Large-scale analysis of structural brain asymmetries during neurodevelopment: Associations with age and sex in 4265 children and adolescents.

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.

Prenatal alcohol exposure and white matter microstructural changes across the first 6-7 years of life: A longitudinal diffusion tensor imaging study of a South African birth cohort.

Prenatal alcohol exposure (PAE) can affect brain development in early life, but few studies have investigated the effects of PAE on trajectories of white matter tract maturation in young children. Here we used diffusion weighted imaging (DWI) repeated over three time points, to measure the effects of PAE on patterns of white matter microstructural development during the pre-school years. Participants were drawn from the Drakenstein Child Health Study (DCHS), an ongoing birth cohort study conducted in a peri-urban community in the Western Cape, South Africa. A total of 342 scans acquired from 237 children as neonates (N = 82 scans: 30 PAE; 52 controls) and at ages 2-3 (N = 121 scans: 27 PAE; 94 controls) and 6-7 years (N = 139 scans: 45 PAE; 94 controls) were included. Maternal alcohol use during pregnancy and other antenatal covariates were collected from 28 to 32 weeks' gestation. Linear mixed effects models with restricted maxium likelihood to accommodate missing data were implemented to investigate the effects of PAE on fractional anisotropy (FA) and mean diffusivity (MD) in specific white matter tracts over time, while adjusting for child sex and maternal education. We found significant PAE-by-time effects on trajectories of FA development in the left superior cerebellar peduncle (SCP-L: p = 0.001; survived FDR correction) and right superior longitudinal fasciculus (SLF-R: p = 0.046), suggesting altered white matter development among children with PAE. Compared with controls, children with PAE demonstrated a more rapid change in FA in these tracts from the neonatal period to 2-3 years of age, followed by a more tapered trajectory for the period from 2-3 to 6-7 years of age, with these trajectories differing from unexposed control children. Given their supporting roles in various aspects of neurocognitive functioning (i.e., motor regulation, learning, memory, language), altered patterns of maturation in the SCP and SLF may contribute to a spectrum of physical, social, emotional, and cognitive difficulties often experienced by children with PAE. This study highlights the value of repeated early imaging in longitudinal studies of PAE, and focus for early childhood as a critical window of potential susceptibility as well as an opportunity for early intervention.

Prevalence and correlates of atypical patterns of drug use progression: findings from the South African Stress and Health Study

Objective: Atypical sequences of drug use progression are thought to have important implications for the development of substance dependence. The extent to which this assumption holds for South African populations is unknown. This paper attempts to address this gap by examining the prevalence and correlates of atypical patterns of drug progression among South Africans.Method: Data on substance use and other mental health disorders from a nationally representative sample of 4351 South Africans were analysed. Weighted cross tabulations were used to estimate prevalence and correlates of atypical patterns of drug use progression. Results: Overall; 12.2of the sample reported atypical patterns of drug use progression. The most common violation was the use of extra-medical drugs prior to alcohol and tobacco. Gender was significantly associated with atypical patterns of drug use with the risk pattern varying by the type of drug. None of the anxiety or mood disorders were associated with atypical patterns of use. Atypical patterns of drug use were not associated with increased risk for a lifetime substance use disorder. Conclusion: Atypical patterns of drug use initiation seem more prevalent in South Africa compared to other countries. The early use of extra-medical drugs is common; especially among young women. Drug availability and social environmental factors may influence patterns of drug use. The findings have important implications for prevention initiatives and future research

