Mental Health Research Center

Moscow, Russia

Mental Health Research Center

Moscow, Russia

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Hough D.,Johnson and Johnson Pharmaceutical Research and Development L.L.C. | Gopal S.,Johnson and Johnson Pharmaceutical Research and Development L.L.C. | Vijapurkar U.,Johnson and Johnson Pharmaceutical Research and Development L.L.C. | Lim P.,Johnson and Johnson Pharmaceutical Research and Development L.L.C. | And 2 more authors.
Schizophrenia Research | Year: 2010

Objective: We assessed efficacy and tolerability of the injectable atypical antipsychotic paliperidone palmitate in delaying time-to-relapse in adults with schizophrenia. Methods: Eligible patients (Positive and Negative Syndrome Scale [PANSS] total score < 120) were transitioned from previous antipsychotics to paliperidone palmitate during a 9-week, open-label phase. Patients received the first 2 intramuscular injections of paliperidone palmitate (50 mg eq) one-week apart, then subsequent injections (25, 50, or 100 mg eq, flexibly-dosed), once-monthly. Stable patients (PANSS total score ≤ 75) continued into the 24-week maintenance phase. At maintenance phase endpoint, stabilized patients were randomized (1:1 ratio) to either continue paliperidone palmitate (at stabilized dose) or begin placebo in the variable-duration, double-blind phase. Results: The preplanned interim analysis (conducted after 68 relapse events) included 312 patients: mean age = 40 years, 55% men, 66% white, and mean transition baseline PANSS total score (SD): placebo, 69.5 (16.89); paliperidone palmitate, 69.3 (17.39). Time-to-relapse (primary endpoint) favored paliperidone palmitate (p < 0.0001, log-rank test) at interim and final analysis (n = 408). The hazard ratio (placebo/paliperidone palmitate) at the final analysis was 3.60 (95% CI: 2.45, 5.28). Treatment-emergent adverse event rates (final analysis set) were: 67% for transition and maintenance phases, and 45% (placebo) and 44% (paliperidone palmitate) for the double-blind phase. Across phases, the incidence of glucose-related adverse events was low (≤ 4%), while mean weight increased by 1.9 kg for paliperidone palmitate and remained unchanged for placebo patients. Injection site tolerability was comparable between groups. Conclusion: Paliperidone palmitate significantly delayed time-to-relapse compared with placebo and presented no new safety signals. © 2009 Elsevier B.V. All rights reserved.


Gopal S.,Johnson and Johnson Pharmaceutical Research and Development L.L.C. | Vijapurkar U.,Johnson and Johnson Pharmaceutical Research and Development L.L.C. | Lim P.,Johnson and Johnson Pharmaceutical Research and Development L.L.C. | Morozova M.,Mental Health Research Center | And 2 more authors.
Journal of Psychopharmacology | Year: 2011

The safety and tolerability of paliperidone palmitate, an injectable atypical antipsychotic agent, were assessed in a 1-year open-label extension of a double-blind study in patients with schizophrenia. Patients from the double-blind study who experienced a recurrence, remained recurrence free until study end, or who were in the transition, maintenance or double-blind phases and had received at least one injection of paliperidone palmitate when enrollment was stopped, were eligible for the open-label extension. Patients received gluteal injections of paliperidone palmitate once every 4 weeks: starting dose 50 mg eq. followed by 25, 50, 75, or 100 mg eq. flexible dosing. Of the 388 patients enrolled, 288 completed the open-label extension. During the open-label extension, the median (range) duration of exposure to paliperidone palmitate was 338 days (10; 390), and 74% of patients received all 12 open-label injections of paliperidone palmitate. The most frequent (≥5% in total group) adverse events were insomnia (7%); worsening of schizophrenia; nasopharyngitis; headache; and weight increase (6% each). Potentially prolactin-related adverse events occurred in 13 (3%) patients, mostly women, and none resulted in study discontinuation. Extrapyramidal treatment-emergent adverse events were reported in 25 (6%) patients; tremor was the most frequently reported (n = 8, 2%). At open-label extension endpoint, investigator-rated redness at the injection site was observed in ≤4% of patients in each group. Injection-site pain was rated by investigators as absent in 82-87% of patients. Schizophrenia symptoms measured by Positive and Negative Syndrome Scale and personal and social performance changes improved during the open-label extension. © 2011 The Author(s).


