Associations between neurocognitive functioning and social and occupational resilience among South African women exposed to childhood trauma.

Background: Prior research on adaptation after early trauma among black South African women typically assessed resilience in ways that lacked contextual specificity. In addition, the neurocognitive correlates of social and occupational resilience have not been investigated. Objective: The primary aim of this exploratory study was to identify domains of neurocognitive functioning associated with social and occupational resilience, defined as functioning at a level beyond what would be expected given exposure to childhood trauma. Methods: A sample of black South African women, N = 314, completed a neuropsychological battery, a questionnaire assessing exposure to childhood trauma, and self-report measures of functional status. We generated indices of social and occupational resilience by regressing childhood trauma exposure on social and occupational functioning, saving the residuals as indices of social and occupational functioning beyond what would be expected given exposure to childhood trauma. Results: Women with lower non-verbal memory evidenced greater social and occupational resilience above and beyond the effects attributable to age, education, HIV status, and depressive and posttraumatic stress symptoms. In addition, women with greater occupational resilience exhibited lower semantic language fluency and processing speed. Conclusion: Results are somewhat consistent with prior studies implicating memory effects in impairment following trauma, though our findings suggest that reduced abilities in these domains may be associated with greater resilience. Studies that use prospective designs and objective assessment of functional status are needed to determine whether non-verbal memory, semantic fluency, and processing speed are implicated in the neural circuitry of post-traumatic exposure resilience.

Planteamiento: Las investigaciones previas sobre la adaptación después del trauma temprano entre las mujeres negras de Sudáfrica generalmente evaluaban la resiliencia de maneras que carecían de especificidad contextual. Además, no se han investigados los correlatos neurocognitivos de la resiliencia social y ocupacional. Objetivo: El objetivo principal de este estudio exploratorio fue identificar los dominios del funcionamiento neurocognitivo asociados con la resiliencia social y ocupacional, que se define como el funcionamiento en un nivel mayor de lo que se esperaría dada la exposición al trauma infantil. Métodos: Una muestra de mujeres negras sudafricanas, N = 314, completó una batería neuropsicológica, un cuestionario que evaluaba la exposición al trauma infantil y medidas de auto informe de su funcionamiento. Generamos índices de resiliencia social y ocupacional mediante la regresión de la exposición al trauma infantil en el funcionamiento social y laboral, conservando los residuos como índices de funcionamiento social y laboral más allá de lo esperado dada la exposición al trauma infantil. Resultados: Las mujeres con menor memoria no verbal mostraron una mayor resiliencia social y ocupacional por encima y más allá de los efectos atribuibles a la edad, la educación, el estado del VIH y los síntomas de depresión y estrés postraumático. Además, las mujeres con mayor resiliencia ocupacional mostraron menor fluidez del lenguaje semántico y de velocidad de procesamiento. Conclusión: Los resultados son algo consistentes con los estudios previos que implican los efectos de la memoria en el deterioro después del trauma, aunque nuestros hallazgos sugieren que las habilidades reducidas en estos dominios pueden asociarse a una mayor resiliencia. Se necesitan estudios que usen diseños prospectivos y una evaluación objetiva del estado funcional para determinar si la memoria no verbal, la fluidez semántica y la velocidad de procesamiento están implicadas en los circuitos neuronales de la resiliencia a la exposición postraumática.

The impact of ethnicity/race on the association between the Veterans Aging Cohort Study (VACS) Index and neurocognitive function among HIV-infected persons.

