Childhood maltreatment and its associations with trauma-related psychopathology: disentangling two classification approaches.

Childhood maltreatment (CM) is associated with various mental health disorders, including PTSD, depression, and anxiety. This study explores how specific classifications - dichotomous (abuse versus neglect) and dimensional (physical, emotional, sexual) - relate to distinct psychopathologies. We recruited 642 individuals, screening them for CM history and symptoms. ANOVA, regression, and SEM analyses compared CM approaches and symptom associations. The dichotomous approach showed significant effects of abuse and neglect on all symptoms. In the dimensional approach, sexual and physical CM were primary features for PTSD, while sexual and emotional CM were primary for depression and anxiety. Overall, the dimensional approach outperformed the dichotomous approach in capturing symptoms, suggesting its importance in understanding psychopathologies and guiding therapeutic interventions. Our findings highlight the differential associations of CM experiences with PTSD, depression, and anxiety symptoms. The findings suggest the importance of a dimensional CM approach for understanding psychopathologies and possibly informing targeted therapeutic interventions.

Trace amine-associated receptor 1 (TAAR1) agonism for psychosis: a living systematic review and meta-analysis of human and non-human data.

Background: Trace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies. Methods: We co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.11.2023), extracted data, and assessed risk of bias. Primary outcomes were standardised mean differences (SMD) for overall symptoms in human studies and hyperlocomotion in animal models. We also examined adverse events and neurotransmitter signalling. We synthesised data with random-effects meta-analyses. Results: Nine randomised trials provided data for two TAAR1 agonists (ulotaront and ralmitaront), and 15 animal studies for 10 TAAR1 agonists. Ulotaront and ralmitaront demonstrated few differences compared to placebo in improving overall symptoms in adults with acute schizophrenia (N=4 studies, n=1291 participants; SMD=0.15, 95%CI: -0.05, 0.34), and ralmitaront was less efficacious than risperidone (N=1, n=156, SMD=-0.53, 95%CI: -0.86, -0.20). Large placebo response was observed in ulotaront phase-III trials. Limited evidence suggested a relatively benign side-effect profile for TAAR1 agonists, although nausea and sedation were common after a single dose of ulotaront. In animal studies, TAAR1 agonists improved hyperlocomotion compared to control (N=13 studies, k=41 experiments, SMD=1.01, 95%CI: 0.74, 1.27), but seemed less efficacious compared to dopamine D 2 receptor antagonists (N=4, k=7, SMD=-0.62, 95%CI: -1.32, 0.08). Limited human and animal data indicated that TAAR1 agonists may regulate presynaptic dopaminergic signalling. Conclusions: TAAR1 agonists may be less efficacious than dopamine D 2 receptor antagonists already licensed for schizophrenia. The results are preliminary due to the limited number of drugs examined, lack of longer-term data, publication bias, and assay sensitivity concerns in trials associated with large placebo response. Considering their unique mechanism of action, relatively benign side-effect profile and ongoing drug development, further research is warranted. Registration: PROSPERO-ID: CRD42023451628.

There is a need for more effective treatments for psychosis, including schizophrenia. Psychosis is a collection of mental health symptoms, such as hearing voices, that can cause distress and impair functioning. These symptoms are thought to be caused by changes in a chemical messenger system in the brain called dopamine. Currently used antipsychotic medications target brain receptors that respond to dopamine. They are not effective in some people and can cause uncomfortable adverse events, such as weight gain and movement disorders, especially with long-term use. A new type of drug is the trace amine-associated receptor 1 (TAAR1) agonists. These drugs act on different brain receptors that can affect the activity of the dopamine system, but do not directly bind to dopamine receptors. We aimed to understand if TAAR1 agonists can reduce symptoms of psychosis, what adverse events they might have, and how they work. We did this by reviewing and collating all available evidence until November 2023. This is a "living" systematic review, so it will be regularly updated in the future. We looked at both human and animal studies investigating TAAR1 agonists. Human studies suggested that two TAAR1 agonists (namely, ulotaront or ralmitaront) might have little to no effect on reducing symptoms of psychosis compared to placebo in people with schizophrenia. They seemed to cause fewer adverse events than current antipsychotics. Data from animal studies suggested that TAAR1 agonists had some positive effects but potentially smaller than other antipsychotics. There were little to no data from both human and animal studies about how TAAR1 agonists actually work. From the current evidence we are uncertain about these results. With the ongoing development of new TAAR1 agonists, more evidence is needed to understand their potential role in the treatment of psychosis.

