Expression Study of NDUFS1, NDUFV1, and NDUFV2 in Schizophrenia and Paranoid Personality Disorder
AbstractBackground: Schizophrenia (SCZ) is a major psychiatric disorder with unclear etiology and biological diagnosis. Paranoid personality disorder (PPD) is a type-A personality disorder characterized by paranoia and generalized mistrust. The etiology and molecular mechanisms of SCZ and PPD are not clarified. The present study aimed to examine the expression alteration of three major genes of mitochondrial complex I in the peripheral blood of patients with SCZ and PPD, and its correlations with clinical features of patients, especially the five major personality traits. Materials and Methods: This case-control study was performed on 735 SCZ, 742 PPD, and 750 non-psychiatric individuals. The mRNAs level of NDUFS1, NDUFV1, and NDUFV2 were assessed using quantitative real-time polymerase chain reaction, and their correlations with psychiatric symptoms were assessed by the positive and negative syndrome scale and the brief psychiatric rating scale tests, as well as personality traits that were evaluated by NEO Five-Factor Inventory. Results: Findings showed significant overexpression of NDUFS1, NDUFV1, and NDUFV2 in patients with SCZ (P=0.001, P=0.002, and P=0.004, respectively) and PPD (P=0.001, P=0.003, and P=0.006, respectively) compared with non-psychiatrists. In addition, these genes were associated with positive psychiatric symptoms and neuroticism in SCZ (P=0.008) and PPD (P=0.01). Conclusion: Overexpression genes that encode subunits of complex I play an important role in SCZ and PPD etiology and severity of symptoms. It may bring evidence about the significant role of bioenergetics dysfunction in psychotic behaviors in different psychiatric situations.
Ben-Shachar D, Karry R. Sp1 expression is disrupted in schizophrenia; a possible mechanism for the abnormal expression of mitochondrial complex I genes, NDUFV1 and NDUFV2. PLoS One. 2007;2(9):e817.
Mehler-Wex C, Duvigneau JC, Hartl RT, Ben-Shachar D, Warnke A, Gerlach M. Increased mRNA levels of the mitochondrial complex I 75-kDa subunit. Eur Child Adolesc Psychiatry. 2006;15(8):504-7.
Karry R, Klein E, Shachar DB. Mitochondrial complex I subunits expression is altered in schizophrenia: a post-mortem study. Biol Psychiatry. 2004;55(7):676-84.
Falk A, Heine VM, Harwood AJ, Sullivan PF, Peitz M, Brüstle O, et al. Modeling psychiatric disorders: from genomic findings to cellular phenotypes. Mol Psychiatry. 2016;21(9):1167-79.
Birnbaum R, Weinberger DR. Genetic insights into the neurodevelopmental origins of schizophrenia. Nat Rev Neurosci. 2017;18(12):727-40.
Dror N, Klein E, Karry R, Sheinkman A, Kirsh Z, Mazor M, et al. State-dependent alterations in mitochondrial complex I activity in platelets: a potential peripheral marker for schizophrenia. Mol Psychiatry. 2002;7(9):995-1001.
Black DW, Zimmerman M. Personality disorders. In: Young Adult Mental Health. USA: Oxfort University Press; 2010. p. 424.
Harper RG. Paranoid personality disorder. In: The Corsini encyclopedia of psychology. Wiley Online Library; 2010. p. 1-3.
Akarsu S, Torun D, Bolu A, Erdem M, Kozan S, Ak M, Akar H, Uzun Ö. Mitochondrial complex I and III gene mRNA levels in schizophrenia, and their relationship with clinical features. J Mol Psychiatry. 2014;2(1):1-6.
Kupfer DJ, First MB, Regier DA, editors. A research agenda for DSM V. American Psychiatric Pub; 2008.
Park C, Park SK. Molecular links between mitochondrial dysfunctions and schizophrenia. Mol Cells. 2012;33(2):105-10.
Whitehurst T, Howes O. The role of mitochondria in the pathophysiology of schizophrenia: A critical review of the evidence focusing on mitochondrial complex one. Neurosci Biobehav Rev. 2022;132:449-64.
Halliwell B. Reactive oxygen species and the central nervous system. J Neurochem. 1992;59(5):1609-23.
Flatow J, Buckley P, Miller BJ. Meta-analysis of oxidative stress in schizophrenia. Biol Psychiatry. 2013;74(6):400-9.
Azadmarzabadi E, Haghighatfard A, Mohammadi A. Low resilience to stress is associated with candidate gene expression alterations in the dopaminergic signalling pathway. Psychogeriatrics. 2018;18(3):190-201.
Abbasy S, Shahraki F, Haghighatfard A, Qazvini MG, Rafiei ST, et al. Neuregulin1 types mRNA level changes in autism spectrum disorder, and is associated with deficit in executive functions. EBioMedicine. 2018;37:483-8.
Leucht S, Kane JM, Kissling W, Hamann J, Etschel E, Engel RR. What does the PANSS mean? Schizophr Res. 2005;79(2-3):231-8.
Ventura J, Nuechterlein KH, Subotnik KL, Gutkind D, Gilbert EA. Symptom dimensions in recent-onset schizophrenia and mania: a principal components analysis of the 24-item Brief Psychiatric Rating Scale. Psychiatry Res. 2000;97(2-3):129-35.
Haghighatfard A, Andalib S, Amini Faskhodi M, Sadeghi S, Ghaderi AH, Moradkhani S, et al. Gene expression study of mitochondrial complex I in schizophrenia and paranoid personality disorder. World J Biol Psychiatry. 2018;19(sup3):S133-46.
Roshan Chesly R, Shaeeri MR, Atrifard M, Nikkhah A, Ghaem Maghami B, Rahimierad A. Investigating psychometric properties of â NEO-five factor inventoryâ (NEO-FFI). Clinical Psychology and Personality. 2006;4(1):27-36.
Gonzalez-Liencres C, Tas C, Brown EC, Erdin S, Onur E, Cubukcoglu Z, et al. Oxidative stress in schizophrenia: a case-control study on the effects on social cognition and neurocognition. BMC Psychiatry. 2014;14(1):1-9.
Ben-Shachar D, Zuk R, Gazawi H, Reshef A, Sheinkman A, Klein E. Increased mitochondrial complex I activity in platelets of schizophrenic patients. Int J Neuropsychopharmacol. 1999;2(4):245-53.
Taurines R, Thome J, Duvigneau JC, Forbes-Robertson S, Yang L, Klampfl K, et al. Expression analyses of the mitochondrial complex I 75-kDa subunit in early onset schizophrenia and autism spectrum disorder: increased levels as a potential biomarker for early onset schizophrenia. Eur Child Adolesc Psychiatry. 2010;19(5):441-8.
Washizuka S, Kametani M, Sasaki T, Tochigi M, Umekage T, Kohda K, et al. Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with schizophrenia in the Japanese population. Am J Med Genet B Neuropsychiatr Genet. 2006;141(3):301-4.
Ni P, Chung S. Mitochondrial dysfunction in schizophrenia. BioEssays. 2020;42(6):1900202.
Bergman O, Karry R, Milhem J, Ben-Shachar D. NDUFV2 pseudogene (NDUFV2P1) contributes to mitochondrial complex I deficits in schizophrenia. Mol Psychiatry. 2020;25(4):805-20.
Shi J, Yao Y, Zhan C, Mao Z, Yin F, Zhao X. The relationship between big five personality traits and psychotic experience in a large non-clinical youth sample: the mediating role of emotion regulation. Front Psychiatry. 2018;9:648.
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