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 30-day suicidal ideation and intent: Results of the South African National Student Mental Health Survey.

BACKGROUND: Although suicide prevention is recognised as a priority among university students in South Africa (SA), it is unclear what proportion of students require urgent indicated interventions and what the characteristics are of these students. OBJECTIVE: To assess the prevalence and sociodemographic correlates of 30-day suicidal ideation, frequency of ideation and self-reported intention to act on ideation in the next year among a national sample of SA university students. METHODS: Self-report cross-sectional data were collected online from students (N=28 268) at 17 universities across SA as part of the national student mental health survey. Students reported suicidal ideation in the past 30 days, frequency of ideation and intention to act on ideation in the next year. Data were weighted within institutions by gender and population group, and across the four main types of universities (historically white, historically disadvantaged, technical and distance learning) to correct for response rate discrepancies. Prevalence was estimated with these weighted in the total sample and across types of universities. Poisson regression with robust error variances was used to investigate associations of sociodemographic characteristics with ideation and intention to act on suicidal ideation. Results are reported as relative risks (RRs) with design-based 95% confidence intervals (CIs). RESULTS: Thirty-day prevalence of suicidal ideation was 24.4% (standard error (SE) 0.3), with 2.1% (SE 0.1) and 4.1% (SE 0.1), respectively, reporting suicidal ideation all/almost all the time, or most of the time. A total of 1.5% (SE 0.1) of respondents reported being very likely to act on their suicidal ideation, while 3.9% (SE 0.2) were somewhat likely, 8.7% (SE 0.2) were not very likely and 85.8 (SE 0.5) either reported no suicidal ideation or that they were not at all likely to act on this ideation. Risk of suicidal ideation with high intent in the total sample was elevated among females (RR 1.9, 95% CI 1.3 - 2.7) and gender non-conforming students (RR 4.3, 95% CI 1.4 - 13.0) relative to males, black African students compared with white students (RR 3.6, 95% CI 1.9 - 7.1), students whose parents did not progress to secondary school compared with students whose parents had a university education (RR 1.6, 95% CI 1.0 - 2.5) and sexual minority students compared with heterosexual students (RR 1.9, 95% CI 1.3 - 2.6). Among students with 30-day ideation (controlling for frequency of ideation), only two of these predictors of high intent remained significant: identifying as black African (RR 2.7, 95% CI 1.4 - 5.1), and having parents with less than secondary education (RR 1.5, 95% CI 1.0 - 2.1). CONCLUSION: Scalable suicide prevention interventions are needed to reach the large number of SA students who report suicidal ideation with intent.

Polygenic risk associations with developmental and mental health outcomes in childhood and adolescence: A systematic review.

Background: Neurodevelopmental and mental health disorders in childhood constitute an emerging global concern, with adverse sequelae which span children's physical, psychological and social well-being. The aetiology of these disorders is likely complex, multifactorial and polygenic. Polygenic risk scores (PRS), an estimate of an individual's genetic liability toward a disorder, have been increasingly used in psychiatric research to explore genetic associations with disorders of interest. However, limited work delineates polygenic associations with development and mental health in childhood populations.We aimed to systematically review existing literature on associations between genetic risk (as measured by PRS) and neurodevelopmental and mental health outcomes in childhood and adolescence. Methods: Following the recommended Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines, databases were searched using key search terms. The search commenced in March 2021 and concluded in June 2021. The studies eligible for inclusion were full-text articles investigating polygenic risk associations with neurodevelopmental and/or mental health outcomes in childhood or adolescence. Results: Fourteen studies were eligible for inclusion in this systematic review. The association between higher PRS for attention-deficit/hyperactivity disorder (ADHD) and adverse developmental/mental health outcomes in childhood and adolescence was reported by five studies. Additionally, associations between PRS for bipolar disorder or major depressive disorder and adverse outcomes of interest were also described by two studies; and two studies highlighted associations between schizophrenia PRS and mental health disorders in childhood. The remaining studies highlighted shared polygenic contributions between and within NDDs and mental health disorders in children. Conclusion: The findings of this systematic review suggest that PRS for neurodevelopmental and mental health disorders may associate with adverse neurodevelopmental and mental health outcomes from early childhood to adolescence. In addition, these associations seemed not to be phenotype-specific, suggesting potential shared genetic variation across the phenotypes of interest.

