Studies comparing DSM-IV and DSM-5 SUD diagnostic criteria have shown increases , no differences , and decreases in prevalence. Increases in SUD prevalences under DSM-5 may relate to the inclusion of ³GLDJQRVWLF RUSKDQV´ in diagnoses² those who meet one or two DSM-IV criteria for dependence, but none for abuse . Nonetheless, concordance of DSM-IV and DSM-5 diagnoses are acceptable, with concordance increasing with severity , suggesting that our findings are likely similar to those resulting had we used DSM-5 criteria. Further research is needed to clarify this issue. GUTS participants are not representative of the U.S. population as they are children of registered nurses and predominantly non-Hispanic White. The prevalence of SUDs in GUTS, however, is comparable to same-aged participants of the NSDUH , as is the distribution of SGMs enrolled in GUTS compared to population-based studies . Additionally, GUTS participants were not enrolled based on their sexual orientation or gender identity. GUTS assessed sexual orientation with a single item tapping both identity and attraction. This limits direct comparisons between our findings and other studies assessing dimensions of sexual orientation separately because research indicates these dimensions have different associations with substance involvement . Further, despite the large sample size, we were limited in our ability to detect within group differences among SGMs. Despite these limitations, our study is strengthened by including multiple SGM subgroups, enabling examination of heterogeneous outcomes that may otherwise be obscured when combining SGM categories. Future research should include more diverse, nationally representative samples to enable examination of interactions between sexual orientation, gender identity,plant growing trays and other sociodemographic factors to further identify higher-risk SGM subgroups.Among the general population, young adults with SUDs experience disproportionate economic and public health burdens and have low utilization of SUD treatment .
For SGM young adults, these issues may be even more persistent, with one study finding that less than 4% of the 14-20% of SMs needing treatment actually accessing treatment . Specific barriers to treatment among SGMs include a lack of targeted interventions, differences in coping strategies and psychiatric comorbidities, discrimination within healthcare settings, lack of provider knowledge about SGM health needs, and lack of insurance . Consequently, increasing access to treatment alone may be insufficient to address SGM SUD disparities. Efforts should also focus on bolstering the provision of culturally tailored, SGM affirming treatment which promotes resilience, coping, and wellness. Further, given high co-morbidity with other mental disorders, interventions are needed which integrate psychological and SUD treatment .Though not known as a primarily neurodegenerative disease, human immunodeficiency virus infection has been linked to cognitive impairment as well as cerebral metabolic changes. HIV has been shown to cause significant impairments of varying severity in higher order brain functions . Currently, a set of research diagnostic criteria have been proposed to categorize HAND into three conditions: asymptomatic neurocognitive impairment, HIV-associated mild neurocognitive disorder, and HIV-associated dementia . Neuropsychological deficits in attention and learning have the highest prevalence in HIV+ patients ; as HIV disease progresses from early to later stages, executive functioning, information-processing speed, and motor functioning are associated with the greatest decline .Structural and functional brain imaging has revealed loss of gray and white matter volumes, increased white matter abnormality, and changes in perfusion and glucose metabolism associated with HIV . One indication of neuronal injury is reduced N-acetylaspartate , a putative marker of neuronal health and integrity, on magnetic resonance spectroscopy imaging .
Increased HIV viral load and decreased CD4+ T-cell counts have been associated with decreased levels of NAA in the frontal white matter, frontal gray matter, and basal ganglia regions, suggesting that HIV infection may result in loss of neuronal integrity . Even when asymptomatic, persons with HIV infection may have decreased NAA levels in the basal ganglia region . With advanced ARV regimens, HIV infected individuals are living longer and in better health now than before. Paradoxically, HAND remains prevalent. For example, a recent study by the CHARTER group reported that 40–50% of people in HIV care, with the majority receiving HAART , have neurocognitive impairments . While the reasons for HAND persistence are unclear, one possibility is that certain coexisting factors might increase the brain’s vulnerability to HIV injury. Among such comorbidities, traumatic brain injury is commonplace. Since TBI still remains as a largely unexplored condition within the HIV population, we were interested in its potential effects in HIV-infected people. TBIs involve disruption of normal brain function that can be caused by a physical insult to the head, subjecting it to sudden acceleration and deceleration forces . The incidence of new TBIs each year in the United States is 2 million, which is approximately 35 times greater than the incidence of new HIV infection per year . The high prevalence of TBI in the general population suggests that TBI may be a common comorbidity in HIV+ persons that requires further investigation. The prevalence of HIV+ patients who have suffered from at least one TBI has not been reported systematically. However, in the 1,599 cases studied in the CHARTER program at the University of California, San Diego, approximately 21% reported head injury. Following a traumatic brain injury, people can experience a wide range of impairments in the cognitive, emotional, physical, and psychosocial domains and interactions amongst them . People with moderate to severe TBI history can experience a range of cognitive deficits, with one of the most prevalent being difficulty in applying optimal strategies for learning and memory . MRS studies have confirmed that TBI patients also evidence lower NAA levels .
