Population neuroscience: challenges and opportunities for psychiatric research in low- and middle-income countries

Objective: Population neuroscience is an emerging field that combines epidemiology and neuroscience to study how genes and the environment shape typical and atypical brain functioning. The objective of this study was to review key studies on population neuroscience from low- and middle-income countries (LMICs) and to identify potential gaps vis-à-vis studies conducted in high-income countries. Methods: We conducted a systematic review to search for longitudinal cohort studies investigating the development of psychiatric disorders in children and adolescents in LMICs. We performed an electronic search in the EMBASE and MEDLINE databases from inception to July 5th, 2019. Results: We found six cohorts from four countries that met our search criteria: three cohorts from Brazil, one from China, one from South Africa, and one from Mauritius. Relevant examples of findings from these studies are reported. Conclusion: Our results demonstrate the impact of the valuable science output these cohort designs promote, allowing LMICs to have a share in frontline global psychiatry research. National and international funding agencies should invest in LMIC population neuroscience in order to promote replication and generalization of research from high-income countries.

The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages.

BACKGROUND: Immune system dysregulation is well-recognized in autism and thought to be part of the etiology of this disorder. The endocannabinoid system is a key regulator of the immune system via the cannabinoid receptor type 2 (CB2R) which is highly expressed on macrophages and microglial cells. We have previously published significant differences in peripheral blood mononuclear cell CB2R gene expression in the autism population. The use of the Gc protein-derived Macrophage Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein responsible for macrophage cell activation has demonstrated positive effects in the treatment of autistic children. In this current study, we investigated the in vitro effects of GcMAF treatment on the endocannabinoid system gene expression, as well as cellular activation in blood monocyte-derived macrophages (BMDMs) from autistic patients compared to age-matched healthy developing controls. METHODS: To achieve these goals, we used biomolecular, biochemical and immunocytochemical methods. RESULTS: GcMAF treatment was able to normalize the observed differences in dysregulated gene expression of the endocannabinoid system of the autism group. GcMAF also down-regulated the over-activation of BMDMs from autistic children. CONCLUSIONS: This study presents the first observations of GcMAF effects on the transcriptionomics of the endocannabinoid system and expression of CB2R protein. These data point to a potential nexus between endocannabinoids, vitamin D and its transporter proteins, and the immune dysregulations observed with autism.

High grade glioblastoma is associated with aberrant expression of ZFP57, a protein involved in gene imprinting, and of CPT1A and CPT1C that regulate fatty acid metabolism.

The diagnosis of glioblastoma is still based on tumor histology, but emerging molecular diagnosis is becoming an important part of glioblastoma classification. Besides the well-known cell cycle-related circuitries that are associated with glioblastoma onset and development, new insights may be derived by looking at pathways involved in regulation of epigenetic phenomena and cellular metabolism, which may both be highly deregulated in cancer cells. We evaluated if in glioblastoma patients the high grade of malignancy could be associated with aberrant expression of some genes involved in regulation of epigenetic phenomena and lipid metabolism. We measured the mRNA levels of ZFP57, TRIM28, CPT1A, CPT1B, and CPT1C in a cohort of 80 patients divided in two groups: grade II and grade IV. We evidenced that high grade glioblastoma is associated with increased level of ZFP57, a protein involved in gene imprinting, and aberrant expression of CPT1A and CPT1C, regulators of fatty acid oxidation. Our study may pave the way to identify new markers that could be potentially useful for diagnosis and/or prognosis of glioblastoma.

Autism spectrum disorders: is mesenchymal stem cell personalized therapy the future?

Autism and autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental disorders. They are enigmatic conditions that have their origins in the interaction of genes and environmental factors. ASDs are characterized by dysfunctions in social interaction and communication skills, in addition to repetitive and stereotypic verbal and nonverbal behaviours. Immune dysfunction has been confirmed with autistic children. There are no defined mechanisms of pathogenesis or curative therapy presently available. Indeed, ASDs are still untreatable. Available treatments for autism can be divided into behavioural, nutritional, and medical approaches, although no defined standard approach exists. Nowadays, stem cell therapy represents the great promise for the future of molecular medicine. Among the stem cell population, mesenchymal stem cells (MSCs) show probably best potential good results in medical research. Due to the particular immune and neural dysregulation observed in ASDs, mesenchymal stem cell transplantation could offer a unique tool to provide better resolution for this disease.

The expression of caspases is enhanced in peripheral blood mononuclear cells of autism spectrum disorder patients.

Autism and autism spectrum disorders (ASDs) are heterogeneous complex neuro-developmental disorders characterized by dysfunctions in social interaction and communication skills. Their pathogenesis has been linked to interactions between genes and environmental factors. Consistent with the evidence of certain similarities between immune cells and neurons, autistic children also show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the activation of caspases, cysteinyl aspartate-specific proteases involved in apoptosis and several other cell functions in PBMCs from 15 ASD children compared to age-matched normal healthy developing controls. The mRNA levels for caspase-1, -2, -4, -5 were significantly increased in ASD children as compared to healthy subjects. Protein levels of Caspase-3, -7, -12 were also increased in ASD patients. Our data are suggestive of a possible role of the caspase pathway in ASD clinical outcome and of the use of caspase as potential diagnostic and/or therapeutic tools in ASD management.