Introduction: Reelin is a neuropeptide responsible for the migration and positioning of pyramidal neurons, interneurons, and Purkinje cells. In adulthood, it still supports neuroplasticity, especially dendritic spines formation and glutamatergic neurotransmission. Genetic studies have confirmed the involvement of reelin system failure in the etiopathogenesis of mental diseases, including schizophrenia. Given the role of reelin in brain cytoarchitectonics and the regularly observed reduction in its activity in prefrontal areas in cases of schizophrenia, dysfunction of the reelin pathway fits the neurodevelopmental hypothesis of schizophrenia, both as a biochemical predisposition and/or the ultimate trigger of psychosis and as a biosocial factor determining the clinical course, and finally, as a potential target for disease monitoring and treatment. Aim: The purpose of this study was to examine associations of the reelin blood level with clinical and neurocognitive parameters during an intensive, structured neurofeedback therapy of patients with schizophrenia. Methods: Thirty-seven male patients with paranoid schizophrenia were randomly divided into two groups: a group with 3-month neurofeedback as an add-on to ongoing antipsychotic treatment (NF, N18), and a control group with standard social support and antipsychotic treatment (CON, N19). The reelin serum concentration, clinical and neurocognitive tests were compared between the groups. Results: After 3-month trial (T2), the reelin serum level increased in the NF group vs. the CON group. The negative and general symptoms of PANSS (Positive and Negative Syndrome Scale) were reduced significantly more in the NF group at T2, and the d2 (d2 Sustained Attention Test) and BCIS (Beck Cognitive Insight Scale) scores improved only in the NF group. The AIS scores improved more dynamically in the NF group, but not enough to differentiate them from the CON group at T2. Conclusions: The clinical and neurocognitive improvement within the 3-month NF add-on therapy trial was associated with a significant increase of reelin serum level in schizophrenia patients.

