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.

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.

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.

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.

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.

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.

Development of a Mobile Application for Detection of Adolescent Mental Health Problems and Feasibility Assessment with Primary Health Care Workers.

Introduction: There has been a sharp increase in the use of digital health interventions in global health, particularly mobile health applications, in recent years. The extreme shortage of health care providers trained in mental health screening and intervention in low- and middle-income countries raises questions about the applicability of mobile applications to deliver these services due to their accessibility and availability. This exploratory paper describes the development and feasibility assessment of a mobile screening application for the detection of mental disorders among adolescents in Zambia and South Africa. Methods: Eighty-two health care workers (HCW) working in primary care evaluated the acceptability and practicality of the mobile screening application after receiving brief training. The evaluation included questions from the Mobile Application Rating Scale (MARS) as well as open-ended questions. Results: The acceptability of the screening app was high and study participants were positive about using the app in routine care. Problems with internet connectivity, and time and staff constraints were perceived as the main barriers to regular use. Conclusion: HCW in primary care were able and willing to use a mobile screening app for the detection of mental health problems among treatment-seeking adolescents. Implementation in clinical practice needs to be further evaluated.

Cognitive insight is associated with perceived body weight in overweight and obese adults.

BACKGROUND: Accurate perception of body weight is necessary for individuals with a high body mass index (BMI) to initiate strategies to improve their health status. Furthermore, identifying factors that influence accurate body weight perception can assist in designing appropriate educational and weight management programs. We therefore aimed to investigate whether levels of cognitive functioning and insight influence the ability to correctly judge body weight. METHODS: One hundred and eighty four overweight and obese adults who participated in a cross- sectional case-control study and were controls in the aforementioned study were included. The study was conducted in Cape Town, South Africa. Demographic, weight-related, neuropsychiatric, neurocognitive and cognitive insight measures were administered. Regression analysis was conducted to determine the factors associated with correct weight perception. RESULTS: The final regression model explained 52.3% of variation in accurate perception of body weight and was significant (p ≤ 0. 001). The model correctly classified 79.3% of individuals who were able to correctly and incorrectly judge their weight. Adults with higher BMI, and lower self-certainty, those who reported that they had gained weight in the previous year and those who were told by a healthcare professional to lose or maintain a healthy weight were more likely to correctly judge their weight. CONCLUSION: Some aspects of cognitive insight (self-certainty) but not cognitive functioning were associated with perception of body weight in this sample. Awareness of recent weight changes, higher BMI and advice from of health care professionals were also significantly associated with perception of body weight, while demographic variables were not. Understanding the factors that contribute to the correct perception of weight is important in identifying appropriate health interventions that may address the burden of associated non-communicable diseases in overweight and obese individuals.

Hair cortisol levels in posttraumatic stress disorder and metabolic syndrome.

Individuals with post-traumatic stress disorder (PTSD) evidence increased rates of metabolic syndrome (MetS), and both PTSD and MetS are associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis function. Few investigations have examined the possible role of HPA-axis dysfunction in the co-occurrence of PTSD and MetS. In a case-control study, we aimed to determine whether hair cortisol concentrations (HCC) were associated with (i) PTSD caseness and severity and (ii) PTSD and MetS co-occurrence. We used the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) to determine PTSD diagnoses and severity scores in 216 females of mixed ancestry aged between 20 and 79 years (M = 43.8, SD =13.3). Hair samples, representing a three-month retrospective window of cortisol levels, were obtained and analyzed utilizing liquid chromatography-tandem mass spectrometry. We constructed multivariate linear regression models to evaluate whether PTSD diagnosis, PTSD severity, and MetS comorbidity were associated with HCC, controlling for potential confounders. HCC were significantly higher (adj ß = 0.154, p = .033; Cohen's d = 0.44) in PTSD patients (n = 110) than trauma-exposed controls (n = 106) and CAPS severity scores (adj ß = 0.207, p = .005) were significantly associated with HCC. MetS was not associated with HCC and there were no significant interactions between PTSD and MetS on HCC. This study provides evidence of a chronically dysregulated neuroendocrine mediated stress response in PTSD, with a clear dose-response relationship. HCC do not, however, appear to have specificity for the comorbidity of PTSD and MetS in this sample.LAY SUMMARYWe found that levels of the stress hormone, cortisol, measured in hair samples were significantly higher in South African women with post-traumatic stress disorder (PTSD) than in women who had also experienced trauma but did not have PTSD. Hair cortisol levels were, however, not associated with metabolic syndrome, a cluster of risk factors for heart disease, in the women studied. We thus show that South African women with PTSD have elevated long-term stress hormone levels and that this effect is related to PTSD and not solely due to trauma exposure.

