[Dynamics of cognitive functions using the rehabilitation program of cognitive training]. / Dinamika kognitivnykh funktsii pri ispol'zovanii reabilitatsionnoi programmy kognitivnogo treninga.

OBJECTIVE: To study the efficiency of the neuropsychological rehabilitation of patients with mild cognitive impairments. MATERIAL AND METHODS: The study included 103 elderly people, aged 59 to 88 years, including 90 women and 13 men with subjective complaints of memory loss (ICD-10: F06.70; F06.71; F06.78; F06.79). Participants were divided into experimental group (n=43) and comparison group (n=42). The estimated impact was the rehabilitation program «The psychosocial therapy and neurocognitive rehabilitation of elderly patients with cognitive impairments¼, within which the principle of complex stimulation of various parameters of the cognitive sphere was used in rehabilitation work with patients in the experimental group in accordance with the «Memory Clinic¼ program. The study was conducted using randomized, equalized comparison groups, and the principle of «triple-blind¼ research. Non-parametric statistics (SPSS) methods were used to assess differences. RESULTS: A significant difference between the comparison and experimental groups has been identified, primarily in relation to high-level mental processes associated with the function of the third structural-functional block according to A.R. Luria. After the training, the number of correct answers significantly increased (t(42)=-2.67, p<0.001) in the experimental group, while in the comparison group the indicator did not change (t(41)=0.50, p=0.617). The number of false alarms in the experimental group decreased significantly (t(42)=2.13, p=0.039). CONCLUSION: The results confirm the leading role of these processes in the hierarchy of mental functions, which suggests that they should primarily be targets of rehabilitation interventions.

[Use of modern classification systems for complex diagnostics of Alzheimer's disease]. / Primenenie sovremennykh klassifikatsionnykh sistem dlya kompleksnoi diagnostiki bolezni Al'tsgeimera.

OBJECTIVE: To compare the content of ß-amyloid (Aß) peptides Aß40, Aß42, total and threonine phosphorylated 181 tau-protein in cerebrospinal fluid (CSF) of patients with the clinical diagnosis of Alzheimer's disease (AD). MATERIAL AND METHODS: The study was performed on 64 patients with a diagnosis of dementia and MMSE scores of 24 or lower. All patients underwent lumbar puncture. Aß40, Aß42, Aß42/40 ratio, total tau, phosphorylated tau at threonine 181 were determined in the CSF using a multiplex assay according to the manufacturer's protocol, the concentration was determined in pkg/ml. RESULTS: The preliminary diagnosis of AD was made in 3 patients (5%). As a result of the study of protein content in the CSF, signs of AD were detected in 48 (75%) people. The findings suggest that the diagnosis of AD is made 10-14 times less frequently than it should be according to the World Health Organization data. The discrepancy between clinical diagnosis and laboratory findings is confirmed by our study. CONCLUSION: Differences in the therapy of dementias and the development of new drugs targeting specific links in the pathogenesis of different types of dementias require accurate and complete diagnosis of dementias, especially AD, as the most common type of dementia.

Riboflavin for COVID-19 Adjuvant Treatment in Patients With Mental Health Disorders: Observational Study.

Background: COVID-19 treatment remains a challenge for medicine because of the extremely short time for clinical studies of drug candidates, so the drug repurposing strategy, which implies the use of well-known and safe substances, is a promising approach. Objective: We present the results of an observational clinical study that focused on the influence of riboflavin (vitamin B2) supplementation on the immune markers of COVID-19 severity in patients with mental health disorders. Results: We have found that 10 mg of flavin mononucleotide (a soluble form of riboflavin) intramuscularly twice a day within 7 days correlated with the normalization of clinically relevant immune markers (neutrophils and lymphocytes counts, as well as their ratio) in COVID-19 patients. Additionally, we demonstrated that total leucocytes, neutrophils, and lymphocytes counts, as well as the neutrophils to leucocytes ratio (NLR), correlated with the severity of the disease. We also found that patients with organic disorders (F0 in ICD-10) demonstrated higher inflammation then patients with schizophrenia (F2 in ICD-10). Conclusion: We suggest that riboflavin supplementation could be promising for decreasing inflammation in COVID-19, and further evaluation is required. This observational clinical trial has been registered by the Sverzhevsky Research Institute of Clinical Otorhinolaryngology (Moscow, Russia), Protocol No. 4 dated 05/27/2020.

