Publications by authors named "Sarah J Heany"

11 Publications

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Alcohol use is associated with mental health problems and brain structural alterations in adolescents with perinatally acquired HIV infection on ART.

Alcohol 2021 Sep 15. Epub 2021 Sep 15.

Department of Psychiatry and Mental Health, University of Cape Town, South Africa. Electronic address:

Alcohol use, presents unique challenges for HIV-1 treatment in adolescents with perinatally acquired infection. The effects of alcohol on host-virus interaction in the brain and the immune system remains understudied in this population. Adolescents with perinatally acquired HIV infection (PHIV) well established on ART, from the Cape Town Adolescent Antiretroviral Cohort who self-reported alcohol use (PHIV+alcohol) (n=26) were compared to age matched 26 PHIV (PHIV-alcohol) and 26 healthy controls (HC) who reported no use of alcohol. Participants completed clinical investigations including highly-sensitive CRP (hs-CRP), a comprehensive neurocognitive test battery and mental health measures. In addition, we investigated the relationship between alcohol use in PHIV and diffusion tensor imaging (DTI) and structural brain magnetic resonance imaging (MRI) to determine fractional anisotropy (FA), mean diffusivity (MD), grey and white matter volumes and cortical thickness. PHIV (mean age 12,5 years; mean age of ART initiation 3.15 years) reported an occasional weekend drinking pattern of alcohol use. hs-CRP was significantly different between groups, with PHIV+alcohol higher than PHIV-alcohol and HC. General intelligence, attention, working memory, processing speed and executive function were more impaired in the PHIV+alcohol than PHIV alone, with HC having the highest scores. In addition, self-concept was significantly lower in PHIV+alcohol. The Child Behavior Checklist (CBCL) Externalizing behaviour, internalising behaviour and CBCL Total problems were significantly higher in PHIV+alcohol. FA of the superior corona radiata, superior fronto-occipital fasciculus and corpus callosum was significantly lower in PHIV+alcohol compared to PHIV-alcohol and MD of the corona radiata was significantly increased in PHIV+alcohol. The cortical thickness of the lateral orbitofrontal, middle frontal and precentral gyri were significantly lower in PHIV+ alcohol compared to PHIV-alcohol and HC. In conclusion PHIV associated impairments in systemic inflammation, cognitive function, mental health and changes in brain structure may be exacerbated by alcohol use, even if only occasional use. However, the study is cross-sectional, which is not able to distinguish between cause and effect.
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http://dx.doi.org/10.1016/j.alcohol.2021.09.006DOI Listing
September 2021

Accelerated epigenetic aging in adolescents living with HIV is associated with altered development of brain structures.

J Neurovirol 2021 Feb 7. Epub 2021 Feb 7.

Department of Neurology, David Geffen School of Medicine, at the University of California, Los Angeles, CA, USA.

We recently demonstrated that adolescents perinatally infected with HIV-1 (PHIV+) have accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock. However, whether epigenetic age acceleration in PHIV+ impacts brain development at the macro- and microstructural levels of brain anatomy has not been studied. We report on a cross-sectional study of PHIV+ enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC). The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 180 PHIV+ aged 9 to 12 years. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration (AgeAccelerationResidual) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent T1 structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). In order to investigate the associations of chronological age, sex, epigenetic age acceleration and treatment variables (CNS penetration effectiveness score (CPE)) of antiretroviral regimen on brain structure in PHIV+, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, cortical surface area and DTI measures of white matter microstructural integrity. The mean DNAm age (16.01 years) of the participants was higher than their mean chronological age (10.77 years). Epigenetic age acceleration contributed more to regional alterations of brain volumes, cortical thickness, cortical surface areas and neuronal microstructure than chronological age, in a range of regions. CPE positively contributed to volume of the brain stem. Understanding the drivers of epigenetic age acceleration could lead to valuable insights into structural brain alterations, and the persistence of neurocognitive disorders in seen in PHIV+ .
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http://dx.doi.org/10.1007/s13365-021-00947-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346577PMC
February 2021

Accelerated epigenetic aging in adolescents from low-income households is associated with altered development of brain structures.

Metab Brain Dis 2020 12 15;35(8):1287-1298. Epub 2020 Jul 15.

SA MRC Unit on Risk & Resilience in Mental Disorders, Cape Town, South Africa.

