[Features of inflammatory reactions in patients with juvenile depression with a clinically high risk of psychosis]. / Osobennosti vospalitel'nykh reaktsii u patsientov s yunosheskimi depressiyami s klinicheski vysokim riskom psikhoza.

OBJECTIVE: To determine the levels of pro-inflammatory and anti-inflammatory cytokines and inflammatory markers such as C-reactive protein, leukocyte elastase, α1-proteinase inhibitor, autoantibodies to neuroantigens in the blood of patients with adolescent depression with clinical high risk for psychosis (CHR-P) and to study the relation of these biological markers to the features of psychopathological symptomatology of the patients. MATERIAL AND METHODS: Eighty young adults, aged 16-24 years, with the first depressive episode (F32.1-2, F32.38, F32.8) were studied. Based on the presence of attenuated positive symptoms in the structure of depression, all patients were divided into two groups: with CHR-P (clinical group, n=58) and without CHR-P (comparative group, n=22). The HDRS-21, SOPS, and SANS were used for psychometric assessment of the patients. Serum levels of cytokines TNF-α, IL-6, IL-8, IL-10, and concentration of C-reactive protein (CRP) were determined. Leukocyte elastase (LE) activity, α1-proteinase inhibitor (α1-PI) activity, and plasma levels of autoantibodies to S100B protein and myelin basic protein (MBP) were assessed. RESULTS: Both groups of patients were characterized by the high levels of inflammation as assessed by LE (250.5 (226.2-280.8) nmol/min·ml vs 248.3 (226.8-284.5) nmol/min·ml) and α1-PI activity (44.4 (37.5-50.1) IE/ml vs 45.2 (36.4-49.9) IE/ml). Higher levels (p<0.05) of IL-6 (1.22 (0.64-2.2) pg/ml), CRP (0.93 (0.18-3.18) mg/l), and TNF-α/IL-10 (0.34 (0.2-0.47)) were detected in the group with CHR-P. This group was also characterized by higher levels of antibodies to the S100B protein 0.78 (0.69-0.84 units of opt.density) compared with the group without CRH-P (p<0.05). In each clinical group, different correlations between clinical, psychometric and biological parameters were revealed. CONCLUSIONS: The results confirm the involvement of inflammation in the development of depression in youth and indicate a different role of the inflammatory markers analyzed in the formation of CHR-P. The differences in the spectrum of inflammatory markers in depressed patients suggest a more pronounced pro-inflammatory potential in the group with CHR-P.

[Inflammatory markers in organic nonpsychotic disorders]. / Vospalitel'nye markery pri organicheskikh nepsikhoticheskikh rasstroistvakh.

OBJECTIVE: To determine the indicators of systemic inflammation in peripheral blood samples of patients with organic non-psychotic disorders. MATERIAL AND METHODS: The study included 60 patients, aged 56.9±7.7 years, with a disease duration of 7.3±5.55 years, with a verified ICD-10 diagnosis «Organic emotionally labile (asthenic) disorder¼ (F06.6) and «Organic Anxiety Disorder¼ (F06.4). Patients with organic asthenic disorder were divided into two groups according to the prevailing symptoms: 36 patients with asthenic-cephalgic syndrome (AC); 10 patients with astheno-dysthymic syndrome (AD); the third group (n=14) included patients with organic anxiety disorder (AND). The control group consisted of 65 people matched for age and sex with patients. The activity of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) was determined by the spectrophotometric method, the levels of aAB to S100b and MBP were determined by ELISA. The protease-inhibitory index (PII), i.e., the ratio of LE activity to α1-PI, was calculated. RESULTS: A significant increase in LE (235.4 [216.4; 258.1] nmol/min*ml, p<0.001), the functional activity of α1-PI (43.1 [38.7; 47.6] u/ml, p<0.001), the level of aAB to S100b (0.78 [0.70; 0.89] opt.units, p<0.05) and a decrease in PII (6.19 [5.32; 6.9], p<0.05) in the group of patients with organic non-mental disorders compared with controls were shown. Deviations from the normal values of immune markers of inflammation in blood samples were also found in various syndromes. Clustering of the total group of patients by LE activity made it possible to identify 2 immunotypes with a balanced and unbalanced inflammatory process, confirming the clinical diversity of the disease: 60% of patients with AC syndrome belong to the 1st cluster, in which the ratio of immune markers characterizes a balanced inflammatory process aimed at restoration of homeostasis; 80% of patients with organic AND belong to the second cluster, which characterizes low proteolytic activity and imbalance of inflammation, which is an unfavorable prognostic factor in terms of the further course of the disease and therapy. CONCLUSION: The results confirm the importance of the inflammatory link in the neuroprogression of organic non-psychotic disorders. The identified features of the immune response can serve as an additional paraclinical criterion for differential diagnosis and evaluation of the prognosis of the further development of the disease.