[Genotype - phenotype relationships in view of recent advances in the understanding of genetic causes of schizophrenia]. / Problema vliyaniya genotipa na fenotip v sovremennykh issledovaniyakh geneticheskikh prichin shizofrenii.

Genotype - phenotype relationships are considered in view of recent advances in our understanding of genome structure. Different DNA elements can contribute to phenotype formation. Genotype - phenotype relationships are mediated by epigenetic effects that can have various origins - from the most studied to date methylation of certain sites in the genome to only developing ideas about the role of remote regulatory genomic elements in the development of schizophrenia. The transition to a more in-depth study of genotype - phenotype relationships is relevant for the current period of molecular-genetic studies of schizophrenia. Obviously, the concept of phenotype as applied to schizophrenia is not limited to a causal reflection of changes in the structure of a particular gene, but is the product of the combined effect of environmental factors and epigenetic changes that affect gene expression, taking into account tissue specificity and the degree of cell stimulation.

[Effects of diet on the gut microbiome in patients with depression]. / Vliyanie diety na mikrobiom kishechnika u patsientov s depressiei.

OBJECTIVE: To investigate the effects of diet on the gut microbiota and to assess the relationship of these factors with depression. MATERIAL AND METHODS: Microorganisms that predominate in depressed patients were identified and associations of the identified organisms with the patients' diet were performed. Fourteen depressed patients and 14 healthy volunteers with the same socio-demographic parameters were included in the study. The Hamilton Depression Scale, Generalized Anxiety Disorder Questionnaire, and the Center for Epidemiologic Studies Questionnaire were used. RESULTS: Erysipelatoclostridium and Clostridium innocuum species were 11.3 and 14.4 times higher in depressed patients compared with healthy controls. Fusicatenibacter saccharivorans, Faecalibacterium prausnitzii and Roseburia faecis species, as well as members of the genus Roseburia were statistically significantly more abundant in the healthy volunteers group (6.5, 2.14, 8.75 and 5.2 times more frequently compared to patients). The presence of these microorganisms was correlated with dietary components. CONCLUSION: Our study revealed groups of microorganisms that differ in healthy volunteers and depressed patients. The association of these microorganisms with the diet was shown, which partially confirmed the influence of a «healthy diet¼ on the development of depressive disorders.

[Questions of primary diagnosis of schizophrenia in middle-aged and older patients]. / Voprosy pervichnoi diagnostiki shizofrenii u patsientov srednego i starshego vozrasta.

OBJECTIVE: An analysis of clinical and social characteristics of patients aged 40 years and older with primary diagnosis of schizophrenia (F 20-21) in a psychiatric hospital. MATERIAL AND METHODS: We studied 114 medical records of patients aged 40 and over who were admitted to a psychiatric hospital for a two-year period (2018-2019) with a first-time diagnosis of schizophrenia (F 20-21) based on the results of inpatient examination and treatment. RESULTS: The analysis shows that 90% of patients were aged 40-59 years, 59.6% of them were women. In every third patient (33.3%), clinical signs of psychosis were observed for five or more years before hospitalization and diagnosis, and in 14.9% for more than 10 years, the average duration of psychosis before diagnosis was 5.1 years. Markers of psychosis were non-specific factors of family adaptation, working capacity, and substance use, which revealed relationships with gender characteristics and age of diagnosis of psychosis. Better adaptation parameters correlated with the female sex and later diagnosis of schizophrenia, lower indicators were more typical for the male sex and earlier diagnosis. CONCLUSION: Signs of increasing social maladjustment should be alarming to the patient's relatives, as well as social and medical services. In addition, the timely diagnosis of psychosis requires psychoeducation of the population, training of social workers and primary health care professionals.

[Features of cognitive impairment in individuals with paranoid schizophrenia combined with alcohol dependence syndrome]. / Osobennosti kognitivnykh narushenii u lits s paranoidnoi shizofreniei v sochetanii s sindromom zavisimosti ot alkogolya.

