. The bisexual cluster in the HIV sample was distinctly different from all of the bisexual main sample clusters. Attempts to generalize from this clinical bisexual group to a larger population would be doomed to failure. This underscores the importance of recruiting nonclinical samples if one wants insight into the nature of bisexuality in the population at large. Our data empirically confirm many previous nonempirical warnings against clinical samples in studies of sexual orientation.</p></div

IgG intrathecal synthesis in HIV-associated neurocognitive disorder (HAND) according to the HIV-1 subtypes and pattern of HIV RNA in CNS and plasma compartments

We hypothesized that humoral immunity stimulation in the CNS in HIV-1C patients would be lower than that in HIV-1B due to a defective Tat chemokine dimotif (C30C31) that might influence cellular trafficking and CNS inflammation. Sixty-eight paired CSF and blood samples from people with HIV (PWH), free of CNS opportunistic infections, were included, HIV-1B (n&nbsp;=&nbsp;27), HIV-1C (n&nbsp;=&nbsp;26), and HIV negative (n&nbsp;=&nbsp;25). IgG intrathecal synthesis was assayed using quantitative and qualitative methods. IgG oligoclonal bands (OCB) in CSF were observed in 51% of PWH, comparable between HIV-1B and HIV-1C, as well as the medians of IgG intrathecal synthesis formulas. The group with HIV infection aviremic in CSF and blood showed 75% of OCB. There was a poor positive correlation between the IgG quotient and GDS. The impact of HIV-1 on IgG intrathecal production was not subtype dependent. Low-grade CNS intrathecal IgG production persists in HIV CNS infection even in PWH with CSF and blood HIV RNA controlled

COMT Val158Met Polymorphism, Executive Dysfunction, and Sexual Risk Behavior in the Context of HIV Infection and Methamphetamine Dependence

Catechol-O-methyltransferease (COMT) metabolizes prefrontal cortex dopamine (DA), a neurotransmitter involved in executive behavior; the Val158Met genotype has been linked to executive dysfunction, which might increase sexual risk behaviors favoring HIV transmission. Main and interaction effects of COMT genotype and executive functioning on sexual risk behavior were examined. 192 sexually active nonmonogamous men completed a sexual behavior questionnaire, executive functioning tests, and were genotyped using blood-derived DNA. Main effects for executive dysfunction but not COMT on number of sexual partners were observed. A COMT x executive dysfunction interaction was found for number of sexual partners and insertive anal sex, significant for carriers of the Met/Met and to a lesser extent Val/Met genotypes but not Val/Val carriers. In the context of HIV and methamphetamine dependence, dopaminergic overactivity in prefrontal cortex conferred by the Met/Met genotype appears to result in a liability for executive dysfunction and potentially associated risky sexual behavior

Methamphetamine use and neuropsychiatric factors are associated with antiretroviral non-adherence.

The present study assesses the impact of methamphetamine (METH) on antiretroviral therapy (ART) adherence among HIV+ persons, as well as examines the contribution of neurocognitive impairment and other neuropsychiatric factors [i.e., major depressive disorder (MDD), antisocial personality disorder (ASPD), and attention deficit disorder (ADHD)] for ART non-adherence. We examined HIV+ persons with DSM-IV-diagnosed lifetime history of METH abuse/dependence (HIV+ /METH+ ; n=67) as compared to HIV+ participants with no history of METH abuse/dependence (HIV+ /METH - ; n=50). Ancillary analyses compared these groups with a small group of HIV+ /METH+ persons with current METH abuse/dependence (HIV+ /CU METH+ ; n=8). Non-adherence was defined as self-report of any skipped ART dose in the last four days. Neurocognitive functioning was assessed with a comprehensive battery, covering seven neuropsychological domains. Lifetime METH diagnosis was associated with higher rates of detectable levels of plasma and CSF HIV RNA. When combing groups (i.e., METH+ and METH- participants), univariate analyses indicated co-occurring ADHD, ASPD, and MDD predicted ART non-adherence (p's &lt; 0.10; not lifetime METH status or neurocognitive impairment). A significant multivariable model including these variables indicated that only MDD uniquely predicted ART non-adherence after controlling for the other variables (p&lt;0.05). Ancillary analyses indicated that current METH users (use within 30 days) were significantly less adherent (50% prevalence of non-adherence) than lifetime METH+ users and HIV+ /METH- participants and that neurocognitive impairment was associated with non-adherence (p's &lt; 0.05). METH use disorders are associated with worse HIV disease outcomes and ART medication non-adherence. Interventions often target substance use behaviors alone to enhance antiretroviral treatment outcomes; however, in addition to targeting substance use behaviors, interventions to improve ART adherence may also need to address coexisting neuropsychiatric factors and cognitive impairment to improve ART medication taking