Lifetime mental disorders and suicidal behaviour in South Africa

There is relatively little data on the relationship between lifetime mental disorders and suicidal behaviour in low and middle income countries. This study examines the relationship between lifetime mental disorders; and subsequent suicide ideation; plans; and suicide attempts in South Africa. Method: A national survey of 4185 South African adults was conducted using the World Health Organization Composite International Diagnostic Interview (CIDI) to generate psychiatric diagnoses and suicidal behaviour. Bivariate; multivariate and discrete-time survival analyses were employed to investigate the associations between mental disorders and subsequent suicide ideation; plans; and attempts. Results: Sixty-one percent of people who seriously considered killing themselves at some point in their lifetime reported having a prior DSM-IV disorder. Mental disorders predict the onset of suicidal ideation; but have weaker effects in predicting suicide plans or attempts. After controlling for comorbid mental disorders; PTSD was the strongest predictor of suicidal ideation and attempts. There is a relationship between number of mental disorders and suicidal behaviour; with comorbidity having significantly sub-additive effects. Conclusion: Consistent with data from the developed world; mental disorders are strong predictors of suicidal behaviour; and these associations are more often explained by the prediction of ideation; rather than the prediction of attempts amongst ideators. This suggests some universality of the relevant mechanisms underlying the genesis of suicidal thoughts; and the progression to suicide attempts

Explanatory models of mental disorders and treatment practices among traditional healers in Mpumulanga, South Africa

Objective: In many traditional belief systems in Africa; including South Africa; mental health problems may be attributed to the influence of ancestors or to bewitchment. Traditional healers are viewed as having the expertise to address these causes. However; there is limited information on their explanatory models and consequent treatment practices. The present study examines traditional healers' explanatory models (EMs) and treatment practices for psychotic and non-psychotic mental illnesses. Method: 4 focus group discussions (8 healers in each group) and 18 in-depth interviews were conducted. Four vignettes were presented (schizophrenia; depression; panic and somatization) and traditional healers' views on the nature of the problem; cause; consequence; treatment and patient expectations were elicited. Results: Traditional healers held multiple explanatory models for psychotic and non-psychotic disorders. Psychotic illnesses appear to be the main exemplar of mental illness and were treated with traditional medicine; while nonpsychotic illnesses were not viewed as a mental illness at all. Additionally; traditional healers do not only use herbs and substances solely from ""traditional"" sources but rather have incorporated into their treatment practices modern ingredients that are potentially toxic. Conclusion: Interventions aimed at increasing the mental health literacy of traditional healers are essential. In addition; investigations of the effectiveness of traditional healer treatment for psychiatric disorders should be conducted

Psychosis and relapse in bipolar disorder are related to GRM3, DAOA, and GRIN2B genotype

Objective: Dysfunction in glutamate signalling is thought to play a role in the pathophysiology of bipolar disorder (BD). There is evidence of associations between single nucleotide polymorphisms (SNPs) in GRM3, GRIN2B, and DAOA genes and the diagnosis of BD. In this pilot study, we investigated the frequency of SNP variants in these 3 genes within South African population groups, and assessed interactions between genes and phenotypes of BD disease severity. Method: Multiplex SNaPshotTM PCR was used to genotype 191 case and 188 control samples. Cases comprised of 191 individuals in a South African cohort of mixed ancestry and Caucasians, with BD Type 1. Phenotypes of BD disease severity were: age of onset, number of illness episodes, number of hospitalisations for depression or mania and history of psychotic symptoms. Results: There were no significant difference in SNP allele frequencies between cases and controls. In the case-only analysis; the GRM3 rs6465084 heterozygote was associated with a 4-fold increased risk of lifetime history of psychotic symptoms, and the specific variants within the gene pair, DAOA and GRIN2B, had a significant interaction with the number of hospitalisations for mania, with lowest admission rates associated with both pairs of ancestral alleles. Conclusion: In BD, variations in glutamatergic genes may influence phenotypes related to the severity of illness. Speculatively; newly derived genes associated with various evolutionary advantages, may also increase the risk for more severe BD. These preliminary findings deserve validation in a larger cohort

Childhood trauma in adults with social anxiety disorder and panic disorder: a cross-national study

