Double dissociation of HIV and substance use disorder effects on neurocognitive tasks dependent on striatal integrity.

OBJECTIVE: Substance use is common among individuals infected with HIV, yet whether neurocognitive effects of HIV can be distinguished from more nonspecific effects of drug dependence and associated comorbidities is not known. DESIGN: Cross-sectional observational study of neurocognitive function among HIV-infected and uninfected individuals with and without substance use disorders (SUDs). METHODS: We compared the performance of 458 (31% HIV-infected) substance-dependent individuals (SDIs) and 90 individuals (23% HIV-infected) with no history of SUDs on measures of delay discounting and probability learning, tasks, which are differentially sensitive to addictive processes and HIV serostatus, respectively. RESULTS: In factorial analyses of covariance adjusted for age, years of education, and sex, we found that SDIs showed significantly higher rates of delay discounting, regardless of HIV serostatus (P < 0.05). Conversely, HIV-infected individuals performed significantly more poorly on probability learning compared with uninfected groups, regardless of SUD history (P < 0.05). CONCLUSION: Theory-driven cognitive neuropsychological tasks may have the capacity to detect neurocognitive effects of HIV not attributable solely to substance use; evidence from functional neuroimaging studies with more selective neurocognitive probes will be critical for hypothesis testing and mapping underlying brain systems more precisely.

Changes in cognition precede changes in HRQoL among HIV+ males: Longitudinal analysis of the multicenter AIDS cohort study.

OBJECTIVES: Despite treatment-related improvements in morbidity and mortality, HIV-1-infected (HIV+) individuals continue to face a wide range of HIV-associated medical and HIV-associated neurocognitive disorders. Little is known about the impact of cognitive impairment on patients' health-related quality of life (HRQoL). To address this, the current study examined the longitudinal relationship between cognitive functioning and HRQoL among HIV+ individuals. METHOD: The sample consisted of 1,306 HIV+ men enrolled in the Multicenter AIDS Cohort Study. Participants received biannual assessments of cognitive functioning (including tests of processing speed, executive functioning, attention/working memory, motor functioning, learning, and memory) and completed questionnaires assessing HRQoL and depression. Multilevel models were used to examine the longitudinal and cross-lagged relationship between HRQoL and cognition, independent of depression and HIV disease severity. RESULTS: There was a significant relationship between HRQoL and cognitive functioning both between and within subjects. Specifically, individuals who reported better HRQoL reported better cognitive functioning, and longitudinal change in cognition was positively related to change in HRQoL. There was a significant unidirectional-lagged relationship; cognition predicted HRQoL at subsequent visits, but HRQoL did not predict cognitive functioning at subsequent visits. Furthermore, analyses of severity of neurocognitive impairment revealed that transition to a more severe stage of cognitive impairment was associated with a decline in HRQoL. CONCLUSIONS: Overall, the current study suggests that changes in HRQoL are partially driven by changes in cognitive functioning. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Elevated Depressive Symptoms Are a Stronger Predictor of Executive Dysfunction in HIV-Infected Women Than in Men.

BACKGROUND: HIV-infected (HIV+) women seem to be more vulnerable to neurocognitive impairment (NCI) than HIV+ men, perhaps in part due to mental health factors. We assessed the association between elevated depressive symptoms and NCI among HIV+ and HIV-uninfected (HIV-) women and men. SETTING: Women's Interagency HIV Study and Multicenter AIDS Cohort Study. METHODS: Eight hundred fifty-eight HIV+ (429 women; 429 men) and 562 HIV- (281 women; 281 men) completed the Center for Epidemiologic Studies Depression (16 cutoff) Scale and measures of psychomotor speed/attention, executive, and motor function over multiple visits (or time points). Women's Interagency HIV Study and Multicenter AIDS Cohort Study participants were matched according to HIV status, age, race/ethnicity, and education. Generalized linear mixed models were used to examine interactions between biological sex, HIV serostatus, and depression on impairment (T-scores <40) after covariate adjustment. RESULTS: Despite a higher frequency of depression among men, the association between depression and executive function differed by sex and HIV serostatus. HIV+ women with depression had 5 times the odds of impairment on a measure of executive control and inhibition versus HIV- depressed women and 3 times the odds of impairment on that measure versus HIV+ depressed men. Regardless of group status, depression was associated with greater impairment on processing speed, executive (mental flexibility), and motor function (P's < 0.05). CONCLUSIONS: Depression contributes to NCI across a broad range of cognitive domains in HIV+ and HIV- individuals, but HIV+ depressed women show greater vulnerabilities in executive function. Treating depression may help to improve cognition in patients with HIV infection.