The Veterans Aging Cohort Study (VACS) Index was developed as a risk index for health outcomes in HIV, and it has been consistently associated with mortality. It shows a significant, yet relatively weak, association with neurocognitive impairment, and little is known about its utility among ethnic/racial minority groups. We examined whether the association between the VACS Index and neurocognition differed by ethnic/racial group. Participants included 674 HIV-infected individuals (369 non-Hispanic whites, 111 non-Hispanic blacks, and 194 Hispanics). Neurocognitive function was assessed via a comprehensive battery. Scaled scores for each neurocognitive test were averaged to calculate domain and global neurocognitive scores. Models adjusting for demographics and HIV disease characteristics not included in the VACS Index showed that higher VACS Index scores (indicating poorer health) were significantly associated with worse global neurocognition among non-Hispanic whites. This association was comparable in non-Hispanic blacks, but nonsignificant among Hispanics (with similar results for English and Spanish speaking). We obtained comparable findings in analyses adjusting for other covariates (psychiatric and medical comorbidities and lifestyle factors). Analyses of individual neurocognitive domains showed similar results in learning and delayed recall. For other domains, there was an effect of the VACS Index and no significant interactions with race/ethnicity. Different components of the VACS Index were associated with global neurocognition by race/ethnicity. In conclusion, the association between the VACS Index and neurocognitive function differs by ethnic/racial group. Identifying key indicators of HIV-associated neurocognitive impairment by ethnic/racial group might play an important role in furthering our understanding of the biomarkers of neuroAIDS.

Neurocognitive deficits in HIV-infected women and victims of childhood trauma.

The study investigated the behavioral and brain effects of childhood trauma and human immunodeficiency virus (HIV) infection, both separately and in combination, and assessed potential interactions in women who were dually affected. Eighty-three HIV-positive and 47 matched HIV-negative South African women underwent neuromedical, neuropsychiatric, and neurocognitive assessments. Univariate tests of significance assessed if either HIV infection or childhood trauma, or the combination, had a significant effect on neurocognitive performance. The majority of women were Black (96%) and had an average age of 30 years. An analysis of covariance revealed significant HIV effects for the Hopkins Verbal Learning Test (HVLT) learning and delay trials (p < 0.01) and the Halstead Category Test (HCT) (p < 0.05). A significant trauma effect was seen on the HVLT delay trial (p < 0.05). The results provide evidence for neurocognitive dysfunction in memory and executive functions in HIV-infected women and memory disturbances in trauma exposed women.

The overlap of systemic lupus erythematosus and sickle cell disease: report of two cases and a review of the literature.

Two cases of Afro-Caribbean women with an association of sickle cell disease (SCD) and systemic lupus erythematosus (SLE) are presented. We discuss the clues to the diagnosis of this combination with a review of the literature. Owing to a substantial overlap between the clinical manifestations of the two disorders, the diagnosis of SLE in patients with SCD may be difficult to establish and is often delayed.

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.

Demographic influences and suggested cut-scores for the Beck Depression Inventory in a non-clinical Spanish speaking population from the US-Mexico border region.

The Beck Depression Inventory-I (BDI-I) is a self-report measure of depressive symptomatology that is widely used in both research and clinical settings. While the Spanish language version of the BDI-I is frequently used in the USA, there are currently no available guidelines to determine depressive symptomatology base rates in Spanish speaking populations using this instrument. In the present study, base rates of depressive symptoms and demographic influences on the BDI-I were measured in a non-clinical Spanish speaking population from the US-Mexico border region. A sample of 198 neurologically normal Spanish speaking individuals, mostly of Mexican decent, completed the BDI-I as part of a larger neuropsychological norming study. The results indicated that while there were no effects of age or education on overall BDI-I scores, those with lower education tended to report higher severity of individual symptoms. Consistent with findings in other populations, women endorsed a greater number of depressive symptoms. Therefore separate cut-scores were derived for men and women to represent these differences. Future research should assess the impact of acculturation and socioeconomic stressors on the BDI scores in this mostly immigrant population.

Negative mood and sexual behavior among non-monogamous men who have sex with men in the context of methamphetamine and HIV.

