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While peripheral viral loads can be largely controlled by combination antiretroviral therapy, a significant number of people with HIV (PWH) suffer from HIV-associated neurocognitive disorders (HAND). Cocaine use is a major risk factor for becoming HIV infected, and data have shown that HIV+ cocaine user individuals have worse neurocognitive impairments than those observed from either disease alone. The HIV protein Tat and cocaine synergize to cause damage to neurons in the brain, but astrocytes in the central nervous system (CNS) are an understudied population in these individuals. Importantly, astrocytes support neurons metabolically by supplying key metabolites such as lactate and cholesterol to meet the large energy demands of neurons. Astrocyte-derived lactate is taken up by neurons to serve as a key substrate for ATP production. Additionally, the brain requires an intricate balance of cholesterol to support synaptodendritic communications. Disruption of cholesterol supply and energy deficits have been implicated in brain aging and many neurodegenerative diseases including Alzheimer’s disease. There have been reports of altered brain metabolite profiles in PWH indicative of changes in energy homeostasis. We hypothesized that cocaine and Tat work together to disrupt astrocyte energy metabolism. These changes in energy demand compromise the astrocyte’s ability to support neurons leading to neuronal dysfunction and worsening HAND. Our data show that exposure of astrocytes to cocaine and Tat significantly enhances aerobic glycolysis and decreases lactate production. Our findings also demonstrate that cocaine and Tat decrease astrocyte-derived cholesterol, pointing to a deficiency in cholesterol supply and efflux for use by neurons. These findings are supported in the Tat transgenic mouse model of chronic cocaine use. Taken together, these data uncover novel alterations in the bioenergetics pathway in astrocytes exposed to cocaine and the HIV protein, Tat. Results from these studies point to a new pathway in the CNS that may contribute to HAND in HIV+ cocaine users. / Biomedical Sciences

Sixty families who came to a county mental health center for a substance abuse evaluation for a teenager were interviewed. The parent(s) and teenager were administered the Emotional Cutoff Scale, a paper-and-pencil measure. The functioning of each parent was assessed by the researcher through the Global Assessment of Functioning. The child was evaluated on the Child and Family Assessment Scale, an eight dimension scale. Data were gathered and analyzed through a correlational matrix. Significant correlations at P>.01 were found for degree of cutoff of the mother from her mother and father and her level of self-functioning but not with the level of impairment of the teenager. The sample of fathers did not result in significant correlations. / Ed. D.

Substance-abusing individuals have been shown to perform poorer on decision-making tasks than non-substance abusing individuals (e.g. Bechara et al., 2001; Grant, Contoreggi, & London, 2000; Sanfey, Loewenstein, McClure, & Cohen, 2006). Research suggests that this difference in performance is likely due to cognitive deficits resulting from impaired functioning of the frontal lobes. Previous research suggests that two important cognitive processes regarding decision making are reversal learning (e.g. Fellows and Farah, 2005) and working memory (e.g. Hinson, Jameson, and Whitney, 2002; Jameson, Hinson, and Whitney, 2004). The purpose of the current research project was to better understand how these processes affect performance on a decision making task and to determine if a previously administered executive stressor can impact current decision making performance. One hundred thirty six individuals categorized as having either high or low working memory functioning were randomly assigned to complete one of three modified Stroop tasks (Stressor, Priming, and Control). Following completion of the modified Stroop task participants completed the Iowa Gambling Task, which is a task requiring appropriate decision making skills to complete successfully. Statistical analyses examining the quantity and frequency of cards drawn from each deck during the IGT suggested that there was no difference in performance between individuals receiving different modified Stroop tasks or high or low working memory functioning. Analyses examining the monetary outcome of performance on the IGT suggest that there may have been no differential effect between the Stressor and Priming groups, but that these active groups may have performed differently than the Control group. Within the Low working memory block, participants in these active groups may have performed worse than Control group participants, but within the High working memory block participants in these active groups may have performed better than Control group participants. These findings are discussed with regards to previous similar investigations as well as within the broader literature of decision making. Limitations of the current study as well as implications for future investigations are also discussed. / Ph. D.