Impact of glycemic status on longitudinal cognitive performance in men with and without HIV infection.

OBJECTIVES: To determine the relationship between glycemic status and cognitive performance in men living with HIV (MLWH) and without HIV infection. DESIGN: A prospective HIV/AIDS cohort study in four US cities between 1999 and 2016. METHODS: Glycemic status was categorized as normal glucose, impaired fasting glucose, controlled diabetes mellitus and uncontrolled diabetes mellitus at each semiannual visit. Cognitive performance was evaluated using nine neuropsychological tests which measure attention, constructional ability, verbal learning, executive functioning, memory and psychomotor speed. Linear mixed models were used to assess the association between glycemic status and cognition. RESULTS: Overall, 900 MLWH and 1149 men without HIV were included. MLWH had significantly more person-visits with impaired fasting glucose (52.1 vs. 47.9%) and controlled diabetes mellitus (58.2 vs. 41.8%) than men without HIV (P < 0.05). Compared with men with normal glucose, men with diabetes mellitus had significantly poorer performance on psychomotor speed, executive function and verbal learning (all P < 0.05). There was no difference in cognition by HIV serostatus. The largest effect was observed in individuals with uncontrolled diabetes mellitus throughout the study period, equivalent to 16.5 and 13.4 years of aging on psychomotor speed and executive function, respectively, the effect of which remained significant after adjusting for HIV-related risk factors. Lower CD4+ nadir was also associated with worse cognitive performance. CONCLUSION: Abnormalities in glucose metabolism were more common among MLWH than men without HIV and were related to impaired cognitive performance. Metabolic status, along with advanced age and previous immunosuppression, may be important predictors of cognition in the modern antiretroviral therapy era.

Differences in Cognitive Function Between Women and Men With HIV.

BACKGROUND: Women may be more vulnerable to HIV-related cognitive dysfunction compared with men because of sociodemographic, lifestyle, mental health, and biological factors. However, studies to date have yielded inconsistent findings on the existence, magnitude, and pattern of sex differences. We examined these issues using longitudinal data from 2 large, prospective, multisite, observational studies of US women and men with and without HIV. SETTING: The Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort Study (MACS). METHODS: HIV-infected (HIV+) and uninfected (HIV-) participants in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study completed tests of psychomotor speed, executive function, and fine motor skills. Groups were matched on HIV status, sex, age, education, and black race. Generalized linear mixed models were used to examine group differences on continuous and categorical demographically corrected T-scores. Results were adjusted for other confounding factors. RESULTS: The sample (n = 1420) included 710 women (429 HIV+) and 710 men (429 HIV+) (67% non-Hispanic black; 53% high school or less). For continuous T-scores, sex by HIV serostatus interactions were observed on the Trail Making Test parts A & B, Grooved Pegboard, and Symbol Digit Modalities Test. For these tests, HIV+ women scored lower than HIV+ men, with no sex differences in HIV- individuals. In analyses of categorical scores, particularly the Trail Making Test part A and Grooved Pegboard nondominant, HIV+ women also had a higher odds of impairment compared with HIV+ men. Sex differences were constant over time. CONCLUSIONS: Although sex differences are generally understudied, HIV+ women vs men show cognitive disadvantages. Elucidating the mechanisms underlying these differences is critical for tailoring cognitive interventions.