Design and Development Process of a Youth Depression Screening m-Health Application for Primary Health Care Workers in South Africa and Zambia: An Overview of the MEGA Project.

Literature indicates a high prevalence and burden of mental illness in youths world-wide, which may be even higher in low- and middle-income countries (LMIC), such as South Africa and Zambia. Additionally, there is a lack of knowledge regarding youth depression amongst many primary health care (PHC) practitioners. The principal goal of the MEGA project is to provide youth with better access to mental health services and appropriate care, by developing a mental health screening mobile application tool to be used in PHC settings in South Africa and Zambia. In this study, we will use a mixed methods multi-center study design. In phase one, we will investigate the mental health literacy of PHC practitioners to identify areas in need of development. Based on the needs identified, we will develop and test a mobile health application to screen for common youth mental health problems in phase two. In phase three, we will implement and evaluate a tiered education and training program in the use of the m-health application. In the final phase, we will evaluate the acceptability and feasibility of the m-health application in PHC centres across South Africa and Zambia. Evidence suggests that PHC practitioners should routinely consider mental illness when assessing youth. However, common psychiatric disorders remain largely undetected and untreated in PHC settings. By identifying limitations in PHC workers knowledge with regard to youth mental health, we aspire to improve the depression care provided to youth in Southern Africa and Zambia by developing and implementing a locally relevant m-health application.

Accelerated theta-burst repetitive transcranial magnetic stimulation for depression in South Africa.

This case series documents local experience using accelerated theta-burst repetitive transcranial magnetic stimulation (rTMS) as a supplementary treatment for depression in both major depressive disorder (MDD) and bipolar disorder (BD). Nine consenting patients (MDD = 7; BD = 2) each received 20 accelerated theta-burst sessions over 8 days. Improvement was monitored using the Centre for Epidemiological Studies Depression (CES-D) Scale and the Clinical Global Impression (CGI) Scale at baseline, at day 5 and at day 8 of rTMS treatment. We performed a Wilcoxon matched-pairs signed-rank test to determine whether there was a difference in scores from baseline to post-treatment. The CES-D scores decreased significantly from baseline to post-treatment (Z = -2.547, p = 0.011) with five patients experiencing at least a 50% symptom reduction on the CES-D. CGI severity scores also decreased significantly between baseline and post-treatment (Z = -2.547, p = 0.011). The most commonly reported adverse effect was mild headaches, lasting a few hours during and after rTMS treatment. The findings suggest that the accelerated theta-burst rTMS protocol for depression is well tolerated with most patients also experiencing symptomatic improvement by day 8.

Validation of the Montreal cognitive assessment against the RBANS in a healthy South African cohort.

BACKGROUND: Mild cognitive impairment (MCI) represents an intermediate state between normal cognition and dementia. Early detection and treatment of reversible contributing factors to progressive cognitive decline currently forms the cornerstone of management. As the population at risk of developing dementia is projected to increase significantly in many low- and middle-income countries where health care services continue to operate under clinical and human resource constraints, there is a need for low-cost, quick and reliable screening tools. The Montreal cognitive assessment (MoCA) was developed as a brief screening tool with high sensitivity and specificity for detecting MCI. The initial validation sample for the MoCA consisted of English and French speaking Canadians. Studies undertaken in a variety of countries show that the reliability and validity of the MoCA in screening for MCI is good; however, it has been recommended that some item modification and adjustment of cut-offs for the diagnosis of MCI in these populations may be needed to account for cultural differences.To date, no studies have evaluated the MoCA in the South African population. We aimed to compare the validity of the MoCA to the RBANS, evaluate the effectiveness of the MoCA as a screening tool for MCI and generate normative data for the MoCA. METHODS: A cross-sectional observational study comprising a sample of 370 cognitively healthy males and females aged 18 years and older of mixed race (Coloured ethnicity) who were administered the MoCA and RBANS during screening. RESULTS: The MoCA showed acceptable internal consistency (Cronbach's alpha of 0.624). MoCA scores were significantly associated with gender (r = -0.199, p = 0.000), and correlated with age (r = -0.203, p = 0.000) and education (r = 0.326, p = 0.000). There was a strong correlation between total scores on the MoCA and RBANS (r = 513; p = 0.000), indicating good criterion-related validity. The MoCA also showed good agreement with the RBANS according to the Bland-Altman plot. ROC statistics demonstrated that the performance of the MoCA for predicting MCI compared to the RBANS was fair with an AUC of 0.794. Using the recommended cut-off score of 26, the MoCA showed high sensitivity (94.23%) but low specificity (28.16%). When the cut-off score was lowered to 23, the sensitivity was 75% and specificity 66.77%, while a cut-off of 24 demonstrated a sensitivity of 84.62% and a specificity of 52.53%. CONCLUSION: Although the MoCA appears fairly reliable at identifying MCI in this population, our findings suggest that some modification to certain domains and items is needed to improve the differentiation between normal ageing and MCI. Until such time that a culturally adapted version of the MoCA has been developed and validated for this population, we suggest lowering the cut-off score to 24 in order to reduce false-positive diagnoses of MCI.

