Deconstructing the functional neuroanatomy of the choroid plexus: an ontogenetic perspective for studying neurodevelopmental and neuropsychiatric disorders.

The choroid plexus (CP) is a delicate and highly vascularized structure in the brain comprised of a dense network of fenestrated capillary loops that help in the synthesis, secretion and circulation of cerebrospinal fluid (CSF). This unique neuroanatomical structure is comprised of arachnoid villi stemming from frond-like surface projections-that protrude into the lumen of the four cerebral ventricles-providing a key source of nutrients to the brain parenchyma in addition to serving as a 'sink' for central nervous system metabolic waste. In fact, the functions of the CP are often described as being analogous to those of the liver and kidney. Beyond forming a barrier/interface between the blood and CSF compartments, the CP has been identified as a modulator of leukocyte trafficking, inflammation, cognition, circadian rhythm and the gut brain-axis. In recent years, advances in molecular biology techniques and neuroimaging along with the use of sophisticated animal models have played an integral role in shaping our understanding of how the CP-CSF system changes in relation to the maturation of neural circuits during critical periods of brain development. In this article we provide an ontogenetic perspective of the CP and review the experimental evidence implicating this structure in the pathophysiology of neurodevelopmental and neuropsychiatric disorders.

Obstetric complications and clinical presentation in first episode of psychosis.

OBJECTIVE: Psychotic disorders exhibit a complex aetiology that combines genetic and environmental factors. Among the latter, obstetric complications (OCs) have been widely studied as risk factors, but it is not yet well understood how OCs relate to the heterogeneous presentations of psychotic disorders. We assessed the clinical phenotypes of individuals with a first episode of psychosis (FEP) in relation to the presence of OCs. METHODS: Two-hundred seventy-seven patients with an FEP were assessed for OCs using the Lewis-Murray scale, with data stratified into three subscales depending on the timing and the characteristics of the obstetric event, namely: complications of pregnancy, abnormal foetal growth and development and difficulties in delivery. We also considered other two groups: any complications during the pregnancy period and all OCs taken altogether. Patients were clinically evaluated with the Positive and Negative Syndrome Scale for schizophrenia. RESULTS: Total OCs and difficulties in delivery were related to more severe psychopathology, and this remained significant after co-varying for age, sex, traumatic experiences, antipsychotic dosage and cannabis use. CONCLUSIONS: Our results highlight the relevance of OCs for the clinical presentation of psychosis. Describing the timing of the OCs is essential in understanding the heterogeneity of the clinical presentation.

Obstetric complications and cognition in schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Schizophrenia (SZ) is a complex brain disorder linked to cognitive and neurostructural abnormalities that involves genetic and environmental factors with obstetric complications (OCs) at birth conferring a high risk for the disease. Indeed, current research in the general population describes the deleterious effect of OCs on cognitive performance in adulthood. With this rationale, we aim to review the relationship between OCs and cognition in SZ and related psychotic disorders. METHODS: A systematic review and meta-analysis describing cognitive function and OCs in patients with SZ and related disorders were conducted. PubMed, EmBase, SCOPUS, and the Cochrane Library were systematically searched to identify eligible studies up to January 2022. We calculated the effect sizes (Hedges' g) of cognitive domains within each study and quantified the proportion of between-study variability using the I2 statistic. Homogeneity was assessed using the Q-statistic (X2). The study was registered on PROSPERO (CRD42018094238). RESULTS: A total of 4124 studies were retrieved, with 10 studies meeting inclusion criteria for the systematic review and eight for meta-analysis. SZ subjects with OCs showed poor verbal memory [Hedges' g = -0.89 (95% CI -1.41 to -0.37), p < 0.001] and working memory performance [Hedges' g = -1.47 (95% CI -2.89 to -0.06), p = 0.01] in a random-effect model compared to those without OCs. CONCLUSIONS: OCs appear to have a moderate impact on specific cognitive such as working memory and verbal memory. Our findings suggest that OCs are associated with brain development and might underlie the cognitive abnormalities described at onset of psychosis.

Gambling Patterns and Problem Gambling Among Youth in Sub-Saharan Africa: A Systematic Review.