[Specific features of immunological reactions in elderly and young patients with exacerbation of schizophrenia]. / Osobennosti immunologicheskikh reaktsii u patsientov pozhilogo i molodogo vozrasta s obostreniem shizofrenii.

OBJECTIVE: To identify levels of inflammation markers (the enzymatic activity of leukocyte elastase (LE), the functional activity of the α1-proteinase inhibitor (α1-PI), autoantibodies to neurotrophin S100b and myelin basic protein (MBP)) in blood plasma of old- and young-aged patients with schizophrenia in comparison with features of the clinical course of schizophrenia. MATERIAL AND METHODS: Two age groups of patients with schizophrenia were examined. The 1st group consisted of 19 female patients, aged 60 to 78 years (mean age 67.3±5.4 years), with disease duration from 0.5 months to 29 years (9.7±7.6). The 2nd group comprised 24 female patients, aged 19 to 42 years (mean age 26.8±6.3 years), with disease duration from 0.15 to 6.6 years (3.3±2.4). Nineteen age-matched healthy women were included in two control groups. Inflammatory and autoimmune markers were measured in blood plasma using «Neuro-immuno-test technology¼. RESULTS: In the 1st group, a relative smoothness and rigidity of the productive symptoms profile, a reduction of disease progression and a tendency to the development of negative symptoms were established. The 2nd group was characterized by polymorphism, severity and dynamism of productive disorders, as well as the progression and lability of the schizophrenic process. The most significant differences in the spectrum of the analysed immune markers relate to the ratio of the activity of LE and its inhibitor α1-PI, i.e. proteinase-inhibitory index (PII). CONCLUSIONS: The identified multidirectional changes of PII in elderly patients compared to the controls may reflect the imbalance of the inflammatory response and the role of this imbalance in shaping the characteristics of psychopathological symptoms in these patients.

[Characteristic of innate and acquired immunity in adaptation disorders]. / Kharakteristika vrozhdennogo i priobretennogo immuniteta pri rasstroistvakh adaptatsii.

OBJECTIVE: To determine factors of innate and acquired immunity in adaptation disorders with a predominance of asthenic or anxiety-depressive syndrome. MATERIAL AND METHODS: Twenty-five patients with ICD-10 diagnosis of «Adaptation Disorders¼ (F43.2), including 9 with asthenic syndrome and 16 with anxiety-depressive syndrome, were examined. The control group consisted of 23 healthy individuals. The relative number of lymphocyte phenotypes was determined by flow cytometry; the concentration of IgM, IgG, IgA, aAB to S100b and MBP - by ELISA; CIC level - by the method of selective precipitation with PEG-6000; phagocytic activity of neutrophils by a test system with melamine-formaldehyde latex; activities of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) by a spectrophotometric method. RESULTS: There were significant changes in the parameters of acquired immunity in the group with asthenic syndrome and those of innate immunity in the group with anxiety-depressive syndrome. An increase in α1-PI activity, in the total number of significant correlations between different immunological parameters, in the involvement of α1-PI in integration of acquired and innate immunity were observed in the anxiety-depressive group compared with the asthenic group. CONCLUSIONS: The peculiarities of stress response in patients with leading anxiety-depressive syndrome are the high activity of α1-PI, which, along with the strengthening of correlation intersystem associations and the involvement of this protein in the integration of acquired and innate immunity, allows us to consider α1-PI as a criterion that improves the accuracy of diagnosis of the nature of the course of adaptation disorders.

