[Features of the immune system and the risk of endogenous psychosis at juvenile age].

OBJECTIVE: To study an immunological profile at prodromal and manifesting stages of endogenous juvenile psychosis. METHODS: Authors studied 77 patients, aged from 16 to 25 years. Patients were stratified into 2 groups. The first group included 39 patients without psychotic symptoms (prodromal group) and the second one -- 38 patients with the first episode of psychosis (psychotic group). A complex of immunological parameters included phagocyte activity, cytotoxic activity, natural killer lymphocytes, production of interleukins (IL-1, IL-4, IL-10 and γ-interferon), content of circulating immune complexes. These parameters were measured at baseline and after treatment. RESULTS: The changes in the immune system emerged at the very early stages of the disease. There was the activation of proinflammatory and anti-inflammatory interleukins, decrease in the phagocyte index and cytotoxic activity of natural killer lymphocytes. The high activity of IL-10 production, decreased levels of the cytotoxic activity of natural killer lymphocytes and reduced phagocyte index as well as the accumulation of circulating immune complexes are maintained during psychosis. CONCLUSIONS: The authors recommend to use immunomodulating drugs, along with psychotropics, at the very early stages of the disease to prevent poor outcome.

[The cytotoxic activity of natural killer cells in patients with the first episode of endogenous psychosis (a comparative study of test methods)].

Authors studied the cytotoxic activity (CA) of natural killer cells (NK) in 16 schizophrenic patients, aged from 18 to 25 years, with the first episode of psychosis. A significant decrease in CA NK was found in the total group of patients compared to healthy controls that suggested the dysregulation of natural immunity at this stage of disease. The addition of serotonin to the cell culture in vitro in concentrations 10-9 M stimulated the NK activity while the elimination of monocytes resulted in the significant reduction of CA NK. The parallel use of two methods for assessment of CA NK (a radioactive method and an easy and safe method using multifunctional particle size analyzer Multisizer MS-4) revealed similar results.

[The effect of serotonin on the cytotoxic activity of natural killer lymphocytes in patients with the first episode of endogenous psychosis].

Authors studied the level of cytotoxic activity of natural killer lymphocytes (NKCA) and the effect of monocytes, serotonin, rate of serotonin reuptake by lymphocytes and psychotropic therapy on NKCA levels in 59 male patients, aged 18-30 years, with the first episode of attack-like progressive schizophrenia (33 patients) and schizoaffective psychosis (26 patients). All patients were examined at baseline, 4 and 8 weeks after the beginning of treatment with haloperidol and clozapine. Before the treatment, the decrease of NKCA was found in a half of patients compared to controls. In other patients, the NKCA levels were high and did not differ from those in controls. The treatment resistance was estimated as 70,6% in patients with schizophrenia with initially low NKCA levels and 30,8% in patients with schizoaffective psychosis with initially low NKCA levels. During the treatment, the initially high NKCA level decreased while the initially low level increased but remained lower compared to controls. These changes suggest the active reaction from the immune system of the patient to treatment with neuroleptics. The changes of NKCA values during the treatment were reciprocally related to the maximal rate of serotonin reuptake by lymphocytes. Serotonin added to the cell culture in vitro normalized the NKCA level in cultures with- and without monocytes. This effect was revealed in both pathologies only in responders, regardless of the presence or absence monocytes, that may be explained by the presence of active serotonin receptors on the NK cell surface in these patients.

[The use of canonical correlation analysis for the evaluation of correlation strength between clinical and biological parameters].

We studied correlations between factors of inherent immunity and the effectiveness of therapy in patients with endogenous psychosis using the method of canonical correlations. There were strong significant (canonical R>0,8; p=0,02) positive correlations between the therapeutic effectiveness of neuroleptics (haloperidol and clozapine) and values of factors of inherent immunity in the group of 34 men with schizophrenia, aged from 16 to 34 years, with the first episode of psychosis. The effectiveness of treatment was assessed by the percentage reduction of total scores on the PANSS scale or scores on PANSS subscales (positive, negative and general psychopathology) at the beginning and the end (after 60 days) of the treatment. Initial parameters of factors of inherent immunity (levels of gamma-interferon production by T-lymphocytes, proportion of phagocytosing neutrophils and monocytes, and cytotoxic activity of lymphocytes - natural killers) contributed to 67,3%, or more than two thirds, of the variance of treatment effects. The contribution of inherent immunity factors was determined mainly by their similar effects on the reduction of positive and general psychopathological symptoms, with the minimal effect on the reduction of negative symptoms. The maximum correlation was found for weighting coefficients for inherent immunity factors estimated as 0,567 for the proportion of phagocytosing neutrophils and monocytes; 0,518 - for the levels of gamma-interferon production by T-lymphocytes and 0,334 - for cytotoxic activity of lymphocytes - natural killers. The authors suggest that the reduction of activity of the cell branch of inherent immunity develops before the disease manifestation. It creates conditions for the activation of latently persistent infections (the cytomegalovirus infection, in our case) in a patient's organism, with the formation of therapeutic resistance. The method described may be widely used in clinical and biological psychiatry and neurology.

