Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup.

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

Fronto-limbic white matter microstructural changes in psychiatrically healthy adults with childhood trauma.

Childhood trauma (CT) may influence brain white matter microstructure; however, few studies have examined the differential impact of distinct CT types on white matter microstructure in psychiatrically healthy adults living in a developing country. In adults without significant medical or psychiatric disorders, we investigated the association(s) between CT, including abuse and neglect, and fractional anisotropy (FA) of limbic tracts previously shown to be associated with CT. Participants underwent diffusion tensor imaging and completed the Childhood Trauma Questionnaire. Multivariate analysis of variance models were used to test the effects of total overall CT, as well as CT subtypes, on FA in six fronto-limbic tracts, adjusting for age, sex, and educational level. The final sample included 69 adults (age 47 ± 17 years; 70% female). Overall, CT had a significant main effect on FA for tracts of interest (p < .001). Greater CT severity was associated with lower FA for the bilateral and left stria terminalis (uncorrected) as well as the bilateral, left, and right anterior limb of the internal capsule (ALIC; corrected). Exposure to total non-violent/deprivational trauma specifically was associated with lower FA of the bilateral, left, and right ALIC, suggesting that distinct types of CT are associated with differential white matter changes in apparently healthy adults. The ALIC predominantly carries fibers connecting the thalamus with prefrontal cortical regions. Microstructural alterations in the ALIC may be associated with functional brain changes, which may be adaptive or increase the risk of accelerated age-related cognitive decline, maladaptive behaviors, and subsyndromal psychiatric symptoms.

EMDR v. other psychological therapies for PTSD: a systematic review and individual participant data meta-analysis.

BACKGROUND: This systematic review and individual participant data meta-analysis (IPDMA) examined the overall effectiveness of eye movement desensitization and reprocessing (EMDR) in reducing posttraumatic stress disorder (PTSD) symptoms, achieving response and remission, and reducing treatment dropout among adults with PTSD compared to other psychological treatments. Additionally, we examined available participant-level moderators of the efficacy of EMDR. METHODS: This study included randomized controlled trials. Eligible studies were identified by a systematic search in PubMed, Embase, PsyclNFO, PTSDpubs, and CENTRAL. The target population was adults with above-threshold baseline PTSD symptoms. Trials were eligible if at least 70% of study participants had been diagnosed with PTSD using a structured clinical interview. Primary outcomes included PTSD symptom severity, treatment response, and PTSD remission. Treatment dropout was a secondary outcome. The systematic search retrieved 15 eligible randomized controlled trials (RCTs); 8 of these 15 were able to be included in this IPDMA (346 patients). Comparator treatments included relaxation therapy, emotional freedom technique, trauma-focused cognitive behavioral psychotherapies, and REM-desensitization. RESULTS: One-stage IPDMA found no significant difference between EMDR and other psychological treatments in reducing PTSD symptom severity (ß = -0.24), achieving response (ß = 0.86), attaining remission (ß = 1.05), or reducing treatment dropout rates (ß = -0.25). Moderator analyses found unemployed participants receiving EMDR had higher PTSD symptom severity at the post-test, and males were more likely to drop out of EMDR treatment than females. CONCLUSION: The current study found no significant difference between EMDR and other psychological treatments. We found some indication of the moderating effects of gender and employment status.

The associations of hair cortisol and DHEA with posttraumatic stress disorder symptoms in refugees.

