Several novel biomarkers in bioenergetic pathways have detected in schizophrenia and paranoid personality disorder

Schizophrenia (SCZ) is a chronic neuropsychiatric disorder with 1 % prevalence worldwide and no certain known etiology. Paranoid personality disorder (PPD) is one of the type A personality disorders which characterized by paranoia and a pervasive, long-standing suspiciousness and generalized mistrust of others with 0.5%–2.5% occurrence in general population and no clear etiology .Present study aimed to assess the role of mitochondrial complex I and cell bioenergetic pathways in etiology and characteristics of SCZ and PPD. mRNA level of all genomic and mitochondrial genes which encoding mitochondrial complex I subunits(44 genes) assessed in blood with quantitative Real time PCR, associated by comprehensive psychiatric and psychological assessments, electroencephalography and biochemical evaluations in 634 SCZ , 340 PPD patients and 528 non psychiatric subjects.Significant expression changes of 18 genes in SCZ patients and 11 genes in PPD patients detected in mitochondrial complex I. Most of these genes were novel candidate biomarkers for SCZ and PPD. Significant over expression of NDUFS1 was found in paranoid schizophrenic patients and PPD patients in compare with other subtypes of schizophrenia. There was a direct correlation between antipsychotic resistance in patients and over expression of NDUFS1 and NDUFV1 and down expression of NDUFB11 and NDUFA1.Several correlations between mRNA levels and severity of symptoms, drug response, and deficits in attention, working memory, executive functions and brain regions activities were found. Findings suggest that deregulations of both core and supernumerary subunits of complex I are involved in etiology of SCZ and PPD. These deregulations have effects on brain activity as well as disorders characteristics. NDUFS1as largest subunit of complex I presented as a special biomarker for paranoid behaviors along with antipsychotic resistance and prefrontal cortex dysfunctions in psychotic patients. Also all of the 11 candidate genes found in PPD were among the 18 differentially expressed genes found in schizophrenia and their change direction were the same in both disorders which refer to important and upper hand effects of cell bioenergetic pathways in behavior and psychosis.

کلیدواژه ها:

Schizophrenia ، Paranoid personality disorder ، mitochondrial complex I ، gene expression ، NDUFS1