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.

Has maternal sensitivity been comprehensively investigated in sub-Saharan Africa? A narrative scoping review.

Child development is strongly influenced by maternal characteristics. Maternal sensitivity, as well as risks to and outcomes of sensitive maternal style, are well studied in industrialised western contexts, but it is unclear if this is the case for other contexts. Sub-Saharan Africa has been subjected to and continues to negotiate socio-economic and psychological sequelae of colonial and race-based politics: exploring the nature and outcomes of early caregiver input in such challenging conditions is imperative. This scoping review thus aims to 1) evaluate the nature and extent of quantified observational assessments of dyadic interactions, with a focus on maternal sensitivity, in Sub-Saharan Africa and 2) ascertain which risk and outcome factors have been examined in relation to maternal sensitivity. Study quality and cross-cultural appropriateness will also be considered. The search using expanded search terms yielded 20 papers -four characterizing maternal sensitivity or style, eight examining maternal sensitivity in relation to risks and outcomes, and eight intervention studies examining efforts to improve maternal sensitivity. Most research was conducted in South Africa - only seven studies were conducted in four other countries. Researchers used a wide array of coding schemes, mostly developed in the west. Ten studies made some adaptations to measures. Language issues and cultural considerations were often not explicitly addressed. Taken together, very limited research on this important topic exists. For the work that does exist, questions around westernized assumptions, language, and appropriateness of measures remain. Substantially more research, informed by both culturally flexible conceptualizations and methodological rigour, is required.

Associations Between Patterns of Alcohol Use and Viral Load Suppression Amongst Women Living with HIV in South Africa.

This study aimed to identify alcohol use patterns associated with viral non-suppression among women living with HIV (WLWH) and the extent to which adherence mediated these relationships. Baseline data on covariates, alcohol consumption, ART adherence, and viral load were collected from 608 WLWH on ART living in the Western Cape, South Africa. We defined three consumption patterns: no/light drinking (drinking ≤ 1/week and ≤ 4 drinks/occasion), occasional heavy episodic drinking (HED) (drinking > 1 and ≤ 2/week and ≥ 5 drinks/occasion) and frequent HED (drinking ≥ 3 times/week and ≥ 5 drinks/occasion). In multivariable analyses, occasional HED (OR 3.07, 95% CI 1.78-5.30) and frequent HED (OR 7.11, 95% CI 4.24-11.92) were associated with suboptimal adherence. Frequent HED was associated with viral non-suppression (OR 2.08, 95% CI 1.30-3.28). Suboptimal adherence partially mediated the relationship between frequent HED and viral non-suppression. Findings suggest a direct relationship between frequency of HED and viral suppression. Given the mediating effects of adherence on this relationship, alcohol interventions should be tailored to frequency of HED while also addressing adherence.

Associations of antenatal maternal psychological distress with infant birth and development outcomes: Results from a South African birth cohort.

BACKGROUND: Antenatal maternal psychological distress is common in low and middle-income countries (LMIC), but there is a dearth of research on its effect on birth and developmental outcomes in these settings, particularly in Sub-Saharan Africa. This study set out to identify risk factors for antenatal maternal psychological distress and determine whether antenatal maternal psychological distress was associated with infant birth and developmental outcomes, using data from the Drakenstein Child Health Study (DCHS), a birth cohort study in South Africa. METHODS: Pregnant women were enrolled in the DCHS from primary care antenatal clinics. Antenatal maternal psychological distress was measured using the Self-Reporting Questionnaire 20-item (SRQ-20). A range of psychosocial measures, including maternal childhood trauma, depression, and posttraumatic stress disorder (PTSD) were administered. Birth outcomes, including premature birth, weight-for-age z-score and head circumference-for-age z-score, were measured using revised Fenton growth charts. The Bayley III Scales of Infant and Toddler Development was administered at 6 months of age to assess infant development outcomes, including cognitive, language, and motor domains in a subset of n=231. Associations of maternal antenatal psychological distress with psychosocial measures, and with infant birth and developmental outcomes were examined using linear regression models. RESULTS: 961 women were included in this analysis, with 197 (21%) reporting scores indicating the presence of psychological distress. Antenatal psychological distress was associated with maternal childhood trauma, antenatal depression, and PTSD, and inversely associated with partner support. No association was observed between antenatal maternal psychological distress and preterm birth or early developmental outcomes, but antenatal maternal psychological distress was associated with a smaller head circumference at birth (coefficient=-0.30, 95% CI: -0.49; -0.10). CONCLUSION: Antenatal maternal psychological distress is common in LMIC settings and was found to be associated with key psychosocial measures during pregnancy, as well as with adverse birth outcomes, in our study population. These associations highlight the potential value of screening for antenatal maternal psychological distress as well as of developing targeted interventions.