Cognitive trajectories over 4 years among HIV-infected women with optimal viral suppression.

OBJECTIVE: To determine whether persistent viral suppression alters cognitive trajectories among HIV-infected (HIV+) women on combination antiretroviral therapy (cART) by investigating performance longitudinally in uninfected (HIV-) and 3 groups of HIV+ women: those with consistent viral suppression after continuous cART use (VS), those without consistent virologic suppression despite continuous cART use (NVS), and those without consistent virologic suppression after intermittent cART use (Int NVS). METHODS: Two hundred thirty-nine VS, 220 NVS, 172 Int NVS, and 301 HIV- women from the Women's Interagency HIV Study (WIHS) completed neuropsychological testing every 2 years for 3 visits between 2009 and 2013. Mixed-effects regressions were used to examine group differences on continuous T scores and categorical measures of impairment (T score <40). RESULTS: On global function, VS women demonstrated lower scores and were more likely to score in the impaired range than HIV- women (p = 0.01). These differences persisted over time (group × time, p > 0.39). VS women demonstrated lower learning and memory scores than HIV- women (p < 0.05) and lower attention/working memory and fluency scores than HIV- and NVS women (p < 0.05). Group differences in scores persisted over time. Categorically, VS women were more likely to be impaired on attention/working memory and executive function than HIV- women (p < 0.05). On motor skills, VS and NVS women showed a greater decline and were more likely to be impaired than HIV- women (p < 0.05). CONCLUSIONS: Cognitive difficulties remain among HIV+ women despite persistent viral suppression. In some instances, VS women are worse than NVS women, reinforcing the need for novel adjunctive therapies to attenuate cognitive problems.

Perceived and post-traumatic stress are associated with decreased learning, memory, and fluency in HIV-infected women.

OBJECTIVE: Psychological risk factors (PRFs) are associated with impaired learning and memory in HIV-infected (HIV+) women. We determined the dynamic nature of the effects of PRFs and HIV serostatus on learning and memory over time. DESIGN: Multi-center, prospective cohort study METHODS:: Every two years between 2009 and 2013 (3 times), 646 HIV+ and 300 demographically-similar HIV-uninfected (HIV-) women from the Women's Interagency HIV Study completed neuropsychological (NP) testing and questionnaires measuring PRFs (perceived stress, post-traumatic stress disorder (PTSD) symptoms, depressive symptoms). Using mixed-effects regressions, we examined separate and interactive associations between HIV-serostatus and PRFs on performance over time. RESULTS: HIV+ and HIV- women had similar rates of PRFs. Fluency was the only domain where performance over time depended on the combined influence of HIV-serostatus and stress or PTSD (p's < 0.05); not depression. In HIV, higher stress and PTSD were associated with a greater cognitive decline in performance (p's < 0.05) versus lower stress and PTSD. Irrespective of time, performance on learning and memory depended on the combined influence of HIV-serostatus and stress or PTSD (p's ≤ 0.05). In the context of HIV, stress and PTSD were negatively associated with performance. Effects were pronounced on learning among HIV+ women without effective treatment or viral suppression. Regardless of time or HIV-serostatus, all PRFs were associated with lower speed, global NP, and executive function. CONCLUSIONS: More than depression, perceived stress and PTSD symptoms are treatment targets to potentially improve fluency, learning, and memory in women living with HIV particularly when HIV treatment is not optimal.

Association of long-term patterns of depressive symptoms and attention/executive function among older men with and without human immunodeficiency virus.

