Mitochondrial complex I and III gene mRNA levels in schizophrenia, and their relationship with clinical features

Abstract

BackgroundThe etiology of schizophrenia is not precisely known; however, mitochondrial function and cerebral energy metabolism abnormalities were determined to be possible factors associated with the etiology of schizophrenia. Impaired mitochondrial function negatively affects neuronal plasticity, and can cause cognitive deficits and behavioral abnormalities observed during the clinical course of schizophrenia. The present study aimed to investigate the relationship between the clinical features of schizophrenia, and mitochondrial complex activation, based on measurement of mRNA levels in the NDUFV1, NDUFV2, NDUFS1, and UQCR10 genes involved in the peripheral mitochondrial complex.MethodsThe study included 138 schizophrenia patients and 42 healthy controls. The schizophrenia group was divided into a chronic schizophrenia subgroup (n = 84) and a first-episode schizophrenia subgroup (n = 54). The symptoms profile and severity of disorder were evaluated using the Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), and Brief Psychiatric Rating Scale (BPRS).ResultsThe level of mRNA expression of NDUFV1, NDUFV2, and NDUFS1 was significantly higher in the schizophrenia group than in the control group. The mRNA level of NDUFV2 was positively correlated with BPRS and SAPS scores in the first-episode schizophrenia subgroup.ConclusionThe findings showed that there was a positive correlation between gene mRNA levels and psychotic symptomatology, especially positive symptoms. Our results suggest that mRNA levels of the NDUFV1, NUDFV2, and NDUFS1 genes of complex I of the mitochondrial electron transport chain might become a possible peripheral marker for the diagnosis of schizophrenia.

Mitochondrial complex I and III mRNA levels in bipolar disorder

“…In a study of the mRNAs of schizophrenia-related genes, the levels in the patients with acute exacerbation were found to be higher than those residual schizophrenia patients (Dror et al, 2002). Mitochondrial gene mRNA levels in schizophrenia patients are associated with clinical severity, particularly the positive symptoms (Akarsu et al, 2014). Future comparisons of data from the same BD patients in manic, depressive and euthymic states will allow for the acquisition of more consistent results.…”

Systems genetic analysis of hippocampal neuroanatomy and spatial learning in mice

“…Ndufs8 [NADH dehydrogenase (ubiquinone) Fe‐S protein 8] is a subunit of the mitochondrial complex I (MCI), the largest multi‐enzyme complex (45 subunits) of the mitochondrial respiratory chain that transfers electrons from NADH2 to ubiquinone. MCI mutations have been found in Leigh syndrome and several other neurological disorders such as Schizophrenia, Parkinson's and Alzheimer's diseases (Akarsu et al ; Mancuso et al ; Procaccio & Wallace ; Song & Cortopassi ). Correlations between Ncam1 / Ndufs8 and Ncam1 / Rps12 are negative, whereas all others are positive ( Rps12 / Ndufs8 , Ncam1 / 2900034C19 , Ncam1 / Ssbp3 and Ssbp3 / Rps12 ).…”

The early growth response protein 1-miR-30a-5p-neurogenic differentiation factor 1 axis as a novel biomarker for schizophrenia diagnosis and treatment monitoring

“… 16 Altered expression of mitochondrial complex I genes in whole-blood cells and platelets has been suggested as a potential peripheral marker for schizophrenia, although these genes are not responsive to neuroleptic treatment. 21 , 22 , 45 Interestingly, the mRNA level of NDUFV2 , one of the mitochondrial complex I genes, is positively correlated with positive symptoms in the first-episode schizophrenia patients, 45 and complex I activity is positively correlated with the severity of positive symptom scores. 22 Decreased AKT1 mRNA level in PBMNCs as assessed by microarray analysis was shown in male, recent-onset (<5 years) patients, which however was not verified by real-time PCR.…”