Abstract
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.
Highlights
Psychotic disorders, including schizophrenia, bipolar disorder and schizoaffective disorder, affect ~ 3% of the general population[1,2] and represent some of the most severe mental diseases.Characteristic symptoms include hallucinations, delusional beliefs, severe mood variations and cognitive impairment
first-episode of psychosis—mania with psychosis (BD) patients presented with poorer global function, as indicated by Global Assessment of Functioning Scale (GAF) (Table 1), compared with first-episode of psychosis—schizophrenia spectrum (SCZ) patients
V-Akt murine thymoma viral oncogene homolog 1 (AKT1) and Dicer 1 (DICER1) detected that AKT1 and DICER1 expression levels were higher in BD expression levels were different between BD and SCZ patients, patients compared with SCZ patients and controls, suggesting that the expression of these genes is associated to manic features
Summary
Psychotic disorders, including schizophrenia, bipolar disorder and schizoaffective disorder, affect ~ 3% of the general population[1,2] and represent some of the most severe mental diseases.Characteristic symptoms include hallucinations, delusional beliefs, severe mood variations and cognitive impairment. Psychotic disorders, including schizophrenia, bipolar disorder and schizoaffective disorder, affect ~ 3% of the general population[1,2] and represent some of the most severe mental diseases. The first-episode psychosis (FEP) is a critical period given that brain abnormalities and cognitive deficits are already present and progress faster, and more aggressively in the first years of the disorder,[3] whereas the patients are not affected yet by factors related to disease progression, that is, duration of illness and exposure to antipsychotics.[4,5]. Different lines of research aim to identify biomarkers capable of distinguishing these disorders, including studies based on gene expression in peripheral tissues.[7] On the other hand, some genes, including microRNAs, show a concordant expression and association for both schizophrenia and bipolar disorder in blood[8] and in brain tissues,[9,10] showing a possible common pathophysiological mechanism between these disorders, beyond the diagnostic boundaries. Previous studies revealed an effect of antipsychotics on gene expression.[11,12,13]
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