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.

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.

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.

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.

Deficits in complex motor functions, despite no evidence of procedural learning deficits, among HIV+ individuals with history of substance dependence.

Human immunodeficiency virus (HIV) and drugs of abuse affect common neural systems underlying procedural memory, including the striatum. The authors compared performance of 48 HIV seropositive (HIV+) and 48 HIV seronegative (HIV-) participants with history of cocaine and/or heroin dependence across multiple Trial Blocks of three procedural learning (PL) tasks: Rotary Pursuit (RP), Mirror Star Tracing (MST), and Weather Prediction (WP). Groups were well matched on demographic, psychiatric, and substance use parameters, and all participants were verified abstinent from drugs. Mixed model analyses of variance revealed that the individuals in the HIV+ group performed more poorly across all tasks, with a significant main effect of HIV serostatus observed on the Mirror Star Tracing and a trend toward significance obtained for the Rotary Pursuit task. No significant differences were observed on the Weather Prediction task. Both groups demonstrated significant improvements in performance across all three procedural learning tasks. It is important to note that no significant Serostatus x Trial Block interactions were observed on any task. Thus, the individuals in the HIV+ group tended to perform worse than those in the HIV- group across all trial blocks of procedural learning tasks with motor demands, but showed no differences in their rate of improvement across all tasks. These findings are consistent with HIV--associated deficits in complex motor skills, but not in procedural learning.

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.

Impaired decision-making in psychopathic heroin addicts.

Substance-dependent individuals (SDIs) often show neurocognitive deficits in decision-making, such that their choices are biased toward the greatest immediate reward rather than the optimal future outcome. However, studies of SDIs are often hampered by two significant methodological challenges: polysubstance dependence and comorbid conditions, which are independently associated with neurocognitive impairments. We addressed these methodological challenges by testing heroin addicts in Bulgaria, where heroin addiction is highly prevalent but polysubstance dependence is rare. The goal of the current study was to evaluate the potential contribution of psychopathy to decision-making processes among this group of Bulgarian heroin addicts. We tested 78 male currently abstaining heroin addicts, classified as psychopathic or non-psychopathic using the Hare Psychopathy Checklist, Revised (PCL-R). Psychopathic heroin addicts showed notable deficits in decision-making in that they made significantly more disadvantageous decisions relative to non-psychopathic heroin addicts. Results indicate that the presence of psychopathy may exacerbate decision-making deficits in heroin addicts.

Are all drug addicts impulsive? Effects of antisociality and extent of multidrug use on cognitive and motor impulsivity.

The purpose of this investigation was to examine the influence of antisociality and extent of multidrug use on cognitive and motor impulsivity among substance-dependent individuals (SDIs) that used primarily cocaine and/or heroin. One hundred currently abstinent male SDIs participated in the study. Extent of multidrug use and degree of antisociality, assessed with the Socialization Scale of the California Psychological Inventory (So-CPI), were used to classify participants into one of four groups: high antisocial/low multidrug use, high antisocial/high multidrug use, low antisocial/low multidrug use, and low antisocial/high multidrug use. All subjects completed the Iowa Gambling Task to assess cognitive impulsivity and the Stroop Task to measure motor impulsivity. Contrary to expectations, antisociality was associated with more advantageous performance on the Iowa Gambling Task, independent of extent of multidrug use. In contrast, greater multidrug use was associated with general psychomotor slowing on the Stroop Task. Results suggest that a subclinical form of antisociality may have a paradoxically facilitating effect on decision-making and cognitive impulsivity among SDIs.

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.

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 between dyads and correct responses on the Paced Auditory Serial Addition Task (PASAT).

The sensitivity of the Paced Auditory Serial Addition Task (PASAT) to working memory deficits may be enhanced by examining "dyads" (i.e., correct responses immediately preceded by a correct response) as a complement to the traditional total correct summary score. In a sample of 397 mostly African American (79%) healthy adults, total dyad and total correct scores were highly correlated (r = .96, p < .001); however, the magnitude of this association diminished in faster stimulus presentation trials, particularly among participants with impaired working memory abilities.

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.

Neuropsychological functioning in a cohort of HIV- and hepatitis C virus-infected women.

