The evidence supports an association between HIV infection in children and adolescents and cognitive impairment in the domains of working memory, executive function and processing speed, with effect size estimates also providing some support for deficits in visual memory and visual-spatial ability.

Mental disorders represent a major public health burden worldwide. This is likely to rise in the next decade, with the highest increases predicted to occur in low- and middle-income countries. Current psychotropic medication treatment guidelines focus on uniform approaches to the treatment of heterogeneous disorders and achieve only partial therapeutic success. Developing a global precision medicine approach in psychiatry appears attractive, given the value of this approach in other fields of medicine, such as oncology and infectious diseases. In this horizon scanning analysis, we review the salient opportunities and challenges for precision medicine in psychiatry over the next decade. Variants within numerous genes involved in a range of pathways have been implicated in psychotropic drug response and might ultimately be used to guide choice of pharmacotherapy. Multipronged approaches such as multi-omics (genomics, proteomics, metabolomics) analyses and systems diagnostics together with high-throughput sequencing and genotyping technologies hold promise for identifying precise and targeted treatments in mental disorders. To date, however, the vast majority of pharmacogenomics work has been undertaken in high-income countries on a relatively small proportion of the global population, and many other challenges face the field. Opportunities and challenges for establishing a global roadmap for precision medicine in psychiatry are discussed in this article.

Post-traumatic stress disorder (PTSD) develops in only some people following trauma exposure, but the mechanisms differentially explaining risk versus resilience remain largely unknown. PTSD is heritable but candidate gene studies and genome-wide association studies (GWAS) have identified only a modest number of genes that reliably contribute to PTSD. New gene-based methods may help identify additional genes that increase risk for PTSD development or severity. We applied gene-based testing to GWAS data from the Grady Trauma Project (GTP), a primarily African American cohort, and identified two genes (NLGN1 and ZNRD1-AS1) that associate with PTSD after multiple test correction. Although the top SNP from NLGN1 did not replicate, we observed gene-based replication of NLGN1 with PTSD in the Drakenstein Child Health Study (DCHS) cohort from Cape Town. NLGN1 has previously been associated with autism, and it encodes neuroligin 1, a protein involved in synaptogenesis, learning, and memory. Within the GTP dataset, a single nucleotide polymorphism (SNP), rs6779753, underlying the gene-based association, associated with the intermediate phenotypes of higher startle response and greater functional magnetic resonance imaging activation of the amygdala, orbitofrontal cortex, right thalamus and right fusiform gyrus in response to fearful faces. These findings support a contribution of the NLGN1 gene pathway to the neurobiological underpinnings of PTSD.

Trichotillomania (hair pulling disorder), excoriation (skin-picking) disorder, and other body-focused repetitive behavior disorders (BFRBDs) have received increasing attention in the psychiatric nomenclature. Trichotillomania was introduced in the Diagnostic and Statistical Manual of Mental Disorders (DSM) in DSM-III-R in 1987, whereas skin-picking disorder was introduced in the most recent edition of the manual, DSM-5.1 DSM-5 includes both disorders and also refers to other less well-studied BFRBDs, such as nail biting, in a new chapter on obsessive-compulsive and related disorders.