Post-traumatic stress disorder symptoms following exposure to acute psychological trauma in children aged 8-16 years in South Africa: protocol for the Sinethemba longitudinal study.

INTRODUCTION: Children exposed to trauma are vulnerable to developing post-traumatic stress disorder (PTSD) and other adverse mental health outcomes. In low-and middle-income countries (LMICs), children are at increased risk of exposure to severe trauma and co-occurring adversities. However, relative to high-income countries, there is limited evidence of the factors that predict good versus poor psychological recovery following trauma exposure in LMIC children, and the role of caregiver support in these high-adversity communities. METHODS AND ANALYSIS: We will conduct a longitudinal, observational study of 250 children aged 8-16 years and their caregivers in South Africa, following child exposure to acute trauma. Dyads will be recruited from community hospitals following a potentially traumatic event, such as a motor vehicle accident or assault. Potential participants will be identified during their hospital visit, and if they agree, will subsequently be contacted by study researchers. Assessments will take place within 4 weeks of the traumatic event, with 3-month and 6-month follow-up assessments. Participants will provide a narrative description of the traumatic event and complete questionnaires designed to give information about social and psychological risk factors. Child PTSD symptoms will be the primary outcome, and wider trauma-related mental health (depression, anxiety, behavioural problems) will be secondary outcomes. Regression-based methods will be used to examine the association of psychosocial factors in the acute phase following trauma, including caregiver support and responding, with child PTSD and wider mental health outcomes. ETHICS AND DISSEMINATION: Ethical approvals have been granted by Stellenbosch University and the University of Bath, with additional approvals to recruit via hospitals and healthcare clinics being granted by the University of Cape Town, the Department of Health and the City of Cape Town. Study findings will be disseminated via publication in journals, workshops for practitioners and policy-makers, and public engagement events.

Adaptation and feasibility of WHO PM+ for adolescents living with HIV in KwaZulu-Natal Province, South Africa: an implementation feasibility study protocol.

INTRODUCTION: Adolescents living with HIV (ALHIV) are an extremely vulnerable population, with the burden of mental health problems carefully documented together with the constraints for receiving timely and adequate management of the problems, especially in rural settings. Problem Management Plus (PM+) is a scalable psychological intervention for individuals impaired by distress in communities exposed to adversity. Initially developed for adult populations, few studies have assessed its potential to address adolescent distress. This study aims to co-adapt PM+ with an adherence component (PM+Adherence) for ALHIV and to evaluate its acceptability and feasibility in rural Kwa-Zulu Natal Province, South Africa. METHODS AND ANALYSIS: We will use a mixed-methods approach over three phases. The first phase will include a realist synthesis and collection of formative data from up to 60 ALHIV, caregivers and healthcare providers to inform the adaptation of WHO PM+, including the components of an adherence module. During the second phase, we will undertake the cultural adaptation of the PM+Adherence intervention. The third phase will involve a hybrid type 3 implementation strategy among ALHIV aged 16-19 years (n=50) to implement and evaluate the feasibility of the culturally co-adapted PM+Adherence. The feasibility indicators to be evaluated include reach, adoption, attrition, implementation and acceptability of the adapted intervention, which will be assessed qualitatively and quantitatively. In addition, we will assess preliminary effectiveness using an intention-to-treat approach on HIV-related indicators and mental health outcomes at baseline, end intervention, 2-month follow-up during the 6-month implementation. DISCUSSION: We expect that the PM+Adherence will be acceptable and can feasibly be delivered by lay counsellors in resource-limited rural KwaZulu-Natal. ETHICS AND DISSEMINATION: Ethical clearance has been obtained from the University of KwaZulu-Natal Biomedical Research Ethics Committee, (BREC/00005743/2023). Dissemination plans include presentations at scientific conferences, peer-reviewed publications and community level.

