Georgina Spies | Stellenbosch University (original) (raw)

Papers by Georgina Spies

Childhood maltreatment (CM) is linked to impairments in various domains of social functioning. He... more Childhood maltreatment (CM) is linked to impairments in various domains of social functioning. Here, we argue that it is critical to identify factors that underlie impaired social functioning as well as processes that mediate the beneficial health effects of positive relationships in individuals exposed to CM. Key research recommendations are presented, focusing on: (1) identifying attachment-related alterations in specific inter-and intrapersonal processes (e.g., regulation of closeness and distance) that underlie problems in broader domains of social functioning (e.g., lack of perceived social support) in individuals affected by CM; (2) identifying internal (e.g., current emotional state) and external situational factors (e.g., cultural factors, presence of close others) that modulate alterations in specific social processes; and (3) identifying mechanisms that explain the positive health effects of intact social functioning. Methodological recommendations include: (1) assessing social processes through interactive and (close to) real-life assessments inside and outside the laboratory; (2) adopting an interdisciplinary, lifespan perspective to assess social processes, using multimethod assessments; (3) establishing global research collaborations to account for cultural influences on social processes and enable replications across laboratories and countries. The proposed line of research will contribute to globally develop and refine interventions that prevent CM and further positive relationships, which-likely through buffering the effects of chronic stress and corresponding allostatic load-foster resilience and improve mental and physical health, thereby reducing personal suffering and the societal and economic costs of CM and its consequences. Interventions targeting euthymia and psychological well-being are promising therapeutic concepts in this context.

Background: HIV/AIDS and potentially traumatic events (PTEs) or stressful life events (SLEs) and/... more Background: HIV/AIDS and potentially traumatic events (PTEs) or stressful life events (SLEs) and/or PTSD are independently associated with neurocognitive impairment (NCI). Literature suggests that HIV and PTE/SLE exposure independently and consistently affect various domains of cognition including language ability, working memory and psychomotor speed. There are limited data on the interaction between HIV infection and PTEs and their combined effect on NCI. Objective: In this systematic review, we synthesise evidence for the combined effect of HIV infection and PTEs and SLEs and/or post-traumatic stress disorder (PTSD) on NCI of people living with HIV/AIDS (PLWHA) from high-, middle-and low-income countries. Method: Our inclusion criteria were observational epidemiological studies (case-control, cohort and cross-sectional designs) that investigated the interaction of HIV infection, PTEs and SLEs and/or PTSD and specifically their combined effect on NCI in adults. We searched a number of electronic databases including Pubmed/Medline, PsycINFO, Scopus and Global Health using the search terms: cognition, HIV/AIDS, observational studies, trauma and permutations thereof. Results: Fifteen studies were included in the review, of which the majority were conducted in high-income countries. Ten of the fifteen studies were conducted in the United States of America (USA) and five in South Africa. Seven of these focused on early life stress/childhood trauma. The remaining studies assessed adult-onset PTEs and SLEs only. Eight studies included women only. Overall, the studies suggest that PTE and SLE exposure and/or PTSD are a significant risk factor for NCI in adults living with HIV, with impairments in memory and executive functions being the most likely consequence of PTE and SLE exposure. Conclusion: These findings highlight the need for trauma screening and for the integration of trauma-focused interventions in HIV care to improve outcomes. La relación entre eventos potencialmente traumáticos o estresantes, infección por VIH y deterioro neurocognitivo (NCI): una revisión sistemática de estudios epidemiológicos observacionales Antecedentes: El VIH/SIDA y los eventos potencialmente traumáticos (PTEs) o los eventos estresantes de la vida (SLEs) y/o TEPT se asocian independientemente con el deterioro neurocognitivo (NCI). La literatura sugiere que la exposición al VIH, PTE y SLE afecta de manera independiente y consistente varios dominios de la cognición, incluida la capacidad del lenguaje, la memoria de trabajo y la velocidad psicomotora. Hay datos limitados sobre la interacción entre la infección por VIH y los PTE, y su efecto combinado sobre el NCI. Objetivo: En esta revisión sistemática sintetizamos evidencia del efecto combinado de la infección por VIH, PTEs y SLEs, y/o TEPT en el NCI de personas que viven con VIH/SIDA (PLWHA) en países de ingresos altos, medios y bajos. Método: Nuestros criterios de inclusión fueron estudios epidemiológicos observacionales (diseño de caso-control, cohortes y diseños transversales) que investigaron la interacción de la infección por VIH, PTEs y SLEs y/o TEPT, y específicamente su efecto combinado sobre el NCI en adultos. Se realizaron búsquedas en varias bases de datos electrónicas, que incluyeron a Pubmed/Medline, PsycINFO, Scopus y Global Health, utilizando los términos de búsqueda: cognición, VIH/SIDA, estudios de observación, trauma y permutaciones de los mismos. Resultados: Quince estudios se incluyeron en la revisión, de los cuales la mayoría se realizaron en países de altos ingresos. Diez de los quince estudios fueron realizados en los Estados Unidos de América (EE.UU.) y cinco en Sudáfrica. Siete de éstos se centraron en el estrés de la vida temprana/trauma infantil. Los estudios restantes evaluaron PTEs y SLEs cuya ARTICLE HISTORY

