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Childhood trauma interacts with ApoE to influence neurocognitive function in women living with HIV.

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 ?4 and CT was associated with worse attention/working memory scores. ApoE ?4, 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.

SUBMITTER: Womersley JS

PROVIDER: S-EPMC7010592 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Childhood trauma interacts with ApoE to influence neurocognitive function in women living with HIV.

Womersley Jacqueline S JS Spies Georgina G Seedat Soraya S Hemmings Sian M J SMJ

Journal of neurovirology 20181126 2

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 f ...[more]

PMID: 30478798

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Project description:BackgroundNeurocognitive impairment (NCI) persists among women living with HIV. Food insecurity is also common among women and may be an important modifiable contributor of NCI.ObjectiveThe goal of this study was to determine the association of food insecurity with neurocognitive function among women living with or without HIV.MethodsFrom 2013 to 2015, we analyzed data from a cross-sectional sample from the Women's Interagency HIV Study (WIHS). Measures included food insecurity and a comprehensive neuropsychological test battery assessing executive function, processing speed, attention/working memory, learning, memory, fluency, and motor function. We conducted multivariable linear regressions to examine associations between food insecurity and domain-specific neurocognitive performance, adjusting for relevant sociodemographic, behavioral, and clinical factors.ResultsParticipants (n = 1,324) were predominantly HIV seropositive (68%), Black/African-American (68%) or Hispanic (16%), and low income (48% reported <$12,000/y), with a median age of 49.6 y (IQR = 43.1, 55.5). Approximately one-third (36%, n = 479) were food insecure. Food insecurity was associated with poorer executive function (b = -1.45, SE = 0.58, P ≤ 0.01) and processing speed (b = -1.30, SE = 0.59, P ≤ 0.05). HIV serostatus modified the association between food insecurity and learning, memory, and motor function (P values <0.05). Food insecurity was positively associated with learning among women living with HIV (b = 1.58, SE = 0.77, P ≤ 0.05) and negatively associated with motor function among HIV-negative women (b = -3.57, SE = 1.08, P ≤ 0.001).ConclusionsFood insecurity was associated with domain-specific neurocognitive function in women, and HIV serostatus modified associations. Food security may be an important point of intervention for ethnically diverse women with low socioeconomic status. Longitudinal studies are warranted to determine potential pathways by which food insecurity is associated with neurocognitive function among women living with or at risk for HIV.

Project description:HIV/AIDS is a major public health burden in South Africa, currently affecting an estimated 13.5% of the population. Despite improved access to antiretroviral therapies, HIV-associated neurocognitive disorders (HAND), characterised by a spectrum of neurocognitive impairment, emotional disturbances and motor abnormalities, continue to persist. Gene-environment interactions contribute to HAND pathophysiology and previous research has identified childhood trauma as an environmental risk factor. Dopaminergic signalling in the prefrontal cortex plays a key role in cognitive function. Thus, variants in genes encoding the dopamine transporter (DAT) and catechol-O-methyltransferase (COMT), which are responsible for dopamine transport and metabolism, could represent genetic risk factors for HAND. This study investigated whether the DAT variable number of tandem repeats (VNTR) and COMT Val158Met (rs4680) polymorphisms are associated with longitudinal change in cognitive function in the context of childhood trauma and HIV. Participants (n = 49 HIV-negative and n = 64 HIV-positive women) completed the Childhood Trauma Questionnaire - Short Form (CTQ-SF) and provided blood for genetic analyses. Global cognitive scores were generated from baseline and one-year follow-up assessments. Following polymerase chain reaction, genotypes were determined using gel electrophoresis and confirmed by Sanger sequencing. Baseline global cognitive scores, genotype, HIV status and CTQ-SF scores were regressed on one-year global cognitive scores in regression models. Analysis of variance was used to examine the effect of including predictor variable interactions on model fit. HIV seropositivity was associated with poorer cognitive performance at one-year follow-up (p = 2.46 ×10-4). The combination of HIV and DAT 10-repeat homozygosity (DAT 10/10) was associated with reduced global cognitive scores in longitudinal models (p = 0.010). Including the interaction between DAT 10/10, childhood trauma, and HIV explained significantly more of the variance in longitudinal cognitive scores (p = 0.008). There were no significant associations with the COMT genotype. Our research indicates that childhood trauma and genetic variation in DAT contribute toward the aetiology of HAND. Future studies in larger cohorts are warranted to verify these results.

Dataset Information

Childhood trauma interacts with ApoE to influence neurocognitive function in women living with HIV.

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Childhood trauma interacts with ApoE to influence neurocognitive function in women living with HIV.

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