BACKGROUND: Exposure to traumatic events, ongoing adversity, and posttraumatic stress disorder (PTSD) are associated with altered activity of the hypothalamic-pituitary-adrenal (HPA) axis, but findings are mixed. This may be explained in part by heterogeneity in PTSD symptom profiles. AIM: The aim of this study was to investigate the complex relationships between the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and dehydroepiandrosterone (DHEA) in refugees. METHODS: Adult (18+ years) Syrian refugees with increased levels of distress participating in a randomized controlled trial completed baseline measures to assess traumatic events (trauma checklist), post-displacement stressors (Post-Migration Living Difficulties checklist), symptoms of PTSD (PTSD Checklist for DSM-5; PCL-5), and provided a hair sample for additional stress hormone analyses. We used R-packages qgraph and bootnet to perform network analysis on the number of traumatic events and post-displacement stressors, individual symptoms of PTSD, and HPA-axis hormones cortisol and DHEA. The final network model was corrected for depression severity. RESULTS: 115 (53% male, M age = 36.9, SD = 12.7) of 206 participants provided a hair sample. A higher number of traumatic events was directly associated with three symptoms of the PTSD cluster arousal and reactivity, i.e., sleep disturbance, hypervigilance and physiological reactivity, and with three other PTSD symptoms, namely flashbacks, avoidance of reminders, and self-destructive behavior. A higher number of post-displacement stressors was associated with four symptoms of the PTSD cluster cognition and mood, i.e., trauma-related amnesia, negative beliefs, blaming of self/others, and detachment, as well as with intrusive thoughts, sleep disturbance, hypervigilance, and exaggerated startle response. The number of traumatic events and post-displacement stressors were not associated with cortisol or DHEA. Cortisol was positively associated with two symptoms of the PTSD cluster cognition and mood, i.e., negative beliefs and negative trauma-related emotions, and negatively associated with avoidance of reminders. DHEA was positively associated with restricted affect and with three symptoms of the PTSD symptom cluster arousal and reactivity, i.e., irritability/anger, sleep disturbance, and self-destructive behavior, and negatively associated with avoidance of thoughts. CONCLUSIONS: This study demonstrated that exposure to traumatic events and post-displacement stressors is not related to cortisol and DHEA, but that cortisol and DHEA are differentially related to individual symptoms of PTSD. While lower levels of both cortisol and DHEA were associated with increased avoidance, higher levels of cortisol were mostly associated with symptoms of the PTSD cluster cognition and mood and higher levels of DHEA were mostly associated with symptoms of the PTSD cluster arousal and reactivity. These findings contribute to explaining the variability of findings in the literature on HPA-axis activity in PTSD. ETHICS: The study was approved by the Research Ethics Review Committee at VU Medical Center, the Netherlands (Protocol ID: NL61361.029.17, 7 September 2017) and prospectively registered online (https://www.trialregister.nl/trial/6665).

Relationships between trauma types and psychotic symptoms: A network analysis of patients with psychotic disorders in a large, multi-country study in East Africa.

BACKGROUND: The link between trauma exposure and psychotic disorders is well-established. Further, specific types of trauma may be associated with specific psychotic symptoms. Network analysis is an approach that can advance our understanding of the associations across trauma types and psychotic symptoms. METHODS: We conducted a network analysis with data from 16,628 adult participants (mean age [standard deviation] = 36.3 years [11.5]; 55.8% males) with psychotic disorders in East Africa recruited between 2018 and 2023. We used the Life Events Checklist and the Mini International Neuropsychiatric Interview to determine whether specific trauma types experienced over the life course and specific psychotic symptoms were connected. We used an Ising model to estimate the network connections and bridge centrality statistics to identify nodes that may influence trauma types and psychotic symptoms. RESULTS: The trauma type "exposure to a war zone" had the highest bridge strength, betweenness, and closeness. The psychotic symptom "odd or unusual beliefs" had the second highest bridge strength. Exposure to a war zone was directly connected to visual hallucinations, odd or unusual beliefs, passivity phenomena, and disorganized speech. Odd or unusual beliefs were directly connected to transportation accidents, physical assault, war, and witnessing sudden accidental death. CONCLUSION: Specific trauma types and psychotic symptoms may interact bidirectionally. Screening for psychotic symptoms in patients with war-related trauma and evaluating lifetime trauma in patients with odd or unusual beliefs in clinical care may be considered points of intervention to limit stimulating additional psychotic symptoms and trauma exposure. This work reaffirms the importance of trauma-informed care for patients with psychotic disorders.

Addressing the challenges of integrating care for perinatal depression in primary care in Nigeria.

PURPOSE: This report provides the results of a task-shared approach for integrating care for perinatal depression (PND) within primary maternal and child healthcare (PMCH), including the factors that may facilitate or impede the process. METHODS: This hybrid implementation-effectiveness study guided by the Replicating Effective Programmes framework was conducted in 27 PMCH clinics in Ibadan, Nigeria. The primary implementation outcome was change in the identification rates of PND by primary health care workers (PHCW) while the primary effectiveness outcome was the difference in symptom remission (EPDS score ≤ 5) 6 months postpartum. Outcome measures were compared between two cohorts of pregnant women, one recruited before and the other after training PHCW to identify and treat PND. Barriers and facilitators were explored in qualitative interviews. RESULTS: Identification of PND improved from 1.4% before to 17.4% after training; post-training rate was significantly higher in clinics where PHCW routinely screened using the 2-item patient health questionnaire (24.8%) compared to non-screening clinics (5.6%). At 6-months postpartum, 60% of cohort one experienced remission from depression, compared to 56.5% cohort two [OR-0.9 (95%CI-0.6, 1.3) p = 0.58]. Identified facilitators for successful integration included existence of policy specifying mental health as a component of PHC, use of screening to aid identification and supportive supervision, while barriers included language and cultural attitudes towards mental health and human resource constraints. PHCW were able to make adaptations to address these barriers. CONCLUSIONS: Successful implementation of task-shared care for perinatal depression requires addressing staff shortages and adopting strategies that can improve identification by non-specialist providers. TRIAL REGISTRATION: This study was retrospectively registered 03 Dec 2019. https://doi.org/10.1186/ISRCTN94230307 .

