HIV Nef Expression Down-modulated GFAP Expression and Altered Glutamate Uptake and Release and Proliferation in Astrocytes.

HIV infection of astrocytes leads to restricted gene expression and replication but abundant expression of HIV early genes Tat, Nef and Rev. A great deal of neuroHIV research has so far been focused on Tat protein, its effects on astrocytes, and its roles in neuroHIV. In the current study, we aimed to determine effects of Nef expression on astrocytes and their function. Using transfection or infection of VSVG-pseudotyped HIV viruses, we showed that Nef expression down-modulated glial fibrillary acidic protein (GFAP) expression. We then showed that Nef expression also led to decreased GFAP mRNA expression. The transcriptional regulation was further confirmed using a GFAP promoter-driven reporter gene assay. We performed transcription factor profiling array to compare the expression of transcription factors between Nef-intact and Nef-deficient HIV-infected cells and identified eight transcription factors with expression changes of 1.5-fold or higher: three up-regulated by Nef (Stat1, Stat5, and TFIID), and five down-regulated by Nef (AR, GAS/ISRE, HIF, Sp1, and p53). We then demonstrated that removal of the Sp1 binding sites from the GFAP promoter resulted in a much lower level of the promoter activity and reversal of Nef effects on the GFAP promoter, confirming important roles of Sp1 in the GFAP promoter activity and for Nef-induced GFAP expression. Lastly, we showed that Nef expression led to increased glutamate uptake and decreased glutamate release by astrocytes and increased astrocyte proliferation. Taken together, these results indicate that Nef leads to down-modulation of GFAP expression and alteration of glutamate metabolism in astrocytes, and astrocyte proliferation and could be an important contributor to neuroHIV.

Investigating the psychometric properties of the Suicide Stroop Task.

Behavioral measures are increasingly used to assess suicidal thoughts and behaviors. Some measures, such as the Suicide Stroop Task, have yielded mixed findings in the literature. An understudied feature of these behavioral measures has been their psychometric properties, which may affect the probability of detecting significant effects and reproducibility. In the largest investigation of its kind, we tested the internal consistency and concurrent validity of the Suicide Stroop Task in its current form, drawing from seven separate studies (N = 875 participants, 64% female, aged 12 to 81 years). Results indicated that the most common Suicide Stroop scoring approach, interference scores, yielded unacceptably low internal consistency (rs = -.09-.13) and failed to demonstrate concurrent validity. Internal consistency coefficients for mean reaction times (RTs) to each stimulus type ranged from rs = .93-.94. All scoring approaches for suicide-related interference demonstrated poor classification accuracy (AUCs = .52-.56) indicating that scores performed near chance in their ability to classify suicide attempters from nonattempters. In the case of mean RTs, we did not find evidence for concurrent validity despite our excellent reliability findings, highlighting that reliability does not guarantee a measure is clinically useful. These results are discussed in the context of the wider implications for testing and reporting psychometric properties of behavioral measures in mental health research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Cognition and self-injurious thoughts and behaviors: A systematic review of longitudinal studies.

There is a long tradition in suicide research, accompanied by recent developments in nonsuicidal self-injury (NSSI) research, of examining cognitive processes as potential precursors of risk. But these cognitive processes are often studied separately, and are rarely integrated or directly compared with each other. In an effort to synthesize this literature, this systematic review (n=109 longitudinal studies conducted over the past 10 years) demonstrates how specific cognitive processes predict self-injurious thoughts and behaviors (SITBs), and examines whether intervening on features of cognition may help mitigate SITB risk. Our review reveals that cognitive processes, measured using self-report and behavioral measures, are most often linked to recurrent suicidal ideation. Overall, several patterns emerged. First, SITB-themed cognitions were robust risk factors and proximally associated with SITB outcomes. Second, negatively-valenced cognitive risk factors were the most commonly studied risk factors, relatively robust, and modestly related to SITB outcomes. Third, cognitive deficits (i.e., basic cognitive processes not characterized by thematic content or negative valence) produced mixed findings that suggest a more distal relationship to SITB outcomes. Moreover, our review of treatment articles revealed that while many interventions are informed by the cognitive literature, potential cognitive mechanisms of treatment change are rarely studied. We conclude by outlining key ways that future research can generate more comprehensive cognitive profiles of self-injurious and suicidal individuals.