The associations of earlier trauma exposures and history of mental disorders with PTSD after subsequent traumas.

Although earlier trauma exposure is known to predict posttraumatic stress disorder (PTSD) after subsequent traumas, it is unclear whether this association is limited to cases where the earlier trauma led to PTSD. Resolution of this uncertainty has important implications for research on pretrauma vulnerability to PTSD. We examined this issue in the World Health Organization (WHO) World Mental Health (WMH) Surveys with 34 676 respondents who reported lifetime trauma exposure. One lifetime trauma was selected randomly for each respondent. DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) PTSD due to that trauma was assessed. We reported in a previous paper that four earlier traumas involving interpersonal violence significantly predicted PTSD after subsequent random traumas (odds ratio (OR)=1.3-2.5). We also assessed 14 lifetime DSM-IV mood, anxiety, disruptive behavior and substance disorders before random traumas. We show in the current report that only prior anxiety disorders significantly predicted PTSD in a multivariate model (OR=1.5-4.3) and that these disorders interacted significantly with three of the earlier traumas (witnessing atrocities, physical violence victimization and rape). History of witnessing atrocities significantly predicted PTSD after subsequent random traumas only among respondents with prior PTSD (OR=5.6). Histories of physical violence victimization (OR=1.5) and rape after age 17 years (OR=17.6) significantly predicted only among respondents with no history of prior anxiety disorders. Although only preliminary due to reliance on retrospective reports, these results suggest that history of anxiety disorders and history of a limited number of earlier traumas might usefully be targeted in future prospective studies as distinct foci of research on individual differences in vulnerability to PTSD after subsequent traumas.

Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

Grey matter structural differences in alcohol-dependent individuals with and without comorbid depression/anxiety-an MRI study.

Although depression and anxiety disorders are common comorbid conditions in alcohol dependence, few structural brain imaging studies have compared alcohol-dependent subjects with and without such comorbidity. In the current study, brain scans of 35 alcohol-dependent with and 40 individuals without diagnosis of a comorbid ICD-10 depressive or anxiety disorder receiving detoxification inpatient treatment were evaluated. Thickness and volumes of automatically segmented neuroanatomical structures were measured in FreeSurfer. Furthermore, associations of brain structure with biological markers and clinical severity markers of alcohol dependence were assessed. Despite comparable addiction severity, the non-comorbid group had evidence of higher cytotoxic effects of alcohol use on hepatic and haematological markers, and showed significantly smaller volumes of total cerebral, and cerebellar grey matter. Similarly, they showed unexpected smaller hippocampal and nucleus accumbens volumes, and thinner frontal, temporal and occipital cortices. Smaller brain volumes correlated with increased markers of hepatic and haematological dysfunction, and with longer duration of alcohol dependence in the non-comorbid group. Evidence of higher biomarkers of alcohol use may be indicative of more severe alcohol dependence or higher vulnerability to ethanol toxicity in this group. Furthermore, psychopathology-related drug treatment, which occurred in 53% of the comorbid group over the recent years, or tissue inflammation may have a moderate effect on the grade of cerebral atrophy in alcohol-dependent patients. Longitudinal studies are needed to investigate this issue more fully.

Polygenic risk for schizophrenia and associated brain structural changes: A systematic review.