The relationship between cognitive performance, macro and microstructural brain anatomy and accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock in healthy adolescents has not been studied. Healthy adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study were studied cross sectionally. The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 44 adolescents aged 9 to 12 years old. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration residual (AAR) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent neurocognitive testing, T1 structural magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI). Correlation tests were run between the two epigenetic aging measures and 10 cognitive functioning domains, to assess for differences in cognitive performance as epigenetic aging increases. In order to investigate the associations of epigenetic age acceleration on brain structure, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, and cortical surface area, as well as DTI measures of white matter microstructural integrity. In addition to negatively affecting two cognitive domains, visual memory (p = .026) and visual spatial acuity (p = .02), epigenetic age acceleration was associated with alterations of brain volumes, cortical thickness, cortical surface areas and abnormalities in neuronal microstructure in a range of regions. Stress was a significant predictor (p = .029) of AAR. Understanding the drivers of epigenetic age acceleration in adolescents could lead to valuable insights into the development of neurocognitive impairment in adolescents.
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http://dx.doi.org/10.1007/s11011-020-00589-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606536PMC
December 2020

Neural responses in the pain matrix when observing pain of others are unaffected by testosterone administration in women.

Exp Brain Res 2020 Mar 21;238(3):751-759. Epub 2020 Feb 21.

Institute of Education and Child Studies, Leiden University, Leiden, The Netherlands.

There is evidence of testosterone having deteriorating effects on cognitive and affective empathic behaviour in men and women under varying conditions. However, whether testosterone influences empathy for pain has not yet been investigated. Therefore, we tested neural responses to witnessing others in pain in a within-subject placebo-controlled testosterone administration study in healthy young women. Using functional magnetic resonance imaging, we provide affirming evidence that an empathy-inducing paradigm causes changes in the activity throughout the pain circuitry, including the bilateral insula and anterior cingulate cortex. Administration of testosterone, however, did not influence these activation patterns in the pain matrix. Testosterone has thus downregulating effects on aspects of empathic behaviour, but based on these data does not seem to influence neural responses during empathy for others' pain. This finding gives more insight into the role of testosterone in human empathy.
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http://dx.doi.org/10.1007/s00221-020-05749-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080706PMC
March 2020

Neural correlates of maintenance working memory, as well as relevant structural qualities, are associated with earlier antiretroviral treatment initiation in vertically transmitted HIV.

J Neurovirol 2020 02 3;26(1):60-69. Epub 2019 Sep 3.

Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.

There is evidence of HIV affecting cognitive functioning across age groups, with adult studies showing related deficits in frontostriatal and hippocampal regional activity. Additionally, delayed initiation of antiretroviral treatment (ART) has been associated with poorer cognitive outcomes in HIV-infected youth. Little is known, however, of the neural correlates underlying such cognitive deficits in youth populations. We investigated maintenance working memory-related brain activity in South African HIV-infected youth and controls, and the effect of ART initiation age on underlying structures. Sixty-four perinatally infected youth (ages 9-12) and 20 controls (ages 9-13) underwent functional magnetic resonance imaging (fMRI) while completing 1-back and 0-back blocks of the N-back task. At an uncorrected p value threshold of 0.001, the HIV-infected group showed decreased activation in the left superior temporal gyrus, pre- and postcentral gyri, insula, and putamen as well as bilateral hippocampus, and mid cingulum. The HIV patients with delayed ART initiation showed less activation during processing conditions in the mid cingulum; left inferior parietal gyrus; and right inferior frontal, bilateral thalamic, and superior temporal regions. When these regions were tested for structural differences, the mid cingulum and right inferior frontal gyrus, insula, and thalamus were found to have less cortical thickness, surface area, or volume in the group with delayed ART initiation. Regional differences between HIV-infected youth and controls noted in the N-back task are consistent with impairments in structures involved in maintenance working memory. These data support earlier ART initiation in perinatally infected individuals.
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http://dx.doi.org/10.1007/s13365-019-00792-5DOI Listing
February 2020

Initiation of antiretroviral therapy after the critical neuronal developmental period of the second postnatal year affects white matter microstructure in adolescents living with HIV.

J Neurovirol 2019 04 7;25(2):254-262. Epub 2019 Jan 7.

Department of Psychiatry and Mental Health, University of Cape Town, Anzio Road Observatory, Cape Town, 7925, South Africa.