OBJECTIVE: To compare the cognitive functioning of patients with paranoid schizophrenia with alcohol dependence syndrome and patients with this disease without comorbid alcohol pathology. MATERIAL AND METHODS: The study included 34 patients with a diagnosis of schizophrenia, paranoid form, aged 24 to 39 years (22 men and 12 women). The experimental group included 17 patients with paranoid schizophrenia combined with alcohol dependence syndrome with diagnosed symptomatic alcoholism. The comparison group included 17 patients with a similar diagnosis without a comorbid disorder. The duration of the disease in both groups was 5-10 years. The main research tool was a neuropsychological examination, which included the Benton test, the pathway test, the Mini-Mental State Examination (MMSE), and the constructive praxis test. RESULTS: Moderate cognitive impairments were found in patients with schizophrenia in combination with comorbid pathology, combined with disorders of intellectual flexibility and cognitive control. Also, in the experimental group, marked disorders of constructive praxis and visual memory were noted, which indicates a lesion of the occipital-parietal parts of the brain. Thus, in the course of the study, cognitive disorders were identified in patients with schizophrenia in combination with alcohol addiction: disturbances of perceptual organization, cognitive flexibility and attention switching, visual memory. CONCLUSION: Concomitant alcohol dependence is a significant factor for changing cognitive functions in patients with schizophrenia: control functions suffer, visual memory is disturbed and constructive apraxia is noted.

[Metacognition as a pathway to the study and treatment of fragmentation in schizophrenia]. / Izuchenie i lechenie fragmentatsii pri shizofrenii s primeneniem kontseptsii metapoznaniya.

This paper explores the potential of recent research on metacognition to offer new avenues to assess and address the phenomenon of fragmentation in schizophrenia, which was described by E.Bleuler as «splitting¼. The concepts of metacognition characterize and quantify alterations or decrements in the processes by which fragments or pieces of information are integrated into a coherent sense of self and others. A method for assessing metacognition is presented along with research examining the presence and importance of metacognitive deficits in schizophrenia. Greater levels of metacognitive deficits have been detected in different phases of schizophrenia and linked to poorer psychosocial outcomes. These data were obtained both in foreign and preliminary Russian studies. The authors suggest that treatments, which successfully target metacognitive capacity, may uniquely promote wellness and recovery in schizophrenia.

[Antioxidant status of blood plasma of acutely psychotic patients and its correlation with Nrf2 activation]. / Antioksidantnyi status plazmy krovi patsientov s ostrym psikhozom i ego svyaz' s aktivatsiei transkriptsionnogo faktora Nrf2.

OBJECTIVE: To study the correlation between the blood plasma antioxidant profile and the transcriptional activity of the Nrf2 gene in acute psychosis in patients with schizophrenia and alcoholism. MATERIAL AND METHODS: The study included 40 patients with the first episode of the paranoid form of schizophrenia, 33 patients with schizophrenic psychosis who had previously received therapy, 22 patients with first-time acute alcohol psychosis, and 25 healthy volunteers. The level of Nrf2 in peripheral blood mononuclear cells was estimated by flow cytometry, and the antioxidant profile of blood plasma was estimated with chemiluminometry. RESULTS: The total and «thiol¼ antioxidant capacity were reduced in patients with initially diagnosed schizophrenic psychosis and alcoholic psychosis. In patients after treatment, the total antioxidant capacity was higher compared to previously untreated patients. The level of Nrf2 protein in mononuclear cells in patients with the first psychotic episode was significantly lower than in patients with alcoholism and lower than in the control group. In patients with alcoholic psychosis, Nrf2 level was correlated with both the total antioxidant capacity due to uric acid and the «thiol¼ antioxidant capacity; in patients with psychosis in schizophrenia, Nrf2 level was correlated only with the «thiol¼ antioxidant capacity. CONCLUSIONS: The correlation between the total and «thiol¼ antioxidant capacity and the level of Nrf2 in mononuclear cells of patients with alcohol delirium indicates the undamaged state of the regulation. The absence of a correlation between the total antioxidant capacity and the level of Nrf2 in patients with schizophrenia indicates a disturbance of the activation of the Nrf2 pathway due to, possibly, a part associated with the participation of uric acid.

[Comorbidity of somatic diseases in psychiatric patients]. / Komorbidnye somaticheskie rasstroistva u patsientov s psikhicheskimi zabolevaniyami.