Your article is protected by copyright and all rights are held exclusively by Springer Science+Bu... more Your article is protected by copyright and all rights are held exclusively by Springer Science+Business Media, LLC, part of Springer Nature. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to selfarchive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".

HIV-associated neurocognitive disorders (HAND) present a challenge in South Africa where the burd... more HIV-associated neurocognitive disorders (HAND) present a challenge in South Africa where the burden of HIV infection is the highest. Identification of biological correlates of HAND is required to improve diagnosis and inform interventions. Telomeres maintain genomic integrity and their shortening is a marker of biological aging sensitive to environmental influences. This study examined relative telomere length (rTL) as a predictor of cognitive function in the context of HIV and childhood trauma (CT), a risk factor for HAND. Two hundred and eighty-six women completed a neurocognitive assessment battery and the Childhood Trauma Questionnaire-Short Form (CTQ). Quantitative polymerase chain reaction for amplification of telomeric repeats and the reference gene human beta-globin was used to calculate rTL. Neurocognitive and rTL assessments were repeated at 1 year in 110 participants. Cross-sectional and longitudinal data were assessed using linear and mixed models, respectively. Participants with HIV (n = 135 in cross-sectional and n = 62 in longitudinal study groups) reported more severe CT and had shorter baseline rTL compared to seronegative controls. Participants without HIV had a greater 1-year decline in rTL. Global cognitive and attention/working memory scores declined in participants with HIV. Our data indicate that baseline rTL in the context of CT and HIV did not predict decline in cognitive scores. HIV-associated pathophysiological processes driving cognitive decline may also engage mechanisms that protect against telomere shortening. The results highlight the importance of examining biological correlates in longitudinal studies.

Individual impacts of alcohol misuse and HIV on brain structure and function have been well demon... more Individual impacts of alcohol misuse and HIV on brain structure and function have been well demonstrated; however, the potential compounded effect of these conditions is seldom considered, despite the high prevalence of alcohol use in HIV infection. We aimed to determine the effects of unhealthy alcohol use on brain morphometry and cognitive function amongst people with HIV (PWH). In 27 (50.9%) HIV-positive users of alcohol and 26 (49.1%) HIV-positive abstainers from alcohol, results revealed significant differences for left and right amygdala (p < 0.01), left and right hippocampus (p = 0.05), left and right posterior cingulate (p < 0.01), left and right precuneus (p < 0.01), left insula (p < 0.01), left and right caudate (p < 0.01), right thalamus (p < 0.01), and corpus callosum (p < 0.05). Mean volume of these regions was significantly smaller in HIVpositive alcohol users compared to HIV-positive abstainers. Homogeneity of slopes ANCOVA revealed significant associations between anterior cingulate cortex, precuneus, amygdala, hippocampus, and insula volumes and cognitive function in the domains of learning and delayed recall, motor function, speed of information processing, executive function, attention/ working memory, and language. Among PWH, unhealthy alcohol use is associated with negative effects on brain structure and cognitive function.