[Features of the immune profile of schizophrenic patients with catatonic syndrome]. / Osobennosti immunnogo profilya bol'nykh shizofreniei s katatonicheskim sindromom.

OBJECTIVE: An analysis of inflammatory and autoimmune markers in schizophrenic patients with- and without catatonic symptoms in comparison to healthy controls. MATERIAL AND METHODS: A sample of 170 patients with paranoid schizophrenia was stratified by the presence of catatonic symptoms in the structure of psychosis (66 patients with catatonia and 104 patients without catatonia), inclusion threshold was >10 points on the Bush-Francis catatonia scale. The examination was carried out in the early days of inpatient treatment using psychopathological, psychometric and immunological methods. RESULTS: Quantitative and qualitative differences in the spectrum of immune indicators in both groups of patients are revealed. A higher level of the immune system activation is found in the group with catatonic symptoms that indicates a worsening of the pathological process. A specific feature of the immunological profile of catatonic syndrome in schizophrenia is a decrease in ratio between leukocyte elastase and a1-proteinase inhibitor (leukocyte-inhibitory index) accompanied by the increase of other inflammatory markers that, presumably, indicates the deterioration of the phagocyte component of the inflammatory response. CONCLUSION: The results suggest that the decrease in leukocyte-inhibitory index is a potential biomarker of catatonic syndrome in schizophrenia.

[Immunological predictors of acute post-stroke period]. / Immunologicheskie prediktory techeniia ostrogo perioda insul'ta.

INTRODUCTION: At the present time, there is an increased interest in the search for biological predictors of the course and outcome of ischemic stroke (IS). Numerous studies have shown the relationship between neuroinflammation (in the brain) and systemic inflammatory response (in the blood). AIM: To study the relationship of inflammatory and autoimmune markers in blood serum of patients with acute ischemic stroke (on the 1st day) with the dynamics of the severity of neurological deficit (on the 1st and 10th day) and to assess the predictive ability of these indicators. MATERIAL AND METHODS: Twenty-two patients in the acute period of IS (mean age 60±15.5 years) were examined. The severity of neurological deficit was assessed by ESS and NIHSS. The enzymatic activity of leukocyte elastase (LE), α1-proteinase inhibitor (α1-PI), level of autoantibodies to S-100B and MBP in serum was determined. The control group consisted of 33 healthy subjects. Blood samples were carried out on the 1st day of the post-stroke period, the clinical examination was performed on the 1st and 10th day of observation. RESULTS: Depending on the dynamics of neurological symptoms by the 10th day of observation, two subgroups of patients were identified. The1st subgroup was characterized by the normalization of neurological deficit (n=10). In the 2nd group, the negative dynamics of neurological deficit/lack of any positive changes was observed (n=12). Both subgroups demonstrated the increase in the LE and α1-PI activity as compared to the control (p=0.0019, p=0.00079; p=0.038, p=0.00041, respectively). The highest LE activity was detected in the 1st subgroup (p=0.035). The high level of autoantibodies to MBP was also observed in the 1st subgroup as compared to the control and the 2nd group (p=0.047, p=0.03, respectively). The 2nd subgroup was characterized by a higher functional activity of acute phase protein α1-PI (p=0.04). Using regression analysis, a model for predicting the course of the early post-stroke period depending on the determined immunological parameters was developed. CONCLUSION: The results suggest that the studied inflammatory and autoimmune markers may be possible predictors of the course of the early post-stroke period.

[The dynamics of markers of apoptosis in the acute period of ischemic stroke]. / Dinamika markerov apoptoza v ostrom periode ishemicheskogo insul'ta.