Rapid maturation of major white matter pathways occurs in the first 2 years of life, indicating a critical neuronal developmental period. The impact of initiating antiretroviral therapy (ART) in children perinatally infected with HIV-1, after the age of 2 years on neurocognitive functioning and white matter development in adolescence has not been studied. Forty-six adolescents who initiated ART during the first 2 years of life (< 2 years) and 79 adolescents who initiated ART after 2 years of age (> 2 years), with perinatally acquired HIV were enrolled in the Cape Town Adolescent Antiretroviral Cohort. Adolescents completed a comprehensive neurocognitive battery testing a number of cognitive domains. Diffusion tensor imaging (DTI) was done to determine fractional anisotropy (FA), mean diffusivity (MD), axial diffusion (AD), and radial diffusion (RD) in a region of interest analysis. Neurocognitive performance was similar between adolescents who initiated ART < 2 years or > 2 years. There was a trend towards attention (p = .07) and working memory (p = .05) being poorer in the group who initiated ART > 2 years. FA was lower in the > 2-year group in the superior corona radiata (p = .03), and the external capsule (p = .04). MD was higher in the > 2-year group in the cerebral peduncle (p = .02), the superior corona radiata (p = .01), and the superior fronto-occipital fasciculus (p = .03). RD was higher in the > 2-year group in the superior corona radiata (p = .02), the cerebral peduncle (p = .01), and the superior fronto-occipital fasciculus (p = .01). However, the higher AD in the > 2-year group in the superior corona radiata was not in the expected direction (p = .01). Initiation of ART after the neuronal development period of the second postnatal year is associated with white matter alterations on neuroimaging.
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http://dx.doi.org/10.1007/s13365-018-0712-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549713PMC
April 2019

Effects of testosterone administration on threat and escape anticipation in the orbitofrontal cortex.

Psychoneuroendocrinology 2018 10 30;96:42-51. Epub 2018 May 30.

Department of Psychiatry and Mental Health, University of Cape Town, South Africa; Department of Experimental Psychology, Utrecht University, The Netherlands. Electronic address:

Recent evidence suggests that the steroid hormone testosterone can decrease the functional coupling between orbitofrontal cortex (OFC) and amygdala. Theoretically this decoupling has been linked to a testosterone-driven increase of goal-directed behaviour in case of threat, but this has never been studied directly. Therefore, we placed twenty-two women in dynamically changing situations of escapable and inescapable threat after a within-subject placebo controlled testosterone administration. Using functional magnetic resonance imaging (fMRI) we provide evidence that testosterone activates the left lateral OFC (LOFC) in preparation of active goal-directed escape and decouples this OFC area from a subcortical threat system including the central-medial amygdala, hypothalamus and periaqueductal gray. This LOFC decoupling was specific to threatening situations, a point that was further emphasized by an absence of such decoupling in a second experiment focused on resting-state connectivity. These results not only confirm that testosterone administration decouples the LOFC from the subcortical threat system, but also show that this is specifically the case in response to acute threat, and ultimately leads to an increase in LOFC activity when the participant prepares a goal-directed action to escape. Together these results for the first time provide a detailed understanding of functional brain alterations induced by testosterone under threat conditions, and corroborate and extend the view that testosterone prepares the brain for goal-directed action in case of threat.
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http://dx.doi.org/10.1016/j.psyneuen.2018.05.038DOI Listing
October 2018

Perinatally acquired HIV infection accelerates epigenetic aging in South African adolescents.

AIDS 2018 07;32(11):1465-1474

MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Mental Health, University of Cape Town, J-Block, Groote Schuur Hospital, Observatory, Cape Town, South Africa.

Objective: Recent studies demonstrate that infection with the HIV-1 is associated with accelerated aging effects in adults according to a highly accurate epigenetic biomarker of aging known as epigenetic clock. However, it is not yet known whether epigenetic age acceleration occurs as early as adolescence in perinatally HIV-infected (PHIV+) youth.

Design: Observational study of PHIV and HIV-uninfected adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study.

Methods: The Illumina EPIC array was used to generate blood DNA methylation data from 204 PHIV and 44 age-matched, uninfected (HIV-) adolescents aged 9-12 years old. The epigenetic clock software and method was used to estimate two measures of epigenetic age acceleration. Each participant completed a comprehensive neuropsychological test battery upon enrollment to Cape Town Adolescent Antiretroviral Cohort.

Results: HIV is associated with biologically older blood in PHIV+ adolescents according to both measures of epigenetic age acceleration. One of the measures, extrinsic epigenetic age acceleration, is negatively correlated with measures of cognitive functioning (executive functioning, working memory, processing speed).

Conclusion: Overall, our results indicate that epigenetic age acceleration in blood can be observed in PHIV+ adolescents and that these epigenetic changes accompany poorer cognitive functioning.
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http://dx.doi.org/10.1097/QAD.0000000000001854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026068PMC
July 2018

The neural correlates of Childhood Trauma Questionnaire scores in adults: A meta-analysis and review of functional magnetic resonance imaging studies.

Dev Psychopathol 2018 10 11;30(4):1475-1485. Epub 2017 Dec 11.