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.

Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders.

Neuropsychiatric disorders are increasingly conceptualized as overlapping spectra sharing multi-level neurobiological alterations. However, whether transdiagnostic cortical alterations covary in a biologically meaningful way is currently unknown. Here, we studied co-alteration networks across six neurodevelopmental and psychiatric disorders, reflecting pathological structural covariance. In 12,024 patients and 18,969 controls from the ENIGMA consortium, we observed that co-alteration patterns followed normative connectome organization and were anchored to prefrontal and temporal disease epicenters. Manifold learning revealed frontal-to-temporal and sensory/limbic-to-occipitoparietal transdiagnostic gradients, differentiating shared illness effects on cortical thickness along these axes. The principal gradient aligned with a normative cortical thickness covariance gradient and established a transcriptomic link to cortico-cerebello-thalamic circuits. Moreover, transdiagnostic gradients segregated functional networks involved in basic sensory, attentional/perceptual, and domain-general cognitive processes, and distinguished between regional cytoarchitectonic profiles. Together, our findings indicate that shared illness effects occur in a synchronized fashion and along multiple levels of hierarchical cortical organization.

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.

A novel brief treatment for methamphetamine use disorders in South Africa: a randomised feasibility trial.

BACKGROUND: Effective brief treatments for methamphetamine use disorders (MAUD) are urgently needed to complement longer more intensive treatments in low and middle income countries, including South Africa. To address this gap, the purpose of this randomised feasibility trial was to determine the feasibility of delivering a six-session blended imaginal desensitisation, plus motivational interviewing (IDMI) intervention for adults with a MAUD. METHODS: We enrolled 60 adults with a MAUD and randomly assigned them 1:1 to the IDMI intervention delivered by clinical psychologists and a control group who we referred to usual care. Feasibility measures, such as rates of recruitment, consent to participate in the trial and retention, were calculated. Follow-up interviews were conducted at 6 weeks and 3 months post-enrollment. RESULTS: Over 9 months, 278 potential particiants initiated contact. Following initial screening 78 (28%) met inclusion criteria, and 60 (77%) were randomised. Thirteen of the 30 participants assigned to the treatment group completed the intervention. Both psychologists were highly adherent to the intervention, obtaining a fidelity rating of 91%. In total, 39 (65%) participants completed the 6-week follow-up and 40 (67%) completed the 3-month follow-up. The intervention shows potential effectiveness in the intention-to-treat analysis where frequency of methamphetamine use was significantly lower in the treatment than in the control group at both the 6 week and 3-month endpoints. No adverse outcomes were reported. CONCLUSIONS: This feasibility trial suggests that the locally adapted IDMI intervention is an acceptable and safe intervention as a brief treatment for MAUD in South Africa. Modifications to the study design should be considered in a fully powered, definitive controlled trial to assess this potentially effective intervention. Trial registration The trial is registered with the Pan African Clinical Trials Registry (Trial ID: PACTR201310000589295).

Comorbidity within mental disorders: a comprehensive analysis based on 145 990 survey respondents from 27 countries.

AIMS: Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys. METHODS: The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women. RESULTS: Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2-110.8, interquartile range = 6.0-19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1-2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs. CONCLUSIONS: Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.

Intermittent explosive disorder subtypes in the general population: association with comorbidity, impairment and suicidality.

