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 Neurobehavioral 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.

The relationship between potentially traumatic or stressful events, HIV infection and neurocognitive impairment (NCI): a systematic review of observational epidemiological studies

“…The average age for fourteen of fifteen studies, (one study reported the age range only) was 40 years. Eight were all-female studies (Malan-Muller et al, 2013 ; Rubin et al, 2017 , 2015 , 2016 ; Spies et al, 2016 , 2012 ; Spies, Fennema-Notestine, Cherner, & Seedat, 2017 ; Womersley, Spies, Seedat, & Hemmings, 2019 ) and two were all-male studies (Deiss et al, 2019 ; Pukay-Martin, Cristiani, Saveanu, & Bornstein, 2003 ), with the remainder (five studies) including both men and women (Clark, Arce Renteria, Hegde, & Morgello, 2018 ; Clark et al, 2012 ; Kapetanovic et al, 2020 ; Lin et al, 2011 ; Watson et al, 2019 ).…”

“…There were ten case-control studies (Clark et al, 2012 ; Kapetanovic et al, 2020 ; Malan-Muller et al, 2013 ; Pukay-Martin et al, 2003 ; Rubin et al, 2017 , 2015 ; Spies et al, 2016 , 2012 , 2017 ; Watson et al, 2019 ) and five cross-sectional studies (Clark et al, 2018 ; Deiss et al, 2019 ; Lin et al, 2011 ; Rubin et al, 2016 ; Womersley et al, 2019 ). Eight studies were longitudinal in design (Malan-Muller et al, 2013 ; Rubin et al, 2017 , 2015 , 2016 ; Spies et al, 2016 , 2012 , 2017 ; Womersley et al, 2019 ) but only one of these presented longitudinal data examining the relationship between childhood trauma and HIV and change in cognition over time (Spies et al, 2017 ) and one examined the relationship between perceived stress and PTSD and NCI over time (Rubin et al, 2017 ).…”

“…Of the fifteen studies, seven studies (Clark et al, 2018 , 2012 ; Malan-Muller et al, 2013 ; Spies et al, 2016 , 2012 , 2017 ; Womersley et al, 2019 ) examined early life trauma only (experienced before the age of 18) and seven studies (Deiss et al, 2019 ; Lin et al, 2011 ; Pukay-Martin et al, 2003 ; Rubin et al, 2017 , 2015 , 2016 ; Watson et al, 2019 ) examined adult-onset trauma only (experienced after age 18). Only one study considered both early life and adult-onset trauma (Kapetanovic et al, 2020 ) but no studies sought to separate out the effects of early-onset versus adult-onset trauma.…”

“…Regarding verbal fluency, five studies demonstrated an association with PTEs and SLEs (Malan-Muller et al, 2013 ; Pukay-Martin et al, 2003 ; Rubin et al, 2017 ; Spies et al, 2016 , 2017 ; Watson et al, 2019 ). For attention/working memory, seven studies demonstrated an association with trauma (Clark et al, 2018 ; Kapetanovic et al, 2020 ; Lin et al, 2011 ; Pukay-Martin et al, 2003 ; Spies et al, 2016 ; Watson et al, 2019 ; Womersley et al, 2019 ); four studies demonstrated an association with processing speed, (Clark et al, 2012 ; Pukay-Martin et al, 2003 ; Spies et al, 2016 , 2012 ); six studies demonstrated an association with learning (Rubin et al, 2017 , 2015 , 2016 ; Spies et al, 2016 , 2012 ; Watson et al, 2019 ) while three studies demonstrated an association with motor function (Pukay-Martin et al, 2003 ; Spies et al, 2016 ; Womersley et al, 2019 ). Two studies (Deiss et al, 2019 ; Pukay-Martin et al, 2003 ) reported an association between global NCI and trauma (i.e.…”

“…In studies that included comparison groups with and without trauma (viz. childhood trauma) (Womersley et al, 2019 ), PTSD (Deiss et al, 2019 ), and TBI (Lin et al, 2011 ), PLWHA who were trauma exposed consistently performed more poorly than their counterparts without trauma.…”