University of Cape Town.

Childhood maltreatment, including abuse and neglect, may have sustained effects on the integrity and functioning of the brain, alter neurophysiological responsivity later in life, and predispose individuals toward psychiatric conditions involving socioaffective disturbances. This meta-analysis aims to quantify associations between self-reported childhood maltreatment and brain function in response to socioaffective cues in adults. Seventeen functional magnetic resonance imaging studies reporting on data from 848 individuals examined with the Childhood Trauma Questionnaire were included in a meta-analysis of whole-brain findings, or a review of region of interest findings. The spatial consistency of peak activations associated with maltreatment exposure was tested using activation likelihood estimation, using a threshold of p < .05 corrected for multiple comparisons. Adults exposed to childhood maltreatment showed significantly increased activation in the left superior frontal gyrus and left middle temporal gyrus, and decreased activation in the left superior parietal lobule and the left hippocampus. Although hyperresponsivity to socioaffective cues in the amygdala and ventral anterior cingulate cortex in correlation with maltreatment severity is a replicated finding in region of interest studies, null results are reported as well. The findings suggest that childhood maltreatment has sustained effects on brain function into adulthood, and highlight potential mechanisms for conveying vulnerability to development of psychopathology.
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http://dx.doi.org/10.1017/S0954579417001717DOI Listing
October 2018

Testosterone abolishes implicit subordination in social anxiety.

Psychoneuroendocrinology 2016 10 14;72:205-11. Epub 2016 Jul 14.

Department of Psychology, Utrecht University, The Netherlands; Department of Psychiatry and Mental Health, University of Cape Town, South Africa; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.

Neuro-evolutionary theories describe social anxiety as habitual subordinate tendencies acquired through a recursive cycle of social defeat and submissive reactions. If so, the steroid hormone testosterone might be of therapeutic value, as testosterone is a main force behind implicit dominance drive in many species including humans. We combined these two theories to investigate whether the tendency to submit to the dominance of others is an implicit mechanism in social anxiety (Study-1), and whether this can be relieved through testosterone administration (Study-2). Using interactive eye-tracking we demonstrate that socially anxious humans more rapidly avert gaze from subliminal angry eye contact (Study-1). We replicate this effect of implicit subordination in social anxiety in an independent sample, which is subsequently completely abolished after a single placebo-controlled sublingual testosterone administration (Study-2). These findings provide crucial evidence for hormonal and behavioral treatment strategies that specifically target mechanisms of dominance and subordination in social anxiety.
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http://dx.doi.org/10.1016/j.psyneuen.2016.07.203DOI Listing
October 2016

A quantitative and qualitative review of the effects of testosterone on the function and structure of the human social-emotional brain.

Metab Brain Dis 2016 Feb 16;31(1):157-67. Epub 2015 Jun 16.

Department of Psychiatry and Mental Health, University of Cape Town, Groote Schuur Hospital, J2, Anzio road, Observatory, Cape Town, South Africa.

Social and affective research in humans is increasingly using functional and structural neuroimaging techniques to aid the understanding of how hormones, such as testosterone, modulate a wide range of psychological processes. We conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of testosterone administration, and of fMRI studies that measured endogenous levels of the hormone, in relation to social and affective stimuli. Furthermore, we conducted a review of structural MRI i.e. voxel based morphometry (VBM) studies which considered brain volume in relation to testosterone levels in adults and in children. In the included testosterone administration fMRI studies, which consisted of female samples only, bilateral amygdala/parahippocampal regions as well as the right caudate were significantly activated by social-affective stimuli in the testosterone condition. In the studies considering endogenous levels of testosterone, stimuli-invoked activations relating to testosterone levels were noted in the bilateral amygdala/parahippocampal regions and the brainstem. When the endogenous testosterone studies were split by sex, the significant activation of the brain stem was seen in the female samples only. Significant stimuli-invoked deactivations relating to endogenous testosterone levels were also seen in the right and left amygdala/parahippocampal regions studies. The findings of the VBM studies were less consistent. In adults larger volumes in the limbic and temporal regions were associated with higher endogenous testosterone. In children, boys showed a positive correlation between testosterone and brain volume in many regions, including the amygdala, as well as global grey matter volume, while girls showed a neutral or negative association between testosterone levels and many brain volumes. In conclusion, amygdalar and parahippocampal regions appear to be key target regions for the acute actions of testosterone in response to social and affective stimuli, while neurodevelopmentally the volumes of a broader network of brain structures are associated with testosterone levels in a sexually dimorphic manner.
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http://dx.doi.org/10.1007/s11011-015-9692-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718938PMC
February 2016
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