HIV-associated neurocognitive disorder (HAND) describes a spectrum of behavioural, motor and cogn... more 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.

Background: The Childhood Trauma Questionnaire-Short Form (CTQ-SF) is widely used around the worl... more Background: The Childhood Trauma Questionnaire-Short Form (CTQ-SF) is widely used around the world but no norms have been established for South African users of the CTQ. The CTQ has been employed in South Africa but not yet validated. The present study aims to address this gap. There is great need in both clinical and research settings for an assessment tool that adequately measures childhood trauma, a sensitive and challenging construct to measure. Objective: This study explores the psychometric properties of the CTQ-SF in an all-female cohort living with and without HIV infection in South Africa, the first study of its kind in this population. Participants and setting: The CTQ-SF was administered to 314 women (170 HIV uninfected; 144 HIV infected) in Cape Town, South Africa. Method: Internal consistency of the CTQ-SF was determined by Cronbach alpha coefficients. Using Lisrel, a confirmatory factor analysis (CFA) was performed, followed by an exploratory factor analysis (EFA) to explore an alternative factor structure model in this cohort. Results: For the group as a whole, the model fit was acceptable but not good. However, for the sub-sample of women living with HIV, the CFA revealed poor model fit. The EFA revealed a three-factor model, with mostly stable factor loadings for four of the five subscales. However, the Physical Neglect (PN) subscale cross loaded on two of the three factors. Conclusion: Our findings revealed an alternative factor structure from the original model in this study cohort. The PN subscale does not have stable factor loadings and is not homogenous. The original instrument may therefore benefit from revision for use in this population. Measures such as the CTQ can be informative for preventative strategies in HIV-infected or at-risk youth and for clinical interventions aimed at mitigating the negative psychological sequelae of childhood maltreatment.

Background: Mood and anxiety disorders are highly prevalent and comorbid with HIV/AIDS. However, ... more Background: Mood and anxiety disorders are highly prevalent and comorbid with HIV/AIDS. However, there is a paucity of research on the effectiveness of cognitive-behavioural interventions (CBI) for common mental disorders in HIV-infected adults. The present study sought to review the existing literature on the use of CBI for depression and anxiety in HIV-positive adults and to assess the effect size of these interventions. Methods: We did duplicate searches of databases (from inception to 17-22 May 2012). The following online databases were searched: PubMed, The Cochrane Central Register of Controlled Trials and PsychArticles. Results: We identified 20 studies suitable for inclusion. A total of 2886 participants were enroled in these studies, of which 2173 participants completed treatment. The present review of the literature suggests that CBI may be effective in the treatment of depression and anxiety in individuals living with HIV/AIDS. Significant reductions in depression and anxiety were reported in intervention studies that directly and indirectly targeted depression and/or anxiety. Effect sizes ranged from 0.02 to 1.02 for depression and 0.04 to 0.70 for anxiety. Limitations: Some trials included an immediate postintervention assessment but no follow-up assessments of outcome. This omission makes it difficult to determine whether the intervention effects are sustainable over time. Conclusion: The present review of the literature suggests that CBI may have a positive impact on the treatment of depression and anxiety in adults living with HIV/AIDS.

We investigated changes in cognitive function and physical health and behavioural outcomes (HIV d... more We investigated changes in cognitive function and physical health and behavioural outcomes (HIV disease progression, health-seeking behaviour, adherence to HIV medications and risky sexual behaviour) at baseline and 12 months later among 1126 Ugandan adults living with HIV. Overall, cognitive function improved from baseline to follow-up, except for gait speed, which was slower at follow-up compared to baseline. There were improvements in physical health and behavioural outcomes by follow-up, with greater improvements among individuals on ART compared to those not on ART. Change in gait speed over time significantly predicted risky sexual behaviours at follow-up. This is the first study to investigate the longitudinal relationships between cognitive function and health outcomes among Ugandan adults living with HIV and provide insights into the possible links between cognitive function and negative clinical and behavioural health outcomes in people living with HIV.