Coping motives as a mediator of the relationship between child maltreatment and substance use problems in south African adolescents.

BACKGROUND: Evidence suggests that adults with a history of child maltreatment (CM) engage in substance misuse driven by 'coping motives': maladaptive beliefs that substances help them cope with negative emotions. However, the specificity of this risk pathway is under-researched in younger and non-Western cohorts. OBJECTIVE: The present study aimed to determine whether coping motives play a distinct role compared to other motives for substance use in mediating the relationship between CM and problematic alcohol and marijuana use in a sample of South African adolescents. PARTICIPANTS AND SETTING: A sample of 688 high school students (M age = 15.03 years; 62.5 % female) in Cape Town, South Africa, completed a cross sectional survey. METHODS: Participants completed self-report measures of CM exposure, motives for using alcohol and marijuana (coping, enhancement, social and conformity), and alcohol and marijuana related problems. Participants who endorsed using alcohol (N = 180) or marijuana (N = 136) were included in analysis. A parallel mediation model was conducted for each substance (alcohol and marijuana, respectively) to assess which motives mediated the relationship between CM exposure and substance-related problems. RESULTS: CM exposure predicted both alcohol-and marijuana related problems. The relationship between CM exposure and alcohol-related problems was partially mediated by coping motives (p < .001, 95%CI 0.028, 0.115) and, to a lesser extent, conformity motives (p < .01, 95%CI 0.001, 0.041), but not by social motives or enhancement motives. The relationship between CM exposure and marijuana-related problems was partially mediated by coping motives (p < .001, 95%CI 0.004, 0.037), but not by conformity, social or enhancement motives. CONCLUSIONS: The findings support the importance of coping motives as a mediator between CM and problematic substance use across different substances of abuse in South African adolescents, and the role of conformity motives in problematic alcohol use. Future research should explore whether these findings hold across other sociocultural contexts, and the utility of interventions to address coping motives for substance use in adolescence.

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.

Attitudes of patients and mental health professionals towards hypothetical use of serious games in psychotherapy.

Serious games are increasingly being applied within healthcare, but their integration in psychotherapeutic settings is less documented. OBJECTIVES: The present study sought to identify the attitudes of psychotherapists and patients towards the hypothetical use of serious games in psychotherapy in the South African context. METHODS: Online surveys assessed acceptance, experience, and requirements for the utilisation of serious games in therapeutic contexts. Clients utilising mental health services (n = 209) and psychotherapists delivering mental health services (n = 156) in South Africa completed the online survey. RESULTS: Knowledge about serious games is limited with only 15% of clients and 16% of therapists reporting knowledge of the existence and application of serious games. Use of serious games is even more infrequent with only 1% of therapists and 6% of clients currently using serious games as an intervention. Despite this, our findings highlight an apparent demand for their use, with 71% of therapists indicating that serious games would be a suitable adjunct treatment modality for their patients. Our results show a general openness toward the use of serious games in psychotherapy. CONCLUSION: The use of serious games as an e-mental health treatment modality is conceivable for both patients and therapists, particularly as a complementary strategy to traditional face-to-face psychotherapy.

A pilot randomised control study to investigate the effect of the South African Adolescence Group Sleep Intervention (SAASI) on adolescent sleep and PTSD.