OBJECTIVE: To study the prevalence of somatic diseases in patients with mental disorders based on the results of medical examination in Moscow mental health clinics in 2018. MATERIAL AND METHODS: A retrospective analysis of the results of the clinical examinations of 6492 outpatients, which accounted for 79.5% of patients who underwent medical examination in this time period. RESULTS: Comorbid somatic diseases were found in 4883 (75%) patients. Hypertension and non-insulin-dependent diabetes mellitus were most frequent with the prevalence higher than in the general population of the Russian Federation. Patients with diagnosed schizophrenia, along with hypertension and diabetes mellitus, have found to be at increased risk of diseases of the endocrine system and metabolic disorders. The incidence of the mentioned diseases is not higher than that reported in literature. CONCLUSION: The higher prevalence of socially relevant diseases (hypertension, diabetes mellitus) among patients with mental disorders demands the development of strategies for prevention, early detection and treatment of these diseases in psychiatric patients.

Neuro-Immune Aspects of Schizophrenia with Severe Negative Symptoms: New Diagnostic Markers of Disease Phenotype.

The aim of the study was to analyze the immune-inflammatory profile of patients with paranoid schizophrenia and relate it to the severity of negative symptoms and the MRI data in order to identify biomarkers of schizophrenia severity, search for new approaches to therapy, and control its effectiveness. Materials and Methods: The main group included 51 patients with paranoid schizophrenia, the control group - 30 healthy subjects. Patients underwent MRI scans and immunological studies, which included an assessment of natural and adaptive immunity, the systemic level of key pro-inflammatory and anti-inflammatory cytokines, and other markers of inflammation. Results: Disorders of immunity and immunoinflammatory profile in patients with paranoid schizophrenia with severe negative symptoms were revealed for the first time: in the presence of severe negative symptoms (>15 points according to the NSA-4 scale), the levels of humoral immunity factors, cytokines IL-10 and IL-12p40 and neurotrophin NGF were increased as well as the markers of systemic inflammation. Morphometric changes in the brain, typical for patients with schizophrenia, and also specific for patients with severe negative symptoms, were determined. The data analysis revealed correlations between the immune changes with structural changes in some of the brain areas, including the frontal cortex and hippocampus. Associations were found between the levels of anti-inflammatory IL-10, IL-12p40 cytokines and morphometric parameters of the brain, specific only for schizophrenic patients with severe negative symptoms. Conclusion: The interdisciplinary approach, combining brain morphometry with in-depth immunological and clinical studies, made it possible to determine neurobiological, immune, and neurocognitive markers of paranoid schizophrenia with severe negative symptoms. The results are important for further deciphering the pathogenesis of schizophrenia and its subtypes, as well as for the search for new approaches to the treatment of severe forms of the disease.

[The relationship between inflammation, cognitive disorders and neuroimaging data in schizophrenia]. / Svyaz' mezhdu vospaleniem, kognitivnymi narusheniyami i dannymi neirovizualizatsii pri shizofrenii.

OBJECTIVE: To search for the relationship between the results of functional imaging, immunological parameters and laboratory markers of inflammation in schizophrenia, taking into account cognitive impairment in patients, and to consider the possibility of using a multidisciplinary approach to diagnosis, treatment and prognosis of schizophrenia. MATERIAL AND METHODS: The study included 25 patients with schizophrenia and 13 healthy volunteers. Psychiatric scales were administered to evaluate the patient's condition. The main indicators of humoral immunity, the level of markers of inflammation, key pro-inflammatory and anti-inflammatory cytokines, and growth factor VEGF were determined by ELISA. Brain MRI was performed. All calculated tractographic data are included in the connection database to study the effect of immunological markers and the degree of severity of cognitive impairment. RESULTS AND CONCLUSION: Levels of markers of systemic inflammation and growth factor VEGF-A as well as the activation of humoral immunity are increased in patients with schizophrenia compared with controls. For the first time, the relationship of immunological parameters with the coefficient of quantitative anisotropy in the area of the corpus callosum in schizophrenia was revealed. The results indicate the possible value of indicators of the activation of the humoral immune response and systemic inflammation as markers of neurophysiological changes and cognitive dysfunction in schizophrenia.

[Molecular Biological Aspects of Depressive Disorders: A Modern View].