BACKGROUND: One of the innovations in the ICD-11grouping \"Schizophrenia and Other Primary Psychotic Disorders\" is the implementation of six symptom domains intended to improve diagnostics and treatment of these mental conditions in clinical practice. In this respect, evaluation of the effects of various psychotropic drugs, primarily antipsychotic agents, on the specified psychotic symptom domains is a critical task. The antipsychotic agent cariprazine, registered in many countries worldwide (including Russia) for schizophrenia treatment, was selected as the psychotropic drug model for the purposes of the present review.
METHODS: For the purposes of this review the MEDLINE, Cochrane Central Register of Controlled Trials, and PubMed databases were searched for randomized controlled trials comparing cariprazine with a placebo, or a placebo and one or several antipsychotic agents, and that was performed within the period from January 2014 to March 2021.
RESULTS: Cariprazine has proved its efficiency in relation to all symptom groups of the ICD-11 domain \"Positive Symptoms\", and may be considered a front-line therapy for treatment of the first and multiple episodes of schizophrenia, disorganized thinking, and behavioral disorders in the form of aggressiveness and hostility. Cariprazine has the best evidential base for treatment of various symptoms within the ICD-11 domain \"Negative Symptoms\" among all antipsychotic agents. The data with regard to the effects of cariprazine on the domain \"Depressive Mood Symptoms\" are controversial. No data concerning the effects of cariprazine on the domain \"Manic Mood Symptoms\" are available, but the effectiveness of cariprazine monotherapy for manic episodes without any psychomotor agitation signs in the instance of bipolar disorder has been demonstrated. The effectiveness of cariprazine therapy for the ICD-11 domain \"Psychomotor Symptoms\" has not been investigated, either within the framework of monotherapy or in the course of adjuvant therapy. The effectiveness of cariprazine has been demonstrated in treatment of the domain \"Cognitive Symptoms\", and the pro-cognitive effect of the drug has developed regardless of its impact on any other schizophrenia symptoms. The drug\'s capability to improve the functioning of patients with schizophrenia was demonstrated regardless of the impact on psychotic symptoms.
CONCLUSIONS: Cariprazine is the first-line drug for treatment of the domain \"Negative Symptoms\" as well as representing front-line therapy for the treatment of ICD-11 domains \"Positive Symptoms\" and \"Cognitive Symptoms\". Additional studies will be required in order to evaluate the effects of cariprazine on the ICD-11 domains \"Manic Mood Symptoms\" and \"Depressive Mood Symptoms\".
UNASSIGNED: Одним из нововведений раздела МКБ-11 «шизофрения и другие первичные психотические расстройства» является имплементация 6 дополнительных доменов, которые должны улучшить диагностику и лечение данных состояний в клинической практике. В связи с этим, актуальной задачей является оценка влияния различных психотропных средств, в первую очередь, антипсихотиков, на выделенные домены психотических расстройств. В данном обзоре в качестве психотропного средства был выбран антипсихотик карипразин, который зарегистрирован во многих странах мира, включая Россию, для лечения шизофрении, который зарегистрирован для лечения шизофрении во многих странах мира, включая Россию.
UNASSIGNED: Для данного обзора был осуществлен поиск рандомизированных контролируемых исследований, сравнивающих карипразин с плацебо, с одним или несколькими антипсихотиками. Поиск произведен по базам данных MEDLINE, Cochrane Central Register of Controlled Trials и PubMed. Глубина поиска с января 2014 по март 2021 года.
UNASSIGNED: Результаты свидетельствуют о том, что карипразин эффективен в отношении всех групп симптомов домена МКБ-11 «позитивные симптомы» и может рассматриваться как препарат выбора при лечении первых и множественных эпизодов болезни, дезорганизации мышления и нарушенного поведения в виде агрессии и враждебности. Карипразин имеет наилучшую среди всех антипсихотиков доказательную базу для лечения разных симптомов домена МКБ-11 «негативные симптомы». Данные о влиянии карипразина на домен «депрессивные симптомы» являются противоречивыми. Отсутствуют данные о влиянии карипразина на домен «маниакальные симптомы», но доказана эффективность монотерапии карипразином маниакальных эпизодов без признаков психомоторного возбуждения при биполярном расстройстве. Исследования эффективности терапии карипразином домена МКБ-11 «психомоторные симптомы» не проводилось ни в рамках монотерапии, ни в рамках адьювантной терапии. Карипразин доказал эффективность в лечении домена «когнитивные симптомы» и прокогнитивный эффект препарата развивался независимо от его влияния на другие симптомы шизофрении. Была показана возможность препарата улучшать функционирования больных шизофренией, независимо от влияния на симптомы заболевания.
UNASSIGNED: Карипразин является препаратом первого выбора при лечении домена «негативные симптомы», а также препаратом выбора при лечении доменов МКБ-11 «позитивные симптомы» и «когнитивные симптомы». Необходимы дополнительные исследования для оценки влияния карипразина на домены МКБ-11 «маниакальные симптомы» и «депрессивные симптомы».