[The influence of atypical neuroleptics on the immune system of patients with schizophrenia].

Humoral and cellular immunological parameters were studied in 59 schizophrenic patients and 38 healthy subjects. It was demonstrated that high level of circulating immune complexes is characteristic of the acute state (a relapse) of schizophrenia. The level of this parameter was higher in patients before treatment vs. healthy controls; after therapy with olanzapine this level decreased and did not differ from that of controls. The functional activity of immunocompetent cells (the phagocyte activity of neutrophiles and monocytes, the cytotoxic activity of natural killer lymphocytes, interleukin-2, and interleukin-10 production) did not depend on the clinical condition of the patients and the therapy and was significantly lower than that of controls both before and during the treatment. Attention should be paid to the fact that the level of IL-1beta production in schizophrenia patients did not differ from that of controls. After eight weeks of therapy the level of IL-1beta production increased significantly in all groups of patients and was significantly higher than that of controls during the whole observation period irrespectively of sex and patients' response to the therapy.

[A change of immune profile of patients with schizophrenia during treatment]. / Izmenenie immunnogo profilia bol'nykh shizofreniei v protsesse lecheniia.

Cellular and humoral immunological parameters have been studied in 59 schizophrenic patients and 38 healthy controls. Immunological indices (CIC, autoantibodies to cardiolipin) were found to be significantly elevated in patients in the acute disease stage before the treatment. After olanzapin therapy, a level of these parameters decreased and did not differ from that of controls. In patients, irrespective of clinical condition and treatment, functional activity of immunocompetent cells (phagocyte activity of neutrophils and monocytes, cytotoxic activity of lymphocytes natural killers, interleukin-2, interleukin-10 and gamma-interferon production), was significantly lower both before the treatment as after therapy, i.e. did not change during the whole study (28 weeks). In responders, a level of IL-1B production was higher than in controls before and during the treatment. In non-responders, it was similar to that in controls before the therapy, and increased during the treatment to a higher level.

[The changes of the function of lymphocytes natural killers in schizophrenics]. / Izmenenie funktsii limfotsitov natural'nykh killerov pri shizofrenii.

Cytotoxic activity and lymphocyte natural killers (NK) number as well as gamma-interferon (gamma-IFN) production were studied in patients with paranoid (22 patients) and progressive attack-like (39 patients) schizophrenia (47 male and 14 female patients aged 16-62 years). Compared to controls, a decrease of NK activity and a trend towards gamma-IFN production decrease were found. In the patients, NK lymphocytes number was not changed. Cytotoxic activity was reduced only in the male patients, a frequency of cases with lower activity level being the highest in those with more severe form of paranoid schizophrenia. A significant difference of both indices was detected between men and women. In the men, the longer was the disease duration, the higher was cytotoxic activity and lymphocyte number increase. It was shown in vitro that monocytes are not involved in mechanisms changing the level of lymphocyte cytotoxicity in the patients and immune modulator enkad stimulats cytotoxic activity in the male patients.

[The functional activity of the lymphocyte subpopulations in patients with schizophrenia and schizoaffective psychosis]. / Funktsional'naia aktivnost' subpopuliatsii limfotsitov u bol'nykh shizofreniei i shizoaffektivnym psikhozom.

The functional activity of natural killer (NK) and of T-helper (TH) lymphocytes was examined both in 19 patients with schizophrenia and in 6 patients with schizoaffective psychosis as well as in 93 control individuals. The patients were examined both before the treatment and two months after it. The cytotoxic level of NK lymphocytes was considerably decreased in all the patients before the treatment. The TH activity was decreased in 8 of 17 schizophrenic patients and in 1 of 4 schizoaffective patients observed during the acute period. The increase of cytotoxic NK activity was seen in patients with schizoaffective psychosis after the treatment while such alterations in schizophrenic patients were absent. The TH activity changed neither in schizophrenic nor in schizoaffective patients after the treatment.

[The immune system characteristics during normal aging and in Alzheimer's disease]. / Osobennosti immunnoi sistemy pri normal'nom starenii i pri bolezni Al'tsgeimera.

The paper presents a review of data available in the literature and the authors' own findings on age-related physiology and pathology of the immune system. Almost all parameters characterizing the functional activity of the immune system in Alzheimer's disease (AD) were demonstrated to significantly differ from those in the healthy elderly, The magnitude of immunological changes clearly correlated with the severity of dementia in AD patients. A hypothesis of the gradual development of immunological changes in an AD patient in relation to his dementia formation is given.

[Beta-adrenoreceptors on the surface membranes of lymphocytes and macrophages]. / Izuchenie beta-adrenoretseptorov na poverstnostnykh membranakh limfotsitov i makrofagov.

In experiments in vivo and in vitro on sensitized and intact guinea pigs and Wistar rats the effect of beta-adrenergic stimulants (adrenaline and izoproterenol) and a beta-adrenergic blocker (propranalol) on lymphocytolysis and the reaction of macrophage adherence inhibition was studied. Adrenaline and izoproterenol were shown to inhibit the antigen interaction with both sensitized and intact cells. Restoring the sensitivity of cells to the antigen, propranalol destroys the defensive action of adrenaline and isoproterenol.