myelin-basic-protein and Psychotic-Disorders

Psychotic disorders affect ~3% of the general population and are among the most severe forms of mental diseases. In early stages of psychosis, clinical aspects may be difficult to distinguish from one another. Undifferentiated psychopathology at the first-episode of psychosis (FEP) highlights the need for biomarkers that can improve and refine differential diagnosis. We investigated gene expression differences between patients with FEP-schizophrenia spectrum (SCZ; N=53) or FEP-Mania (BD; N=16) and healthy controls (N=73). We also verified whether gene expression was correlated to severity of psychotic, manic, depressive symptoms and/or functional impairment. All participants were antipsychotic-naive. After the psychiatric interview, blood samples were collected and the expression of 12 psychotic-disorder-related genes was evaluated by quantitative PCR. AKT1 and DICER1 expression levels were higher in BD patients compared with that in SCZ patients and healthy controls, suggesting that expression of these genes is associated more specifically to manic features. Furthermore, MBP and NDEL1 expression levels were higher in SCZ and BD patients than in healthy controls, indicating that these genes are psychosis related (independent of diagnosis). No correlation was found between gene expression and severity of symptoms or functional impairment. Our findings suggest that genes related to neurodevelopment are altered in psychotic disorders, and some might support the differential diagnosis between schizophrenia and bipolar disorder, with a potential impact on the treatment of these disorders.

Topics: Adult; Bipolar Disorder; Carrier Proteins; Case-Control Studies; DEAD-box RNA Helicases; Diagnosis, Differential; Female; Gene Expression Regulation; Humans; Male; Myelin Basic Protein; Proto-Oncogene Proteins c-akt; Psychiatric Status Rating Scales; Psychometrics; Psychotic Disorders; Reference Values; Ribonuclease III; Schizophrenia; Schizophrenic Psychology; Statistics as Topic; Young Adult

Schizophrenia is a multifactorial neurodevelopmental disorder with high heritability. First-episode psychosis (FEP) is a critical period for determining the disease prognosis and is especially helpful for identifying potential biomarkers associated with the onset and progression of the disorder. We investigated the mRNA expression of 12 schizophrenia-related genes in the blood of antipsychotic-naïve FEP patients (N=73) and healthy controls (N=73). To evaluate the influences of antipsychotic treatment and progression of the disorder, we compared the gene expression within patients before and after two months of treatment with risperidone (N=64). We observed a significantly increased myelin basic protein (MBP) and nuclear distribution protein nudE-like 1 (NDEL1) mRNA levels in FEP patients compared with controls. Comparing FEP before and after risperidone treatment, no significant differences were identified; however; a trend of relatively low NDEL1 expression was observed after risperidone treatment. Animals chronically treated with saline or risperidone exhibited no significant change in Ndel1 expression levels in the blood or the prefrontal cortex (PFC), suggesting that the trend of low NDEL1 expression observed in FEP patients after treatment is likely due to factors other than risperidone treatment (i.e., disease progression). In addition to the recognized association with schizophrenia, MBP and NDEL1 gene products also play an essential role in the functions that are deregulated in schizophrenia, such as neurodevelopment. Our data strengthen the importance of these biological processes in psychotic disorders, indicating that these changes can be detected peripherally and potentially represent putative novel blood biomarkers of susceptibility and disorder progression.

Topics: Adolescent; Adult; Age Factors; Animals; Antipsychotic Agents; Carrier Proteins; Female; Gene Expression Regulation; Humans; Male; Myelin Basic Protein; Psychiatric Status Rating Scales; Psychotic Disorders; Rats; Rats, Inbred SHR; Rats, Wistar; Sex Factors; Statistics as Topic; Young Adult

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.

Topics: Adaptive Immunity; alpha 1-Antitrypsin; Autoantibodies; C-Reactive Protein; Child; Child Development Disorders, Pervasive; Child, Preschool; Female; Humans; Immunity, Innate; Leukocyte Elastase; Male; Myelin Basic Protein; Nerve Growth Factor; Psychotic Disorders

Cerebrospinal fluid (CSF) and peripheral blood (PB) lymphocyte sensitization to rabbit myelin basic protein (MBP) in 44 multiple sclerosis (MS) patients, 21 patients with other neurological diseases (OND) and 14 persons with neurosis was studied with the antigen-active rosette forming cells (Ag-ARFC) assay. The frequency of sensitization of CSF lymphocytes to MBP in groups of MS patients in the relapse stage and the chronic progressive stage was higher than in the group of MS patients in the stable stage and the OND patients. None of the healthy subjects showed a positive reaction with MBP. In BP there were no differences in the incidence of sensitization to MBP between patients in various stages of the disease, but it was higher than in the group of patients with OND and neuroses. In the patients who had suffered from MS for less than 4 years, sensitization to MBP was more common in CSF lymphocytes than in BP lymphocytes. The results suggest that primary sensitization to MBP occurs in CSF, and is probably secondary to myelin damage. However at present it is difficult to determine the extent to which sensitization of CSF and PB lymphocytes to MBP play a role in further demyelination processes.

Topics: Adolescent; Adult; Aged; Follow-Up Studies; Humans; Lymphocytes; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Nervous System Diseases; Psychotic Disorders