Effects of unhealthy alcohol use on brain morphometry and neurocognitive function among people with HIV.

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 HIV-positive 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.

Hazardous or harmful alcohol use and reward processing in people with HIV.

The intersecting epidemics of HIV and hazardous or harmful alcohol use (HAU) can have significant detrimental consequences. Both HIV and HAU have independent negative influences on executive function. Dysfunction in reward processing may play a role in these co-occurring epidemics. In this cross-sectional case-control study, we investigated the association of HAU with reward processing amongst people with HIV (PWH). We investigated the function of the ventral-striatal reward system using a functional MRI (fMRI) monetary incentive delay (MID) task in a sample of 60 South African adults (mean age 32.7 years): 42 living with HIV and on ART (21 with harmful alcohol use [HIV + HAU], 21 without [HIV-HAU]) and 18 healthy controls, matched for age, gender, and resident community. Education significantly influenced task performance, with those with a secondary level of education demonstrating a greater increase in reaction time (p = 0.048) and accuracy (p = 0.002) than those without. There were no significant differences in reward anticipation in the ventral striatum (VS) between HIV + HAU, HIV-HAU, and healthy controls when controlling for level of education. There were also no significant differences in reward outcome in the orbitofrontal cortex (OFC) between HIV + HAU, HIV-HAU, and healthy controls when controlling for level of education. In a sample of South African adults, we did not demonstrate significant differences in reward anticipation in the VS and reward outcome in the OFC in PWH, with and without HAU, and controls. Factors, such as task performance, education, and depression may have influenced our results. Further studies are needed to better delineate the potential links between HIV, HAU, and depression and reward system function.

Effects of HIV and childhood trauma on brain morphometry and neurocognitive function.

A wide spectrum of neurocognitive deficits characterises HIV infection in adults. HIV infection is additionally associated with morphological brain abnormalities affecting neural substrates that subserve neurocognitive function. Early life stress (ELS) also has a direct influence on brain morphology. However, the combined impact of ELS and HIV on brain structure and neurocognitive function has not been examined in an all-female sample with advanced HIV disease. The present study examined the effects of HIV and childhood trauma on brain morphometry and neurocognitive function. Structural data were acquired using a 3T Magnetom MRI scanner, and a battery of neurocognitive tests was administered to 124 women: HIV-positive with ELS (n = 32), HIV-positive without ELS (n = 30), HIV-negative with ELS (n = 31) and HIV-negative without ELS (n = 31). Results revealed significant group volumetric differences for right anterior cingulate cortex (ACC), bilateral hippocampi, corpus callosum, left and right caudate and left and right putamen. Mean regional volumes were lowest in HIV-positive women with ELS compared to all other groups. Although causality cannot be inferred, findings also suggest that alterations in the left frontal lobe, right ACC, left hippocampus, corpus callosum, left and right amygdala and left caudate may be associated with poorer neurocognitive performance in the domains of processing speed, attention/working memory, abstraction/executive functions, motor skills, learning and language/fluency with these effects more pronounced in women living with both HIV and childhood trauma. This study highlights the potential contributory role of childhood trauma to brain alterations and neurocognitive decline in HIV-infected individuals.

Brief online negative affect focused functional imagery training (FIT) improves four-week drinking outcomes in hazardous student drinkers: A pilot randomised controlled trial replication in South Africa.

Background: Previous study has shown that functional imagery training (FIT) to utilise positive mental imagery in response to negative affect could improve alcohol-related outcomes. The current study aimed to replicate whether this negative affect focused FIT would improve alcohol-related outcomes in hazardous student drinkers in South Africa at four-week follow-up. Methods: 50 hazardous student drinkers who reported drinking to cope with negative affect were randomised into two groups. The active group (n = 25) was trained online over two weeks to respond to personalised negative drinking triggers by retrieving a personalised adaptive strategy they might use to mitigate negative affect, whereas the control group (n = 25) received standard risk information about binge drinking. Outcome measures including alcohol consumption, drinking motives, anxiety and depression, self-efficacy and use of protective behavioural strategies were obtained at baseline and four-week follow-up. Results: FIT effects were revealed by three significant group-by-timepoint interactions in a per-protocol analysis: there was a significant decrease in depressive symptoms, drinking to cope and drinking for social reasons from baseline to follow-up in the active group, but not the control group. No effects were observed on alcohol consumption, self-efficacy, protective behaviour strategies and anxiety. Conclusions: Preliminary evidence supports that online negative affect focused FIT can improve depression as well as coping and social drinking motives in South African hazardous student drinkers who drank to cope, at four-week follow-up, suggesting that the principles of this FIT approach might be adapted and incorporated into a clinical intervention to test for efficacy in mitigating substance use problems.

Altered white matter integrity in the corpus callosum in adults with HIV: a systematic review of diffusion tensor imaging studies.

We systematically reviewed studies comparing differences in the integrity of the corpus callosum in adults with HIV compared to healthy controls, using Diffusion Tensor Imaging (DTI), using search engines Science Direct, Web of Science and PubMed. The search terms used were "HIV", "corpus callosum", and a variation of either "DTI" or "Diffusion Tensor Imaging" with or without the term "adults". We specifically examined the corpus callosum as it is the largest white matter tract in the brain, plays a primary role in cognition, and has been shown to be morphologically altered in people living with HIV. Lower fractional anisotropy (FA) was consistently found in the corpus callosum in people with HIV compared to controls. As most studies used only FA as a measure of diffusion, it would be informative for future research if other DTI metrics, such as mean diffusivity (MD), were also investigated as these metrics may be more sensitive markers of HIV-related neuropathology.