The Microbiome in Posttraumatic Stress Disorder and Trauma-Exposed Controls: An Exploratory Study.

OBJECTIVE: Inadequate immunoregulation and elevated inflammation may be risk factors for posttraumatic stress disorder (PTSD), and microbial inputs are important determinants of immunoregulation; however, the association between the gut microbiota and PTSD is unknown. This study investigated the gut microbiome in a South African sample of PTSD-affected individuals and trauma-exposed (TE) controls to identify potential differences in microbial diversity or microbial community structure. METHODS: The Clinician-Administered PTSD Scale for DSM-5 was used to diagnose PTSD according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Microbial DNA was extracted from stool samples obtained from 18 individuals with PTSD and 12 TE control participants. Bacterial 16S ribosomal RNA gene V3/V4 amplicons were generated and sequenced. Microbial community structure, α-diversity, and ß-diversity were analyzed; random forest analysis was used to identify associations between bacterial taxa and PTSD. RESULTS: There were no differences between PTSD and TE control groups in α- or ß-diversity measures (e.g., α-diversity: Shannon index, t = 0.386, p = .70; ß-diversity, on the basis of analysis of similarities: Bray-Curtis test statistic = -0.033, p = .70); however, random forest analysis highlighted three phyla as important to distinguish PTSD status: Actinobacteria, Lentisphaerae, and Verrucomicrobia. Decreased total abundance of these taxa was associated with higher Clinician-Administered PTSD Scale scores (r = -0.387, p = .035). CONCLUSIONS: In this exploratory study, measures of overall microbial diversity were similar among individuals with PTSD and TE controls; however, decreased total abundance of Actinobacteria, Lentisphaerae, and Verrucomicrobia was associated with PTSD status.

Probable postpartum hypomania and depression in a South African cohort.

The aim of this study was to evaluate the frequency of, and factors associated with, postpartum hypomania (PPH) and postpartum depression (PPD) in a South African sample. Data from 57 women were analysed as part of a larger prospective study of maternal stress in pregnancy. On day 3 postpartum, women were assessed for probable PPH using the Highs scale. On day 3 and at week 6, probable PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS), while social support was evaluated using the Multidimensional Scale of Perceived Social Support (MSPSS). PPH was present in 49.1% of the participants at day 3 postpartum whilst PPD was present in 33.3% of participants on day 3 postpartum and in 45.6% at week 6. Participants meeting the clinical cut-off for both PPH and PPD on day 3 (17.5%) had significantly higher depression scores at week 6 than those with only PPH (p = 0.010) or only PPD (p = 0.035) on day 3. Depression scores on day 3 and lower social support scores at week 6 were predictive of PPD at week 6. Consistent with findings in other settings, early-onset PPD and poor social support were predictive of persisting PPD (i.e. at week 6). Women meeting criteria for both PPH and PPD on day 3 had greater depressive symptomatology at week 6. This may be indicative of an underlying bipolar disorder and warrants further investigation.

The psychopharmacological management of eating disorders in children and adolescents.