Mounting evidence suggests that youth in sub-Saharan Africa (SSA) find themselves increasingly drawn to gambling related activities; an issue, that if left unchecked, can lead to adverse consequences including financial difficulties, crime and mental health problems. To better understand the psychosocial mechanisms underlying problem gambling, there is a pressing need to conduct more research on gambling related disorders amongst this vulnerable stratum of society. Against this background, the present review explores gambling patterns, attitudes and behaviors among youth in SSA-in a manner aligning with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We systematically searched 8 databases including PubMed, Science Direct, Scopus, ProQuest, Wiley Online, Google Scholar, PsycINFO and PsycARTICLES for published research articles up until July 2019. A total of 1624 articles were screened, of which, only 13 studies met inclusion criteria. All of these studies were cross-sectional in nature and the quality of each study was evaluated using the Newcastle-Ottawa Scale. Studies varied considerably ranging from neuropsychological and personality trait assessment to application of item response theory. Due to this study heterogeneity we could not conduct a meta-analysis. The results presented here suggest that the existing body of evidence pertaining to patterns of gambling-related harm among youth in SSA is weak. This study highlights the need for additional good quality studies focusing on gambling related behaviors and prevalence levels among the continent's youth. Additionally, the findings reported herein emphasise the need for implementing social policies alongside effective public health interventions to tackle gambling addiction.

A strategy to analyse activity-based profiling of tyrosine kinase substrates in OCT-embedded lung cancer tissue.

The use of optimal cutting temperature (OCT) medium has served to improve the long-term preservation of surgical tissue specimens. Unfortunately, the presence of polymers in OCT has been found to generate signal interference in proteomic-based techniques. Indeed the presence of OCT medium in tissue lysates precludes the analysis of activity based proteomic profiles obtained from lung adenocarcinoma (LuAdCa) resection specimens. In order to probe this question further tissue lysates were prepared from 47 lung non-neoplastic and tumour, node, metastasis (TNM) stage 1 LuAdCa resection specimens embedded with or without OCT, and data of activity based multiplex profiles of protein tyrosine kinase peptide substrates were obtained. We found that changes in overall phosphorylation level coincided with the use of OCT and subsequently developed an OCT per peptide median correcting strategy by performing median centering on the values of each peptide. Application of this post-analytical strategy not only can identify changes in kinase activity but can also assist in identifying novel targets for therapeutic intervention against LuAdCa.

Gambling in Sub-Saharan Africa: Traditional Forms and Emerging Technologies.

Purpose of Review: The gambling industry in Africa has seen substantial growth and evolution over recent years with a growing body of literature describing these shifts. Here, we provide a narrative synthesis of the extant literature on the origins, trends and consequences of the expansion and intensification of the commercial gambling industry in sub-Saharan Africa with a reference for future research on gambling as a growing public health concern. Recent Findings: The historical shift and permeation of gambling in sub-Saharan Africa is diverse with evidence of certain countries following a neo-colonial logic. Advances in technology have made gambling more accessible and created new markets in Africa. A key motive driving gambling on the continent is a lack of stable employment. While the intensification and growth of Africa's gambling industry has brought economic benefits to some African investors and individuals, this has been accompanied by a range of gambling harms. Legislation and policies designed to better regulate the gambling industry and redress these harms are needed. In this context, a small number of services and campaigns designed to mitigate gambling harms demonstrate promise, but more research is needed in this area. Summary: The gambling industry in sub-Saharan Africa has undergone a dramatic transformation. While it is true that the growth of the African gambling industry has provided an additional revenue stream to governments, it is also necessary to acknowledge the concurrent rise in gambling addiction and the health-related and social harms that it elicits. As such, designing effective regulatory measures and policy interventions that can reduce the public health burden of gambling harms is vital. However, these interventions need to take in to account the significance of cultural differences that exist among countries on the continent.

The health and economic burden of the coronavirus in sub-Saharan Africa.