BACKGROUND: The pandemic of the new coronavirus infection has become one of the most significant global social shocks in the past decade. It influenced the lifestyle of many people, including those with mental disorders.
OBJECTIVE: To compare the psychopathological structure of psychotic states in young patients (up to 40 years old) with first-episode psychosis before the COVID-19 pandemic and during the COVID-19 pandemic.
METHODS: The research was conducted at the First psychotic episode clinic of the Mental-health clinic No. 1 n.a. N.A. Alexeev, Moscow, Russia. In total, 66 patients were enrolled, who met the inclusion criteria: first-in-life admission to a mental healthcare unit that occurred during the spring of 2019 (control group) or spring 2020 (experimental group), diagnosis on admission that belonged to the group \"Acute and transient psychotic disorders\" (F23.XX) of ICD-10. Patients with a disability or concurrent somatic or neurologic conditions were excluded from the study. Assessment of clinical and psychopathological characteristics with the allocation of the leading syndrome within the psychotic state, psychometric assessment according to the PANSS scale was carried out, the above indicators were compared between the experimental and control group.
RESULTS: We observed statistically insignificant increase in the rates of affective and catatonic subtypes of psychoses, a decrease in the rate of the delusional subtype of paranoid syndrome. PANSS scores differed significantly for different clinical subtypes of psychoses, although the differences between the experimental and control groups showed no statistical significance. Additionally, in spring 2020, a considerable decrease in the total number of hospitalizations was revealed.
CONCLUSIONS: The differences in the clinical and psychopathological structure of psychotic states revealed during the COVID-19 pandemic were statistically insignificant. Additional results of the study may indicate a decrease in the availability of mental healthcare for patients with psychoses, which requires further investigation.
UNASSIGNED: Пандемия новой коронавирусной инфекции стала одним из социально значимых потрясений всемирного масштаба в последнее десятилетие. Она оказала существенное влияние на уклад жизни многих людей, в том числе на больных с психическими расстройствами.
UNASSIGNED: Сравнить психопатологическую структуру манифестных психотических состояний у пациентов молодого возраста (до 40 лет) до пандемии COVID-19 и во время пандемии COVID-19.
UNASSIGNED: Работа выполнена в клинике первого психотического эпизода, подразделении ГБУЗ «ПКБ №1 им. Н.А. Алексеева» ДЗМ. Всего в исследование включены 66 пациентов, отвечавших критериям включения — первичная госпитализация в ПКБ№1 весной 2019 (группа сравнения — 45 пациентов) или 2020 (основная группа — 21 пациент) года, диагноз из рубрики F23, отсутствие инвалидности, сопутствующей соматической или неврологической патологии, которая затрудняла обследование или требовала дополнительных лекарственных назначений. Проведена оценка клинико-психопатологических характеристик с выделением ведущего синдрома в рамках психотического состояния, психометрическая оценка по шкале PANSS, вышеуказанные показатели сопоставлены между основной группой и группой сравнения.
UNASSIGNED: Выявлено статистически незначимое увеличение доли аффективно-бредовых и кататоно-бредовых состояний, а также уменьшение доли параноидных состояний за счет бредового их варианта. Результаты психометрической оценки по PANSS достоверно различались между пациентами с разными клинико-психопатологическими вариантами психозов, однако значимых различий между основной группой и группой сравнения обнаружено не было. Дополнительно было обнаружено уменьшение общего количества госпитализаций весной 2020 года.
UNASSIGNED: Выявленные в ходе исследования различия клинико-психопатологической структуры манифестных психотических состояний в период пандемии COVID-19 не продемонстрировали статистической значимости. Побочные результаты исследования могут указывать на изменение доступности психиатрической помощи для пациентов с манифестными психотическими состояниями, что требует дальнейшего изучения.

UNASSIGNED: The Positive and Negative Syndrome Scale (PANSS) is one of the most commonly used assessment tools for measuring psychotic symptoms. The Psychotic Symptom Rating Scales (PSYRATS) is another instrument created specifically to assess delusions and auditory hallucinations. However, research on the concurrent validity of PSYRATS with PANSS is limited. There are also inconsistent findings regarding the association between the PSYRATS scales and the PANSS positive scale. The present study aims to add to the understanding of the concurrent validity of these measures, while also incorporating a broader measure of psychiatric symptoms (the symptom scale from the Global Assessment of Functioning Scale - split version, GAF-S).
UNASSIGNED: Spearman\'s Rank Order Correlations (rho) were calculated for scores from the PANSS positive scale, PSYRATS and GAF-S in a sample of 148 participants with psychotic disorders at three time points.
UNASSIGNED: The findings indicate concurrent validity between PSYRATS and PANSS, while the PSYRATS scales were not consistently correlated with GAF-S.
UNASSIGNED: PSYRATS may be a valid assessment tool for evaluating psychotic symptoms. The utility of PSYRATS in research and clinical practice should be investigated further.