Vikhreva O.V.,Mental Health Research Center | Rakhmanova V.I.,Mental Health Research Center | Orlovskaya D.D.,Mental Health Research Center | Uranova N.A.,Mental Health Research Center
Schizophrenia Research | Year: 2016

Objective: Neuroimaging studies showed abnormalities in frontal white matter (WM) in schizophrenia that were associated with clinical symptoms. Previously, we reported ultrastructural alterations of myelinated fibers and reduction in the numerical density of oligodendrocytes in BA 10 WM in patients with schizophrenia. We aimed to perform a qualitative and morphometric study of the ultrastructure of oligodendrocytes in BA 10 WM in schizophrenia and in normal controls. Methods: The study was performed using electron microscopy and morphometry. Size, volume density (Vv) and the number (N) of organelles of oligodendrocytes were estimated in 21 patients with schizophrenia and 20 normal controls. The data were examined using the Kolmogorov-Smirnov test for normality. Pearson correlation analysis was performed to assess possible correlations between the parameters measured and age, post-mortem interval, neuroleptic treatment and duration of the disease. Comparisons between the schizophrenia patients and controls were performed using ANCOVA tests. Results: We found oligodendrocyte swelling, vacuolation, paucity of ribosomes and mitochondria and accumulation of lipofuscin granules in schizophrenia as compared to controls. Morphometry detected a significant reduction in Vv and N of mitochondria and the increase in Vv and N of lipofuscin granules and vacuoles in oligodendrocytes in the schizophrenic group as compared to controls. Conclusion: Alterations of oligodendrocytes in schizophrenia provide evidence for the disturbance of their energy, lipid and protein metabolism in prefrontal WM. Oligodendrocyte abnormalities might disturb axonal integrity and circuitry and contribute to the pathophysiology of schizophrenia. © 2016 Elsevier B.V.


Lebedeva I.S.,Mental Health Research Center
Zhurnal Nevrologii i Psihiatrii imeni S.S. Korsakova | Year: 2015

Objective. The search of the structural and functional brain characteristics is one of the most studied directions in the modern biological psychiatry. However, in spite of the numerous studies the results are still controversial. As the necessity of the shift of the current paradigm in schizophrenia research evolves it has been suggested to discriminate not only abnormal but stable functioning neuronal circuits as well. Consequently, the aim is formulated as the search of the minimal brain damage sufficient for disease development. Material and methods. Author analyzed the auditory oddball P300 latency (as a marker of information processing speed), N-acetylaspartate level in the dorsolateral prefrontal cortex (as a marker of neuronal integrity in this brain area) and fractional anisotropy of the fasciculus uncindtus which connects the frontal and temporal lobes (as a marker of white matter bundles microstructure) in 30 patients with schizophrenia and 27 healthy people. Results and conclusion. The findings showed that all the tested characteristics are not «obligatory» for schizophrenia. © 2015, Media Sphera. All rights reserved.


Vostrikov V.M.,Mental Health Research Center | Kolomeets N.S.,Mental Health Research Center | Uranova N.A.,Mental Health Research Center
European Journal of Psychiatry | Year: 2014

Background and Objectives: Previously we reported a significant reduction in the numerical density of oligodendrocytes and oligodendrocyte clusters in the inferior parietal lobule (IPL) in schizophrenia that was associated with lack of insight. We also found a significant decrease in the number of perineuronal oligodendrocytes (PnOl) in the prefrontal cortex in schizophrenia and therefore we hypothesized that there may also be a deficit of PnOl in the IPL in schizophrenia and that it could be associated with poor insight. Methods: We estimated the number of PnOl adjacent to pyramidal neurons in layer 3 of BA39 and BA40 in Nissl stained sections from 24 males with schizophrenia and 24 normal male controls from the Stanley Parietal Collection. The schizophrenia group was divided into three subgroups based on level of insight: poor, fair or good. Results: We found a significant deficit of PnOl in layer 3 of BA39 and BA40 in the schizophrenia group as compared to the control group (p<0.01). In the control group but not in the schizophrenia group in BA39 the number of PnOl was significantly higher in the left hemisphere compared to the right hemisphere. In schizophrenia, in BA39 the number of PnOl was decreased in the subgroup with poor insight vs. controls. In BA40 the subgroups with both poor and fair insight were decreased vs. controls (p<0.01). In BA40 the subjects with fair insight also differed from those with good insight (p<0.01). Conclusions: The reduction of PnOl in the IPL in schizophrenia is associated with impaired insight and lack of hemispheric asymmetry.


Vostrikov V.M.,Mental Health Research Center | Kolomeets N.S.,Mental Health Research Center | Uranova N.A.,Mental Health Research Center
European Journal of Psychiatry | Year: 2013

Background and Objectives: Alterations and deficits of oligodendrocytes reported in the grey and white matter in schizophrenia may contribute to neuronal disconnectivity. Prefrontal-parietal functional disconnections have been implicated in diverse clinical symptoms of schizophrenia, including poor insight. We studied the effects of schizophrenia diagnosis and insight on numerical density (Nv) of oligodendrocytes in the inferior parietal lobule (IPL). Methods: Nissl-stained sections from the Stanley "Parietal Collection" from male schizophrenia subjects (n = 24) having poor, fair, or good insight and healthy matched controls (n = 24) were examined. The Nv of oligodendrocytes was estimated in layer 3 of BA 39 and BA 40 of the IPL and in white matter underlying layer 6 by optical dissector method. Results: In BA 39 we found a significant 15% decrease in the Nv of oligodendrocytes in layer 3 in the schizophrenia group. Nv of oligodendrocytes in the poor+fair insight subgroup was 20% lower compared to controls (p< 0.05) and to good insight subgroup (p = 0.055). Nv of oligodendrocytes in the good insight subgroup did not differ from the control group. A significant lateralization of oligodendrocyte density was detected in layer 3 (L>R) only in the control group. There were no significant group differences in the Nv of oligodendrocytes in BA 40 or in the white matter underlying BA 39/40 areas. Conclusions: Lack of insight in schizophrenia may be associated with a deficit of oligodendroglia in the grey matter of IPL.