In this review we synthesised current literature on the psychopharmacological management of eating disorders (EDs) in children and adolescents (C&As). We focus specifically on anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED). The treatment of EDs is determined by physical and psycho-social factors and needs. Pharmacological management should therefore be viewed and incorporated as one component of a multi-disciplinary comprehensive treatment plan for specific requirements of a patient depending on the stage of the disorder. As there is a dearth of studies evaluating the use of psychopharmacology for EDs in C&As we first review the findings from studies performed in adults and then discuss specific studies performed in C&As. We include information from reviews and treatment guidelines to assist the clinician with an approach to the use of psychopharmacological agents in the treatment of EDs in C&As.

The relationship between nutrient intake and executive function in adults with post-traumatic stress disorder.

BACKGROUND: Executive function (EF) deficits are common in adults with post-traumatic stress disorder (PTSD). Macro- and micronutrient intake are potential modifiable factors that may influence EF in PTSD. OBJECTIVES: To explore the relationship between the daily dietary intake of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs), vitamin C, vitamin E, vitamin D, vitamin B12 and folate, and EF in adults with PTSD. METHODS: This was a cross-sectional observational study of adults with PTSD who completed neurocognitive assessments (n = 201). Digit span backwards, spatial span backwards, Stroop test and the Ruff Figural Fluency Task were used to assess EF. FoodFinder nutrient intake based on 24-h dietary recalls was used to calculate average daily nutrient intake. Multivariable linear regression models were used to regress EF on the nutrient variables. RESULTS: Intake of vitamin E, ω-3 PUFAs, and ω-6 PUFAs were all positively associated with planning and set-shifting, with vitamin E (adjusted ß = 0.20, p = 0.004) and ω-6 (adjusted ß = 0.17, p = 0.01) remaining significant after adjustment for age; sex; education and body mass index. Vitamin D intake was negatively associated with interference (adjusted ß = -0.21, p = 0.01). Vitamin C, vitamin B12 and folate intake were not associated with EF. LIMITATIONS: 24-h dietary recall data is limited by recall bias. Circulating nutrient levels were not measured. CONCLUSIONS: Dietary intake of vitamins E, ω-3 and ω-6 may be important modifiable factors affecting EF in adults with PTSD. Randomised controlled trials are needed to investigate whether micro- and macronutrient interventions can improve EF and other outcomes in PTSD.

Post-traumatic stress disorder as a risk factor for major adverse cardiovascular events: a cohort study of a South African medical insurance scheme.

AIMS: Prior research, largely focused on US male veterans, indicates an increased risk of cardiovascular disease among individuals with post-traumatic stress disorder (PTSD). Data from other settings and populations are scarce. The objective of this study is to examine PTSD as a risk factor for incident major adverse cardiovascular events (MACEs) in South Africa. METHODS: We analysed reimbursement claims (2011-2020) of a cohort of South African medical insurance scheme beneficiaries aged 18 years or older. We calculated adjusted hazard ratios (aHRs) for associations between PTSD and MACEs using Cox proportional hazard models and calculated the effect of PTSD on MACEs using longitudinal targeted maximum likelihood estimation. RESULTS: We followed 1,009,113 beneficiaries over a median of 3.0 years (IQR 1.1-6.0). During follow-up, 12,662 (1.3%) persons were diagnosed with PTSD and 39,255 (3.9%) had a MACE. After adjustment for sex, HIV status, age, population group, substance use disorders, psychotic disorders, major depressive disorder, sleep disorders and the use of antipsychotic medication, PTSD was associated with a 16% increase in the risk of MACEs (aHR 1.16, 95% confidence interval (CI) 1.05-1.28). The risk ratio for the effect of PTSD on MACEs decreased from 1.59 (95% CI 1.49-1.68) after 1 year of follow-up to 1.14 (95% CI 1.11-1.16) after 8 years of follow-up. CONCLUSION: Our study provides empirical support for an increased risk of MACEs in males and females with PTSD from a general population sample in South Africa. These findings highlight the importance of monitoring cardiovascular risk among individuals diagnosed with PTSD.

Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods.

Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks. PTSD diagnosis was most strongly associated with diminished CT in SCNs that encompassed the bilateral superior frontal cortex, motor cortex, insular cortex, orbitofrontal cortex, medial occipital cortex, anterior cingulate cortex, and posterior cingulate cortex. CT in these networks was significantly negatively correlated with PTSD symptom severity. Collectively, these findings suggest that PTSD diagnosis is associated with widespread reductions in CT, particularly within prefrontal regulatory regions and broader emotion and sensory processing cortical regions.