The current coronavirus (COVID-19) pandemic continues to overwhelm healthcare systems and to exert a negative influence on the global economy. Of particular concern is the impact of COVID-19 in low-income settings - especially in terms of their capacity to mitigate a surge in COVID-19 cases. Indeed, response measures currently in place to tackle the spread of COVID-19 in geographic regions predominantly consisting of low-income nations, such as Sub-Saharan Africa (SSA), remain tenuous and will require context-appropriate interventions. Control measures to tackle COVID-19 in SSA should therefore be informed through lessons learned from past outbreaks and emergencies on the continent. These lessons will represent a key source of guidance for the strategic implementation and promotion of public health interventions to assist scale-up of COVID-19 case management, infection prevention and control. Importantly, as governments in SSA continue to combat the spread of COVID-19, there will be a need to expand the coverage of social safety net programs and fiscal policy responses to tackle the socio-economic and health impact of COVID-19.

Pacing Forward in the Face of Fragility: Lessons From African Institutions and Governments' Response to Public Health Emergencies.

Africa is home to 54 United Nation member states, each possessing a wealth of ethno-cultural, physiographic, and economic diversity. While Africa is credited as having the youngest population in the world, it also exhibits a unique set of "unfortunate realties" ranging from famine and poverty to volatile politics, conflicts, and diseases. These unfortunate realities all converge around social inequalities in health, that are compounded by fragile healthcare systems and a lack of political will by the continent's leaders to improve smart investment and infrastructure planning for the benefit of its people. Noteworthy are the disparities in responsive approaches to crises and emergencies that exist across African governments and institutions. In this context, the present article draws attention to 3 distinct public health emergencies (PHEs) that have occurred in Africa since 2010. We focus on the 2013-2016 Ebola outbreak in Western Africa, the ongoing COVID-19 pandemic which continues to spread throughout the continent, and the destructive locust swarms that ravaged crops across East Africa in 2020. Our aim is to provide an integrated perspective on how governments and institutions handled these PHEs and how scientific and technological innovation, along with educational response played a role in the decision-making process. We conclude by touching on public health policies and strategies to address the development of sustainable health care systems with the potential to improve the health and well-being of the African people.

Towards an integrated model for supervision for mental health and psychosocial support in humanitarian emergencies: A qualitative study.

BACKGROUND: Despite recent advances in the development and provision of mental health and psychosocial support (MHPSS) in humanitarian settings, inadequate supervision remains a significant barrier to successful implementation. The present study sought to incorporate broad stakeholder engagement as part of the first phase of development of a new Integrated Model for Supervision (IMS) for use within MHPSS and protection services in humanitarian emergencies. METHODS: Semi-structured interviews were conducted with 26 global mental health professionals. Data was analysed thematically, using a combination of inductive and deductive methods. Codes and themes were validated through co-author cross-checks and through a webinar with an expert advisory group. RESULTS: Results reinforce the importance of effective supervision to enhance the quality of interventions and to protect supervisees' wellbeing. Participants generally agreed that regular, supportive supervision on a one-to-one basis and as a separate system from line management, is the ideal format. The interviews highlight a need for guidance in specific areas, such as monitoring and evaluation, and navigating power imbalances in the supervisory relationship. Several approaches to supervision were described, including some solutions for use in low-resource situations, such as group, peer-to-peer or remote supervision. CONCLUSION: An integrated model for supervision (IMS) should offer a unified framework encompassing a definition of supervision, consolidation of best practice, and goals and guidance for the supervisory process.

Cognitive impairment following prenatal immune challenge in mice correlates with prefrontal cortical AKT1 deficiency.

Accumulating evidence indicates that genetically determined deficiency in the expression of the cytoplasmic serine-threonine protein kinase AKT1 may contribute to abnormal prefrontal cortical structure and function relevant to the cognitive disturbances in schizophrenia. However, it remains essentially unknown whether prefrontal AKT1 expression may also be influenced by environmental factors implicated in the aetiology of this mental illness. One of the relevant environmental risk factors of schizophrenia and related disorders is prenatal exposure to infection and/or immune activation. This study therefore explored whether prenatal immune challenge may lead to prefrontal AKT1 deficiency and associated changes in cognitive functions attributed to the prefrontal cortex. For these purposes, we used a well-established experimental mouse model of prenatal exposure to a viral-like acute phase response induced by the synthetic analogue of double-stranded RNA, polyriboinosinic-polyribocytidilic acid (PolyI:C). We found that adult offspring born to PolyI:C-treated mothers showed delay-dependent impairments in spatial working memory and recognition memory together with a marked reduction of AKT1-positive cells in the prefrontal cortex. These effects emerged in the absence of concomitant changes in prefrontal catechol-O-methyltransferase (COMT) density. Correlative analyses further demonstrated a significant positive correlation between the number of AKT1-positive cells in distinct prefrontal cortical subregions and cognitive performance under high storage load in the temporal domain. Our findings thus highlight that schizophrenia-related alterations in AKT1 signalling and associated cognitive dysfunctions may not only be precipitated by genetically determined factors, but may also be produced by (immune-associated) environmental insults implicated in the aetiology of this disabling brain disorder.