Older HIV-infected men are at higher risk for both depression and cognitive impairments, compared to HIV-uninfected men. We evaluated the association between longitudinal patterns of depressive symptoms and attention/executive function in HIV-infected and HIV-uninfected men aged 50+ years to understand whether HIV infection influenced the long-term effect of depression on attention/executive function. Responses to the Center for Epidemiologic Studies-Depression scale and attention/executive function tests (Trail Making Test Part B and Symbol Digit Modalities Test) were collected semiannually from May 1986 to April 2015 in 1611 men. Group-based trajectory models, stratified by HIV status, were used to identify latent patterns of depressive symptoms and attention/executive function across 12 years of follow-up. We identified three depression patterns for HIV-infected and HIV-uninfected men (rare/never 50.0 vs. 60.6%, periodically depressed 29.6 vs. 24.5%, chronic high 20.5 vs.15.0%, respectively) and three patterns of attention/executive function for HIV-infected and HIV-uninfected men (worst-performing 47.4 vs. 45.1%; average 41.9 vs. 47.0%; best-performing 10.7 vs. 8.0%, respectively). Multivariable logistic regression models were used to assess associations between depression patterns and worst-performing attention/executive function. Among HIV-uninfected men, those in the periodically depressed and chronic high depressed groups had higher odds of membership in the worst-performing attention/executive function group (adjusted odds ratio [AOR] = 1.45, 95% CI 1.04, 2.03; AOR = 2.25, 95% CI 1.49, 3.39, respectively). Among HIV-infected men, patterns of depression symptoms were not associated with patterns of attention/executive function. Results suggest that HIV-uninfected, but not HIV-infected, men with chronic high depression are more likely to experience a long-term pattern of attention/executive dysfunction.

Sex differences in HIV effects on visual memory among substance-dependent individuals.

HIV's effects on episodic memory have not been compared systematically between male and female substance-dependent individuals. We administered the Brief Visuospatial Memory Test-Revised (BVMT-R) to 280 substance-dependent HIV+ and HIV- men and women. Groups were comparable on demographic, substance use, and comorbid characteristics. There were no significant main effects of sex or HIV serostatus on BVMT-R performance, but HIV+ women performed significantly more poorly on delayed recall. This effect was most prominent among cocaine-dependent HIV+ women. Our findings are consistent with recent speculation that memory impairment may be more common among HIV+ women, particularly those with a history of cocaine dependence.

Cortical brain atrophy and intra-individual variability in neuropsychological test performance in HIV disease.

To characterize the relationship between dispersion-based intra-individual variability (IIVd) in neuropsychological test performance and brain volume among HIV seropositive and seronegative men and to determine the effects of cardiovascular risk and HIV infection on this relationship. Magnetic Resonance Imaging (MRI) was used to acquire high-resolution neuroanatomic data from 147 men age 50 and over, including 80 HIV seropositive (HIV+) and 67 seronegative controls (HIV-) in this cross-sectional cohort study. Voxel Based Morphometry was used to derive volumetric measurements at the level of the individual voxel. These brain structure maps were analyzed using Statistical Parametric Mapping (SPM2). IIVd was measured by computing intra-individual standard deviations (ISD's) from the standardized performance scores of five neuropsychological tests: Wechsler Memory Scale-III Visual Reproduction I and II, Logical Memory I and II, Wechsler Adult Intelligence Scale-III Letter Number Sequencing. Total gray matter (GM) volume was inversely associated with IIVd. Among all subjects, IIVd -related GM atrophy was observed primarily in: 1) the inferior frontal gyrus bilaterally, the left inferior temporal gyrus extending to the supramarginal gyrus, spanning the lateral sulcus; 2) the right superior parietal lobule and intraparietal sulcus; and, 3) dorsal/ventral regions of the posterior section of the transverse temporal gyrus. HIV status, biological, and cardiovascular disease (CVD) variables were not linked to IIVd -related GM atrophy. IIVd in neuropsychological test performance may be a sensitive marker of cortical integrity in older adults, regardless of HIV infection status or CVD risk factors, and degree of intra-individual variability links with volume loss in specific cortical regions; independent of mean-level performance on neuropsychological tests.

Crack cocaine use impairs anterior cingulate and prefrontal cortex function in women with HIV infection.

