Alexander M. Dupin

Medical article медицинская статья

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. 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. 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. Patients with nonpsychotic mental disorders with higher levels of inflammation markers may be attributed to high risk group.

To identify inflammatory markers in schizophrenia in aged. The main group included 29 patients with schizophrenia, mean age 72.1 ± 6.9 years. A comparison group comprised 34 patients with Alzheimer's disease, mean age 73.4 ± 7.9 years. Seven plasma inflammatory indicators were determined. There was a significant increase in the activity/content of acute inflammation stage proteins: α1-proteinase inhibitor and C-reactive protein as well as anti-inflammatory interleukin-10 compared to the controls while the activity of other inflammatory molecules (leukocyte elastase, tumor necrosis factor alpha, interleukin-1 receptor antagonist) was not changed. No correlations between immunological parameters and clinical presentations were found. The results suggest that inflammation does not play a significant role in the remote stages of schizophrenia, in contrast to earlier stages of the disease, and the activity of the pathological process decreased in the late stages. These characteristics can reflect the body reactivity in elderly patients.

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.

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.

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.

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.

A sample included 59 patients, 38 males and 21 females, mean age (M+/-SD) 33,4+/-10,2 years, age-at-onset 26+/-9,5 years, illness duration 7,8+/-6,1 years, with episodic progressive schizophrenia (ICD-10: schizophrenia, paranoid type, F20.0) with continuous course at the stage of exacerbation. Clinical symptoms were assessed using the PANSS. Platelet 5-HT content, 3H-serotonin uptake (Vmax), 3H-imipramine receptor density (Bmax), high- and low molecular weight human serotonin platelet transporter protein immunoreactivity (HMW-SERT and LMW-SERT values) were measured. The most frequent psychotic symptoms were delusions, conceptual disorganization and hallucinations, with the majority of patients experiencing from one to three symptoms. A significant increase of platelet 5-HT content and 3H-imipramine receptor density (Bmax) was found in male patients. In the male group, delusions, conceptual disorganization and hallucinations as well as PANSS psychotic cluster scores were correlated positively with 5-HT content and negatively with HMW-SERT and LMW-SERT values. Possible reasons of the differences in correlations of platelet 5-HT serotonin and serotonin transporter values with psychotic symptoms are discussed. The results are additional evidence for the involvement of serotonergic dysfunction in the pathogenesis of schizophrenic psychoses. They confirm the usefulness of testing of platelet 5-HT content and SERT immunoreactivity as biological markers of schizophrenic psychoses, in particular for male patents.

Fifty-nine patients, 21 women and 38 men, with ICD-10 diagnosis of schizophrenia (F20.0), attack-like type, were treated with olanzapine during 28 weeks (8-weeks of acute and 20-weeks of maintenance therapy). Evaluation of clinical symptoms measured by the Positive and Negative Syndromes scale (PANSS) revealed that female patients responded better to therapy as compared to male ones, with PANSS total, PANSS negative and PANSS general psychopathological scores being significantly reduced (p < 0.006) in females after 1 week of the treatment and in males--after 2 weeks. In the female group, a reduction of PANSS total score by 50% in the acute stage of treatment qualified as a very good response was observed in 7 (33%) patients and in the male group--in 1 (2.7%). The between-groups difference was highly significant (p = 0.002). When examined for a rate of 3H-serotonin uptake into platelets, density of sites of 3H-imipramine binding on the whole platelets, platelet serotonin level and levels of high- also low-molecular weight forms of platelet immunoreactive serotonin transporter protein, a significant decrease of the platelet serotonin level, comparing to controls, was detected in the female group before treatment. During the treatment, this parameter gradually increased up to control level. Other parameters did not change significantly for 28-weeks of therapy and did not differ from the control values. There were positive correlations between the levels of platelet serotonin before treatment and subsequent reduction of the PANSS total and positive subscale scores in the female group. In responders with a very good treatment-related response, the serotonin level in the platelets before treatment was higher compared to the values in resistant patients: 5.4 +/- 2.5 and 2.7 +/- 1.3 nmol/10(9) cells, respectively. Relative risk (RR) of unfavorable treatment outcome in patients with initially reduced levels of platelet serotonin was approximately twice lower (RR = 1.83; Cl 95% 1.1-34.9) than that in patients with normal or elevated levels of platelet serotonin. The results suggest that selection of patients with initial higher level of platelet serotonin before olanzapine treatment can reduce the risk of non-responding to therapy by 36%.