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Geyer, M. A.

Publications and source records attributed to Geyer, M. A..

2 recordsLinked to original sources

Sustained attention and vigilance deficits associated with HIV and a history of methamphetamine dependence

BackgroundHuman immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy (ART). One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is methamphetamine dependence (METH+). Such dependence may further increase cognitive impairment among PWH, by delaying HIV diagnosis (and thus, ART initiation), which has been posited to account for persistent cognitive impairment among PWH, despite subsequent treatment-related viral load suppression (VLS; [≤]50 copies of the virus per milliliter in plasma or cerebrospinal fluid). This study examined the independent and combined (additive versus synergistic) effects of HIV and history of METH+ on the sustained attention and vigilance cognitive domain, while controlling for VLS. MethodsParticipants included 205 (median age=44 years; 77% males; HIV-/METH- n=67; HIV+/METH - n=49; HIV-/METH+ n=36; HIV+/METH+ n=53) individuals enrolled in the Translational Methamphetamine AIDS Research Center, who completed Conners and the 5- Choice continuous performance tests (CPTs). ResultsMETH+ participants exhibited deficits in sustained attention and vigilance; however, these effects were not significant after excluding participants who had a positive urine toxicology screen for methamphetamine. Controlling for VLS, PWH did not have worse sustained attention and vigilance, but consistently displayed slower reaction times across blocks, relative to HIV-participants. There was no HIV x METH interaction on sustained attention and vigilance. ConclusionsRecent methamphetamine use among METH+ people and detectable viral loads are detrimental to sustained attention and vigilance. These findings highlight the need for prompt diagnosis of HIV and initiation of ART, and METH use interventions.

neuroscience↗

Analysis of Genetically Regulated Gene Expression identifies a trauma type specific PTSD gene, SNRNP35

PTSD has significant genetic heritability; however, it is unclear how genetic risk influences tissue-specific gene expression. We used brain and non-brain transcriptomic imputation models to impute genetically regulated gene expression (GReX) in 9,087 PTSD-cases and 23,811 controls and identified thirteen significant GReX-PTSD associations. The results suggest substantial genetic heterogeneity between civilian and military PTSD cohorts. The top study-wide significant PTSD-association was with predicted downregulation of the Small Nuclear Ribonucleoprotein U11/U12 Subunit 35 (SNRNP35) in the BA9 region of the prefrontal cortex (PFC) in military cohorts. In peripheral leukocytes from 175 U.S. Marines, the observed PTSD differential gene expression correlated with the predicted blood GReX differences for these individuals, and deployment stress downregulated SNRNP35 expression, primarily in Marines with post-deployment PTSD. SNRNP35 is a subunit of the minor spliceosome complex and SNRNP35 knockdown in cells validated its functional importance in U12-intron splicing. Finally, mimicking acute activation of the endogenous stress axis in mice downregulated PFC Snrnp35 expression.

genetics↗