Crack cocaine use is associated with impaired verbal memory in HIV-infected women more than uninfected women. To understand the neural basis for this impairment, this study examined the effects of crack cocaine use on activation of the prefrontal cortex (PFC) and strategic encoding during a verbal memory task in HIV-infected women. Three groups of HIV-infected women from the Chicago Consortium of the Women's Interagency HIV Study were compared: current users of crack cocaine (n = 10), former users of cocaine (n = 11), and women who had never used cocaine (n = 9). Participants underwent functional magnetic resonance imaging during a verbal memory task and completed a neuropsychological test of verbal memory. On the neuropsychological test, current crack users performed significantly worse than other groups on semantic clustering, a measure of strategic encoding, p < 0.05. During encoding, activation in left anterior cingulate cortex (ACC) was lower in current and former cocaine users compared to never users. During recognition, activation in bilateral PFC, specifically left dorsal medial PFC and bilateral dorsolateral PFC, was lower in current and former users compared to women who had never used cocaine. Lower activation in left dorsolateral PFC was correlated with worse performance on the recognition task, p < 0.05. The verbal learning and memory deficits associated with cocaine use in women with HIV may be partially accounted for by alterations in ACC and PFC function.

Investigation of menopausal stage and symptoms on cognition in human immunodeficiency virus-infected women.

OBJECTIVE: We evaluated the separate and interactive associations of menopausal stage, menopausal symptoms, and human immunodeficiency virus (HIV) infection with cognition. We hypothesized that HIV-infected perimenopausal women would show the greatest cognitive difficulties and that menopausal symptoms would be inversely associated with cognition. METHODS: This cross-sectional study included 708 HIV-infected and 278 HIV-uninfected premenopausal, perimenopausal, or postmenopausal women (64% African American; median age, 44 y) from the Women's Interagency HIV Study. Participants completed tests of verbal learning and memory, attention/processing speed, and executive function. We administered a menopausal symptom questionnaire that assessed anxiety, vasomotor, and sleep symptoms and obtained measures of depressive symptoms. RESULTS: In multivariable regression analyses controlling for relevant covariates, HIV infection, but not menopausal stage, was associated with worse performance on all cognitive measures (P's < 0.05). Depressive symptoms were associated with lower cognitive performance on measures of verbal learning and memory, attention, and executive function (P's < 0.05); anxiety symptoms were associated with lower performance on measures of verbal learning and memory (P's < 0.05). Vasomotor symptoms were associated with worse attention (P < 0.05). HIV and anxiety symptoms interacted to influence verbal learning (P's < 0.05); elevated anxiety was associated with worse verbal learning in HIV-infected women only. CONCLUSIONS: Vasomotor, depressive, and anxiety symptoms, but not menopausal stage, are associated with worse cognitive performance in both HIV-infected and HIV-uninfected women, although elevated anxiety symptoms are more associated with verbal learning deficits in HIV-infected women. Because cognitive problems can interfere with everyday functioning, including treatment adherence, it may be important to screen and treat anxiety in HIV-infected women.

Heroin and amphetamine users display opposite relationships between trait and neurobehavioral dimensions of impulsivity.

The multidimensional construct of impulsivity is implicated in all phases of the addiction cycle. Substance dependent individuals (SDIs) demonstrate elevated impulsivity on both trait and laboratory tests of neurobehavioral impulsivity; however our understanding of the relationship between these different aspects of impulsivity in users of different classes of drugs remains rudimentary. The goal of this study was to assess for commonalities and differences in the relationships between trait and neurobehavioral impulsivity in heroin and amphetamine addicts. Participants included 58 amphetamine dependent (ADIs) and 74 heroin dependent individuals (HDIs) in protracted abstinence. We conducted Principal Component Analyses (PCA) on two self-report trait and six neurobehavioral measures of impulsivity, which resulted in two trait impulsivity (action, planning) and four neurobehavioral impulsivity composites (discriminability, response inhibition efficiency, decision-making efficiency, quality of decision-making). Multiple regression analyses were used to determine whether neurobehavioral impulsivity is predicted by trait impulsivity and drug type. The analyses revealed a significant interaction between drug type and trait action impulsivity on response inhibition efficiency, which showed opposite relationships for ADIs and HDIs. Specifically, increased trait action impulsivity was associated with worse response inhibition efficiency in ADIs, but with better efficiency in HDIs. These results challenge the unitary account of drug addiction and contribute to a growing body of literature that reveals important behavioral, cognitive, and neurobiological differences between users of different classes of drugs.