AIMS: Intermittent explosive disorder (IED) is characterised by impulsive anger attacks that vary greatly across individuals in severity and consequence. Understanding IED subtypes has been limited by lack of large, general population datasets including assessment of IED. Using the 17-country World Mental Health surveys dataset, this study examined whether behavioural subtypes of IED are associated with differing patterns of comorbidity, suicidality and functional impairment. METHODS: IED was assessed using the Composite International Diagnostic Interview in the World Mental Health surveys (n = 45 266). Five behavioural subtypes were created based on type of anger attack. Logistic regression assessed association of these subtypes with lifetime comorbidity, lifetime suicidality and 12-month functional impairment. RESULTS: The lifetime prevalence of IED in all countries was 0.8% (s.e.: 0.0). The two subtypes involving anger attacks that harmed people ('hurt people only' and 'destroy property and hurt people'), collectively comprising 73% of those with IED, were characterised by high rates of externalising comorbid disorders. The remaining three subtypes involving anger attacks that destroyed property only, destroyed property and threatened people, and threatened people only, were characterised by higher rates of internalising than externalising comorbid disorders. Suicidal behaviour did not vary across the five behavioural subtypes but was higher among those with (v. those without) comorbid disorders, and among those who perpetrated more violent assaults. CONCLUSIONS: The most common IED behavioural subtypes in these general population samples are associated with high rates of externalising disorders. This contrasts with the findings from clinical studies of IED, which observe a preponderance of internalising disorder comorbidity. This disparity in findings across population and clinical studies, together with the marked heterogeneity that characterises the diagnostic entity of IED, suggests that it is a disorder that requires much greater research.

Investigating hair zinc concentrations in children with and without atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin condition that disproportionately affects children and is associated with reduced quality of life. Zinc deficiency may contribute to the pathogenesis of AD because zinc plays a role in epidermal barrier integrity and the immune system. Systematic review evidence suggests that low zinc is associated with AD, but limitations of included studies support further investigation. OBJECTIVES: To investigate hair zinc concentrations in children with AD v. healthy controls in a low- to middle-income country setting. METHODS: One hundred and five children aged 1 - 12 yea-rs participated in a frequency-matched for age case-control study. The outcome variable, AD, was confirmed by a clinician and corroborated using the UK Working Party criteria. The primary predictor, long-term average zinc concentration, was determined by measuring hair zinc using inductively coupled mass spectrometry. Baseline demographic characteristics, anthropometry and measures of socioeconomic status were included in our logistic regression analysis. Subgroup analysis was performed where interaction terms suggested effect modification. RESULTS: Using data from the overall sample, population median hair zinc was not significantly different between children with AD and healthy controls. However, subgroup analysis suggested a clinically and statistically significant difference in median zinc between children with AD (175.35 µg/g) and healthy controls (206.4 µg/g) in the older age group (5 - 12 years) (p=0.01). In this age group, multivariable logistic regression analysis also found significantly decreased hair zinc concentrations in AD (odds ratio 0.83; 95% confidence interval 0.66 - 0.96; p=0.046). CONCLUSIONS: The inverse association between zinc status and AD in children aged 5 - 12 years in our setting is consistent with the international literature. The clinical importance of decreased zinc levels in AD is not yet known. Further investigation into relevant underlying mechanisms seems warranted given the global reach of AD, its effect on quality of life, and the low cost of potential zinc-based interventions.

Genetics of schizophrenia in the South African Xhosa.

Africa, the ancestral home of all modern humans, is the most informative continent for understanding the human genome and its contribution to complex disease. To better understand the genetics of schizophrenia, we studied the illness in the Xhosa population of South Africa, recruiting 909 cases and 917 age-, gender-, and residence-matched controls. Individuals with schizophrenia were significantly more likely than controls to harbor private, severely damaging mutations in genes that are critical to synaptic function, including neural circuitry mediated by the neurotransmitters glutamine, γ-aminobutyric acid, and dopamine. Schizophrenia is genetically highly heterogeneous, involving severe ultrarare mutations in genes that are critical to synaptic plasticity. The depth of genetic variation in Africa revealed this relationship with a moderate sample size and informed our understanding of the genetics of schizophrenia worldwide.