N-methyl-D-aspartate receptor expression in parvalbumin-containing inhibitory neurons in the prefrontal cortex in bipolar disorder.

OBJECTIVES: Inhibitory neural circuits and the glutamatergic regulation of these circuits in the cerebral cortex appear to be disturbed in bipolar disorder. In this study, we addressed the hypothesis that, in the prefrontal cortex (PFC), disturbances of glutamatergic regulation of the class of inhibitory neurons that contain the calcium buffer parvalbumin (PV) via N-methyl-D-aspartate (NMDA) receptor may contribute to the pathophysiology of bipolar disorder. METHODS: We used double in situ hybridization with a sulfur-35-labeled riboprobe for the NR2A subunit of the NMDA receptor and a digoxigenin-labeled riboprobe for PV in a cohort of 18 subjects with bipolar disorder and 18 demographically matched normal control subjects. RESULTS: We observed no differences in the relative density and laminar distribution of the PV-expressing neurons between subjects with bipolar disorder and matched normal control subjects. Furthermore, the density of the PV neurons that co-expressed NR2A messenger RNA (mRNA) or the cellular expression of NR2A mRNA in the PV neurons that exhibited a detectable level of this transcript was unaltered in subjects with bipolar disorder. CONCLUSIONS: These findings suggest that, in the PFC, glutamatergic regulation of PV-containing inhibitory neurons via NR2A-containing NMDA receptors does not appear to be altered in bipolar disorder. However, the possibility that other subsets of gamma-aminobutyric acid (GABA) neurons or other glutamate receptor subtypes are affected cannot be excluded.

Implications of early life stress on fetal metabolic programming of schizophrenia: A focus on epiphenomena underlying morbidity and early mortality.

The fetal origin of adult disease hypothesis postulates that a stressful in utero environment can have deleterious consequences on fetal programming, potentially leading to chronic disease in later life. Factors known to impact fetal programming include the timing, intensity, duration and nature of the external stressor during pregnancy. As such, dynamic modulation of fetal programming is heavily involved in shaping health throughout the life course, possibly by influencing metabolic parameters including insulin action, hypothalamic-pituitary-adrenal activity and immune function. The ability of prenatal insults to program adult disease is likely to occur as a result of reduced functional capacity in key organs-a "thrifty" phenotype-where more resources are re-allocated to preserve critical organs such as the brain. Notably, it has been postulated that the manifestation of neuropsychiatric disorders in individuals priorly exposed to prenatal stress may arise from the interaction between hereditary factors and the intrauterine environment, which together precipitate disease onset by disrupting the trajectory of normal brain development. In this review we discuss the evidence linking prenatal programming to neuropsychiatric disorders, mainly schizophrenia, via a "Thrifty psychiatric phenotype" concept. We start by outlining the conception of the thrifty psychiatric phenotype. Next, we discuss the convergence of potential mechanistic pathways through which prenatal insults may trigger epigenetic changes that contribute to the increased morbidity and early mortality observed in neuropsychiatric disorders. Finally, we touch on the public health importance of fetal programming for these disorders. We conclude by providing a brief outlook on the future of this evolving field of research.

A conceptualized model linking matrix metalloproteinase-9 to schizophrenia pathogenesis.