BACKGROUND: Advancement in mental health care requires easily accessible, efficient diagnostic and treatment assessment tools. Viable biomarkers could enable objectification and automation of the diagnostic and treatment process, currently dependent on a psychiatric interview. Available wearable technology and computational methods make it possible to incorporate heart rate variability (HRV), an indicator of autonomic nervous system (ANS) activity, into potential diagnostic and treatment assessment frameworks as a biomarker of disease severity in mental disorders, including schizophrenia and bipolar disorder (BD).
METHODS: We used a commercially available electrocardiography (ECG) chest strap with a built-in accelerometer, i.e. Polar H10, to record R-R intervals and physical activity of 30 hospitalized schizophrenia or BD patients and 30 control participants through ca. 1.5-2 h time periods. We validated a novel approach to data acquisition based on a flexible, patient-friendly and cost-effective setting. We analyzed the relationship between HRV and the Positive and Negative Syndrome Scale (PANSS) test scores, as well as the HRV and mobility coefficient. We also proposed a method of rest period selection based on R-R intervals and mobility data. The source code for reproducing all experiments is available on GitHub, while the dataset is published on Zenodo.
RESULTS: Mean HRV values were lower in the patient compared to the control group and negatively correlated with the results of the PANSS general subcategory. For the control group, we also discovered the inversely proportional dependency between the mobility coefficient, based on accelerometer data, and HRV. This relationship was less pronounced for the treatment group.
CONCLUSIONS: HRV value itself, as well as the relationship between HRV and mobility, may be promising biomarkers in disease diagnostics. These findings can be used to develop a flexible monitoring system for symptom severity assessment.

UNASSIGNED: The association between schizophrenia and toxoplasmosis has been demonstrated in a number of studies: the prevalence of schizophrenia is significantly higher in toxoplasmosis positive subjects than in those with T. gondii negative status. However, the clinical significance of this association remains poorly understood.
UNASSIGNED: To identify clinical phenomena that are typical for toxoplasmosis-associated (T. gondii seropositive) schizophrenia compared to Toxoplasma-seronegative schizophrenia.
UNASSIGNED: A retrospective database analysis of serum samples from 105 inpatients with schizophrenia (ICD-10code: F20; including 55 male patients; mean age of 27.4 6.4 years) was carried out. The clinical examination involved a structured interview including ICD-10 and E. Bleulers criteria for schizophrenia and psychometric tests(Positive and Negative Scales of PANSS). Serum antibodies (IgG) to T. gondii were identified using ELISA. The statistical significance of any differences were evaluated using the non-parametric Mann-Whitney (U) and X2 tests.
UNASSIGNED: The proportion of seropositive patients in the sample was 16.2%. Comparing schizophrenia patients, who were seropositive or seronegative for toxoplasmosis, there were no statistically significant differences for the mean total PANSS score, mean PANSS-P, PANSS-N or PANSS-G scores. For the majority of PANSS items, differences were also statistically insignificant, except for G5 and G6mannerism and posturing. Seropositive patients had a higher score for this item than seronegative patients: 3.5 versus 2.1 points (U=389.5; р=0.001). Depression, on the contrary,was less pronounced in seropositive than seronegative patients: 1.4 versus 2.4 points (U=509.5; р=0.023). In addition,in seropositive patients, the frequency of symptoms such as mutism according to ICD-10 criteria for schizophrenia was significantly higher (23.5% versus 3.4%, X2=9.27, р=0.013), and the whole group of catatonic symptoms according to the E. Bleulers criteria for schizophrenia was higher (52.9% versus 28.4%, X2=3.916, p = 0.048).
UNASSIGNED: The association between a positive toxoplasmosis status in patients with schizophrenia and catatonic symptoms has been revealed for the first time and should be verified in larger studies.

To investigate the clinical application value of pharmacogenetic testing in individualized drug therapy for adult male patients with schizophrenia. A total of 186 adult patients with schizophrenia were enrolled and randomised into the pharmacogenetic (PGx) intervention group and the standard care group. In the PGx intervention group, PGx testing was performed, and the medication regimen was adjusted according to the results of the pharmacogenomic analysis. In contrast, in the standard care group, patients were treated according to the physician\'s medication experience. Differences in the primary indicator of schizophrenia, the Positive and Negative Symptom Scale (PANSS), and the secondary efficacy measures, the Clinical Global Impressions-Severity of Illness scale (CGI-SI) and Clinical Global Impressions-Global Improvement (CGI-GI) scale, were compared between the intervention and standard care groups. At baseline, the PGx intervention group consisted of 109 individuals, while the standard care group had 77 participants. After 12 weeks of treatment, 49 individuals withdrew from the PGx group (a dropout rate of 45.0%), and 34 withdrew from the standard care group (a dropout rate of 44.2%), with no significant difference in dropout rates between the two groups. The PANSS score reduction rate in the PGx intervention group significantly exceeded that of the standard care group during weeks 3, 6, and 12 of follow-up (P < 0.05). At the 12th week, the PGx intervention group achieved a treatment response rate of 81.7%, significantly surpassing the 48.8% of the standard care group (odds ratio of 4.67, 95% confidence interval of 1.96-11.41; P = 0.001). Furthermore, the PGx intervention was significantly more effective than standard care regardless of whether the patient had a first episode or a relapse (P < 0.05). Furthermore, the Global Assessment of Functioning (GAF) scores and the Personal and Social Performance Scale (PSP) score changes in the PGx intervention group were both significantly different from those in the standard care group (P < 0.05). It is noteworthy that the PGx intervention similarly improves the prognostic outcomes for patients with and without a family history of mental disorders. In conclusion, the application of a PGx intervention treatment model based on PGx testing can significantly improve medication efficacy and shorten the time to achieve the effects of medication in schizophrenia.