BACKGROUND: Genome wide association studies (GWAS) of schizophrenia allow the generation of Polygenic Risk Scores (PRS). PRS can be used to determine the contribution to altered brain structures in this disorder, which have been well described. However, findings from studies using PRS to predict brain structural changes in schizophrenia have been inconsistent. We therefore performed a systematic review to determine the association between schizophrenia PRS and brain structure. METHODS: Following PRISMA systematic review guidelines, databases were searched for literature using key search terms. Inclusion criteria for the discovery sample required case-control schizophrenia GWAS summary statistics from European populations. The target sample was required to be of European ancestry, and have brain structure and genotype information. Quality assessment of the publications was conducted using the Mixed Methods Appraisal Tool for quantitative non-randomised studies. MAIN FINDINGS: A total of seven studies were found to be eligible for review. Five studies found no significant association and two studies found a significant association of schizophrenia PRS with total brain, reduced white matter volume, and globus pallidus volume. However, the latter studies were conducted using smaller discovery (ncases = 9394 ncontrols = 12,462) and target samples compared to the studies with substantially larger discovery (ncases = 33,636 ncontrols = 43,008) and target samples where no association was observed. Taken together, the results suggest that schizophrenia PRS are not significantly associated with brain structural changes in this disorder. CONCLUSIONS: The lack of significant association between schizophrenia PRS and brain structural changes may indicate that intermediate phenotypes other than brain structure should be the focus of future work. Alternatively, however, the lack of association found here may point to limitations of the current evidence-base, and so point to the need for future better powered studies.

Zinc and atopic dermatitis: a systematic review and meta-analysis.

Zinc plays a central role in skin integrity via barrier and immune mechanisms and may also be relevant in the pathogenesis of atopic dermatitis (AD). However, little is known about the relationship between zinc and AD. We performed a systematic review to determine (i) the association between zinc levels or zinc deficiency and AD and (ii) the efficacy of oral zinc supplementation in the treatment of AD. We searched PubMed, Scopus, Web of Science and article references for observational studies on zinc levels or zinc deficiency in participants with AD vs. controls and for randomized control trials (RCTs) on zinc supplementation in AD. For observational studies, we calculated pooled standardized mean differences (SMDs) or odds ratios (ORs) along with 95% confidence intervals (CIs) using a random effects model. We included 14 observational studies and two RCTs. The pooled SMD demonstrated significantly lower serum (SMD 0.66, 95% CI 0.21-1.10, P = 0.004), hair (SMD 0.95, 95% CI 0.38-1.52, P = 0.001) and erythrocyte (SMD 0.95, 95% CI 0.38-1.52, P = 0.001) zinc levels in participants with AD compared to controls. Pooled unadjusted data from three studies showed a non-significant increased odds of AD in those with zinc deficiency compared with those without zinc deficiency (OR = 1.50, 95% CI 0.71-3.16, P = 0.28). One RCT of oral zinc supplementation among AD patients with zinc deficiency showed improvement in extent and severity of AD, while another RCT among all AD patients showed no significant improvement. All the studies were of low or moderate quality. We conclude that low serum, hair and erythrocyte zinc levels are associated with AD. However, the poor quality of included studies makes interpretation of these results problematic. High-quality observational studies are needed to confirm the association between low zinc levels and AD, and RCTs are required to evaluate the merit of zinc supplementation for the treatment or prevention of AD.

Post-traumatic stress disorder associated with sexual assault among women in the WHO World Mental Health Surveys.

BACKGROUND: Sexual assault is a global concern with post-traumatic stress disorder (PTSD), one of the common sequelae. Early intervention can help prevent PTSD, making identification of those at high risk for the disorder a priority. Lack of representative sampling of both sexual assault survivors and sexual assaults in prior studies might have reduced the ability to develop accurate prediction models for early identification of high-risk sexual assault survivors. METHODS: Data come from 12 face-to-face, cross-sectional surveys of community-dwelling adults conducted in 11 countries. Analysis was based on the data from the 411 women from these surveys for whom sexual assault was the randomly selected lifetime traumatic event (TE). Seven classes of predictors were assessed: socio-demographics, characteristics of the assault, the respondent's retrospective perception that she could have prevented the assault, other prior lifetime TEs, exposure to childhood family adversities and prior mental disorders. RESULTS: Prevalence of Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) PTSD associated with randomly selected sexual assaults was 20.2%. PTSD was more common for repeated than single-occurrence victimization and positively associated with prior TEs and childhood adversities. Respondent's perception that she could have prevented the assault interacted with history of mental disorder such that it reduced odds of PTSD, but only among women without prior disorders (odds ratio 0.2, 95% confidence interval 0.1-0.9). The final model estimated that 40.3% of women with PTSD would be found among the 10% with the highest predicted risk. CONCLUSIONS: Whether counterfactual preventability cognitions are adaptive may depend on mental health history. Predictive modelling may be useful in targeting high-risk women for preventive interventions.