Medical Students' Experiences of Mistreatment by Clinicians and Academics at a South African University.

Phenomenon: Tertiary education in post-apartheid South Africa has faced many challenges regarding class, language, and race. Even though previously white Afrikaans-rooted universities now have a diverse student population, recent student protests have highlighted the ongoing need for decolonization in higher education. In addition, the majority of public hospitals in the country function under significant staffing, infrastructure, and equipment shortages. Although the mistreatment of medical students has been well described internationally, to date no South African data exists. The aim of this study was to identify experiences of mistreatment of medical students by clinicians and academics at a South African university and to describe the type of mistreatment experienced, the perceived mental health effects, and the influence on academic performance, resilience, and students' knowledge of current reporting systems. Approach: A cross-sectional study was conducted through a locally developed online survey of 443 medical students at a South African university in May to June 2018, comprising of both open and closed ended questions. Levels of psychological distress (K10) and resilience (CD-RISC -10) were measured. Chi-square and student t-tests were used for the analysis of associations, and linear regressions were used to assess predictors of psychological distress. Qualitative data were analyzed thematically using the approach described by Braun and Clarke. Findings: Of 800 eligible medical students at Stellenbosch University, 443 students (55.4%) completed the survey. Mistreatment, comprising of being ignored/excluded (83.4%), offensive gestures (75.0%), verbal abuse (65.1%) and discrimination (64.4%), was prevalent and pervasive, and was perpetrated mainly by registrars (46.7%) and other medical staff (43.8%). Mistreatment was associated with psychological distress, which was generally high and more severe for females. Resilience, which was higher for males, moderated the effects of gender and perpetrator type on distress. Only 15% of students who had experienced mistreatment, either directly or indirectly, reported it, of which more than half (52.8%) were not happy with the outcome. Most students (80.9%) were not aware of the systems in place to report mistreatment. Insights: Student mistreatment is more highly prevalent among medical students at a South African university compared with studies conducted internationally. Despite over 20 years of democracy in South Africa, high rates of racial and gender discrimination were reported and descriptions of racial, language and gender discrimination were particularly concerning. Since the findings of this study, an anti-bullying poster-campaign has been initiated at the university as well as an online reporting system.

Identifying genetic loci that are associated with changes in gene expression in PTSD in a South African cohort.

The molecular mechanisms underlying posttraumatic stress disorder (PTSD) are yet to be fully elucidated, especially in underrepresented population groups. Expression quantitative trait loci (eQTLs) are DNA sequence variants that influence gene expression, in a local (cis-) or distal (trans-) manner, and subsequently impact cellular, tissue, and system physiology. This study aims to identify genetic loci associated with gene expression changes in a South African PTSD cohort. Genome-wide genotype and RNA-sequencing data were obtained from 32 trauma-exposed controls and 35 PTSD cases of mixed-ancestry, as part of the SHARED ROOTS project. The first approach utilised 108 937 single-nucleotide polymorphisms (SNPs) (MAF > 10%) and 11 312 genes with Matrix eQTL to map potential eQTLs, while controlling for covariates as appropriate. The second analysis was focused on 5638 SNPs related to a previously calculated PTSD polygenic risk score for this cohort. SNP-gene pairs were considered eQTLs if they surpassed Bonferroni correction and had a false discovery rate <0.05. We did not identify eQTLs that significantly influenced gene expression in a PTSD-dependent manner. However, several known cis-eQTLs, independent of PTSD diagnosis, were observed. rs8521 (C > T) was associated with TAGLN and SIDT2 expression, and rs11085906 (C > T) was associated with ZNF333 expression. This exploratory study provides insight into the molecular mechanisms associated with PTSD in a non-European, admixed sample population. This study was limited by the cross-sectional design and insufficient statistical power. Overall, this study should encourage further multi-omics approaches towards investigating PTSD in diverse populations.