BACKGROUND: Endothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls.
METHODS: The study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls. The potential confounders age, gender, smoking and body mass index (BMI) were adjusted for in linear regression models.
RESULTS: The total patient group showed significantly higher levels of ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) compared to controls. Previously medicated patients showed higher ICAM-1 levels compared to drug-naïve patients (p = 0.042) and controls (p < 0.001), and elevated VCAM-1 levels compared to controls (p < 0.001). Drug-naive patients had elevated levels of VCAM-1 (p = 0.031) compared to controls.
CONCLUSIONS: In our study, patients with schizophrenia - including the drug-naïve - have higher levels of soluble CAMs compared to healthy controls. These findings suggest activation of the endothelial system as in inflammation.

After over a hundred years of research, the question whether the symptoms of schizophrenia are rather trait-like (being a relatively stable quality of individuals) or state-like (being substance to change) is still unanswered. To assess the trait and the state component in patients with acute schizophrenia, one group receiving antipsychotic treatment, the other not. Data from four phase II/III, 6-week, randomized, double-blind, placebo-controlled trials of similar design that included patients with acute exacerbation of schizophrenia were pooled. In every trial, one treatment group received a third-generation antipsychotic, cariprazine, and the other group placebo. To assess symptoms of schizophrenia, the Positive and Negative Symptom Scale (PANSS) was applied. Further analyses were conducted using the five subscales as proposed by Wallwork and colleagues. A latent state-trait (LST) model was developed to estimate the trait and state components of the total variance of the observed scores. All symptom dimensions behaved more in a trait-like manner. The proportions of all sources of variability changed over the course of the observational period, with a bent around weeks 3 and 4. Visually inspected, no major differences were found between the two treatment groups regarding the LST structure of symptom dimensions. This high proportion of inter-individual stability may represent an inherent part of symptomatology that behaves independently from treatment status.

UNASSIGNED: Research on glutamate (Glu) in schizophrenia has so far been inconclusive. Based on preclinical studies on Glu lactate interaction, researchers have now focused on brain lactate level as a sign of major pathology, including cognitive dysfunctions in the brain. Our study aimed to examine changes at resting and activated states in brain lactate and Glu-glutamine (Glx) at the anterior cingulate cortex (ACC) in schizophrenia.
UNASSIGNED: A hospital-based prospective study was conducted with twenty-two male cases of schizophrenia and matched healthy controls (HCs). Positive and Negative Syndrome Scale (PANSS), Montreal Cognitive Assessment (MoCA), and Stroop tasks were administered among patients. Brain lactate and Glx at ACC were measured at resting state and during the Stroop test with proton magnetic resonance spectroscopy (1H-MRS) both at baseline and at remission and once among HC.
UNASSIGNED: Though MoCA scores improved significantly (P < 0.001) at remission from baseline among cases, repeated-measures analysis of variance (RM-ANOVA) did not find a significant time effect for Glx (P = 0.82) and lactate (P = 0.30) among cases from baseline to remission. Glx and lactate changed differently from baseline to remission.
UNASSIGNED: Our study did not find significant differences in Glx and lactate between schizophrenia patients and HC. No significant time effect on Glx and lactate was observed from baseline to remission among schizophrenia cases. Different changes observed in Glx and lactate from baseline to remission require replication in future studies with larger sample size, longer follow-up period, and multivoxel MR assessment.