BACKGROUND: Research comparing the independent and combined contextual effects of methamphetamine dependence (METH) and HIV-infection (HIV) on mood and sexual behavior among men who have sex with men (MSM) has been sparse and inconsistent. This study examined the contextual influence of METH, HIV-infection and their combination on mood states and sexual behavior. METHODS: 175 non-monogamous MSM concordant or discordant for METH and HIV were included. Multivariate analysis was conducted to examine mood and sexual behavior differences between groups, as well as to elucidate the relationship between mood and sexual risk behavior and explore the potential moderator (i.e. contextual) effects of METH and/or HIV on this relationship. RESULTS: METH+/HIV+ participants reported condom use less than 25% of the time whereas METH-/HIV+ participants reported condom use 51-75% of the time. METH+ and HIV+ status were associated with higher depression and confusion scores. Univariate regressions revealed negative relationships between mood states (depression, tension, anger, fatigue and confusion) and condom use. Neither METH nor HIV status moderated the relationships between negative mood and condom use. LIMITATIONS: Results are derived from cross-sectional data, sample sizes for each of the four groups were relatively small, and condom use could not be linked to specific sexual practices and/or partner types. CONCLUSION: METH dependence, HIV seropositivity, and negative moods are associated with reduced condom use among non-monogamous MSM. Independent effects of METH dependence and negative mood on condom use suggest that sexual risk reduction interventions for MSM should incorporate multi-faceted approaches, including substance abuse and mental health treatment.

Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy.

OBJECTIVE: To rigorously evaluate the time course of cognitive change in a cohort of individuals with HIV-associated neurocognitive disorders (HAND) initiating combination antiretroviral therapy (CART), and to investigate which demographic, laboratory, and treatment factors are associated with neuropsychological (NP) outcome (or "any NP improvement"). METHODS: Study participants included 37 HIV+ individuals with mild to moderate NP impairment who initiated CART and underwent NP testing at 12, 24, 36, and 48 weeks thereafter. NP change was assessed using a regression-based change score that was normed on a separate NP-stable group thereby controlling for regression toward the mean and practice effect. Mixed-effect regression models adjusting for loss to follow-up were used to evaluate the time course of cognitive change and its association with baseline and time-varying predictors. RESULTS: In persons with HAND initiating CART, cognitive improvement happens soon after initiation (13% at week 12), but more often 24, 36, and up to 48 weeks after initiation (up to 41%), with fewer than 5% demonstrating significant worsening. In multivariate analyses, unique predictors of NP improvement included more severe baseline NP impairment and higher CART CNS penetration index. Greater viral load decrease was associated with NP improvement only in univariate analyses. CONCLUSION: Clinically meaningful neuropsychological improvement seemed to peak around 24-36 weeks after combination antiretroviral therapy initiation and was prolonged over the 1-year study period. This study also provides new evidence that benefit may be maximized by choosing antiretroviral medications that reach therapeutic concentrations in the CNS.

Cliniconeuropathologic correlates of human immunodeficiency virus in the era of antiretroviral therapy.

The objective of this study was to examine the spectrum of human immunodeficiency virus (HIV) brain pathology and its clinical correlates in the antiretroviral era. We carried out a cross-sectional survey, analyzing prospective clinical and neuropathological data collected by the National NeuroAIDS Tissue Consortium (NNTC), comprising 589 brain samples from individuals with advanced HIV disease collected from 1999 onwards. We assessed gender, ethnicity/race, mode of transmission, age, year of death, nadir CD4, plasma viral load, last antiretroviral regimen, presence of parenchymal HIV brain pathology, HIV-associated neurocognitive disorder, and major depressive disorder. We compared cohort demographic variables with Centers for Disease Control and Prevention US HIV/AIDS statistics and examined associations of parenchymal HIV brain pathology with demographic, clinical, and HIV disease factors. With regard to Centers for Disease Control and Prevention US data, the NNTC was similar in age distribution, but had fewer females and African Americans and more Hispanics and men who have sex with men. Only 22% of the brains examined were neuropathologically normal. Opportunistic infections occurred in 1% to 5% of the cohort. Parenchymal HIV brain pathology was observed in 17.5% of the cohort and was associated with nadir CD4 and plasma viral load. Brains without parenchymal HIV brain pathology often had other noninfectious findings or minimal nondiagnostic abnormalities that were associated with HIV-associated neurocognitive disorder. Clinically, 60% of the cohort reported a lifetime episode of major depressive disorder and 88% had a HIV-associated neurocognitive disorder. No pathological finding correlated with major depressive disorder. Both antiretroviral treatment regimen and elevated plasma HIV viral load were associated with presence of parenchymal HIV brain pathology; however, multivariate analyses suggest a stronger association with plasma viral load. The frequency of HIV brain pathology was lower than previous pre-antiretroviral reports, and was predicted by lower nadir CD4 and higher plasma viral load. Noninfectious pathologies and minimal changes correlated with HIV-associated neurocognitive disorder, suggesting a shift in pathogenesis from florid HIV replication to other, diverse mechanisms.