FKBP5 intron 7 methylation is associated with higher anxiety proneness and smaller right thalamus volume in adolescents.

Dysregulation of stress response systems may mediate the detrimental effects of childhood trauma (CT) on mental health. FKBP5 regulates glucocorticoid receptor sensitivity and exerts pleiotropic effects on intracellular signaling, neurobiology and behavior. We investigated whether CT, alone and in combination with rs1360780 genotype, is associated with altered FKBP5 methylation and whether CT-associated methylation profiles are associated with anxiety proneness (AP) and structural brain volumes. Ninety-four adolescents completed the Childhood Trauma Questionnaire, and a composite AP score was generated from the Childhood Anxiety Sensitivity Index and the State-Trait Anxiety Inventory-Trait measure. Mean methylation values for 12 regulatory regions and 25 individual CpG sites were determined using high-accuracy measurement via targeted bisulfite sequencing. FKBP5 rs1360780 genotype and structural MRI data were available for a subset of participants (n = 71 and n = 75, respectively). Regression models revealed an inverse association between methylation of three intron 7 CpG sites (35558438, 35558566 and 35558710) and right thalamus volume. CpG35558438 methylation was positively associated with AP scores. Our data indicate that an intron 7 methylation profile, consistent with lower FKBP5 expression and elevated high sensitivity glucocorticoid receptor levels, is associated with higher AP and smaller right thalamus volume. Research into the mechanisms underlying the intron 7 methylation-thalamus volume relationship, and whether it confers increased risk for long-term psychopathology by altering the regulatory threshold of stress responding, is required.

Childhood emotional neglect and oxytocin receptor variants: Association with limbic brain volumes.

Objectives: Childhood emotional neglect (EN) is a predictor for the development of affective disorders. Oxytocin (OXT) may mediate the interplay between EN and changes in stress biological systems, brain development, and mental health outcomes. We investigated, in a cross-sectional study, the associations between EN, (epi)genetic variation in the OXT receptor (OXTR) gene, and amygdalar and hippocampal volumes, two brain regions implicated in emotional processing.Methods: We recruited 63 Caucasian South African adults (35 women) with and without social anxiety disorder. Childhood EN was assessed using the Childhood Trauma Questionnaire. rs53576 and rs2254298 genotypes, as well as methylation status, was determined using DNA purified from whole blood. Bilateral amygdalar and hippocampal volumes were determined by structural magnetic resonance imaging. The relationships between these variables were investigated using linear regression.Results: The interaction of the rs2254298 A risk allele and EN was nominally associated with reduced left hippocampal volume. The rs2254298 A risk allele was independently associated with reduced bilateral amygdalar volumes. We found no association between EN, OXTR methylation and amygdalar or hippocampal volumes. The rs53576 GG risk genotype was, however, associated with decreased OXTR methylation.Conclusions: The rs2254298 A allele may increase susceptibility to the structural brain effects of EN.

Posttraumatic stress disorder, social anxiety disorder and childhood trauma: Differences in hippocampal subfield volume.

Volume-based hippocampal findings in Social Anxiety Disorder (SAD) and Posttraumatic Stress Disorder (PTSD) have been inconsistent, with very little investigation of hippocampal subfields. We assessed the effects of early childhood trauma on hippocampal subfields in participants with SAD with and without early childhood trauma and PTSD, compared to healthy controls. The sample comprised 26 participants SAD with early childhood trauma, 22 participants with SAD without early childhood trauma, 17 with PTSD secondary to early childhood trauma and 25 control participants. We used Freesurfer version 6 to determine hippocampal subfield volumes. Findings included significant reduction in right parasubiculum volume between the PTSD group secondary to early childhood trauma and the SAD group without early childhood trauma, as well as a significant reduction in left HATA (Hippocampal Amygdala Transition Area) volume between PTSD with early childhood trauma compared to controls, as well as compared to SAD with early childhood trauma. These findings did withstand correction for multiple resting using the false discovery rate. Our findings of an association of reduced volumes in the parasubiculum and HATA regions with PTSD secondary to childhood trauma are interesting. Further work should investigate whether parasubiculum and HATA regional volume reductions in PTSD are a specific effect of early childhood trauma or a specific manifestation of PTSD pathology. Further work should also be undertaken to determine if hippocampal subfield atrophy is associated with SAD in the setting of early childhood maltreatment.

Hippocampal and amygdala volumes in adults with posttraumatic stress disorder secondary to childhood abuse or maltreatment: A systematic review.

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 -0.66 and -0.67 for the left and right hippocampus (p<0.00001 and p=0.002) and -1.08 and -1.15 for the left and right amygdala, (p=0.013 and p=0.003), respectively. Confidence intervals were -0.93,-0.39 and -1.26,-0.29 for the left and right hippocampus, respectively. For the amygdala, confidence intervals were -1.92,-0.23 and -1.19, -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.