Etiopathogenesis of the first psychotic episode

Abstract

Materials and methods. A review of 30 sources were studied based mainly on the etiology, pathogenesis of early psychotic manifestations, and risk factors. Results. Among all the hypotheses, theories, risk factors, pathogenetic mechanisms that can trigger psychosis, the most significant are: genetic predisposition, neurotransmitter and hormonal imbalance, progressive neurodegenerative changes and environmental factors. Multiple genetic risk loci for schizophrenia have been identified by modern science. The neurotransmitter dopamine plays a critical role in the pathophysiology of schizophrenia. Other neurotransmitter systems (as serotonin, glutamate) are also involved in the pathophysiology of this disorder. Molecular, cellular, structural and behavioral disorders in schizophrenia are associated with a decrease in neurotransmission on the NMDA glutamate receptors in the brain. Polymorphism in several genes associated with glutamate significantly increases the risk of schizophrenia. Estradiol significantly interacts with dopaminergic, serotonergic and glutamatergic systems, giving it the properties of atypical antipsychotic drugs. The limbic system, tonsils, hippocampus, basal ganglia and many areas of the cerebral cortex are rich in estrogen receptors. Due to the genomic and non-genomic interactions, estrogens act as a “neuroactive steroid” and affects neurodegenerative processes in the central nervous system. Anatomical abnormalities of the brain in patients with schizophrenia are reported (a decrease in the amount of gray matter in the frontal, temporal, limbic, striatal and thalamic areas, ventricular dilatation and anomalies of the medial temporal lobe and prefrontal cortex, irregular synaptic organization, ectopic neurons). Shortfall of astrocyte function is associated with incorrect glucose utilization, oxidative stress in the cerebral cortex in people with schizophrenia. Activation of inflammatory mediators (including microglia) in utero in genetically predisposed individuals increases the risk of schizophrenia. Conclusions. The etiology remains unknown, schizophrenia is considered a disorder of neural development with polymorphic clinical manifestations and widespread pathological changes in the forebrain that are the interaction results of many risk genes with environmental factors. Understanding the influence of risk factors leading to this pathology can reveal more effectiveness in pharmacological and behavioral interventions.