An investigation of the effects of antiretroviral central nervous system penetration effectiveness on procedural learning in HIV+ drug users.

Treatment with combination antiretroviral therapy (cART) regimens with a high capacity to penetrate the blood-brain barrier has been associated with lower levels of human immunodeficiency virus (HIV) in the central nervous system (CNS). This study examined neurocognitive performance among a sample of 118 HIV+ substance-dependent individuals (SDIs) and 310 HIV- SDIs. HIV+ participants were prescribed cART regimens with varying capacity to penetrate the CNS as indexed by the revised CNS Penetration Effectiveness (CPE) scale. Participants completed the Rotary Pursuit Task (RPT) and the Weather Prediction Task (WPT)-two measures of procedural learning (PL) with known sensitivity to HIV infection-and a control task of sustained attention. HIV+ SDIs prescribed cART with relatively high CNS penetrance performed significantly more poorly on both tasks than HIV- controls. Task performance of HIV+ SDIs prescribed cART with relatively low CNS penetrance did not differ significantly from either HIV- controls or the HIV+/high CPE group, although a trend toward lower RPT performance than that of HIV- participants was observed. Between-group differences were not seen on a control task of motor impulsivity (Immediate Memory Task), indicating that the observed deficits among HIV+/high CPE SDIs may have some specificity.

Decision making among HIV+ drug using men who have sex with men: a preliminary report from the Chicago Multicenter AIDS Cohort Study.

HIV+ substance-dependent individuals (SDIs) make significantly poorer decisions than HIV- SDIs, but the neurocognitive mechanisms underlying this impairment have not been identified. We administered the Iowa Gambling Task (IGT), a measure of decision making under uncertain risk, and the Cups Task, a measure of decision making under specified risk, to a group of 56 HIV+ and 23 HIV- men who have sex with men (MSMs) with a history of substance dependence enrolled in the Multicenter AIDS Cohort Study. The IGT provides no explicit information regarding the contingencies for each possible choice, and the probability of each outcome remains ambiguous at least for the early trials; in contrast, the Cups Task provides explicit information about the probability of each outcome. The HIV+ group made significantly poorer decisions on the IGT than the HIV- group. Cups Task performance did not differ significantly between HIV- and HIV+ groups. Exploratory analyses of the IGT data suggested that HIV+ subjects tended to perform more poorly during the early learning phase when uncertainty about specific outcomes was greatest. Additionally, performance on the final two trial blocks was significantly correlated with Stroop Interference scores, suggesting that IGT performance is driven increasingly by executive control during the later portion of the task. Potential cognitive mechanisms to be explored in later studies are discussed, including impairment in implicit learning processing.

Performance of young adult cannabis users on neurocognitive measures of impulsive behavior and their relationship to symptoms of cannabis use disorders.

Recent studies suggest that abstinent cannabis users show deficits on neurocognitive laboratory tasks of impulsive behavior. But results are mixed, and less is known on the performance of non-treatment-seeking, young adult cannabis users. Importantly, relationships between performance on measures of impulsive behavior and symptoms of cannabis addiction remain relatively unexplored. We compared young adult current cannabis users (CU, n = 65) and nonusing controls (NU, n = 65) on several laboratory measures of impulsive behavior, as well as on a measure of episodic memory commonly impacted by cannabis use. The CU group performed more poorly than the NU group on the Hopkins Verbal Learning Test-Revised Total Immediate Recall and Delayed Recall. No significant differences were observed on the measures of impulsive behavior (i.e., Iowa Gambling Task, IGT; Go-Stop Task; Monetary Choice Questionnaire; Balloon Analogue Risk Task). We examined relationships between neurocognitive performance and symptoms of cannabis use disorder symptoms (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, DSM-IV CUD) among the CU group, which revealed that poorer IGT performance was associated with more symptoms of DSM-IV CUD. Our results show poorer memory performance among young adult cannabis users than among healthy controls, but no differences on measures of impulsive behavior. However, performance on a specific type of impulsive behavior (i.e., poorer decision making) was associated with more cannabis use disorder symptoms. These results provide preliminary evidence to suggest that decision-making deficits may be more strongly associated with problems experienced from cannabis use, rather than solely being a consequence of cannabis use, per se.