Objectives: The influence of childhood trauma as a specific environmental factor on the development of adult psychopathology is far from being elucidated. As part of a collaborative project between research groups from South Africa (SA) and Sweden focusing on genetic and environmental factors contributing to anxiety disorders; this study specifically investigated rates of childhood trauma in South African and Swedish patients respectively; and whether; in the sample as a whole; different traumatic experiences in childhood are predictive of social anxiety (SAD) or panic disorder (PD) in adulthood. Method: Participants with SAD or PD (85 from SA; 135 from Sweden) completed the Childhood Trauma Questionnaire (CTQ). Logistic regression was performed with data from the two countries separately; and from the sample as a whole; with primary diagnoses as dependent variables; gender; age; and country as covariates; and the CTQ subscale totals as independent variables. The study also investigated the internal consistency (Cronbach alpha) of the CTQ subscales. Results: SA patients showed higher levels of childhood trauma than Swedish patients. When data from both countries were combined; SAD patients reported higher rates of childhood emotional abuse compared to those with PD. Moreover; emotional abuse in childhood was found to play a predictive role in SAD/PD in adulthood in the Swedish and the combined samples; and the same trend was found in the SA sample. The psychometric qualities of the CTQ subscales were adequate; with the exception of the physical neglect subscale. Conclusion: Our findings suggest that anxiety disorder patients may differ across countries in terms of childhood trauma. Certain forms of childhood abuse may contribute specific vulnerability to different types of psychopathology. Longitudinal studies should focus on the potential sequential development of SAD/PD among individuals with childhood emotional abuse

Maternal aggression in Wistar rats: effect of 5-HT2A/2C receptor agonist and antagonist microinjected into the dorsal periaqueductal gray matter and medial septum

The objective of the present study was to assess the role of the 5-HT2A/2C receptor at two specific brain sites, i.e., the dorsal periaqueductal gray matter (DPAG) and the medial septal (MS) area, in maternal aggressive behavior after the microinjection of either a 5-HT2A/2C receptor agonist or antagonist. Female Wistar rats were microinjected on the 7th postpartum day with the selective agonist alpha-methyl-5-hydroxytryptamine maleate (5-HT2A/2C) or the antagonist 5-HT2A/2C, ketanserin. The agonist was injected into the DPAG at 0.2 (N = 9), 0.5 (N = 10), and 1.0 æg/0.2 æl (N = 9), and the antagonist was injected at 1.0 æg/0.2 æl (N = 9). The agonist was injected into the medial septal area (MS) at 0.2 (N = 9), 0.5 (N = 7), and 1.0 æg/0.2 æl (N = 6) and the antagonist was injected at 1.0 æg/0.2 æl (N = 5). For the control, saline was injected into the DPAG (N = 7) and the MS (N = 12). Both areas are related to aggressive behavior and contain a high density of 5-HT receptors. Non-aggressive behaviors such as horizontal locomotion (walking) and social investigation and aggressive behaviors such as lateral threat (aggressive posture), attacks (frontal and lateral), and biting the intruder were analyzed when a male intruder was placed into the female resident's cage. For each brain area studied, the frequency of the behaviors was compared among the various treatments by analysis of variance. The results showed a decrease in maternal aggressive behavior (number of bites directed at the intruder) after microinjection of the agonist at 0.2 and 1.0 æg/0.2 æl (1.6 ± 0.7 and 0.9 ± 0.3) into the DPAG compared to the saline group (5.5 ± 1.1). There was no dose-response relationship with the agonist. The present findings suggest that the 5-HT2A/2C receptor agonist has an inhibitory effect on maternal aggressive behavior when microinjected into the DPAG and no effect when microinjected into the MS. Ketanserin (1.0 æg/0.2 æl) decreased locomotion when microinjected into the DPAG and MS, but did not affect aggressive behavior. We interpret these findings as evidence for a specific role of 5-HT2A/2C receptors in the DPAG in the inhibition of female aggressive behavior, dissociated from those on motor activity.