Recovery from DSM-IV post-traumatic stress disorder in the WHO World Mental Health surveys.

BACKGROUND: Research on post-traumatic stress disorder (PTSD) course finds a substantial proportion of cases remit within 6 months, a majority within 2 years, and a substantial minority persists for many years. Results are inconsistent about pre-trauma predictors. METHODS: The WHO World Mental Health surveys assessed lifetime DSM-IV PTSD presence-course after one randomly-selected trauma, allowing retrospective estimates of PTSD duration. Prior traumas, childhood adversities (CAs), and other lifetime DSM-IV mental disorders were examined as predictors using discrete-time person-month survival analysis among the 1575 respondents with lifetime PTSD. RESULTS: 20%, 27%, and 50% of cases recovered within 3, 6, and 24 months and 77% within 10 years (the longest duration allowing stable estimates). Time-related recall bias was found largely for recoveries after 24 months. Recovery was weakly related to most trauma types other than very low [odds-ratio (OR) 0.2-0.3] early-recovery (within 24 months) associated with purposefully injuring/torturing/killing and witnessing atrocities and very low later-recovery (25+ months) associated with being kidnapped. The significant ORs for prior traumas, CAs, and mental disorders were generally inconsistent between early- and later-recovery models. Cross-validated versions of final models nonetheless discriminated significantly between the 50% of respondents with highest and lowest predicted probabilities of both early-recovery (66-55% v. 43%) and later-recovery (75-68% v. 39%). CONCLUSIONS: We found PTSD recovery trajectories similar to those in previous studies. The weak associations of pre-trauma factors with recovery, also consistent with previous studies, presumably are due to stronger influences of post-trauma factors.

Chronic light exposure alters serotonergic and orexinergic systems in the rat brain and reverses maternal separation-induced increase in orexin receptors in the prefrontal cortex.

Maternal separation (MS) is a well-established rodent model of depression. Chronic constant light (CCL) treatment during adolescence has been shown to reverse the depression-like behaviour induced by MS. We aimed to further delineate the antidepressant effect of light by investigating the involvement of the dopaminergic, serotonergic and orexinergic systems. MS was used to induce changes in adult male Sprague-Dawley rats, some of whom were also treated with CCL for 3 weeks during adolescence. At P80, rats were decapitated and brain tissue collected for analysis of glutamate- and potassium-stimulated dopamine release in the nucleus accumbens (NAc) using an in vitro superfusion technique. Enzyme-linked immunosorbent assays were employed to measure 5-hydroxytryptamine (5-HT) levels in the hypothalamus and prefrontal cortex (PFC). Western blotting was used to measure orexin receptor 1 (OXR-1) and 2 (OXR-2) in the PFC. MS did not affect 5-HT levels in these rats. However, CCL increased hypothalamic 5-HT and reduced 5-HT levels in the PFC. CCL had opposite effects on OXR levels in the PFC of maternally separated and non-separated rats. MS increased OXR-1 and OXR-2 levels in the PFC, an effect that was normalized by CCL treatment. MS reduced glutamate-stimulated dopamine release in the NAc, an effect that was not reversed by CCL. The present results suggest that CCL treatment affects 5-HT and orexinergic systems in the MS model while not affecting the MS-induced decrease in dopamine release in the NAc. The reversal of changes in the orexinergic system may be of particular relevance to the antidepressant effect of CCL in depression.

The association between biopsychosocial factors and disability in a national health survey in South Africa.

The association between psychosocial factors and disability is less clear. This study investigated the biological and psychosocial (employment and psychological distress) factors associated with level of disability in an adult sample in South Africa. Data were analysed from a cross-sectional survey among adults aged 18-64 (n = 4974). Multiple linear regression was used to investigate the associations of the selected variables with disability. The mean percentage score on the WHODAS scale of disability was 5.31% (95% CI: 4.74-5.88). Age (p < 0.001) and race (p = 0.0002) were significantly associated with disability, and history of stroke (ß = 7.19, 95% CI: 3.19-11.20) and heart-related conditions (ß = 2.08, 95% CI: [0.23-3.93) showed positive associations. Of the psychosocial variables, psychological distress (ß = 10.49 [8.63-12.35]) showed a strong positive association while employment (-1.62 [-2.36 to -0.88]) showed a negative association with disability. The association between demographic factors, medical conditions and increased disability confirms the findings in the literature. The finding that psychological distress is associated with increased disability has not been frequently reported. This study highlights specific psychosocial targets that may be usefully addressed by health policies and interventions in order to improve disability management.