Accumulating evidence indicates that variants in genes that encode for neural mechanisms involved... more Accumulating evidence indicates that variants in genes that encode for neural mechanisms involved in PTSD may confer risk for PTD (Almli, Fani, Smith, & Ressler, 2014; Marinova & Maercker, 2015). The hypothalamic-pituitary-adrenal (HPA)-axis plays a key role in neuroendocrine stress response and HPA-dysregulation is thought to underlie PTSD pathogenesis (van Zuiden, Kavelaars, Geuze, Olff, & Heijnen, 2013). The HPA axis is vulnerable to persistent changes in function following childhood trauma, as evidenced by dysregulated glucocorticoid cortisol release. Genetic variants of the glucocorticoid receptor (GR), for example, single nucleotide polymorphisms (SNPs) in the FK506 binding protein 5 (FKBP5) gene, appear to contribute to inter-individual variability in HPA-axis function (Castro-Vale, van Rossum, Machado, Mota-Cardoso, & Carvalho, 2016a). FKBP5 SNPs have been shown to interact with childhood abuse to predict adult PTSD symptoms (Binder et al., 2008; Watkins et al., 2016a). Interestingly, preliminary data exists demonstrating an association between FKBP5 and PTD (Koenen et al., 2005). This study investigates potential associations between selected FKBP5-alleles and childhood trauma exposure in predicting the

Attitudes among South African university staff and students towards disclosing secondary genetic ... more Attitudes among South African university staff and students towards disclosing secondary genetic findings For the SHARED ROOTS Group 1 2 3 Your article is protected by copyright and all rights are held exclusively by Springer-Verlag GmbH Germany, part of Springer Nature. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".

Your article is protected by copyright and all rights are held exclusively by Journal of NeuroVir... more Your article is protected by copyright and all rights are held exclusively by Journal of NeuroVirology, Inc.. This e-offprint is for personal use only and shall not be selfarchived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".

Objective: Gene-environment interactions contribute to the development of HIV-associated neurocog... more Objective: Gene-environment interactions contribute to the development of HIV-associated neurocognitive disorders. We examined whether childhood trauma, apolipoprotein E isoforms and viral protein R (Vpr) variants were associated with change in cognitive performance. Seventy-three seropositive women completed neuropsychological assessments at baseline and 1-year follow-up. We conducted genetic analyses using DNA obtained from blood and calculated risk scores based on Vpr amino acid 37, 41 and 55 variants that were previously associated with cognitive performance. Results: Global cognitive scores declined significantly over the 1-year study period (p = 0.029). A reduction in global cognitive scores was associated with childhood trauma experience (p = 0.039).

There are individual differences in health outcomes following exposure to childhood maltreatment,... more There are individual differences in health outcomes following exposure to childhood maltreatment, yet constant individual variance is often assumed in analyses. Among 286 Black, South African women, the association between childhood maltreatment and neurocognitive health, defined here as neurocognitive performance (NP), was first estimated assuming constant variance. Then, without assuming constant variance, we applied Goldstein's method (Encyclopedia of statistics in behavioral science, Wiley, 2005) to model "complex level-1 variation" in NP as a function of childhood maltreatment. Mean performance in some tests of information processing speed (Digit-symbol, Stroop Word, and Stroop Color) lowered with increasing severity of childhood maltreatment, without evidence of significant individual variation. Conversely, we found significant individual variation by severity of childhood maltreatment in tests of information processing speed (Trail Making Test) and executive function (Color Trails 2 and Stroop Color-Word), in the absence of mean differences. Exploratory results suggest that the presence of individual-level heterogeneity in neurocognitive performance among women exposed to childhood maltreatment warrants further exploration. The methods presented here may be used in a person-centered framework to better understand vulnerability to the toxic neurocognitive effects of childhood maltreatment at the individual level, ultimately informing personalized prevention and treatment. Only a proportion of individuals exposed to traumatic events develop adverse mental health conditions 1 , even though global surveys suggest that most people are exposed to life-threatening events 2. There has been significant progress in understanding sources of this heterogeneity from the life-course perspective 3. Additional progress has been made using approaches that estimate population heterogeneity, most notably by using latent growth mixture modelling (LGMM) 4-6. The LGMM approach, which basically separates a general population of individuals into subgroups characterized by distinct patters of change over time, has been applied to a wide body of traumatic stressors ranging from wartime combat exposure 7 , job loss 8 , spousal and child bereavement 9 , campus shootings 10 , and natural disasters 11. These studies have suggested that in part, heterogeneity in post-exposure outcomes can be explained by differences among individuals across domains as varied as cognitive style 12,13 , self-enhancement 14 , and subjective well-being 15. Identifying these individual difference domains has clinical and public health implications because it can inform the early identification of individuals who might be vulnerable to adverse outcomes, ultimately informing prevention strategies to avert downstream adverse outcomes 16,17 .