Variable patterns of neuropsychological performance in HIV-1 infection.

Based upon prior findings with group means, a "prototypical pattern" of neuropsychological results with HIV infection has emerged: impaired executive functioning, motor skills, speed of information processing, and learning, with intact memory retention, most language skills, and visuospatial functioning. We examined neuropsychological results from 553 HIV+ adults to determine the number of patterns seen among individuals with HIV infection. Factor analysis of a relatively comprehensive neuropsychological battery identified 6 component factors: verbal memory (VeM), visual memory (ViM), processing speed (PS), attention/working memory (A/WM), executive function (EF), and motor (M). These factor scores were submitted to hierarchical cluster analysis, to determine the appropriate number of clusters or patterns in the cohort. Final cluster membership was then determined by K-means analysis, based on the Lange, Iverson, Senior, and Chelune (2002) method. A 6-cluster solution was found to be most appropriate. The definitions of the clusters were based upon ipsative scoring of factor scores to indicate relative strengths and weaknesses (independent of overall level of performance): Cluster 1: strong EF; Cluster 2: strong M, weak VeM and EF; Cluster 3: strong PS, weak ViM and EF; Cluster 4: strong VeM, weak M; Cluster 5: strong A/WM; Cluster 6: strong VeM, weak EF. Neuropsychological-impairment rates differed across clusters, but all 6 clusters contained substantial numbers of impaired and unimpaired individuals. Cluster membership was not explained by demographic variables or psychiatric or neuromedical confounds. Thus, there does not appear to be a single, prototypical pattern of neuropsychological impairment associated with HIV infection for this battery of representative neuropsychological tests.

Low CSF leptin levels are associated with worse learning and memory performance in HIV-infected men.

OBJECTIVE: The main objective of this study was to investigate the association between human CSF leptin levels and neuropsychological (NP) performance in the setting of HIV infection. We hypothesized that human CSF leptin levels positively correlate with NP performance. BACKGROUND: Leptin is an adipocyte-derived hormone that influences brain development and function, particularly learning and memory, in the mouse model. The extent to which leptin contributes to neurocognitive functioning in humans is less clear. METHOD: A cross-sectional evaluation of CSF leptin and NP performance was performed. Leptin levels in CSF and serum samples from 59 HIV-positive men were measured by ELISA. Comprehensive, standardized NP testing was used to determine impairment status in global and specific domains. RESULTS: Lower CSF leptin levels and reduced leptin uptake into the central nervous system (CNS) correlated with impaired learning and memory performance in both univariate and multivariate analyses. In multivariate analyses, lower CSF leptin levels and reduced CNS leptin uptake were associated with worse NP performance in learning and memory, adjusting for CD4 nadir, antiretroviral treatment exposure, and HIV RNA levels in CSF. CONCLUSIONS: Low CSF leptin levels are associated with poorer performance in learning and memory among HIV-infected men adjusting for usual predictors of HIV-associated neurocognitive impairment. This association is consistent with prior in vitro and animal data suggesting leptin has a trophic or facilitatory role in the hippocampus, above and beyond its role in hypothalamic regulation.

Updated research nosology for HIV-associated neurocognitive disorders.