Posttraumatic stress disorder in the World Mental Health Surveys.

BACKGROUND: Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking. METHODS: Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics. RESULTS: The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed. CONCLUSIONS: PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.

Comorbidity, age of onset and suicidality in obsessive-compulsive disorder (OCD): An international collaboration.

OBJECTIVES: To collate data from multiple obsessive-compulsive disorder (OCD) treatment centers across seven countries and five continents, and to report findings in relation to OCD comorbidity, age of onset of OCD and comorbid disorders, and suicidality, in a large clinical and ethnically diverse sample, with the aim of investigating cultural variation and the utility of the psychiatric diagnostic classification of obsessive-compulsive and related disorders. METHODS: Researchers in the field of OCD were invited to contribute summary statistics on current and lifetime psychiatric comorbidity, age of onset of OCD and comorbid disorders and suicidality in their patients with OCD. RESULTS: Data from 3711 adult patients with primary OCD came from Brazil (n=955), India (n=802), Italy (n=750), South Africa (n=565), Japan (n=322), Australia (n=219), and Spain (n=98). The most common current comorbid disorders were major depressive disorder (28.4%; n=1055), obsessive-compulsive personality disorder (24.5%, n=478), generalized anxiety disorder (19.3%, n=716), specific phobia (19.2%, n=714) and social phobia (18.5%, n=686). Major depression was also the most commonly co-occurring lifetime diagnosis, with a rate of 50.5% (n=1874). OCD generally had an age of onset in late adolescence (mean=17.9years, SD=1.9). Social phobia, specific phobia and body dysmorphic disorder also had an early age of onset. Co-occurring major depressive disorder, generalized anxiety disorder and psychotic disorders tended to have a later age of onset than OCD. Suicidal ideation within the last month was reported by 6.4% (n=200) of patients with OCD and 9.0% (n=314) reported a lifetime history of suicide attempt. CONCLUSIONS: In this large cross-continental study, comorbidity in OCD was common. The high rates of comorbid major depression and anxiety disorders emphasize the need for clinicians to assess and monitor for these disorders. Earlier ages of onset of OCD, specific phobia and social phobia may indicate some relatedness between these disorders, but this requires further study. Although there do not appear to be significant cultural variations in rates or patterns of comorbidity and suicidality, further research using similar recruitment strategies and controlling for demographic and clinical variables may help to determine whether any sociocultural factors protect against suicidal ideation or psychiatric comorbidity in patients with OCD.

Maternal and infant factors had a significant impact on birthweight and longitudinal growth in a South African birth cohort.

AIM: This birth cohort study investigated longitudinal infant growth and associated factors in a multiethnic population living in a low-resource district surrounding the town of Paarl in South Africa. METHODS: Between March 2012 and October 2014, all mothers attending their second trimester antenatal visit at Paarl Hospital were approached for enrolment. Mother-infant pairs were followed from birth until 12 months of age. Comprehensive socio-demographic, nutritional and psychosocial data were collected at birth, two, six and 12 months. Infant anthropometry was analysed as z-scores for weight and height. Linear regression was used to investigate predictors of birthweight, and linear mixed-effects models were used to investigate predictors of infant growth. RESULTS: Longitudinal anthropometric data from 792 infants were included: 53% were Black African, 47% were mixed race, and 15% were born preterm. Stunting occurred in 13% of infants at 12 months. Maternal height, antenatal alcohol and tobacco use, ethnicity and socioeconomic status were significant predictors of birthweight. In the adjusted mixed-effects model, birthweight was a significant predictor of growth during the first year of life. CONCLUSION: Birthweight was an important predictor of growth trajectory during infancy. Birthweight and growth were influenced by several important modifiable factors.