AIM: To study the dynamics of markers of apoptosis (Bcl-2, p53) in serum in the acute period of ischemic stroke (IS) in comparison to the severity of the neurological condition and the volume of infarct. MATERIAL AND METHODS: Fifty-one patients (mean age 60.5±2.2 years) with the first ever carotid IS were examined within the first 24 hours. The comparison group consisted of 20 patients (mean age 58.7±2.1 years) with chronic cerebral insufficiency. Clinical and neurological dynamic examinations with assessment of neurological deficit using (NIHSS), CT/MRI of the brain; ELISA immunoassay of p53 and Bcl-2 in blood serum were carried out. RESULTS AND CONCLUSION: Significantly higher levels of p53 and of Bcl-2 were shown on the 3rd and 10th days in patients with IS compared to the control group (p<0.05). An increase in the content of p53 was positively correlated with the severity of neurological deficit (NIHSS≥10) on the first and third days of acute IS and with larger amounts of damage to the brain parenchyma according to the MRI study from the first day of IS and all subsequent days. High levels of Bcl-2 were positively correlated with the large volume of brain damage only on the 10th day of IS (p<0.045). The results confirm the active involvement of pro- and antiapoptotic processes in the formation of delayed neuronal death in the brain, which are important components of damaged brain tissue in IS.

[The possibility of using immunological parameters for the evaluation of the clinical state of patients with childhood-onset schizophrenia].

OBJECTIVE: To compare clinical and immunological parameters in children with schizophrenia and to analyze the possibility of using them in the assessment of the pathological process activity. MATERIAL AND METHODS: We examined 62 patients, 39 boys and 23 girls, aged from 4 to 17 years, with childhood-onset schizophrenia. Mental state of the patients was assessed using a psychopathological method and with PANSS and CGI scales. The activity of leukocyte elastase (LE) and alpha(1)-proteinase inhibitor (α1-PI) was measured by spectrophotometric method. ELISA was used to determine the level of autoantibodies to neuroantigenes to S-100B and basic myelin protein. RESULTS AND CONCLUSION: The activation of innate immunity assessed by the activity of LE and α1-PI and adaptive immunity (levels of autoantibodies to neuroantigenes to S-100B and basic myelin protein) was identified. Significant correlations of the level of immune system activation with the severity of patient's state on СGI-S (r=0.64, p=0.000001) as well as scores on the PANSS negative symptom subscale (r=0.34, p=0.0077) were found. The results suggest the possibility of using these immunological parameters for the objectification of clinical state of children with schizophrenia.

[Inflammatory and autoimmune reactions in different forms of nervous system functioning disorders].

Parameters of innate (the leukocyte elastase (LE) and alpha1-proteinase inhibitor (α-1-PI) activity) and adaptive immunity (the level of autoantibodies to neuroantigens nerve growth factor (NGF) and myelin basic protein (MPB)) were studied over time in the blood serum of 107 children with perinatal hypoxic-ischemic encephalopathy; 188 children with autism spectrum disorder; 108 patients with schizophrenia. The correlations between immunological parameters and clinical status assessment in all groups of patients using psychometric scales were analyzed. The involvement of innate immunity, i.e. inflammatory reactions, in pathogenesis of all analyzed forms of nervous system functioning disorders was confirmed. The activation of adaptive immunity, i.e. autoimmune reactions, was found only in the group of patients with the most severe forms of nervous system functioning endogenous disorders. The results indicate that the inflammatory and autoimmune reactions are pathogenic mechanism of all studied forms of nervous system functioning disorders.

[Immunological monitoring of endogenous attack-like psychoses].

To analyze the possibility of using immunological parameters for the assessment of the activity of the process and prediction of the quality and completion of remission, we compared the dynamics of clinical and immunological parameters in 76 patients with endogenous attack-like psychoses during pharmacotherapy of a psychotic episode. Authors confirmed evidence for the activation of innate and adaptive immunity in the acute stage of psychosis as well as the correlation between immunological parameters (leukocyte elastase (LE) activity, alpha(1)-proteinase inhibitor (alpha(1)-PI), the level of autoantibodies to nerve growth factor (Aab-NGF)) and clinical symptoms assessed with the PANSS. The improvement of the clinical state assessed by the reduction in PANSS total score was noted in all patients though there were variations in the dynamics of immunological parameters. The increase of immunological parameters, along with the absence of changes at the discharge from the hospital, suggests that the remission was of low quality and the pathological process did not attenuate. Outpatient examination revealed the different dynamics of psychopathological disorders: stable state in 50% patients, moderate worsening of psychological state in 50% patients. Worsening of clinical symptoms after the discharge and in the outpatient stage was correlated with the elevation of the activity/level of immunological parameters. The changes in LE activity and Aab-NGF level precede the changes in mental state of patients in the following 1-2 months. These parameters may be used for monitoring of patients and prediction of quality and completion of remission.