In 1991, the AIDS Task Force of the American Academy of Neurology published nomenclature and research case definitions to guide the diagnosis of neurologic manifestations of HIV-1 infection. Now, 16 years later, the National Institute of Mental Health and the National Institute of Neurological Diseases and Stroke have charged a working group to critically review the adequacy and utility of these definitional criteria and to identify aspects that require updating. This report represents a majority view, and unanimity was not reached on all points. It reviews our collective experience with HIV-associated neurocognitive disorders (HAND), particularly since the advent of highly active antiretroviral treatment, and their definitional criteria; discusses the impact of comorbidities; and suggests inclusion of the term asymptomatic neurocognitive impairment to categorize individuals with subclinical impairment. An algorithm is proposed to assist in standardized diagnostic classification of HAND.

Demographically corrected norms for the Brief Visuospatial Memory Test-revised and Hopkins Verbal Learning Test-revised in monolingual Spanish speakers from the U.S.-Mexico border region.

The large number of primary Spanish speakers both in the United States and the world makes it imperative that appropriate neuropsychological assessment instruments be available to serve the needs of these populations. In this article we describe the norming process for Spanish speakers from the U.S.-Mexico border region on the Brief Visuospatial Memory Test-revised and the Hopkins Verbal Learning Test-revised. We computed the rates of impairment that would be obtained by applying the original published norms for these tests to raw scores from the normative sample, and found substantial overestimates compared to expected rates. As expected, these overestimates were most salient at the lowest levels of education, given the under-representation of poorly educated subjects in the original normative samples. Results suggest that demographically corrected norms derived from healthy Spanish-speaking adults with a broad range of education, are less likely to result in diagnostic errors. At minimum, demographic corrections for the tests in question should include the influence of literacy or education, in addition to the traditional adjustments for age. Because the age range of our sample was limited, the norms presented should not be applied to elderly populations.

Cognitive deficits and degeneration of interneurons in HIV+ methamphetamine users.

The cellular basis for cognitive deficits in HIV+ patients with and without a history of methamphetamine (METH) use is unclear. We found that HIV+ METH users had more severe loss of interneurons that was associated with cognitive impairment. Compared with other markers, loss of calbindin and parvalbumin interneurons in the frontal cortex was the most significant correlate to memory deficits, suggesting a role in neurobehavioral alterations of HIV+ METH users.

Significance testing of a cluster of multivariate binary variables: comparison of the tripartite T index to three common similarity measures.

Similarity measures quantify resemblance between pairs of items when each consists of a pattern of two-state (eg, presence versus absence) variables. Numerous similarity measures, many of which are straightforward to calculate and interpret, have been developed and characterized. Methods for testing if items within a specified cluster are significantly more similar to each other than to items outside the cluster have not been extensively developed for binary responses, but a permutation test procedure using a measure of distinctness is available to do this. We compare three well known similarity measures, the Dice, Jaccard and simple matching coefficients, with the more complex tripartite T similarity index recently proposed by Tulloss. Each measure is used in significance tests of whether hypothesized subsets of items are legitimately grouped for resemblance. Theoretically derived measures reflecting diverse scenarios found in medical research and data from neuropsychological research illustrate the methods. Results for the tripartite T measure were comparable to the other methods in some settings, and essentially the same as the Dice coefficient overall when compared theoretically and on the same clinical data. Some shortcomings with the Tulloss algorithm were found and limit the usefulness of the tripartite T index in medical applications.

Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine.

OBJECTIVE: To examine the contribution of hepatitis C virus (HCV) infection to neurocognitive dysfunction in individuals with comorbid HIV infection or methamphetamine (METH) dependence. METHODS: Neurocognitive functioning was examined in 430 study participants who were either normal controls or had HCV infection, HIV infection, history of METH dependence, or combinations of these factors as risks for cognitive deficits. RESULTS: Rates of global and domain-specific neuropsychological (NP) impairment increased with the number of risk factors. HCV serostatus was a significant predictor of NP performance both globally and in the areas of learning, abstraction, and motor skills, with trends in speeded information processing and delayed recall. HCV serostatus did not predict scores in attention/working memory or verbal fluency. CONCLUSION: Hepatitis C virus infection contributes to the neuropsychological deficits observed among HIV-infected and stimulant-dependent populations.