In recent years there have been significant insights into the complex aetiologies of neurodevelopmental brain disorders. For example, neuropsychiatric genetics has achieved success with the identification of 108 loci for schizophrenia (Schizophrenia Working Group of the Psychiatric Genomics ConsortSchizophrenia Working Group of the Psychiatric Genomics Consortium Biological insights from 108 schizophrenia-associated genetic loci.Nature. 2014; 511: 421-427Crossref PubMed Scopus (5316) Google Scholar). Furthermore, meta-analyses of genome-wide association study (GWAS) results encompassing thousands of samples have been completed for other psychiatric disorders including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders, bipolar disorder, and major depressive disorder. However, published results on neuropsychiatric disorders have – thus far – predominantly included samples of European ancestry. In Fig. 1a , we compare world ancestry to the ancestry of individuals in the largest psychiatric GWAS meta-analyses published prior to 2015 (Total N = 121,985). The lack of African samples in the meta-analyses so clearly depicted here, raises concern that Africa will be left behind in terms of neuropsychiatric genetic research and subsequent treatment innovation. There is biological rationale for conducting genetic research in African populations. It has been shown that modern humans originated in Africa and subsequently migrated to other parts of the world (Campbell and Tishkoff, 2008Campbell M.C. Tishkoff S.A. African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping.Annu. Rev. Genomics Hum. Genet. 2008; 9: 403-433Crossref PubMed Scopus (505) Google Scholar). As the cradle of humanity, Africa and its indigenous populations are a valuable resource when it comes to genetic research. Modern African genomes are characterised by a unique pattern of variation as a result of migration and admixture in earlier generations as well as recombination, natural selection and mutation. With an increase in allelic diversity and shorter segments of linkage disequilibrium, African genomes hold informative alleles which are useful for fine mapping of disease causing alleles (Campbell and Tishkoff, 2008Campbell M.C. Tishkoff S.A. African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping.Annu. Rev. Genomics Hum. Genet. 2008; 9: 403-433Crossref PubMed Scopus (505) Google Scholar). However, there is limited knowledge on African-specific functional variants highlighting the need to investigate African population groups, particularly for neuropsychiatric disorders. As genetic findings are translated into intervention, genetic research focused solely on European populations threatens to widen the existing large disparity between Africa and the rest of the world in mental health treatment. The vast majority of work is being conducted in high-income settings, such as the U.S.A. and Denmark, with a large proportion of subjects of Northern European ancestry (Fig. 1a). To date, there have been no large-scale studies on the genetics of neuropsychiatric disorders in African populations. The few studies that have been conducted have been on small samples, typically under a thousand in number (Kolassa et al., 2010Kolassa I. Kolassa S. Ertl V. Papassotiropoulos A. Dominique J. The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-O-methyltransferase Val 158 Met polymorphism.Biol. Psychiatry. 2010; 67: 304-308Summary Full Text Full Text PDF PubMed Scopus (202) Google Scholar). Recent successes in studies of schizophrenia have demonstrated that very large scale meta-analysis is necessary to identify genetic variants associated with neuropsychiatric disorders. Without engaging African scientists and physicians and performing studies of African populations, there is a significant risk that the recent advances in neuropsychiatric genetics will result in a widening of the massive research and treatment gaps between Africa and the rest of the world. Indeed, one of the aims of the movement for global mental health is to decrease inequality in mental health outcomes particularly for low- and middle-income countries (Patel, 2012Patel V. Global mental health: from science to action.Harv. Rev. Psychiatry. 2012; 20: 6-12Crossref PubMed Scopus (112) Google Scholar), typical of much of the African continent. Researchers in Africa are faced with a number of unique challenges. Research funding is scarce, and African scientists are often not eligible for training mechanisms offered by the National Institutes of Health and other funding agencies. Much of the funding that is available focuses on public mental health issues rather than on neuroscience or the integration of neuroscience with public mental health (Stein et al., 2015Stein D.J. He Y. Phillips A. Sahakian B.J. Williams J. Patel V. Global mental health and neuroscience: potential synergies.. 2015; 2: 178-185Google Scholar). Also, many African countries lack the infrastructure required to conduct large-scale neuropsychiatric genetics research, e.g. refrigeration for blood samples and cloud-based technology for phenotypic data collection. Furthermore, there is a shortage of highly skilled geneticists and clinician-scientists, highlighting the need for training and capacity building in African countries. In particular, clinicians need to develop culturally appropriate tools for the diagnosis and phenotyping of these disorders. There are also several ethical considerations, especially in the context of collaborative global health partnerships between high and low to middle income countries. These include ethical issues about informed consent; poverty, low literacy, language barriers and poor access to healthcare (De Vries et al., 2011De Vries J. Bull S.J. Doumbo O. Ibrahim M. Mercereau-Puijalon O. Kwiatkowski D. et al.Ethical issues in human genomics research in developing countries.BMC Med. Ethics. 2011; 12 (5–6939-12-5)Google Scholar). Additionally, fairness in international collaboration needs to be ensured, with researchers having equal access to data, and intellectual property rights adequately addressed. When working with individuals with mental health problems, in countries with a lack or paucity of mental health prioritization, these types of challenges are exacerbated. Lastly, existing microarray panels may not adequately capture common haplotypes in African populations. This highlights the need for genotyping chips which contain tag single nucleotide polymorphisms (SNPs) that are able to encapsulate common variation across African population groups (Gurdasani et al., 2015Gurdasani D. Carstensen T. Tekola-Ayele F. Pagani L. Tachmazidou I. Hatzikotoulas K. et al.The African Genome Variation Project shapes medical genetics in Africa.Nature. 2015; 517: 327-332Crossref PubMed Scopus (358) Google Scholar). Despite these challenges, a number of emerging studies may hold promise for future neurogenetics research in Africa. For example, the Drakenstein Child Health Study (http://www.paediatrics.uct.ac.za/scah/dclhs) is a multidisciplinary South African birth cohort study investigating genetic and environmental risk factors for common mental disorders. The cohort consists of 1200 mother–child pairs and a subset of these individuals has already been genotyped with a genome-wide panel of markers shown to be relevant to psychiatric disorders. The post-traumatic stress disorder (PTSD) subgroup of the multi-national Psychiatric Genomics Consortium (PGC) (http://www.med.unc.edu/pgc) aims to carry out large-scale GWASs and has included South African samples in their analyses. To date, the PTSD-PGC group has access to approximately 20,000 samples from study sites. As depicted by Fig. 1b, the ancestry of individuals in the PGC-PTSD studies is more diverse than large psychiatric GWAS in general. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Network (http://enigma.ini.usc.edu/about-2/), a consortium investigating brain structure, function and disease using brain imaging and genomics, has also included samples from South Africa. This consortium comprises 70 institutions world-wide and consists of different disease working groups including those for schizophrenia, bipolar disorder and PTSD, respectively. Lastly, the Human Heredity and Health in Africa (H3Africa) (http://h3africa.org/) initiative seeks to improve health in African populations by investigating genomic and environmental factors contributing to common disease. This initiative includes a study investigating the genetic basis of schizophrenia in the southern African Xhosa-speaking population group. Using exome-sequencing and by investigating genome-wide copy-number variation, this study aims to identify genes associated with schizophrenia. Similarly, an initiative tentatively called the Neuropsychiatric Genetics in African Populations (Neuro-GAP), by the Stanley Center for Psychiatric Research of the Broad Institute of MIT and Harvard University, in collaboration with the University of Cape Town and a number of other African institutions, aims to improve and achieve equity in mental health by expanding the infrastructure and research findings from large-scale psychiatric genetic epidemiology to Africa. This will be achieved by enhancing neuropsychiatric genetic research capacity in Africa through the training of scientists, conducting very large-scale sample collection and analysis through supporting the development of locally led research programmes in neuropsychiatric genetics and leveraging unique opportunities in population genetics. In conclusion, while there is a clear need for further work in elucidating the genetics of neuropsychiatric disorders in African populations, several challenges will first need to be tackled. An effective local network of neurogenetic researchers needs to be established in order to discover genetic variation predisposing to neuropsychiatric disorders. This research needs to avoid prior pitfalls of “safari research” by engaging and training African scientists and physicians to improve phenotyping and perform studies of African populations to ensure long-term capacity to translate genetic findings in a way that will benefit African peoples. Dan Stein has received research grants and/or consultancy honoraria from AMBRF, Biocodex, Cipla, Lundbeck, National Responsible Gambling Foundation, Novartis, Servier, and Sun. The authors are members of the Neuropsychiatric Genetics in African Populations (Neuro-GAP) consortium. Dan Stein is funded by the Medical Research Council of South Africa.