Sex differences in the severity and natural recovery of child PTSD symptoms: a longitudinal analysis of children exposed to acute trauma.

BACKGROUND: Higher levels of PTSD symptoms are present among trauma-exposed females v. males in adulthood; however, much less is known about the emergence of this sex difference during development. METHODS: In a multi-study sample of 7-18-year-olds (n = 3397), we examined the effect of sex and age on the severity of PTSD symptoms after a single incident trauma at 1 month (T1), and on symptom change after a natural recovery period of 3 (T2) and 6 months (T3). PTSD scores were harmonised across measurement types, and linear regressions were used to determine sex and age effects, adjusting for study level variance and trauma type. RESULTS: A sex × age interaction was observed at T1 (p < 0.001) demonstrating that older age was associated with greater PTSD symptom severity in females (ß = 0.008, p = 0.047), but less severe symptoms in males (ß = -0.011, p = 0.014). The same pattern was observed at T2 and T3, with sex differences beginning to emerge by age 12 years. PTSD symptoms decreased naturally by ~25% at T2 with little further improvement by T3. Further, females showed a greater reduction in symptoms at T3 than males, although the same effect was not observed at T2. CONCLUSIONS: Sex differences in PTSD symptoms become apparent during adolescence, due to opposing changes in susceptibility occurring in females and males with age. Understanding the factors contributing to these findings is likely to provide wider insight into sex-specific psychological vulnerability to trauma-related psychopathology.

Neuropsychological Test Norms for the Assessment of HIV-Associated Neurocognitive Impairment Among South African Adults.

Reliable and valid neurocognitive (NC) test batteries that assess multiple domains of cognitive functioning are vital tools in the early detection of HIV-associated NC impairment. The HIV Neurobehavioral Research Center's International Neurobehavioral Battery (HNRC Battery) is one such diagnostic tool and has shown cultural validity in several international neuroHIV studies. However, no published norms are currently available for the full HNRC Battery in South Africa. To accurately interpret NC test results, appropriate reference norms are required. In light of this challenge, data were collected from 500 healthy, HIV-uninfected participants to develop demographically corrected South African norms. When demographically corrected United States of America (U.S.) norms were applied to the performance scores of our neurologically intact, HIV-negative sample, an impairment rate of 62.2% was observed compared to a 15.0% impairment rate when the newly generated South African norms were applied. These results reiterate the findings of other low- and middle-income countries, highlighting the need for localized, country-specific norms when interpreting NC performance.

Sex-Based Contributors to and Consequences of Post-traumatic Stress Disorder.

PURPOSE OF REVIEW: Women are twice as likely to develop post-traumatic stress disorder (PTSD) compared to men after a traumatic experience. The purpose of this mini review was to explore recent research on biological contributors to this sex difference. RECENT FINDINGS: We identified 51 studies published since 2019. Studies found that beyond the influence of sex on the prevalence and symptoms of PTSD, there is evidence for and against sex-based differences in genetic and epigenetic factors (n = 8), brain structure and function (n = 11), neuroendocrine and inflammatory responses (n = 5), and in the role of sleep on emotional memory processing (n = 1). Sex differences were also observed in recovery and during PTSD treatment (n = 16). Finally, there is emerging evidence of sex-differentiated risk for medical and psychiatric comorbidities in PTSD (n = 10). Rapid advances are being made using integrated multidisciplinary approaches to understand why females are at a heightened risk for developing PTSD.

Childhood maltreatment and internalizing/externalizing disorders in trauma-exposed adolescents: Does posttraumatic stress disorder (PTSD) severity have a mediating role?

Childhood maltreatment is associated with wide-ranging psychopathology at all stages of life. In the current study, we investigated whether posttraumatic stress disorder (PTSD) severity mediated the association between childhood maltreatment and internalizing and externalizing disorders among 262 South African trauma-exposed adolescents (aged 12-18 years). Childhood maltreatment and PTSD symptom severity were assessed using the Childhood Trauma Questionnaire and the Child PTSD Checklist, respectively. Psychiatric disorders were assessed utilizing the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version and were grouped into internalizing or externalizing disorders. Hierarchal logistic regression was used to assess the association of childhood maltreatment subtype with internalizing and externalizing disorders, controlling for age and gender, with PTSD symptom severity added to the final model. We found that sexual abuse was significantly associated with internalizing disorders, although this effect was no longer significant when PTSD was added to the model demonstrating that PTSD mediated the association between sexual abuse and internalizing disorders. Physical abuse, but not PTSD, was associated with externalizing disorders. Physical abuse, emotional neglect, and PTSD were associated with comorbid internalizing and externalizing disorders. These findings have implications for intervention and prevention strategies targeted at trauma-exposed adolescents with a history of childhood maltreatment.

