The folate-centric concept of pathogenesis and GBINC personalized multidisciplinary approach to the clinical management of children with neuropsychiatric syndromes. Review

Abstract

Solving the problem of children’s neuropsychiatric diseases is a priority task of modern medicine. The latest scientific achievements in the field of genetics, molecular biology and immunology, which demonstrate biochemical and immune‑dependent ways of formation of human neuropsychiatric disorders, shed light on the mechanisms of brain damage in children with ASD. These research give reason for optimism about overcoming this severe psychiatric pathology in the future thanks to the implementation of genetic, biochemical and immunodiagnostic approaches, as well as metabolic and immunotherapeutic interventions with neuroprotective effects. Currently, the folate‑centric concept of polygenic inheritance of predisposition to the development of neuropsychiatric syndromes in children with multisystem damage has been established. Biochemical and immune‑dependent (infectious, autoimmune, immunoinflammatory, and allergic) pathways of microbe‑induced autoimmune inflammatory encephalopathy with neuropsychiatric clinical manifestations are discussed in the context of the folate‑centric concept. Taking into account the new data, two personalized multidisciplinary approaches to the management of children with ASD and other neuropsychiatric syndromes are proposed. The first approach of J. J. Bradstreet et al. (2010) is based on the empirical analysis of a large group of laboratory biomarkers, the relevance of which has been demonstrated in clinical studies, and the targeted correction of abnormalities identified by biomarkers (so‑called biomarker‑guided interventions). In 2022, Frye R. developed a multidisciplinary personalized approach called BaS‑BiSTOR (collect Baseline data, search for Symptoms, measure Biomarkers, Select Treatment, Observe for Response), which systematizes and stratifies diagnostic and treatment interventions based on the assessment of biomarkers. In order to improve existing recommendations regarding specific subtypes of neuropsychiatric syndromes in children, this article proposes an improved personalized multidisciplinary approach to the clinical management of patients with autistic spectrum disorders and neuropsychiatric manifestations associated with genetic deficiency of the folate cycle, called GBINS (Genetic‑Biochemical‑Immunological‑Neurological‑Symptomatic evaluation). There are reasons to believe that the successful testing in clinical practice of evidence‑based personalized multidisciplinary diagnostic and treatment strategies will allow making a breakthrough in the clinical management of children with severe mental disorders in the near future, which will provide not only the possibility of recovery from a prognostically unfavorable and currently incurable neuropsychiatric disorder, but also and will contribute to stopping the large‑scale threatening epidemic of neuropsychiatric syndromes in the modern child population.