The human body is faced with stress throughout ontogeny. At the stage of intrauterine development, the mother\'s body serves as a source of resources and most of the humoral factors supporting the development of the fetus. In normal conditions, maternal stress-related humoral signals (e.g., cortisol) regulate fetal development; however, distress (excessive pathological stress) in the perinatal period leads to serious and sometimes irreversible changes in the developing brain. The mother being in an unfavorable psychoemotional state, toxins and teratogens, environmental conditions, and severe infectious diseases are the most common risk factors for the development of perinatal nervous system pathology in the modern world. In this regard, the challenge of modeling situations in which prenatal or early postnatal stresses lead to serious impairments to brain development and functioning is extremely relevant. This review addresses the various models of perinatal pathology used in our studies (hypoxia, exposure to valproate, hyperserotoninemia, alcoholization), and assesses the commonality of the mechanisms of the resulting disorders and behavioral phenotypes forming in these models, as well as their relationship with models of perinatal pathology based on the impact of psychoemotional stressors.

In this report we describe the first human case of hypertryptophanemia confirmed to be due to tryptophan 2,3-dioxygenase deficiency. The underlying etiology was established by sequencing the TDO2 gene, in which there was compound heterozygosity for two rare variants: c.324G>C, p.Met108Ile and c.491dup, p.Ile165Aspfs*12. The pathogenicity of these variants was confirmed by molecular-level studies, which showed that c.491dup does not produce soluble protein and c.324G>C results in a catalytically less efficient Met108Ile enzyme that is prone to proteolytic degradation. The biochemical phenotype of hypertryptophanemia and hyperserotoninemia does not appear to have significant clinical consequences.