Translational neuroscience of basolateral amygdala lesions: Studies of Urbach-Wiethe disease.

Urbach-Wiethe disease (UWD) is an extremely rare autosomal recessive disorder characterized by mutations in the extracellular matrix protein 1 gene on chromosome 1. Typical clinical manifestations include voice hoarseness in early infancy and neuropsychiatric, laryngeal, and dermatological pathologies later in life. Neuroimaging studies have revealed a pattern of brain calcification often but not exclusively leading to selective bilateral amygdala damage. A large body of work on amygdala lesions in rodents exists, generally employing a subregion model focused on the basolateral amygdala (BLA) and the central-medial amygdala. However, human work usually considers the amygdala as a unified structure, not only complicating the translation of animal findings to humans but also providing a unique opportunity for further research. To compare data from rodent models with human cases and to complement existing data from Europe and North America, a series of investigations was undertaken on UWD subjects with selective BLA damage in the Namaqualand region, South Africa. This review presents key findings from this work, including fear processing, social-economic behavior, and emotional conflict processing. Our findings are broadly consistent with and support rodent models of selective BLA lesions and show that the BLA is integral to processing sensory stimuli and exhibits inhibitory regulation of responses to unconditioned innate fear stimuli. Furthermore, our findings suggest that the human BLA mediates calculative-instrumental economic behaviors and may compromise working memory via competition for attentional resources between the BLA salience detection system and the dorsolateral prefrontal cortex working memory system.

The epidemiology of traumatic event exposure worldwide: results from the World Mental Health Survey Consortium.

BACKGROUND: Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs. METHOD: General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure. RESULTS: Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types - witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury - accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events. CONCLUSIONS: Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization.

Obtaining informed consent for genomics research in Africa: analysis of H3Africa consent documents.

BACKGROUND: The rise in genomic and biobanking research worldwide has led to the development of different informed consent models for use in such research. This study analyses consent documents used by investigators in the H3Africa (Human Heredity and Health in Africa) Consortium. METHODS: A qualitative method for text analysis was used to analyse consent documents used in the collection of samples and data in H3Africa projects. Thematic domains included type of consent model, explanations of genetics/genomics, data sharing and feedback of test results. RESULTS: Informed consent documents for 13 of the 19 H3Africa projects were analysed. Seven projects used broad consent, five projects used tiered consent and one used specific consent. Genetics was mostly explained in terms of inherited characteristics, heredity and health, genes and disease causation, or disease susceptibility. Only one project made provisions for the feedback of individual genetic results. CONCLUSION: H3Africa research makes use of three consent models-specific, tiered and broad consent. We outlined different strategies used by H3Africa investigators to explain concepts in genomics to potential research participants. To further ensure that the decision to participate in genomic research is informed and meaningful, we recommend that innovative approaches to the informed consent process be developed, preferably in consultation with research participants, research ethics committees and researchers in Africa.

Polymorphisms within the neuronal cadherin (CDH2) gene are associated with obsessive-compulsive disorder (OCD) in a South African cohort.

OCD is characterised by recurrent obsessions and compulsions that result in severe distress and increased risk for comorbidity. Recently published findings have indicated that the neuronal cadherin gene (CDH2) plays a role in the development of canine OCD, and led us to investigate the human ortholog, CDH2, in a human OCD cohort. Seven CDH2 polymorphisms were selected and genotyped in a South African Caucasian cohort of 234 OCD patients and 180 healthy controls using TaqMan assays. Polymorphisms were analysed in a single-locus and haplotypic context. Of the seven polymorphisms, two reached statistical significance for OCD under additive and codominant models of inheritance (rs1120154 and rs12605662). CDH2 SNP, rs1120154, C-allele carriers were found to be significantly associated with lower risk to develop OCD compared to TT-homozygotes (OR = 0.49; 95% CI: 0.32-0.75; p < 0.001), and rs12605662 G-allele carriers were significantly associated with reduced risk OCD compared to TT-homozygotes (OR = 0.46; 95% CI: 0.30-0.71; p < 0.001), Furthermore, a single haplotype was found to infer an increased risk for OCD diagnosis (*rs8087457-rs1148374: A-T). Polymorphisms within the CDH2 gene are associated with susceptibility to OCD in a South African cohort.