Objective: Schizophrenia is a chronic psychiatric disorder with unclear etiology. Mitochondrial electron transport chain (ETC) complex dysfunctions had been reported in patients with schizophrenia. Neuronal plasticity and brain circuits are affected by impaired function of mitochondria. Consequently behavioral abnormalities and cognitive deficits seen in the clinical course of schizophrenia may occur. The relationship between psychotic symptoms and mRNA levels of certain genes located in the mitochondrial ETC of schizophrenia cases were researched in this study.
Method: 158 male patients with psychotic symptoms hospitalized in the psychiatric clinic of Gulhane Military Medical Academy were enrolled to the study. 84 of 158 patients had been followed up with schizophrenia diagnosis at least one year prior to the study. These patients were defined as chronic schizophrenic. 74 patients without any previous psychiatric history and showing schizophrenia-like psychotic symptoms for the first time have been followed for six months. At the end of the six-months follow-up, 54 of 74 patients met Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria for schizophrenia. These cases are defined as first-episode schizophrenia. 42 healthy male with similar socio-economic characteristics of the patients constituted the control group. Diagnostic interview and the disease severity of patients were evaluated by Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), Brief Psychiatric Rating Scale (BPRS). mRNA levels of genes from peripheral blood samples of the patients were investigated by relative quantification method in the genetic laboratory.
Results: mRNA levels of all of the genes representing subunits of complex I (NDUFV1, NDUFV2, NDUFS1) was significantly higher in schizophrenic cases than the control subjects. Statistically significant difference was observed between first-episode schizophrenia and control subjects in mRNA levels of complex I genes. There was statistically significant difference between chronic schizophrenia and control subjects in mRNA levels of NDUFV2 gene. There was positive correlation between mRNA levels of NDUFV2 gene and BPRS, SAPS scores in first-episode schizophrenia cases. Negative correlation was detected between the mRNA levels of NDUFV2 gene and SANS scores in chronic schizophrenia cases.
Conclusion: We suggested that mRNA levels of mitochondrial complex I genes could be used as a peripheral marker in the diagnosis of schizophrenia. Additionally, the results showed that there was a positive correlation between gene mRNA levels and psychotic symptomatology especially positive symptoms. The unclear etiology of schizophrenia reveals the need for peripheral biological marker in schizophrenia. Therefore, clinical and experimental studies related to dysfunctions of mitochondria are thought to make an important contribution to the confirmation of the schizophrenia diagnosis.