Effectiveness of family-based therapy for depressive symptoms in children and adolescents: A systematic review and meta-analysis.

Early-onset depression contributes significantly to the global health burden and has long-term negative effects. This meta-analysis collates and examines the effectiveness of family-based interventions, where family members are involved in the treatment of depression in children and adolescents. A literature search was performed up to 8th March 2023. Randomised controlled trials of family-based interventions were included for participants aged 3-18 years with a diagnosis of major depressive disorder or dysthymia, according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013) or with a score above a cut-off on a standardised self-report depression measure. The overall effect size for treatment versus active control was g = 0.22 (95% confidence interval [CI]: -0.05-0.50) (nine studies; 659 participants), and for treatment versus non-active control it was g = 0.46 (95% CI: -0.09-1.01) (four studies; 385 participants). Effect sizes were not statistically significant, and heterogeneity was high, ranging between I2 = 64.3-81.1%. Subgroup analysis comparing attachment-based family therapy with family therapy using other theoretical frameworks did not yield a significant difference between the two. The effects of family-based therapies were larger than those in the comparison groups, but family-based therapy did not demonstrate a significant treatment benefit compared to the controls. More randomised controlled trials are warranted, considering that evidence for other psychotherapies for depression in children and adolescents, indicates modest effects. Family-based therapy may be an alternative for children and adolescents whose needs are not addressed by these treatments.

Neurological and neuropsychiatric manifestations in hospitalised patients with COVID-19.

Background: Although literature globally indicates varied neurological and/or neuropsychiatric manifestations (NNM) and complications associated with coronavirus disease 2019 (COVID-19), information about NNM in infected hospitalised patients on the African continent remains limited. Aim: To describe the presentation of NNM and compare patients with and without NNM considering demographic and clinical profiles, treatment, and outcomes. Setting: Tygerberg Hospital, Cape Town, South Africa. Methods: Retrospective medical record review of the first 100 consecutively admitted COVID-19 patients (64 females, mean age 47.6 years) between March and June 2020. Results: Of the 98 patients included in the analysis, 56.1% had at least one NNM. The most common NNM were myalgia (32.7%), headache (21.4%), loss of smell and/or taste (15.3%), and delirium (10.2%). Patients with and without NNM did not differ with respect to demographic characteristics. Patients with NNM had significantly more constitutional symptoms (p = 0.017) and were more likely to have neurological and/or neuropsychiatric comorbid conditions (10.9% vs. 0.0%, p = 0.033) than those without NNM. Patients without documented NNM were more likely to have abnormalities on chest X-ray (p = 0.009) than those with NNM. Coronavirus disease 2019 related treatment and mortality did not differ between the groups. Conclusion: Neurological and/or neuropsychiatric manifestations were common in hospitalised patients with COVID-19. The results suggest that while COVID-19 patients with NNM may have less of a respiratory phenotype they nonetheless have equivalent mortality rates. Contribution: This study highlights the common NNM in patients with COVID-19 admitted to Tygerberg Hospital early in the pandemic and adds to the growing evidence of COVID-19 NNM.

South Africa's Psychiatric training capacity in 2008 and in 2018. Has training capacity improved?

Background: There is a deficit of psychiatrists in South Africa, and to our knowledge, there is no situational analysis of training posts for psychiatrists in the country. Aim: To compare the number of specialists and subspecialists in training and training posts available in 2008 and 2018. Setting: South African medical schools with departments of psychiatry. Methods: A situational analysis involving data collection through a survey completed by eight heads of academic psychiatric departments followed by a comparative analysis of the two aforementioned years. Results: Data shows an 11% increase in funded and unfunded posts combined and a 9.3% increase in funded posts. The occupancy of funded posts decreased (92% in 2008 to 82% in 2018). When considering both funded and unfunded posts, only three more psychiatrists were being trained in 2018. Supernumeraries appointed in unfunded posts can be expected to return to their countries of origin. As such, a decrease in filled funded posts likely reflects a decrease in training psychiatrists destined to work in South Africa. While child and adolescent psychiatry was the only sub-speciality with accredited training posts in 2008, all sub-specialities included on the questionnaire had accredited training posts in 2018, and the number of accredited training posts in child and adolescent psychiatry doubled. That said, many of the posts were unfunded and vacant. Conclusion: While there was an increase in posts from 2008 to 2018, many posts remained unfilled. As such, not only are additional funded training posts required but also strategies to increase post-occupancy and successful completion of training. Contribution: This study is the first situational analysis of specialist and subspecialist training posts in Psychiatry in South Africa, at two time points over a 10 year period, that draws on academic heads of departments of psychiatry as respondents. The study highlights the nominal increase in funded training posts over this period, especially subspecialist training posts. The majority of Health Professions Council of South Africa (HPCSA) accredited subspecialities in Psychiatry have no funded training posts which is particularly concerning.