Background: Trauma exposure prevalence and consequent post-traumatic stress disorder among South African adolescents are significant. Sleep disturbances are among the most frequently reported difficulties faced by those dealing with PTSD. The current study examined the feasibility and preliminary efficacy of the South African Adolescence Group Sleep Intervention on PTSD symptom severity and sleep disturbance.Method: Sixty-one adolescents with PTSD diagnoses and sleep disturbance were randomly assigned (1:1) to one individual and four group sessions of a sleep intervention (SAASI) or a control group. Participants completed the Child PTSD symptom scale for DSM5 (CPSS-5) and the Pittsburgh Sleep Quality Index (PSQI) among other sleep and psychiatric measures. The trial was registered on the Pan African Trial Registry (PACTR202208559723690).Results: There was a significant but similar decrease in PSQI scores in both groups over time indicating no overall intervention effect (Wald test = -2.18, p = .029), mean slope = -0.2 (95% CI: -0.37 to -0.02) (p = .583). On the CPSS-5, interaction between groups was also not significant (p = .291). Despite this overall finding, the mean difference in CPSS-SR-5 scores increased over time, with the difference between groups post-treatment -9.10 (95%CI: -18.00 to -0.21), p = .045 and the 1-month follow-up contrast - 11.22 (95%CI: -22.43 to -0.03), p = .049 suggesting that PTSD symptom severity decreased more in the intervention group than the control group. The dropout rate was higher than expected for both the intervention (n = 10; 32%) and control (n = 8; 26.7%) groups. Dropout were mostly school commitments or travel related.Conclusions: Early findings suggest a trend towards dual improvement in sleep quality and PTSD symptom severity in adolescents with a sleep disturbance and PTSD receiving a group sleep intervention (SAASI). Further investigation in a properly powered RCT with detailed retention planning is indicated.

A four-week group sleep intervention seems feasible in adolescents with PTSD and sleep disturbances in a low-resource South African setting.Utilising less specialised mental health resources such as nurses and counsellors in intervention delivery was feasible and effective.Preliminary results are promising and support further research to establish the efficacy of the intervention.

Influence of childhood trauma and traumatic stress on a woman's risk of having a child with a fetal alcohol spectrum disorder.

BACKGROUND: Maternal risk factors for having a child diagnosed on the fetal alcohol spectrum disorders (FASD) continuum are complex and include not only the quantity, frequency, and timing of alcohol use but also a woman's physical stature, socio-economic status, and pregnancy-related factors. Exposure to trauma may predispose women to a range of physiological and mental disorders. A woman's mental and physical health may in turn influence her probability of having a child with FASD. This study investigated the role of maternal childhood trauma and lifetime traumatic stress on prenatal alcohol consumption and on the risk of having a child with FASD. METHODS: A nested, case-control study was conducted for maternal risk assessment. Study participants were mothers of first-grade learners from five rural communities in the Western Cape Province of South Africa who were assessed for FASD. Face-to-face surveys were conducted, which included mental health and trauma assessment questionnaires. RESULTS: In logistic regression analyses, higher maternal childhood trauma scores were associated with an increased likelihood of having a child diagnosed with FASD, although the increase in risk was modest (OR = 1.014, p = 0.015). In addition, structural equation modeling investigated relationships between maternal drinking, childhood trauma, traumatic stress, and a child's FASD diagnosis. Traumatic stress and drinking during pregnancy, but not lifetime alcohol use, were associated with maternal childhood trauma. Lifetime alcohol use influenced drinking during pregnancy, which in turn was significantly associated with having a child diagnosed on the continuum of FASD. CONCLUSION: No direct influence of maternal childhood trauma on FASD diagnosis could be demonstrated. However, maternal trauma may indirectly contribute to the risk of having a child diagnosed with FASD.

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.

Participants' experiences of a counsellor-supported PTSD Coach intervention in a resource-constrained setting.

We explored participants' experiences of a counsellor-supported PTSD Coach mobile application intervention (PTSD Coach-CS) in a randomised controlled trial. PTSD Coach-CS participants, who received the intervention and self-completed a custom-designed questionnaire at intervention completion were included (n = 25; female = 20; ages 19-59; isiXhosa = 22). This questionnaire comprised questions regarding the feasibility, acceptability and potential impact of the PTSD Coach-CS intervention, and general psychological support in our setting. Data were analysed using Braun and Clarke's thematic analysis. Three main themes emerged. (i) Participants' largely positive experiences of treatment procedures included the safe space created by the counsellor support in combination with the PTSD Coach application, allowing them to learn about and understand their lived experiences, and to accept their PTSD diagnoses. (ii) Positive perceptions of the PTSD Coach application, yet raising important concerns (e.g., lack of family involvement) for future consideration. (iii) Intervention-specific and systemic treatment barriers (e.g., stigma) providing important information to inform and increase the usefulness of the PTSD Coach-CS intervention. The findings suggest that the PTSD Coach-CS intervention may help address the need for access to suitable care for South African adults with PTSD. Some contextual barriers must be considered in further intervention implementation.

Effects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes.

Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD and co-morbid autoimmune conditions. We investigated the shared genetic contributions and causal relationships between PTSD, 18 autoimmune diseases, and 3 immune/inflammatory biomarkers. Univariate MiXeR was used to contrast the genetic architectures of phenotypes. Genetic correlations were estimated using linkage disequilibrium score regression. Bi-directional, two-sample Mendelian randomization (MR) was performed using independent, genome-wide significant single nucleotide polymorphisms; inverse variance weighted and weighted median MR estimates were evaluated. Sensitivity analyses for uncorrelated (MR PRESSO) and correlated horizontal pleiotropy (CAUSE) were also performed. PTSD was considerably more polygenic (10,863 influential variants) than autoimmune diseases (median 255 influential variants). However, PTSD evidenced significant genetic correlation with nine autoimmune diseases and three inflammatory biomarkers. PTSD had putative causal effects on autoimmune thyroid disease (p = 0.00009) and C-reactive protein (CRP) (p = 4.3 × 10-7). Inferences were not substantially altered by sensitivity analyses. Additionally, the PTSD-autoimmune thyroid disease association remained significant in multivariable MR analysis adjusted for genetically predicted inflammatory biomarkers as potential mechanistic pathway variables. No autoimmune disease had a significant causal effect on PTSD (all p values > 0.05). Although causal effect models were supported for associations of PTSD with CRP, shared pleiotropy was adequate to explain a putative causal effect of CRP on PTSD (p = 0.18). In summary, our results suggest a significant genetic overlap between PTSD, autoimmune diseases, and biomarkers of inflammation. PTSD has a putative causal effect on autoimmune thyroid disease, consistent with existing epidemiologic evidence. A previously reported causal effect of CRP on PTSD is potentially confounded by shared genetics. Together, results highlight the nuanced links between PTSD, autoimmune disorders, and associated inflammatory signatures, and suggest the importance of targeting related pathways to protect against disease and disability.

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.

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 .

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.

A counsellor-supported 'PTSD Coach' intervention versus enhanced Treatment-as-Usual in a resource-constrained setting: A randomised controlled trial.

To widen treatment access for posttraumatic stress disorder (PTSD) in resource-constrained South Africa, we evaluated the feasibility and effectiveness of a counsellor-supported PTSD Coach mobile application (app) (PTSD Coach-CS) intervention on PTSD and associated sequelae in a community sample. Participants (female = 89%; black = 77%; aged 19-61) with PTSD were randomised to PTSD Coach-CS (n = 32) or enhanced Treatment-as-Usual (n = 30), and assessed with the Clinician-Administered PTSD Scale (CAPS-5), PTSD Checklist (PCL-5) and Depression, Anxiety and Stress Scale-21 items, at pre- to post-treatment and follow-up (1 and 3 months). We also collected data on user experiences of the PTSD Coach app with self-administered surveys. We conducted an intent-to-treat analysis and linear mixed models. A significant (group × time) effect for the CAPS-5 (F3.136 = 3.33, p = 0.02) indicated a greater reduction in PTSD symptom severity over time for the intervention group with a significant between-group effect size detected at 3-month follow-up. Significant between-group effect sizes were detected in self-reported stress symptom reduction in the intervention group at post-treatment and 3-month follow-up. Participants perceived the app as helpful and were satisfied with the app. Findings suggest PTSD Coach-CS as a suitable low-cost intervention and potential treatment alternative for adults with PTSD in a resource-constrained country. Replication in larger samples is needed to fully support effectiveness. Pan African Trial Registry: PACTR202108755066871.

The definition of treatment resistance in anxiety disorders: a Delphi method-based consensus guideline.

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment-resistant anxiety disorders (TR-AD) informing such trials is currently lacking. We used a Delphi method-based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR-AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free-text responses to a 29-item questionnaire on relevant aspects of TR-AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR-AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR-AD vs. "difficult-to-treat" anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method-based consensus on operational criteria for TR-AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence-based stepped-care treatment algorithms for patients with anxiety disorders.

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.

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.