Matrix metalloproteinase 9 (MMP-9) is an extracellularly operating zinc-dependent endopeptidase that is commonly expressed in the brain, other tissues. It is synthesized in a latent zymogen form known as pro-MMP-9 that is subsequently converted to the active MMP-9 enzyme following cleavage of the pro-domain. Within the central nervous system, MMP-9 is localized and released from neurons, astrocytes and microglia where its expression levels are modulated by cytokines and growth factors during both normal and pathological conditions as well as by reactive oxygen species generated during oxidative stress. MMP-9 is involved in a number of key neurodevelopmental processes that are thought to be affected in schizophrenia, including maturation of the inhibitory neurons that contain the calcium-binding protein parvalbumin, developmental formation of the specialized extracellular matrix structure perineuronal net, synaptic pruning, and myelination. In this context, the present article provides a narrative synthesis of the existing evidence linking MMP-9 dysregulation to schizophrenia pathogenesis. We start by providing an overview of MMP-9 involvement in brain development and physiology. We then discuss the potential mechanisms through which MMP-9 dysregulation may affect neural circuitry maturation as well as how these anomalies may contribute to the disease process of schizophrenia. We conclude by articulating a comprehensive, cogent, and experimentally testable hypothesis linking MMP-9 to the developmental pathophysiologic cascade that triggers the onset and sustains the chronicity of the illness.

Obstetric Complications and Brain Imaging in Schizophrenia: A Systematic Review.

Schizophrenia is a complex disorder in which clinical symptomatology typically reflects underlying brain abnormalities that coalign with multiple physical health comorbidities. The pathogenesis of schizophrenia involves the interplay between genetic and environmental factors, with obstetric complications widely described as key players in elevating the risk of psychosis. In this regard, understanding the anatomical and functional alterations associated with obstetric complications may help to elucidate potential mechanisms through which birth complications could contribute to schizophrenia pathogenesis. We conducted a systematic review of the extant literature describing brain abnormalities and obstetric complications in patients with schizophrenia and related disorders in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. A total of 471 studies were retrieved and screened, and 33 studies met inclusion criteria for our review. Studies varied considerably in their methods, with 11 studies employing computed tomography, 1 using magnetic resonance spectroscopy, and 21 using magnetic resonance imaging. The scientific quality of the included studies was assessed and documented. Obstetric complications increase the risk of provoking brain abnormalities. These abnormalities range from decreased gray matter volume and abnormal brain-ventricle ratios to a reduction of volume in limbic regions-which relate to what is commonly observed in schizophrenia. However, current evidence from neuroimaging studies remains scant in relation to establishing obstetric complications as an independent risk factor for schizophrenia.

Zinc: the brain's dark horse.

Zinc is a life-sustaining trace element, serving structural, catalytic, and regulatory roles in cellular biology. It is required for normal mammalian brain development and physiology, such that deficiency or excess of zinc has been shown to contribute to alterations in behavior, abnormal central nervous system development, and neurological disease. In this light, it is not surprising that zinc ions have now been shown to play a role in the neuromodulation of synaptic transmission as well as in cortical plasticity. Zinc is stored in specific synaptic vesicles by a class of glutamatergic or "gluzinergic" neurons and is released in an activity-dependent manner. Because gluzinergic neurons are found almost exclusively in the cerebral cortex and limbic structures, zinc may be critical for normal cognitive and emotional functioning. Conversely, direct evidence shows that zinc might be a relatively potent neurotoxin. Neuronal injury secondary to in vivo zinc mobilization and release occurs in several neurological disorders such as Alzheimer's disease and amyotrophic lateral sclerosis, in addition to epilepsy and ischemia. Thus, zinc homeostasis is integral to normal central nervous system functioning, and in fact its role may be underappreciated. This article provides an overview of zinc neurobiology and reviews the experimental evidence that implicates zinc signals in the pathophysiology of neuropsychiatric diseases. A greater understanding of zinc's role in the central nervous system may therefore allow for the development of therapeutic approaches where aberrant metal homeostasis is implicated in disease pathogenesis.

Menstrual hygiene management among adolescent girls in sub-Saharan Africa.

Menstruation is a delicate physiological process through which a shedding of uterine lining occurs each month in females of reproductive age. Often considered a taboo subject, menstruation is seldom openly discussed in developing parts of the world. This article explores menstrual hygiene management (MHM) in sub-Saharan Africa and emphasizes the urgent and neglected need for feasible solutions, especially among adolescent girls. Optimizing menstrual hygiene interventions will require an integration of both knowledge and skill training gained through education on MHM alongside an improvement of access to girl-friendly water, sanitation and hygiene facilities in addition to access to low-cost hygienic sanitary products. To facilitate the identification and implementation of feasible and cultural relevant programs we recommend the utilization of public health intervention research.