We systematically reviewed differences in hippocampal and amygdala volumes between adults with ch... more We systematically reviewed differences in hippocampal and amygdala volumes between adults with childhood maltreatment-related posttraumatic stress disorder (PTSD) and healthy controls. Using the terms "adults", "MRI", "magnetic resonance imaging", with "posttraumatic stress disorder" "PTSD", "child abuse", and "child maltreatment", we conducted searches on several electronic databases. We identified 10 studies that met our inclusion criteria; 7 of which were included in a meta-analysis of hippocampal volume and 4 that were included in a meta-analysis of amygdala volume. Mean hippocampal and amygdala volumes were used to determine effect sizes. We found bilateral reduction of both the hippocampus and amygdala in the PTSD group compared to healthy controls, with effect sizes of À 0.66 and À 0.67 for the left and right hippocampus (po0.00001 and p ¼0.002) and À 1.08 and À 1.15 for the left and right amygdala, (p ¼0.013 and p ¼0.003), respectively. Confidence intervals were À 0.93, À0.39 and À 1.26, À 0.29 for the left and right hippocampus, respectively. For the amygdala, confidence intervals were À 1.92, À 0.23 and À 1.19, À 0.39 for the left and right amygdala. The relatively few studies available for analysis is a limitation. Additionally, sex diverse MRI studies in PTSD are needed to determine whether sex plays a significant role in the hippocampal effects associated with childhood-onset trauma.

The present study sought to assess the relationship between depressive symptomatology and resilie... more The present study sought to assess the relationship between depressive symptomatology and resilience among women infected with HIV and to investigate whether trauma exposure (childhood trauma, other discrete lifetime traumatic events) or the presence of post-traumatic stress symptomatology mediated this relationship.

Objective: Demographically corrected norms typically account for the effects of age, education, a... more Objective: Demographically corrected norms typically account for the effects of age, education, and in some cases, sex and other factors (e.g. race/ethnicity). However, generalizability of normative standards to different countries and ethnic groups is not universal. This study sought to determine whether demographically specific Zambian neuropsychological norms would generalize to a group of South African women. Method: 212 English-Xhosa bilingual, South African (SA) women were administered a comprehensive neuropsychological (NP) test battery in either English or Xhosa. We examined rates of "impairment" using Global Deficit Scores (GDS) based upon published, demographically corrected norms from a nearby African country (Zambia). Using multiple regression, we examined the extent to which Zambian norms "corrected" for the effects of age and education in this SA sample. Results: Compared to the normative standards from Zambia, the South African women performed somewhat worse than expected on a few test measures and better than expected on others, but their GDS and associated "impairment" rates were close to what was seen in Zambia. Demographically corrected Zambian norms adequately adjusted for the effects of age and years of education in this sample of SA women, with the exception that Zambian norms appeared to "under correct" for the positive effects of years of education on tests of information processing speed. Conclusions: Demographically corrected norms developed for Zambia may adequately adjust for the effects of age in SA women. Further research is needed to determine whether additional corrections for education are needed in SA, especially for tests of information processing speed.

The accuracy of the Content should not be relied upon and should be independently verified with p... more The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden.