Leigh van den Heuvel

Stellenbosch University | SUN · Department of Psychiatry

Background The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at...

Introduction: Common mental disorders, such as anxiety disorders, depression, and posttraumatic stress disorder (PTSD), present a substantial health and economic burden. The gut microbiome has been associated with these psychiatric disorders via the microbiome-gut-brain axis. However, previous studies have focused on the associations between the gu...

Background The occurrence of post-traumatic stress disorder (PTSD) following a traumatic event is associated with biological differences that can represent the susceptibility to PTSD, the impact of trauma, or the sequelae of PTSD itself. These effects include differences in DNA methylation (DNAm), an important form of epigenetic gene regulation, at...

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European anc...

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...

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) bet...

Background The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the M...

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; Con...

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...

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 dimensional...

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...

Trauma exposure is prevalent globally and is a defining event for the development of posttraumatic stress disorder (PTSD), characterised by intrusive thoughts, avoidance behaviours, hypervigilance and negative alterations in cognition and mood. Exposure to trauma elicits a range of physiological responses which can interact with environmental facto...

Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ance...

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 sys...

Introduction: Posttraumatic stress disorder (PTSD) and metabolic syndrome (MetS) are associated with overlapping brain structural differences. These often involve brain structures involved in the regulation of appetite, food intake, satiety, and reward processing. We examined the individual and interactive effects of PTSD diagnosis and MetS on cor...

Chronic systemic inflammation has been implicated in trauma exposure, independent of a psychiatric diagnosis, and in posttraumatic stress disorder (PTSD) and its highly comorbid conditions, such as metabolic syndrome (MetS). The present study used network analysis to examine the interacting associations between pro-inflammatory cytokines, posttraum...

In this narrative review, we examine the association between gut dysbiosis, neuroinflammation, and stress-linked disorders, including depression, anxiety, and post-traumatic stress disorder (PTSD), and investigate whether tryptophan (TRP) metabolism and platelets play a role in this association. The mechanisms underlying the aetiology of stress-lin...

There is a dearth of research regarding eating disorders (EDs) in Africa. The first reports of EDs in Africa emerged in the 1970s and 1980s. Recent systematic reviews on the prevalence of EDs did not include any studies from Africa. The few studies undertaken suggest that the prevalence of anorexia nervosa (AN) and bulimia nervosa (BN) is lower in...

Evidence suggests that shared pathophysiological mechanisms in neuropsychiatric disorders (NPDs) may contribute to risk and resilience. We used single-gene and network-level transcriptomic approaches to investigate shared and disorder-specific processes underlying posttraumatic stress disorder (PTSD), Parkinson’s disease (PD) and schizophrenia in a...

Background Childhood maltreatment leads to lifelong health risks, particularly in women. Although reproductive health has been linked to such maltreatment, limited literature exists on its association with polycystic ovary syndrome (PCOS). Objectives In a sample of psychiatrically healthy women, we evaluated the impact of child maltreatment (subty...

Background The cerebellum critically contributes to higher-order cognitive and emotional functions such fear learning and memory. Prior research on cerebellar volume in PTSD is scant and has neglected neuroanatomical subdivisions of the cerebellum that differentially map on to motor, cognitive, and affective functions. Methods We quantified cerebe...

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 ass...

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...

Aims. The coronavirus disease 2019 (COVID-19) pandemic and ensuing restrictions have negatively affected the mental health and well-being of the general population, and there is increasing evidence suggesting that lockdowns have led to a disruption of health services. In March 2020, South Africa introduced a lockdown in response to the COVID-19 pan...

Posttraumatic stress disorder (PTSD) can be a chronic and disabling condition. Post-traumatic nightmares (PTNs) form a core component of PTSD and are highly prevalent in this patient population. Nightmares in PTSD have been associated with significant distress, functional impairment, poor health outcomes, and decreased quality of life. Nightmares i...

Structural brain differences have been described in first-episode schizophrenia spectrum disorders (FES), and often overlap with those evident in the metabolic syndrome (MetS). We examined the associations between body mass index (BMI) and brain structures involved in food intake regulation in minimally treated FES patients (n = 117) compared to he...

Objective Several studies suggest a relationship between atopy and psychiatric disorders, but few have investigated the association between atopic conditions and posttraumatic stress disorder (PTSD). We sought to compare the rates of atopy and allergies in a South African case-control study of 220 patients with PTSD (mean age 41.7 years. SD = 11.7)...

Aims: In March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic, entailing the suspension of all non-essential activities and a complete ban of tobacco and alcohol sales. We studied the effect of the lockdown on mental health care utilisation rates in private-sector care in South Africa. Methods: We did an interrupted...

Background Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWAS). Meth...

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 d...

Posttraumatic stress disorder (PTSD) imposes a significant burden on patients and communities. Although the microbiome-gut-brain axis has been proposed as a mediator or moderator of PTSD risk and persistence of symptoms, clinical data directly delineating the gut microbiome's relationship to PTSD are sparse. This study investigated associations bet...