[Possibilities of the use of immunological indicators for the assessment of the risk of manifestation of endogenous psychoses in patients with nonpsychotic disorders of the juvenile age].

OBJECTIVE: To study parameters of innate and adaptive immunity in the blood serum of patients with nonpsychotic mental disorders and to classify them by risk of psychosis manifestation. MATERIAL AND METHODS: Authors studied 49 male patients, aged from 16 to 25 years, with nonpsychotic mental disorders corresponded to the premanifest stage of endogenous psychosis. The activity of leukocyte elastase (LE), functional activity of alpha-1-proteinase inhibitor (α1-PI) and the level of autoantibodies (aAB) to S-100 and basic myelin protein were measured. RESULTS: A significant increase in LE and α1-PI was found in patients compared to controls (p<0.001). The level of aAB to neuroantigens was similar in patients and controls. The increase in LE activity was positively correlated with HAM-D depressive symptoms and SOPS total scores (r=0.47, p=0.02). Correlations between α1-PI activity and scores on SOPS positive subscale (r= -0.61, p=0.002) and SOPS total scores (r= -0.43, p=0.04) were identified. After treatment, the improvement of patient's state assessed by SOPS and HAM-D was correlated with the decrease in LE activity in 80% (p<0.01). The further increase of LE activity in 20% may be considered as an indicator of low quality remission and risk of psychosis manifestation. CONCLUSION: Patients with nonpsychotic mental disorders with higher levels of inflammation markers may be attributed to high risk group.

[Innate and adaptive immunity in children with psychotic forms of autism-spectrum disorders].

Leukocyte elastase (LE) activity, functional activity of alpha1-proteinase inhibitor, C-reactive protein, autoantibodies to nerve growth factor and to basic myelin protein have been studied in the blood serum of children with psychotic forms of autistic disorders - children psychosis (F84.02) and atypical children psychosis (F84.11). The activation of innate immunity (the increase in LE activity and acute phase proteins) was seen in children psychosis. The more severe mental disturbances, that are characteristic of endogenous atypical children psychosis, were accompanied by the activation of both innate and adaptive immunity ( the increase of the level of autoantibodies to neuroantigenes in the peripheral blood). Correlations between immunological and clinical parameters suggest the involvement of innate and adaptive immunity in the formation of autistic and cognitive disorders in children.

[The state of the immune system in endogenous mental diseases with pronounced affective disorders].

Parameters of innate and adaptive immunity were studied in the blood serum of 180 patients, aged 15-25 years, with different endogenous mental diseases with depressive and mania disorders in the clinical picture (affective psychoses (29 patients), schizoaffective psychoses (106 patients) , slow-progressive schizophrenia (23 patients) and intermittent-progressive schizophrenia (22 patients)). The activation of innate immunity (the increase in the degranulation activity of leukocyte elastase (LE) and functional activity of alpha-1-proteinase inhibitor (α1-PI) were found in all the diseases. The increase in disease severity (from affective disorders to intermittent-progressive schizophrenia) was correlated with the significant elevation of LE activity. The LE activity did not depend on the polarity and severity of affective pathology in each diagnostic group. The mean levels of autoantibodies to the nerve growth factor and the myelin basic protein did not differ from the control values in all the groups of patients.

[Dynamics of immunological and clinical parameters in the treatment of childhood schizophrenia].