Depression is a serious mental disorder that affects more than 300 million people worldwide. Due to the lack of effective treatment methods, the pathogenesis of depression is necessary to study in order to understand its development and find new therapies. The review describes the main mechanisms of depression, including the monoamine hypothesis, impairment of the hipotalamic-pituitary-adrenal axis, decreased production of neurotropic factors, and neuroinflammation. Genetic correlations, gene polymorphisms, and epigenetic mechanisms are also considered. Common and different features of the etiology are analyzed for depression and depressive conditions associated with other pathologies (schizophrenia, Parkinson disease, and Alzheimer's disease). Modern experimental methods used to investigate the molecular mechanisms of depressive conditions are described with a focus on gene knockouts in laboratory animals and the CRISPR/Cas technology. Consideration is given to optogenetic and chemogenetic methods and analyses of genetic polymorphisms and their combinations. The data may provide for a better integral understanding of the modern ideas about the pathogenesis of depression as an isolated or comorbid disorder and the prospects in studying the mechanisms of depressive conditions.

Copy number variations of satellite III (1q12) and ribosomal repeats in health and schizophrenia.

OBJECTIVE: Earlier we studied the copy number variations (CNVs) of ribosomal repeat (rDNA) and the satellite III fragment (1q12) (f-SatIII) in the cells of schizophrenia patients (SZ) and healthy controls (HC). In the present study we pursued two main objectives: (1) to confirm the increased rDNA and decreased f-SatIII content in the genomes of enlarged SZ and HC samples and (2) to compare the rDNA and f-SatIII content in the same DNA samples of SZ and HC individuals. METHODS: We determined the rDNA CN and f-SatIII content in the genomes of leukocytes of 1770 subjects [HC (N = 814) and SZ (N = 956)]. Non-radioactive quantitative hybridization method (NQH) was applied for analysis of the various combinations of the two repeats sizes in SZ and HC groups. RESULTS: f-SatIII in human leukocytes (N = 1556) varies between 5.7 and 44.7 pg/ng DNA. RDNA CN varies between 200 and 896 (N = 1770). SZ group significantly differ from the HC group by lower f-SatIII content and by rDNA abundance. The f-SatIII and rDNA CN are not randomly combined in the genome. Higher rDNA CN values are associated with higher f-SatIII index values in SZ and HC. The f-SatIII variation interval in SZ group increases significantly in the subgroup with the high rDNA CN index values (>300 copies). CONCLUSION: Schizophrenia patients' genomes contain low number of f-SatIII copies corresponding with a large ribosomal repeats CN. A scheme is proposed to explain the low f-SatIII content in SZ group against the background of high rDNA CN.

[Schizophrenia and other psychotic disorders in ICD-11 and DSM-5: evolution of the concepts and current status]. / Shizofreniya i drugie psikhoticheskie rasstroistva v MKB-11 i DSM-5: razvitie kontseptsii i sovremennoe sostoyanie.

The concepts of schizophrenia and other primary psychotic disorders have been changed a lot since their beginnings more than century ago due to many factors such as the dominance of a certain hypothesis during a particular period of time, the development of new clinical research and specific treatments as well as different understanding of the boundaries between mental disorders. It was appeared the diagnosis of schizophrenia spectrum disorders which still based only on clinical symptoms. Whether psychotic disorders can be better represented dimensionally or categorically remains a challenging question. Regarding schizophrenia and other primary psychotic disorders, there are some important changes in DSM-5 and ICD-11 concerning the use of quantitative assessment of psychopathological domains, course of psychosis and remission as well as giving more attention to cognitive issues. The main differences between these classifications are the structure of corresponding sections and different criteria of some disorders. Before the ICD-11 implementation in 2022 into clinical practice, it is highly recommended to conduct a set of trainings for clinicians along with the comments to Diagnostic guidelines for Schizophrenia and other primary psychotic disorders.

Proteome data of serum samples from patients with schizophrenia.

Schizophrenia is a complex chronic disease. The molecular determinants and neuropathology of schizophrenia are multifaceted; an important role in the pathogenesis is played by the dysregulation of molecular and epigenetic mechanisms. However, the molecular mechanisms of the development of the disease have not yet been studied. An important task is the accumulation and systematization of "OMICS"-knowledge of the molecular profiles (transcriptome, proteome, metabolome) of blood specific to pathology. Thereby the development and improvement of mass spectrometric methods for the detection of biological molecules has become increasingly important in biomedical research. In the field of applied problems in biomedical research, the most prevalent issue involves the identification of serological protein markers associated with the development of schizophrenia, which account for the diseases that cause the a life-shortening illness, disability, decreased of functioning and quality of life and wellbeing or health status. OMICS approaches are designed to detect genes (genomics), mRNA (transcriptomics), proteins (proteomics) and metabolites (metabolomics) in a specific biological sample. We report the proteomic datasets on the serum samples from patients with schizophrenia (series "SCZ") and healthy volunteers (series "CNT"). Data were acquired using shotgun ultra-high resolution mass spectrometry.