Problem Gambling among Young People in Sub-Saharan Africa.

Gambling is a cross-cultural and global activity which typically involves the wagering of money or an item of monetary value on an outcome that is governed by chance. Although gambling is positioned as a legitimate recreational and leisure activity within sub-Saharan Africa (SSA), there is widespread recognition among healthcare professionals and policy-makers that gambling has the capacity to become dysfunctional in a minority. Emerging knowledge suggests that problem gambling is rapidly evolving in to a public health concern in SSA, especially among youth. This article focuses on problem gambling among young people in SSA with an emphasis on three key themes: (1) gambling behavior and patterns in SSA; (2) public health and socioeconomic implications of gambling in SSA; and (3) public health policies and interventions for addressing this issue. We believe that collaborative efforts between government, prevention specialists, legislators, researchers, treatment providers, and other stake holders can influence the uptake of research findings necessary to implement social policies and design effective public health intervention options to combat problem gambling and its associated implications among young people in SSA.

Scaling-up innovation as a means of tackling health inequalities. Commentary.

ISSUE: The introduction of inclusive healthcare innovations as a means of improving the welfare of marginalized groups is now being witnessed in developing countries as a crucial process of modernization and industrialization. In this respect, there has been much discussion regarding the most effective strategies of scaling up innovative healthcare interventions in these parts of the world. EVIDENCE: The topics of discussion have included accessibility and cost-effectiveness; sustainability; infrastructure to support implementation; political will; advocacy; strong leadership; tailoring the scaled-up approach to the local context; and various potential models of funding. IMPLICATIONS: Given that policy advocacy plays a critical role in creating a favourable environment for inclusive healthcare innovations, intensive lobbying will be necessary as a means to achieve effective scaling-up in addition to tackling the respective development challenges more efficiently. With this in mind, funders will need to mobilize substantial investment for innovations that respond to the most pressing global public health issues.

Monitoring and managing mental health in the wake of Ebola. Commentary.

Infectious disease continues to have dramatic effects on morbidity and mortality around the world. Few events could cause such loss of life and damage to livelihoods. As witnessed with the recent West African Ebola outbreak, raising alerts and identifying the outbreak in the community took too long. As a consequence local health systems were quickly overwhelmed. In addition, response at the international level proved slow and poorly coordinated. Rapid diagnostics, effective therapeutics, protective equipment, and a vaccine were all lacking. The crisis was however ultimately halted, thanks to a massive deployment of international resources in combination with the bravery and compassion of the medical staff, scientists, healthcare and aid workers on the ground. Despite this triumph, the lingering psychological sequalae of Ebola remain a significant public health challenge. The importance of mental health service delivery and policy implementation in addition to public health funding resources will prove integral in tackling this issue in the long run. With this in mind, adopting a political ecology approach towards health and disease will be crucial in order to depathologize the clinically significant mental distress related to Ebola.

Weaving a Net of Neurobiological Mechanisms in Schizophrenia and Unraveling the Underlying Pathophysiology.

Perineuronal nets (PNNs) are enigmatic structures composed of extracellular matrix molecules that encapsulate the soma, dendrites, and axon segments of neurons in a lattice-like fashion. Although most PNNs condense around parvalbumin-expressing gamma-aminobutyric acidergic interneurons, some glutamatergic pyramidal cells in the brain are also surrounded by PNNs. Experimental findings suggest pivotal roles of PNNs in the regulation of synaptic formation and function. Also, an increasing body of evidence links PNN abnormalities to schizophrenia. The number of PNNs progressively increases during postnatal development until plateauing around the period of late adolescence and early adulthood, which temporally coincides with the age of onset of schizophrenia. Given the established role of PNNs in modulating developmental plasticity, the PNN represents a possible candidate for altering the onset and progression of schizophrenia. Similarly, the reported function of PNNs in regulating the trafficking of glutamate receptors places them in a critical position to modulate synaptic pathology, considered a cardinal feature of schizophrenia. We discuss the physiologic role of PNNs in neural function, synaptic assembly, and plasticity as well as how they interface with circuit/system mechanisms of cognition. An integrated understanding of these neurobiological processes should provide a better basis to elucidate how PNN abnormalities influence brain function and contribute to the pathogenesis of neurodevelopmental disorders such as schizophrenia.