A state of innate and adaptive immunity (leukocyte elastase (LE) activity, alpha(1)-proteinase inhibitor (alpha(1)-PI), the level of autoantibodies to nerve growth factor (Aab-NGF) and to basic myelin protein), have been studied in the blood serum of children with schizophrenia and compared to the changes of their clinical-psychopathological state. It has been shown that the exacerbation of schizophrenic process with early onset is accompanied by the activation of some parameters of innate immunity. But the higher activity of LE and alpha(1)-PI before the treatment cannot be considered as a predictive marker of therapeutic efficacy. At the same time, the decrease of LE activity during the treatment is a significant predictor of favorable therapeutic response. The unchanged level of Aab-NGF comparing to controls is also a favorable factor associated with therapeutic efficacy.

[Immunological reactions in different forms of mental disorders].

State of innate and adaptive immunity has been assessed by the indices of activity of leukocyte elastase, alpha1-proteinase inhibitor (alpha(1)-PI), level of C-reactive protein and autoantibodies to neuroantigens (nerve growth factor and basic myelin protein) in different forms of mentalopathology: schizophrenia-spectrum disorders, mental retardation with behavioral abnormalities, organic mental disorders, affective disorders, psychogenias (adaptation disorders), early alcoholism. The increase of activity or levels of all immunological parameters was characteristic of these diseases. However within each group were patients with different levels of immunity activation. A number of patients with significant immunity activation was higher in the groups of schizophrenia-spectrum disorders, early alcoholism, organic mental disorders, mental retardation with behavioral abnormalities and affective disorders. The lowest frequency of such cases was observed for psychogenias (adaptation disorders). These results give grounds to suggest that the extent of immunity activation depends as on severity of psychopathogy as well on individual peculiarities of immunological reactivity in response to a brain pathological process.

[Correlations between clinical and immunological parameters in endogenous psychoses with a first episode at the juvenile age].

Sixty-seven patients, aged 16-25 years, with the first episode of endogenous psychosis (ICD-10 items F20.03, F20.23, F25) have been examined. Positive, negative and general psychopathological symptoms were assessed with the PANSS. Activities of leukocyte elastase (LE) and alpha1-proteinase inhibitor were used for measuring of innate immunity and the level of autoantibodies to nerve growth factor (Aab-NGF) was used for measuring of adaptive immunity. The manifestation of endogenous psychosis was accompanied by the activation of innate immunity, the level of activation was not related with the syndrome structure of episode (the prevalence of catatonic, hallucinatory-delusional or affective-delusional symptoms). The LE activity and dynamics of Aab-NGF during the treatment may be considered as prognostic markers of treatment effectiveness: the higher LE activity during the episode and decrease of Aab-NGF in the treatment process may predict a favorable therapeutic response.

[Changes of the level of serum antibodies to neuroantigens in patients with schizophrenia during the treatment].

The level of antibodies (AT) to neuroantigens (nerve growth factor and basic myelin protein) has been studied in the serum of 80 patients with schizophrenia, attack-like type, (ICD-10 items F20.01-02) during the treatment with psychotropic drugs. Therapeutic effectiveness has been measured clinically and with the PANSS. It has been shown that the autoimmune component is present during the acute episode of schizophrenia in about 30% of cases. No statistically significant differences have been found in the mean values of AT before and after the treatment however the dynamics of their changes has been closely related with the results of therapy: the decrease of AT level during the therapy is a predictive factor for good therapeutical remission; on the contrary, the increase of this level may be considered as an unfavorable prognostic factor.

[Serum immunological markers as predictors of effectiveness of antipsychotic therapy in patients with schizophrenia].

Serum immunological parameters - activity of leukocyte elastase (LE) and a1-proteinase inhibitor (a1-PI), content of C-reactive protein, von Willebrand factor, interleukin 8 as well as a level of autoantibodies to neuroantigens (nerve growth factor and basic myelin protein) were studied in patients with schizophrenia during their treatment with psychotropic drugs. All parameters studied differed in the groups of patients and controls. However, the pronounced dynamics was found only for LE and a1-PI activity. After the therapeutic course, the reduction of LE activity accompanied by the increase of a1-PI activity was observed. The correlation study between the biological parameters during disease exacerbation and therapeutic effectiveness assessed by the PANSS scores revealed that activity of LE and a1-PI may be considered as a prognostic marker of therapeutic efficacy, i.e. the high enzyme activity at the moment of maximal activity of the process was predictive of good therapeutic response.