Aim Individuals with schizophrenia demonstrate higher rates of metabolic syndrome (MetS) than the general population. Hair cortisol concentrations (HCC) reflect longer-term cortisol secretion and can provide additional insights into the role of the hypothalamic pituitary adrenal (HPA) axis in schizophrenia and co-occurring MetS. Methods In a case–...

Glucocorticoids and inflammatory markers can influence cognitive function. Hair cortisol concentrations (HCC) reflect longer-term hypothalamic pituitary adrenal (HPA) axis function and combined with immune markers can provide insight into how HPA-axis and immune pathways interact to influence cognition. We examined the association between HCC and h...

Arachnoid cysts have been linked to neuropsychiatric morbidity. We describe two patients presenting with dissociative and manic symptoms believed to be associated with middle fossa arachnoid cysts. They were managed medically and remitted eventually, but symptoms were resistant. We briefly review the literature to discuss mechanisms by which cysts...

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for,...

Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symp...

Posttraumatic stress disorder (PTSD) is a trauma-related disorder that frequently co-occurs with metabolic syndrome (MetS). MetS is characterized by obesity, dyslipidemia, and insulin resistance. To provide insight into these co-morbidities, we performed a genome-wide association study (GWAS) meta-analysis to identify genetic variants associated wi...

Background Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensit...

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),...

Background and purpose Most research regarding child and adolescent mental health prevention and promotion in low-and middle-income countries is undertaken in high-income countries. This systematic review set out to synthesise findings from epidemiological studies, published between 2008 and 2020, documenting the prevalence of mental health problem...

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 inve...

Background Brain-derived neurotrophic factor (BDNF) plays a crucial role in the survival, differentiation, growth, and plasticity of the central nervous system (CNS). Post-traumatic stress disorder (PTSD) is a complex syndrome that affects CNS function. Evidence indicates that changes in peripheral levels of BDNF may interfere with stress. However,...

Despite the progress made in HIV treatment and prevention, HIV remains a major cause of adolescent morbidity and mortality in sub-Saharan Africa. As perinatally infected children increasingly survive into adulthood, the quality of life and mental health of this population has increased in importance. This review provides a synthesis of the prevalen...

Background: Mental disorders can adversely affect HIV treatment outcomes and survival. Data are scarce on premature deaths in people with mental disorders in HIV-positive populations, particularly in low-income and middle-income countries. In this study, we quantified excess mortality associated with mental disorders in HIV-positive people in Sout...

Background: Mental disorders are common in people living with HIV (PLWH) but often remain untreated. We aimed to explore the gap in access to treatment (treatment gap) for mental disorders in adults followed-up in antiretroviral therapy (ART) programs in South Africa and disparities in access to mental health services. Methods: We conducted a cohor...

Background Parkinson’s disease (PD) and metabolic syndrome (MetS) share certain pathophysiological pathways, including hypothalamic pituitary adrenal (HPA) axis dysfunction. Hair glucocorticoid (GC) levels reflect longer-term HPA-axis function and can provide additional insights into the role of a dysregulated HPA-axis in PD and co-occurring cardio...

This chapter discusses the management of stress-related disorders, with an emphasis on post-traumatic stress disorder (PTSD). The chapter aims to provide a synthesis reflecting the scope of interventions that have been investigated in the management of stress-related disorders, mainly in adults, including both established and emerging interventions...

The third edition of the textbook presents psychiatry as a medical specialty. The application of science has transformed much of medicine by providing an understanding of the mechanisms of pathology. The genetic basis of psychiatry guarantees a future for explanation by neuroscience. The book sets the scene for such development by explaining the ke...

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-contro...

Study Objectives Sleep problems are common, serving as both a predictor and symptom of posttraumatic stress disorder (PTSD), with these bidirectional relationships well established in the literature. While both sleep phenotypes and PTSD are moderately heritable, there has been a paucity of investigation into potential genetic overlap between sleep...

Background: Hair cortisol concentrations (HCC) are increasingly used as a biomarker of stress, however limited research exists regarding the relationship between HCC and protective factors, such as resilience. Additionally, studies measuring HCC need to account for possible confounders, and these factors have not been examined in sufficiently dive...

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. Improve...

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genom...

Background: Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder, and is frequently comorbid with metabolic syndrome (MetS). Epigenetic changes in response to trauma may provide insight into the biological mechanisms involved in PTSD-MetS comorbidity. The aim of this study was to identify genome-wide alterations in DNA methylati...

Background PTSD and depression commonly co-occur and have been associated with smaller hippocampal volumes compared to healthy and trauma-exposed controls. However, the hippocampus is heterogeneous, with subregions that may be uniquely affected in individuals with PTSD and depression. Methods We used random effects regressions and a harmonized neu...

Abstract Background Although a large number of clinical trials on interventions demonstrating efficacy (or lack thereof) are conducted annually, much of this evidence is not accessible to scientists and clinicians. Objectives We aimed to determine the publication rate of posttraumatic stress disorder (PTSD) trials that have been registered in clini...

Background: HIV-infected children and adolescents (CA-HIV) face significant mental health challenges related to a broad range of biological and psychosocial factors. Data are scarce on the agreement and discrepancy between caregivers and CA-HIV regarding emotional and behavioral problems (EBPs) in CA-HIV. Objectives: We determined agreement between...