Neurocognitive dysfunction predicts postmortem findings of HIV encephalitis.

OBJECTIVE: To investigate the value of antemortem cognitive functioning in predicting postmortem evidence of HIV encephalitis (HIVE). METHODS: Thirty-nine subjects were assessed during life with a comprehensive neuropsychological battery and went on to autopsy within 18 months of testing. Cognitive impairment was determined by blind clinical ratings, based on demographically corrected test scores. Presence of HIVE was based on postmortem immunocytochemical detection of the viral protein gp41 or by measurement of HIV RNA by PCR in multiple brain areas as well as by histopathologic evidence such as microgliosis, presence of multinucleated giant cells, and myelin pallor in several brain regions. RESULTS: The sensitivity and specificity of neurocognitive impairment in detecting the occurrence of HIVE were 67 and 92%. Eighteen of 19 subjects with antemortem neurocognitive impairment had evidence of HIV-related brain disease (positive predictive value = 95%). CONCLUSION: Neuropsychological assessment can help select HIV-positive patients for treatment of CNS disease.

Utility of a composite measure to detect problematic alcohol use in persons with traumatic brain injury.

OBJECTIVES: To examine factors complicating the study of alcohol-related effects in traumatic brain injury (TBI) patients and to evaluate a composite measure to categorize such patients according to degree of alcohol-related problems. DESIGN: Inception cohort. SETTING: Level I trauma center. PATIENTS: Consecutively hospitalized adult TBI patients (n = 156; 73% men; 87% Caucasian; mean age, 30yr; mean education, 12yr). Selection criteria required objective evidence of brain trauma; minimum survival of 1 month postinjury; age 15 years or older; and English speaking. MAIN OUTCOME MEASURES: An index of problematic drinking based on a measure created by combining blood-alcohol level, quantity-frequency of consumption, and the Short Michigan Alcoholism Screening Test. Preinjury characteristics were obtained through structured interview. RESULTS: Participants with highly problematic drinking showed poorer premorbid psychosocial functioning, including lower educational attainment, greater likelihood of problems with the law, lower perceived social support, and greater prevalence of other substance abuse. CONCLUSION: The composite index is useful in identifying problematic drinkers among TBI patients. Results have implications for interpreting and planning research on the role of alcohol in TBI outcomes.

Relationship of psychosocial factors to HIV disease progression.

Based on the existing empirical evidence that psychosocial variables may predict the course of human immunodeficiency virus (HIV) illness, disease progression (described by advance in symptoms, decline in CD4+ cell count, and mortality) in 414 HIV-positive (HIV+) males was studied using Cox Proportional Hazards Models (survival analysis). Depressive symptoms predicted shorter longevity after controlling for symptoms and CD4+ cell count. Large social network sizes predicted longevity among those with acquired immune deficiency syndrome (AIDS)-defining symptoms at baseline, but not among other subjects. Therefore, psychosocial variables and affective states may be related to disease outcome only during later stages of HIV disease. Although the results provide support for psychoneuroimmunologic effects in HIV, other confounding explanations may still apply.

Fears and fearfulness in children and adolescents: a genetic analysis of twin data.

A sample of 175 same sex dizygotic pairs and 144 monozygotic twin pairs aged between 8:00 and 18:00 completed the Fear Survey Schedule for Children--Revised. The heritabilities were significant for Fear of the Unknown (h2 = 0.46, p less than 0.001), Fear of Injury and Small Animals (h2 = 0.46, p less than 0.001), Fear of Danger (h2 = 0.34, p less than 0.001) and for Total Fear Score (h2 = 0.29, p less than 0.001). Multiple regression was used to estimate the heritability of extreme fearfulness (h2g). For each of the fear factors the values of h2g were of similar magnitude to those of h2 suggesting that there is no evidence of greater genetic influences at more extreme levels of fearfulness.