Abstract
HIV-associated neurocognitive disorder (HAND) describes a spectrum of behavioural, motor and cognitive disturbances that can occur secondary to HIV infection. Less severe forms of the disorder persist despite advances in antiretroviral medication efficacy and availability. Childhood trauma (CT) may predispose individuals to developing HAND. As genetic variation in human apolipoprotein E (ApoE) has been implicated in cognitive decline and may mediate the development of long-term health outcomes following CT, we investigated the influence of ApoE and CT on cognitive function in the context of HIV. One hundred twenty-eight HIV-positive Xhosa women completed the Childhood Trauma Questionnaire-Short Form (CTQ-SF) as well as the HIV Neurobehavioural Research Center neurocognitive test battery. rs7412 and rs429358 were genotyped using KASP assays, and this data was used to determine the ApoE isoform. Baseline differences in demographic and clinical variables according to CT exposure were calculated. Analysis of covariance was used to assess the contributions of CT and ApoE variants, as well as their interaction, to cognitive function. Eighty-eight participants reported experiencing CT. The rs7412 C allele protected against the harmful effect of CT on motor scores using an additive model. The interaction of ApoE ε4 and CT was associated with worse attention/working memory scores. ApoE ε4, alone and in combination with CT, is associated with poorer cognitive function. Further research into this gene-environment interaction may assist in identifying at-risk individuals for targeted interventions.
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The authors declare that they have no conflict of interest.
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This study was supported by a CFAR grant awarded to SS (“Biological Endophenotypes of HIV and Childhood Trauma: A Genetics, Cognitive and Imaging Study”), grant number P30 AI036214. JSW, GS, SMJH and SS are supported by the South African Research Chair in PTSD from the Department of Science and Technology and the National Research Foundation. SMJH and SS are supported by a South African Medical Research Council “SHARED ROOTS” Flagship Project, grant MRC-RFA-FSP-01-2013/SHARED ROOTS.
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Womersley, J.S., Spies, G., Seedat, S. et al. Childhood trauma interacts with ApoE to influence neurocognitive function in women living with HIV. J. Neurovirol. 25, 183–193 (2019). https://doi.org/10.1007/s13365-018-0700-y
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DOI: https://doi.org/10.1007/s13365-018-0700-y