Abstract
BackgroundMitochondrial dysfunction was reported in schizophrenia, bipolar disorderand major depression. The present study investigated whether mitochondrial complex I abnormalities show disease-specific characteristics.Methodology/Principal FindingsmRNA and protein levels of complex I subunits NDUFV1, NDUFV2 and NADUFS1, were assessed in striatal and lateral cerebellar hemisphere postmortem specimens and analyzed together with our previous data from prefrontal and parieto-occipital cortices specimens of patients with schizophrenia, bipolar disorder, major depression and healthy subjects. A disease-specific anatomical pattern in complex I subunits alterations was found. Schizophrenia-specific reductions were observed in the prefrontal cortex and in the striatum. The depressed group showed consistent reductions in all three subunits in the cerebellum. The bipolar group, however, showed increased expression in the parieto-occipital cortex, similar to those observed in schizophrenia, and reductions in the cerebellum, yet less consistent than the depressed group.Conclusions/SignificanceThese results suggest that the neuroanatomical pattern of complex I pathology parallels the diversity and similarities in clinical symptoms of these mental disorders.
Highlights
The past decade has witnessed an abundance of studies focusing on mitochondrial abnormalities in several mental disorders including schizophrenia, bipolar disorder and major depression
Protein and mRNA levels of complex I subunits, 51, 24- and 75kDa, were analyzed in two brain specimens obtained from the striatum and the lateral cerebellar hemisphere (Fig 1) of patients with schizophrenia, bipolar disorder, major depression and normal subjects
Complex I subunits in the cerebellum The lateral cerebellar hemisphere, which was planned to serve as a control area, showed interesting significant inter-group differences in mRNA of complex I subunits (NDUFV1-F(3,56) = 23.780, p = 0.0001, NDUFV2-F(3,56) = 12.234, p = 0.0001 and NDUFS1F(3,56) = 4.331, p = 0.008)
Summary
The past decade has witnessed an abundance of studies focusing on mitochondrial abnormalities in several mental disorders including schizophrenia, bipolar disorder and major depression. In bipolar disorder similar mitochondrial abnormalities have been reported [9,10,11], while in major depression, the current literature on MRS studies is sparse and inconsistent [12,13,14]. Additional genetic variations in mitochondrial DNA encoded ND3 and ND4 subunits of complex I were associated with bipolar disorder and schizophrenia, respectively [17,18]. These studies suggest the genetic variation in complex I as a risk factor in both disorders. The present study investigated whether mitochondrial complex I abnormalities show disease-specific characteristics
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