The prevalence of mental health problems in sub-Saharan adolescents living with HIV: a systematic review.

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 prevalence of mental health problems in this population and explores associated factors. A systematic database search (Medline, PsycINFO, Scopus) with an additional hand search was conducted. Peer-reviewed studies on adolescents (aged 10-19), published between 2008 and 2019, assessing mental health symptoms or psychiatric disorders, either by standardized questionnaires or by diagnostic interviews, were included. The search identified 1461 articles, of which 301 were eligible for full-text analysis. Fourteen of these, concerning HIV-positive adolescents, met the inclusion criteria and were critically appraised. Mental health problems were highly prevalent among this group, with around 25% scoring positive for any psychiatric disorder and 30-50% showing emotional or behavioral difficulties or significant psychological distress. Associated factors found by regression analysis were older age, not being in school, impaired family functioning, HIV-related stigma and bullying, and poverty. Social support and parental competence were protective factors. Mental health problems among HIV-positive adolescents are highly prevalent and should be addressed as part of regular HIV care.

Structural brain differences between ultra-endurance athletes and sedentary persons.

Participation in ultra-endurance events has increased in recent years and requires extreme levels of moderate to vigorous physical activity (MVPA). Moderate levels of MVPA have been associated with increased brain volume but the effects of extreme levels of MVPA on brain volume is unknown. As a result, we sought to compare the brains of those who engage in extremely high levels of MVPA with those who are sedentary using magnetic resonance imaging. We performed whole brain volumetric analyses and voxel-based morphometry on 12 ultra-endurance athletes (1078.75 ±â€¯407.86 min of MVPA/week) and 9 sedentary persons (18.0 ±â€¯56.9 min of MVPA/week). Whole-brain analyses revealed that those who participate in ultra-endurance training have increased grey (p< 0.0001), white (p = 0.031), and total matter volume (p < 0.0001), while regional analyses revealed that ultra-endurance athletes have smaller regional grey matter volume in the right primary sensory and motor cortex, inferior and middle frontal gyrus, and left thalamus. Future research is warranted to determine why ultra-endurance athletes have lower regional volumes in these areas despite having overall increased grey and white matter volumes.

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.

Potential use of clinical polygenic risk scores in psychiatry - ethical implications and communicating high polygenic risk.

Psychiatric disorders present distinct clinical challenges which are partly attributable to their multifactorial aetiology and the absence of laboratory tests that can be used to confirm diagnosis or predict risk. Psychiatric disorders are highly heritable, but also polygenic, with genetic risk conferred by interactions between thousands of variants of small effect that can be summarized in a polygenic risk score. We discuss four areas in which the use of polygenic risk scores in psychiatric research and clinical contexts could have ethical implications. First, there is concern that clinical use of polygenic risk scores may exacerbate existing health inequities. Second, research findings regarding polygenic risk could be misinterpreted in stigmatising or discriminatory ways. Third, there are concerns associated with testing minors as well as eugenics concerns elicited by prenatal polygenic risk testing. Fourth, potential challenges that could arise with the feedback and interpretation of high polygenic risk for a psychiatric disorder would require consideration. While there would be extensive overlap with the challenges of feeding back genetic findings in general, the potential clinical use of polygenic risk scoring warrants discussion in its own right, given the recency of this possibility. To this end, we discuss how lay interpretations of risk and genetic information could intersect. Consideration of these factors would be necessary for ensuring effective and constructive communication and interpretation of polygenic risk information which, in turn, could have implications for the uptake of any therapeutic recommendations. Recent advances in polygenic risk scoring have major implications for its clinical potential, however, care should be taken to ensure that communication of polygenic risk does not feed into problematic assumptions regarding mental disorders or support reductive interpretations.

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.

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.