Genome-wide association study of neurocognitive impairment and dementia in HIV-infected adults.

The neuropathogenesis of HIV-associated neurocognitive disorders (HAND) is unclear. Candidate gene studies have implicated genetic susceptibility loci within immune-related genes; however, these have not been reliably validated. Here, we employed genome-wide association (GWA) methods to discover novel genetic susceptibility loci associated with HAND, and validate susceptibility loci implicated in prior candidate gene studies. Data from 1,287 participants enrolled in the Multicenter AIDS Cohort Study between 1985 and 2010 were used. Genotyping was conducted with Illumina 1M, 1MDuo, or 550K platform. Linear mixed models determined subject-specific slopes for change over time in processing speed and executive functioning, considering all visits including baseline and the most recent study visit. Covariates modeled as fixed effects included: time since the first visit, depression severity, nadir CD4+ T-cell count, hepatitis C co-infection, substance use, and antiretroviral medication regimen. Prevalence of HIV-associated dementia (HAD) and neurocognitive impairment (NCI) was also examined as neurocognitive phenotypes in a case-control analysis. No genetic susceptibility loci were associated with decline in processing speed or executive functioning among almost 2.5 million single nucleotide polymorphisms (SNPs) directly genotyped or imputed. No association between the SNPs and HAD or NCI were found. Previously reported associations between specific genetic susceptibility loci, HIV-associated NCI, and HAD were not validated. In this first GWAS of HAND, no novel or previously identified genetic susceptibility loci were associated with any of the phenotypes examined. Due to the relatively small sample size, future collaborative efforts that incorporate this dataset may still yield important findings.

Neurocognitive performance in drug-dependent males and females with posttraumatic stress disorder symptoms.

Sex differences in neurobiological mechanisms of substance dependence are well documented but studies of sex differences in associated neurocognitive deficits have produced inconsistent results. Posttraumatic stress disorder (PTSD) is comorbid with substance dependence and frequently affects neurocognition. Thus, we investigated the effects of sex and PTSD symptoms on sustained attention and inhibition abilities among 126 female and 297 male substance-dependent individuals (SDIs) using the Immediate Memory Test (IMT). Females with significant PTSD (PTSD+) symptoms demonstrated significantly impaired IMT performance relative to other participants. These results represent progress in efforts to delineate sex-specific risk factors for neurocognitive deficits among SDIs.

A comparison of delay discounting among substance users with and without suicide attempt history.

Although substance use disorders are associated with overall increased suicide risk, there is considerable variability in suicide risk among substance-dependent individuals (SDIs). Impairment in impulse control is common among SDIs, and it may contribute to vulnerability to suicidal behavior. The present study examined the relation between one specific aspect of impulsivity-delay discounting-and suicide attempt history in a sample of SDIs. An interaction was observed between suicide attempt history and discounting rates across delayed reward size. Specifically, SDIs with no history of attempted suicide, devalued small relative to large delayed rewards. In contrast, SDIs with a history of suicide attempts appeared comparatively indifferent to delayed reward size, discounting both small and large delayed rewards at essentially identical rates. These findings provide evidence that, despite the view that SDIs are characterized by marked difficulties in impulsivity, significant variability exists within this group in delay-discounting tendencies. Furthermore, these differences provide preliminary evidence that specific aspects of impulsivity may help to identify those most at risk for suicidal behavior in this population. The potential implications of our findings for suicide prevention efforts are discussed.