Childhood trauma, the stress response and metabolic syndrome: A focus on DNA methylation.

Childhood trauma (CT) is well established as a potent risk factor for the development of mental disorders. However, the potential of adverse early experiences to exert chronic and profound effects on physical health, including aberrant metabolic phenotypes, has only been more recently explored. Among these consequences is metabolic syndrome (MetS), which is characterised by at least three of five related cardiometabolic traits: hypertension, insulin resistance/hyperglycaemia, raised triglycerides, low high-density lipoprotein and central obesity. The deleterious effects of CT on health outcomes may be partially attributable to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, which coordinates the response to stress, and the consequent fostering of a pro-inflammatory environment. Epigenetic tags, such as DNA methylation, which are sensitive to environmental influences provide a means whereby the effects of CT can be biologically embedded and persist into adulthood to affect health and well-being. The methylome regulates the transcription of genes involved in the stress response, metabolism and inflammation. This narrative review examines the evidence for DNA methylation in CT and MetS in order to identify shared neuroendocrine and immune correlates that may mediate the increased risk of MetS following CT exposure. Our review specifically highlights differential methylation of FKBP5, the gene that encodes FK506-binding protein 51 and has pleiotropic effects on stress responding, inflammation and energy metabolism, as a central candidate to understand the molecular aetiology underlying CT-associated MetS risk.

Childhood trauma exposure and reward processing in healthy adults: A functional neuroimaging study.

The association between childhood trauma exposure and risk of developing psychopathology may in part be mediated by the effects of chronic stress on dopaminergic neurotransmission. However, little is known about the differential effects of distinct trauma types on reward processing, particularly in adults without concurrent medical or psychiatric disorders. We examined the association of childhood trauma exposure, including the differential effects of abuse and neglect, with reward processing in healthy adults (n = 114). Functional magnetic resonance imaging during a monetary incentive delay task was used to assess neural activity in the ventral striatum and orbitofrontal cortex in relation to reward anticipation and reward outcome, respectively. Exposure to childhood trauma, including abuse and neglect, was assessed using the Childhood Trauma Questionnaire-Short Form. We found a significant effect for abuse on ventral striatal activation during reward anticipation, adjusting for age, sex, scanner site, educational level, and household monthly income. There were no effects for abuse or neglect, independently or combined, on orbitofrontal cortex activation during reward outcome. Our findings suggest differential effects of childhood abuse on ventral striatum activation during reward anticipation in healthy adults.

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.

HIV-1 subtype C Tat exon-1 amino acid residue 24K is a signature for neurocognitive impairment.

Variation and differential selection pressures on Tat genes have been shown to alter the biological function of the protein, resulting in pathological consequences in a number of organs including the brain. We evaluated the impact of genetic variation and selection pressure on 147 HIV-1 subtype C Tat exon 1 sequences from monocyte-depleted peripheral lymphocytes on clinical diagnosis of neurocognitive impairment. Genetic analyses identified two signature amino acid residues, lysine at codon 24 (24K) with a frequency of 43.4% and arginine at codon 29 (29R) with a frequency of 34.0% in individuals with HIV-associated neurocognitive impairment. The analyses also revealed two signature residues, asparagine, 24 N (31.9%), and histidine, 29H (21.3%), in individuals without neurocognitive impairment. Both codons, 24 and 29, were associated with high entropy but only codon 29 was under positive selection. The presence of signature K24 increased by 2.08 times the risk of neurocognitive impairment, 3.15 times higher proviral load, and 69% lower absolute CD4 T-cell count compared to those without the signature. The results support a linkage between HIV-1 C Tat N24K polymorphism, proviral load, immunosuppression, and neurocognitive impairment. The signature may induce more neurotoxic effects, which contributes to establishment and severity of HIV-associated neurocognitive impairment.