Kolomeets N.S.,Mental Health Research Center | Vostrikov V.M.,Mental Health Research Center | Uranova N.A.,Mental Health Research Center
European Journal of Psychiatry | Year: 2013

Background and Objectives: Deficits in oligodendrocytes have been consistently reported in the brains of patients with schizophrenia and include alterations in the clustering pattern of oligodendrocytes. Recently it has been shown that oligodendrocyte progenitors proliferate in the adult mammalian brain to form oligodendrocyte clusters (OlC). We previously found a deficit of oligodendrocytes in layer 3 of the inferior parietal lobule (IPL) in subjects with schizophrenia with poor insight into disorder. We hypothesized that the number of OlC might be reduced in schizophrenia subjects with poor insight. Methods: Nissl-stained sections from the Stanley "Parietal Collection" from male schizophrenia subjects (n = 24) that have poor, fair, or good insight into their disorder and normal matched controls (n = 24) were studied. The numerical density (Nv) of OlC was estimated in layer 3 of BA 39 and BA 40 by optical disector method. Results: The Nv of OlC was 23% lower in BA 39 and 30% lower in BA40 in the schizophrenia group compared to the control group (p<0.01). Normal hemispheric differences in the Nv of OlC in BA 39 were absent in the schizophrenia group. The Nv of OlC was significantly decreased in BA39 in the subgroup with poor insight and in BA40 in the subgroups with fair and good insight as compared to controls. In BA40 lower Nv of OlC (-40%, p<0.01) was found in the subgroup with adolescent onset of disease as compared to controls. Conclusions: The deficit of OlC may be associated with altered proliferation and/or maturation of oligodendrocyte progenitors in schizophrenia.


Golimbet V.E.,Mental Health Research Center
Zhurnal Nevrologii i Psihiatrii imeni S.S. Korsakova | Year: 2016

Advanced genome technologies, including genome-wide association studies, next generation sequencing analysis, whole exome sequencing, encourage the development of theoretical insights on the role of genetic factors in schizophrenia. In this context, the author considers a monogenic model of schizophrenia and its evolution. © 2016, Media Sphera. All rights reserved.


Kolomeets N.S.,Mental Health Research Center | Uranova N.,Mental Health Research Center
World Journal of Biological Psychiatry | Year: 2010

There is a lot of evidence of astrocytic dysfunction in schizophrenia. We performed an electron microscopic morphometric study of astrocytes in the CA3 hippocampal region in 19 cases of schizophrenia and 16 normal controls. No significant group differences were found in cell size, volume fraction (Vv) and area density (Na) of mitochondria and lipofuscin granules. Young control subjects (<50 years old) had significantly lower area of cell, nucleus and cytoplasm and higher Vv and Na of mitochondria than old controls (>50 years old), and young and old schizophrenic cases. No significant differences between young and old schizophrenic subgroups were found. Vv and Na of mitochondria correlated negatively (r=-0.66, r=-0.72, P<0.01) and Vv of lipofuscin granules correlated positively (r=0.72, P=0.001) with duration of illness. These parameters did not correlate with age in controls and in schizophrenic subjects. Both Vv and Na of mitochondria were significantly lower in the subgroup of cases with duration of disease of>21 years. than in the control group and in the subgroup of cases with duration of illness of<21 years (P<0.01). The data suggest progressive disturbances of astrocyte function due to the deficit of mitochondria in schizophrenia. © 2010 Informa UK Ltd.


Barkhatova A.N.,Mental Health Research Center
Zhurnal Nevrologii i Psihiatrii imeni S.S. Korsakova | Year: 2015

Objective. To study the structure of deficit disorders identified in the initial phase (first 5 years) of youth-onset endogenous psychosis. Materials and methods. Author examined 232 patients with the first episode of juvenile endogenous psychosis during the period from 2005 to 2015 using integrated phenomenological and clinical/psychopathological approaches. The follow-up was administered to 151 patients. Results and conclusion. The working hypothesis on the formation of deficit symptom variants based on the mutual competition of its components was formulated. Identified typological species allowed to hypothesize the existence of continual series of variations of deficit disorders manifested as phenomena with multilateral dependencies, characterized by dynamism and a wide range of modifications and verifiable in remission at the initial stages of attack-like endogenous psychosis. © 2015, Media Sphera. All rights reserved.

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