We extended previous epidemiological data to a cross-national context. The presence of recurrent PAs in particular is associated with subsequent onset and course of mental disorders beyond agoraphobia and PD, and might serve as a generic risk marker for psychopathology.

The length of LP may influence the observed time trends in incident AMIs. This effect is more evident in older women.

Antenatal and early life tobacco smoke exposure is highly prevalent in this community, and may impact on birth outcomes and subsequent child health. Smoking cessation interventions are urgently needed to reduce tobacco smoke exposure in African communities.

Periconceptional folic acid supplement use showed no association with severe CHDs in the newborn. An unexpected association with an increased risk of septal defects warrants further investigation.

Social and affective research in humans is increasingly using functional and structural neuroimaging techniques to aid the understanding of how hormones, such as testosterone, modulate a wide range of psychological processes. We conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of testosterone administration, and of fMRI studies that measured endogenous levels of the hormone, in relation to social and affective stimuli. Furthermore, we conducted a review of structural MRI i.e. voxel based morphometry (VBM) studies which considered brain volume in relation to testosterone levels in adults and in children. In the included testosterone administration fMRI studies, which consisted of female samples only, bilateral amygdala/parahippocampal regions as well as the right caudate were significantly activated by social-affective stimuli in the testosterone condition. In the studies considering endogenous levels of testosterone, stimuli-invoked activations relating to testosterone levels were noted in the bilateral amygdala/parahippocampal regions and the brainstem. When the endogenous testosterone studies were split by sex, the significant activation of the brain stem was seen in the female samples only. Significant stimuli-invoked deactivations relating to endogenous testosterone levels were also seen in the right and left amygdala/parahippocampal regions studies. The findings of the VBM studies were less consistent. In adults larger volumes in the limbic and temporal regions were associated with higher endogenous testosterone. In children, boys showed a positive correlation between testosterone and brain volume in many regions, including the amygdala, as well as global grey matter volume, while girls showed a neutral or negative association between testosterone levels and many brain volumes. In conclusion, amygdalar and parahippocampal regions appear to be key target regions for the acute actions of testosterone in response to social and affective stimuli, while neurodevelopmentally the volumes of a broader network of brain structures are associated with testosterone levels in a sexually dimorphic manner.

Abstract Since the publication of the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), this classification system has not only drawn on empirical investigations of anxiety and related disorders, but has also played a key role in influencing clinical practice and research. After the publication of the DSM-IV, work on the anxiety and related disorders continued to accumulate, so that publication of DSM-5 provided a timely opportunity to review this body of research. This chapter reviews some of the key decisions taken by DSM-5 with regard to the anxiety disorders, the obsessive-compulsive and related disorders, and the trauma- and stressor-related disorders, including the decision to revise the metastructure and establish these new groupings and to address a number of the notable controversies and criticisms that have been put forward from within and without the field.

Obesity and economic development were positively associated. Our findings suggest that education might mitigate this effect. Global and national action aimed at the obesity epidemic should take this into account.

Antenatal depression and associated risk factors are highly prevalent in this setting and are associated with adverse fetal growth. Maternal mental health may be an important predictor of infant growth in utero.