[Perspectives of the use of pharmacogenetic tests in neurology and psychiatry]. / Perspektivy primeneniia farmakogeneticheskikh testov v psikhiatrii i nevrologii.

The review is devoted to the analysis of the current state of pharmacogenetic research and their use in psychiatric practice. The main genes responsible for the pharmacodynamics and pharmacokinetics of drugs used in psychiatry are listed. Foreign pharmacogenetic clinical recommendations and progress on their implementation in medical practice in various countries of Europe and the USA are analyzed. The need to create Russian clinical guidelines on pharmacogenomics to improve the effectiveness of patient care and to implement a personalized approach to therapy is discussed.

Accumulation of Circulating Cell-Free CpG-Enriched Ribosomal DNA Fragments on the Background of High Endonuclease Activity of Blood Plasma in Schizophrenic Patients.

INTRODUCTION: Schizophrenia (SZ) increases the level of cell death, leading to an increase in the concentration of circulating cell-free DNA (cfDNA). Ribosomal DNA (rDNA) contains many unmethylated CpG motifs that stimulate TLR9-MyD88-NF-κB signaling and the synthesis of proinflammatory cytokines. The number of rDNA copies in the genomes of SZ patients is increased; therefore, we expect that the concentration of cell-free rDNA in the plasma of the SZ patients also increases. This may be one of the explanations of the proinflammatory cytokine increase that is often observed in SZ. The major research question is what is the rDNA copy number in cfDNA (cf-rDNA CN) and its putative role in schizophrenia? Materials and Methods. We determined cfDNA concentration (RNase A/proteinase K/solvent extraction; fluorescent dye PicoGreen) and endonuclease activity (NA) of blood plasma (radial diffusion method) in the untreated male SZ group (N = 100) and in the male healthy control group (HC) (N = 96). Blood leukocyte DNA and cfDNA rDNA CN were determined with nonradioactive quantitative hybridization techniques. Plasma concentration of cf-rDNA was calculated. RESULTS: In the subjects from the SZ group, the mean cfDNA plasma concentration was twofold higher and NA of the plasma was fourfold higher than those in the healthy controls. rDNA CN in the blood leukocyte genome and in the cfDNA samples in the SZ group was significantly higher than that in the HC group. cf-rDNA concentration was threefold higher in the SZ group. CONCLUSION: Despite the abnormally high endonuclease activity in the blood plasma of SZ patients, the circulating cfDNA concentration is increased. Fragments of cf-rDNA accumulate in the blood plasma of SZ patients. Potentially, SZ patients' cfDNA should be a strong stimulating factor for the TLR9-MyD88-NF-κB signaling pathway.

[Isolation of neurospheres and neural progenitor cells from the olfactory epithelium]. / Poluchenie neirosfer i neironal'nykh progenitornykh kletok iz oboniatel'nogo épiteliia.

The olfactory epithelium (OE) is an accessible source of neural stem cells and progenitor cells. The objective of the study was to compare the effectiveness of various biopsy sites to isolate and propagate neural progenitor cells from the olfactory epithelium (OE). The authors assessed OE cell count in OE in different sites of the nasal cavity and showed the possibility of isolation neurospheres from nasal biopsies. In total, 45 inpatinets were included in the study. Biopsy specimens were obtained from 30 patients undergoing septoplasty and/or turbinate surgery. Three areas of OE were biopsied: lower third section of the nasal septum (A), anterior part of the middle turbinate (B), upper third of the nasal septum (C). Immunocytochemistry and fluorescence-activated cell sorting showed that OE cells were NCAM-positive. Mean percentage of NCAM+ cells was 7.8% for A, 42.7% for B and 18.2% for C. The difference was significant between A and B (p=0.0001) and B and C (p=0.01). Therefore, the anterior part of the middle turbinate was an easily accessible and safe site to obtain neural cells. To confirm this, neurospheres were obtained in 15 patients with schizophrenia who underwent in-office endoscopy.