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Expression Alteration of Disrupted in Schizophrenia 1 (DISC1) Gene, a Potential Peripheral Marker for Schizophrenia and Paranoid Personality Disorder

Jalal Rostampour1, Arvin Haghighatfard2,3*, Masoume Ghasemzadeh Qazvini4, Talie Karimi5, Elham Rastegarimoghaddam6, Atieh Alizadenik7 and Zahrasadat Hosseini8

Introduction: Schizophrenia (SCZ) is a major psychiatric disorder with unclear etiology or biological diagnosis. Paranoid Personality Disorder (PPD) is a type A personality disorder characterized by paranoia and generalized mistrust. Disrupted in schizophrenia 1 (DISC1) is a gene located on human chromosome 1 that is involved in neurodevelopment of brain. Variations and translocations in this gene were found associated with schizophrenia and other psychiatric disorders. Present study aimed to evaluate the expression alteration of DISC1 gene in peripheral blood of SCZ and PPD patients and its correlation with clinical features.

Material and methods: Study was included 300 SCZ, 300 PPD and 300 non-psychiatric individuals. Total blood was collected and expression level of DISC1 evaluated by using quantitative Real time PCR SYBR green. Lymphocyte DISC1 protein levels in all subjects were examined. Also, to assess psychiatric symptoms severity, Positive and Negative Syndrome Scale (PANSS) was obtained from SCZ and PPD patients. For analysis of executive functions abilities, Wisconsin Card Sorting Test (WCST) had been conducted from all subjects.

Results: Findings showed significant DISC1 gene down expression in SCZ and PPD patients vs. non-psychiatrics. DISC1 protein levels were significantly decreased in SCZ and PPD vs. non-psychiatrics. Also in SCZ patients, general and negative symptoms score were associated with down regulation of DISC1 mRNA level. Executive functions deficiency had detected in SCZ and PPD and correlations were found between decrease in WSCT correct response and down expression of DISC1 in SCZ and PPD patients.

Discussion and conclusion: Results presented DISC1 as potential peripheral marker for schizophrenia as well as paranoid personality disorder. Correlation between DISC1 mRNA level reduction and severity of general and negative symptoms in one side and executive functions abnormalities in the other side may support the neurodevelopment hypothesis about pathophysiology of schizophrenia and related personality disorder especially paranoid personality disorder.