Mild traumatic brain injury patients have also been shown to exhibit a 12% deficit in WBNAA , suggesting a loss in neuronal health following a head injury . To explore the possibility that TBI might enhance the effects of HIV on the brain, we performed comprehensive neuropsychological assessments with HIV-infected persons who did and did not have histories of TBI. We hypothesized that neurocognitive function in those with TBI would be worse than in those without, particularly in areas of cognition that have been implicated in each etiology—that is, working memory, attention, and executive function. We also performed a nested study on a subset of cases to examine changes in brain metabolites via MRS. Since HIV and TBI are each associated with decreases in NAA levels, we hypothesized that people with both HIV and TBI would evidence greater NAA reductions, suggestive of more neuronal injury.For the neuropsychological study, we selected from the HIV participants with negative TBI history those that matched the HIV+TBI+ on the demographic characteristics of age, sex, education, and ethnicity,as well as on HIV-associated characteristics of current antiretroviral status, antiretroviral history, nadir CD4,rolling grow tables plasma HIV viral loads, CSF HIV viral loads, AIDS or non-AIDS classification, and presence of hepatitis C infection. Wide Range Achievement Test–Third Edition Reading scores were also used as added matching criteria to ensure general intellectual equivalence across the groups . This resulted in a sample of 590 HIV+TBI– and 110 HIV+TBI+ participants whose characteristics are summarized in Table 1.Participants were also compared for potential differences in depressive symptoms and substance abuse, as these can have independent effects on neuropsychological performance. Depressive symptoms were assessed using the Beck Depression Inventory . Participants were also given a Composite International Diagnostic Interview , which permits diagnosis of participants with mood disorders according to the Diagnostic and Statistical Manual of Mental Disorders–Fourth Editioncriteria . The mood disorders specifically assessed for CHARTER participants included major depressive disorder and dysthymia. The CIDI was also used to diagnose a substance use abuse or dependency disorder, and we define “history of substance use disorder” as any individual who met criteria for substance abuse or dependency, either currently or in the past. Data were also gathered on current use of prescription medications with psychotropic effects, including antidepressants, sedatives, and opioid analgesics.The results of this study indicate that HIV-infected participants who report substantial TBI, defined as a history of loss of consciousness greater than 30 minutes or complicated by neurological symptoms persisting more than 2 weeks after the injury, were significantly more impaired in working memory and executive functioning than the HIV+ TBI– group.
Consistent with our neuropsychological test results, the HIV+TBI+ group also reported more neurocognitive problems, including memory and sensory complaints. From our MRS subset, we found that HIV and TBI together were associated with decreased NAA in the frontal gray matter and basal ganglia brain regions when compared to HIV participants without TBI. Our results are consistent with studies that have showed decreased levels of NAA associated with HIV alone and TBI alone; they also suggest greater reduction in neuronal integrity in those regions among the HIV+TBI+ group . Our groups were well equated on many factors that could have independently contributed to worse NP performance or metabolite changes. These matching factors included age, education, race/ethnicity, reading proficiency, and several HIV disease and treatment characteristics, including nadir CD4 count.
Though individuals within the HIV+TBI+ group were somewhat more likely to be male , our use of gender-adjusted norms available for most of the neuropsychological tests make it unlikely that gender influenced the results. Furthermore, a study on neuropsychological performance in mild TBI patients revealed no statistically significant differences between male and female patients . The groups also had equivalent levels of depressive symptoms as well as current and past diagnoses of MDD, dysthymia, or both. Substance disorders were also comparable, with the exception of alcohol disorders, which were about 10% higher in the HIV+TBI+ group. However, analyses taking alcohol disorder diagnosis into account did not reveal any systematic effect for alcohol on CNS outcomes. From these data, we believe it is accurate to say that a history of more than minimal TBI in the setting of HIV is associated with mild enhancement of neurocognitive symptoms and signs, as well as more evidence of metabolite change in the brain. At the same time, the effect sizes for neuropsychological performance are surprisingly small , given that these were more than minimal injuries by history. The effect sizes on reported cognition were somewhat higher and were not explained by differences in mood. This, coupled with the more robust effect on the metabolite NAA in the MRS sub-study, opens the possibility that TBI may be associated with more lingering brain effects than are being captured by neuropsychological testing. Our data are also consistent with another study that demonstrated that people who are HIV+TBI+ have significantly greater number of symptoms associated with mild TBI than do an HIV+TBI– group. The authors used the TIRR symptom checklist, which included the cluster of 25 symptoms specific to mild TBI that were higher in those with previous head injuries . Though the authors were the first to state the importance of recognizing the functional impact of TBI within the HIV population, our report has further explored what the impact is through analysis of neuropsychological tests, spectroscopy information, depressive symptoms, alcohol and drug abuse, and biological markers of HIV infection and AIDS disease. Although the effects of TBI on HIV neurocognitive outcomes have not received wide attention, there are indications that history of TBI can amplify the effects of other neurological diseases. For example, traumatic brain injury appears to increase the risk of neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease . Persisting difficulties with abstraction associated with alcoholism may also be amplified by head injury history .Reduction in NAA is consistent with neuronal injury associated with TBI leading to a disruption of neuronal mitochondrial activity, which subsequently leads to cognitive compromise. The lower NAA levels may also be compatible with the common neural injury mechanism of increased excitotoxicity: TBI alone could potentiate large fluxes of calcium that induce apoptosis in neurons associated with cognition . TBI has also been associated with inflammation . However, given that in the MRS sub-study there were no significant differences between HIV+TBI+ and HIV+TBI– in levels of myoinositol and choline, metabolites indicative of inflammation, it appears that an inflammatory process may not be linked to the TBI-associated cognitive worsening that follows. Instead, the patterns in our data suggest that persistent neuronal injury may be a factor.