OBJECTIVE: To evaluate the neurocognitive function in 220 women enrolled in the Women's Interagency HIV Study (WIHS), a study of disease progression in women living with HIV/AIDS and in HIV-negative controls. METHODS: We evaluated the prevalence of abnormal neuropsychological (NP) results in hepatitis C virus (HCV)-positive compared with HCV-negative women in combination with HIV serostatus. RESULTS: NP impairment was significantly higher for HCV-positive women in comparison with HCV-negative women [odds ratio (OR), 2.03; 95% confidence interval (CI), 1.17-3.51]. Women co-infected with HCV and HIV demonstrated greater abnormal NP performance than those not infected with either, particularly if there was evidence of CD4 T-lymphocyte immunosuppression [> 200 x 10(6) CD4 cells/l (OR, 3.48; 95% CI, 1.49-8.15) and < or = 200 x 10(6) CD4 cells/l (OR, 5.38; 95% CI, 1.46-19.84)]. Women who were HCV-positive/HIV-positive and not taking antiretroviral therapy (ART) were more likely (OR, 7.03; 95% CI, 2.63-18.82) to demonstrate NP impairment than those who were HCV-negative/HIV-negative. In analyses controlling separately for education, intelligence quotient, depression, sedating drug use, head injury, ethnicity, and history of substance use, HCV continued to significantly predict NP impairment. The HCV effect did not reach significance when controlling for age in bivariate or multivariate analyses although the odds ratio for NP abnormalities in HCV-infected patients was only slightly reduced (ORs above 1.9). After testing for an interaction between age and infection status, we conducted age-stratified analysis and showed a significant effect of infection status for those aged under 40 years. CONCLUSIONS: The effect of aging on co-infected populations will require further study. This study has demonstrated the association of HCV with the risk of neurocognitive impairment in women living with HIV/AIDS and suggests that co-infection has an additive effect.

Investigating neurocognitive features of hepatitis C virus infection in drug users: potential challenges and lessons learned from the HIV literature.

Studies of neurocognition in drug users with hepatitis C virus (HCV) infection are urgently needed but face many challenges. We review similarities between human immunodeficiency virus (HIV) and HCV infection in their neurocognitive features, discuss challenges associated with research among drug users, advocate that the HIV literature can usefully inform studies of HCV, and review findings by our group on neurocognition among substance users with HIV and/or HCV infection.

Immune-specific immunoglobulin G-mediated enhancement of human immunodeficiency virus-induced IFN-alpha production.

Interferon-alpha (IFN-alpha) is synthesized as an integral part of innate immunity to viral infection. We previously provided preliminary evidence that antibody-containing serum from HIV-infected individuals enhanced HIV-induced production of IFN-alpha. Subsequently, preparations of pooled human immunoglobulin G (IgG) have also been shown to enhance poliovirus (PV)-induced IFN-alpha production. The current work establishes IgG as the serum mediator that enhances induction of IFN-alpha by HIV. Our studies also establish the ability of sera from individual subjects to enhance PV-induced IFN-alpha production. HIV-induced IFN-alpha production was enhanced maximally by >4000-fold and by an average of 25-fold. Sera from 74 people enhanced PV- induced IFN-alpha from undetectable levels to an average of 615 units (range 7-4679 units). The ability of individual sera to enhance IFN-alpha production by HIV and PV persisted undiminished in patients with AIDS. IgG-mediated enhancement of IFN-alpha production was similar to that induced by IgG and PV and was blocked by IgG Fc fragments. Demonstration of the selective enhancement of HIV-induced IFN-alpha production by IgG from HIV-seropositive individuals provides further evidence for the existence of antigen-specific upregulation of a critical component of innate antiviral immunity by the adaptive Th2 immune response.

Impaired decision making related to working memory deficits in individuals with substance addictions.

This study examined whether individuals with substance dependence (ISDs) show impairments in working memory and whether there is a relationship between their impairments in decision making as measured by the gambling task (GT) paradigm and working memory as measured by a delayed nonmatching to sample (DNMS) task. Using the GT, 11% of healthy control participants and 61% of ISDs opted for choices with high immediate gains in spite of higher future losses. For the ISDs and controls with equal GT impairments, the ISDs performed significantly lower than controls on the DNMS task. The nonimpaired ISDs on the GT also performed significantly worse than matched controls on the DNMS task. The DNMS task deficit in ISDs was across all delay times, suggesting the deficit may lie in the "executive" process of working memory, which supports earlier findings (E. M. Martin et al., 2003). The authors suggest that the prefrontal cortex hosts multiple distinct mechanisms of decision making and inhibitory control and that ISDs may be affected in any one or combination of them.