Basic Cognitive Architecture, Systemic Inflammation, and Immune Dysfunction in Schizophrenia

The aims of the project were to study the architecture of the brain's neural networks in the process of perceiving individual stimuli that are personally significant, to evaluate the main parameters of immunity and systemic inflammation, and to relate those to brain damage markers and patterns of cognitive-affective disorders in patients with schizophrenia. Materials and Methods. The study involved 35 patients with paranoid schizophrenia and 17 people without cognitive impairment. Clinical information about patients was obtained from the database created in the Alekseev Psychiatric Clinical Hospital No.1, Moscow Department of Health. The immunological arm of the study included the determination of key cytokines, neurotrophic factors, circulating immune complexes, C-reactive protein, cortisol, and immunoglobulins in the blood serum of patients. To study the cognitive functions, original methods of selecting the stimuli and recording the vegetative reactions were used; those allowed for identifying the architecture of neural networks involved in the pathogenesis of schizophrenia. Results. In this study, for the first time, changes in humoral immunity and parameters of systemic inflammation were found in patients with schizophrenia. Those changes included an increase in the levels of cytokines IL-6, IL-8, and interferon y, persisted regardless of the duration and nature of the antipsychotic therapy. Moreover, the immunological deviations were associated with the phase of the disease, it indicating their endogenous nature and connection with the pathogenesis of schizophrenia. Our pilot neuroimaging studies showed the feasibility of using MRI-compatible polygraphy for creating a group of fMRI images suitable for statistical analysis thus providing an objective assessment of physiological reactions to the presentation of personally-significant stimuli (based on keywords and images from the patient's anamnesis). By using this approach, we were able to detect the activation of neural networks in the associative zones of the left cuneus and precuneus and the ventrolateral prefrontal cortex of both hemispheres, i.e., the areas responsible for the working memory and processes of consciousness. Conclusion. Important novel data have been obtained on the relations between neurophysiological parameters, the cytokine profile and the immune status in schizophrenia.