Gene expression study of mitochondrial complex I in schizophrenia and paranoid personality disorder.

Objectives: The aetiology and molecular mechanisms of schizophrenia (SCZ) and paranoid personality disorder (PPD) are not yet clarified. The present study aimed to assess the role of mitochondrial complex I and cell bioenergetic pathways in the aetiology and characteristics of SCZ and PPD.

Methods: mRNA levels of all genomic and mitochondrial genes which encode mitochondrial complex I subunits (44 genes) were assessed in blood in 634 SCZ, 340 PPD patients and 528 non-psychiatric subjects using quantitative real-time PCR, and associated comprehensive psychiatric, neurological and biochemical assessments.

Results: Significant expression changes of 18 genes in SCZ patients and 11 genes in PPD patients were detected in mitochondrial complex I. Most of these genes were novel candidate genes for SCZ and PPD. Several correlations between mRNA levels and severity of symptoms, drug response, deficits in attention, working memory, executive functions and brain activities were found.

Conclusions: Deregulations of both core and supernumerary subunits of complex I are involved in the aetiology of SCZ and PPD. These deregulations have effects on brain activity as well as disorder characteristics.