Molecular-genetic and immunological aspects of the formation of psychopathological symptoms in schizophrenia

Background: imbalance in the energy processes, such as oxidative phosphorylation intensity, and antioxidant systems, and impaired glutamate metabolism in the brain are important biochemical pathogenetic links in the development of schizophrenia. Changes in the activity of a number of platelet enzymes involved in these biochemical pathways were found in patients with schizophrenia.Aim: to assess the relationship between the treatment effciency of acute psychotic episode in patients with paranoid schizophrenia and the activity levels of platelet enzymes involved in energy metabolism (cytochrome c-oxidase, COX), in the antioxidant glutathione system (glutathione reductase, GR), and glutamate metabolism (glutamate dehydrogenase, GDH).Patients and methods: we examined hospitalized adult patients with a diagnosis of paranoid schizophrenia, episodic course, exacerbation of the disease (F20.01), receiving antipsychotic therapy, and healthy volunteers as a control group for assessment of control ranges for enzymatic activities. Psychometric assessment was carried out using the Positive and Negative Syndrome Scale (PANSS). Treatment response was assessed as good with a reduction in PANSS scores of 20% or more. The evaluation was performed on the first days after hospitalization and immediately before discharge.Results: 113 subjects were recruited. 50 healthy volunteers formed the control group and 63 patients, including 60 men and 3 women made up the study group. All indicators were obtained in all control group members and in 42 patients. In the group with a good treatment response, the baseline COX, GDH and GR activities proved to be significantly more often met within the control range, and the GR activity in half of the patients increased after the treatment course. In the group with insuffcient response, half of the patients had an increase in GDH activity after treatment. Of all the biochemical indices, the parameter most associated with therapeutic response was GDH activity.Conclusion: GDH activity can be considered as a possible candidate for predicting the therapeutic response to antipsychotic therapy.

Section: таблица 4 динамика активности ферментов в группе с недостато...unclassified

The Relationship between Treatment Response in Patients with Acute Psychotic Episodes of Schizophrenia and the Activity of Their Platelet Enzymes

Morozova,

Burminskiy,

Beniashvili

et al. 2023

Microglial Reactivity in the Prefrontal Cortex in Schizophrenia

Uranova,

Vikhreva

2023

Background: schizophrenia is associated with neuroinflammation and dysregulation of the immune system involving microglia. The study of microglial reactivity in schizophrenia is at an early stage. The results of neuroimaging and postmortem studies are contradictory. Aim of the study: to analyze and summarize the results of morphometric studies of the microglial reactivity at the ultrastructural level in postmortem prefrontal cortex in schizophrenia compared to healthy controls. Material and methods: the study was performed in layer 5 of the prefrontal cortex in 21 cases of schizophrenia and 20 control cases using transmission electron microscopy and morphometry. Results and conclusion: we found that chronic schizophrenia is characterized by a combination of signs of activation, progressive dystrophy and accelerated aging of microglia. The reactivity of microglia in schizophrenia is associated with age, the age of onset of the disease, the duration of the disease and the type of course of the disease, which indicates the participation of microglia in the pathological process in schizophrenia. Damage and deficit mitochondria and the disturbance of energy metabolism can play a key role in microglial dysfunction in schizophrenia.

Gut Microbiota and (Neuro)Inflammation: Involvement of Endotoxin in the Pathogenesis of Endogenous Psychoses

Zozulya,

Yakovlev,

Klyushnik

2023

Self Cite

Background: there is a two-way relationship between the gut microbiota (GM) and the brain, both in normal and pathological conditions. It has been suggested that disturbances in GM composition and function can lead to the activation of (neuro) inflammation or its maintenance in mental disorders. Objective: analysis of scientific publications, including the results of our own research on the gut microbiota, its role in the modulation of brain functions and involvement in the maintenance of (neuro)inflammation in endogenous mental disorders. Material and method: using the keywords “gut–microbiota” and “microbiota–gut–brain axis/mental disorders”, “inflammation”, “neuroinflammation”, articles and reviews were searched in databases and electronic libraries of scientific publications Medline/PubMed, Scopus, Google Scholar, RSCI, and other sources. Results: on the basis of the analysis of literature sources, general information about GM, its composition, functions and main ways of interaction with the brain is given. The role of GM in the development and maintenance of (neuro)inflammation, currently considered as one of the pathogenetic mechanisms of mental disorders, is discussed. Particular attention is paid to the results of own studies on the role of endotoxin (ET) (lipopolysaccharide — LPS) and inflammation in the development of endogenous psychoses and the relationship of these indicators with the effectiveness of pharmacotherapy. Conclusion: it has been established that GM is an important participant and regulator of neuro-immune interactions. The possible role of GM in the maintenance of (neuro)inflammation in endogenous mental disorders and the participation of endotoxin aggression (EA) in the formation of therapeutic resistance in endogenous psychoses were revealed.