Immunological characteristics of patients with schizophrenia and various degrees of severity of neurocognitive disorders
O. Lobacheva1, V. Nikitina1, D. Petkun2, T. Popova3, E. Kornetova2, N. Bokhan4
1Mental Health Research Institute of Tomsk NRMC, Laboratory of Psychoneuroimmunology, Tomsk, Russian Federation, 2Mental Health Research Institute of Tomsk NRMC, Endogenous Disorders Department, Tomsk, Russian Federation, 3Mental Health Research Institute of Tomsk NRMC, Clinics, Tomsk, Russian Federation, 4Mental Health Research Institute of Tomsk NRMC, Administration, Tomsk, Russian Federation
Background: Neurocognitive deficits in schizophrenia are a significant factor in the poor prognosis of the disease and contribute significantly to social maladjustment and disability. The pathophysiological mechanisms underlying cognitive dysfunction in schizophrenia remain unclear. The brain and the peripheral immune system are in constant interaction, mediated by cytokines. Microglia are a key factor in the pathogenesis of brain diseases. Microglia are the main immunocompetent cells in the brain, performing innate and acquired (specific) immunity functions, and their functional status is closely linked to the state of the peripheral immune system.
Aims & Objectives: Aim of research was study of the features of the functioning of the immune system in patients with schizophrenia and varying degrees of severity of neurocognitive impairment.
Method: 34 patients diagnosed with schizophrenia (ICD-10 codes F20.01, F20.02, and F20.06; mean age 43.29 ±11.16 years) were examined. Cognitive functions were assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) scale.
Two groups of patients with schizophrenia were formed: Group 1 – with pronounced neurocognitive deficit (13 patients), Group 2 – with mild cognitive impairment (21 patients).
The laboratory study included phenotyping of immunocompetent cells by clusters of differentiation using flow cytometry, determination of humoral immunity factors using ELISA, and determination of neutrophil phagocytic activity using light microscopy. The control group consisted of 59 apparently healthy individuals.
Two groups of patients with schizophrenia were formed: Group 1 – with pronounced neurocognitive deficit (13 patients), Group 2 – with mild cognitive impairment (21 patients).
The laboratory study included phenotyping of immunocompetent cells by clusters of differentiation using flow cytometry, determination of humoral immunity factors using ELISA, and determination of neutrophil phagocytic activity using light microscopy. The control group consisted of 59 apparently healthy individuals.
Results: As a result of the study, in the 1st group of patients, in relation to the control, a quantitative deficiency of mature T-lymphocytes (CD3+ CD19‒, p=0.037), T-helpers/inducers (CD3+ CD4+ CD45+, p = 0.004) and cytotoxic T-lymphocytes (CD3+ CD8+, p=0.006), an increase in B-lymphocytes (CD3– CD19+ , p=0.0001), serum concentrations of immunoglobulins of classes M and E and neutrophil phagocytic activity. Patients in group 2 had less pronounced changes in immune status parameters compared to group 1 patients. An increase in baseline levels of NK cells (CD3– CD16+ CD56+, p=.047) was established. and B-lymphocytes (CD3– CD19+, p=0.002), and a decrease in the number of cytotoxic T-lymphocytes (CD3+ CD8+, p=0.009). Significant disturbances in the parameters of the immune status were detected in 11 of 13 patients in the 1st group and in 3 of 21 patients in the 2nd group (χ 2 = 4.94, p=0.026).
Schizophrenia patients with severe verbal memory impairment were characterized by higher values of the number of lymphocytes with natural killer activity (CD3– CD16+ CD56+ phenotype) compared to the group of patients without such impairments (p=0.025) and the control group (p=0.03). Severe visual memory impairment in the examined subjects was associated with high values of B-lymphocytes (CD3– CD19+ phenotype) and lymphocytes with FAS receptors for apoptosis readiness CD95 (p=0.002 and p=0.008).
Schizophrenia patients with severe verbal memory impairment were characterized by higher values of the number of lymphocytes with natural killer activity (CD3– CD16+ CD56+ phenotype) compared to the group of patients without such impairments (p=0.025) and the control group (p=0.03). Severe visual memory impairment in the examined subjects was associated with high values of B-lymphocytes (CD3– CD19+ phenotype) and lymphocytes with FAS receptors for apoptosis readiness CD95 (p=0.002 and p=0.008).
Discussion & Conclusions: Immunological characteristics of patients with schizophrenia have been established, both with the severity of neurocognitive disorders and with individual components of neurocognitive deficit. Elevated levels of natural killer cells and B lymphocytes, and low levels of cytotoxic T lymphocytes are immunological markers of severe neurocognitive deficit.
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