Expression Study of NDUFS1, NDUFV1, and NDUFV2 in Schizophrenia and Paranoid Personality Disorder
DOI:
https://doi.org/10.31661/gmj.v11i.2165Keywords:
Schizophrenia, Paranoid Personality Disorder, Personality Traits, Mitochondrial Complex I, NDUFS1, NDUFV1, NDUFV2Abstract
Background: 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.
References
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. https://doi.org/10.1371/journal.pone.0000817PMid:17786189 PMCid:PMC1950689 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. https://doi.org/10.1007/s00787-006-0560-5PMid:16788776 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. https://doi.org/10.1016/j.biopsych.2003.12.012PMid:15038995 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. https://doi.org/10.1038/mp.2016.89https://doi.org/10.1038/mp.2016.100 Birnbaum R, Weinberger DR. Genetic insights into the neurodevelopmental origins of schizophrenia. Nat Rev Neurosci. 2017;18(12):727-40. https://doi.org/10.1038/nrn.2017.125PMid:29070826 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. https://doi.org/10.1038/sj.mp.4001116PMid:12399953 Black DW, Zimmerman M. Personality disorders. In: Young Adult Mental Health. USA: Oxfort University Press; 2010. p. 424. https://doi.org/10.1093/med:psych/9780195332711.003.0026 Harper RG. Paranoid personality disorder. In: The Corsini encyclopedia of psychology. Wiley Online Library; 2010. p. 1-3. https://doi.org/10.1002/9780470479216.corpsy0637 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. https://doi.org/10.1186/s40303-014-0006-9PMid:25713723 PMCid:PMC4307627 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. https://doi.org/10.1007/s10059-012-2284-3PMid:22358509 PMCid:PMC3887718 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. https://doi.org/10.1016/j.neubiorev.2021.11.047PMid:34864002 Halliwell B. Reactive oxygen species and the central nervous system. J Neurochem. 1992;59(5):1609-23. https://doi.org/10.1111/j.1471-4159.1992.tb10990.xPMid:1402908 Flatow J, Buckley P, Miller BJ. Meta-analysis of oxidative stress in schizophrenia. Biol Psychiatry. 2013;74(6):400-9. https://doi.org/10.1016/j.biopsych.2013.03.018PMid:23683390 PMCid:PMC4018767 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. https://doi.org/10.1111/psyg.12312PMid:29423959 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. https://doi.org/10.1016/j.ebiom.2018.10.022PMid:30415889 PMCid:PMC6284419 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. https://doi.org/10.1016/j.schres.2005.04.008PMid:15982856 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. https://doi.org/10.1016/S0165-1781(00)00228-6PMid:11166085 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. https://doi.org/10.1080/15622975.2017.1282171PMid:28635542 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. https://doi.org/10.1186/s12888-014-0268-xPMid:25248376 PMCid:PMC4180831 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. https://doi.org/10.1017/S1461145799001649PMid:11285140 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. https://doi.org/10.1007/s00787-009-0074-zPMid:19894076 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. https://doi.org/10.1002/ajmg.b.30285PMid:16508936 Ni P, Chung S. Mitochondrial dysfunction in schizophrenia. BioEssays. 2020;42(6):1900202. https://doi.org/10.1002/bies.201900202PMid:32338416 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. https://doi.org/10.1038/s41380-018-0309-9PMid:30531937 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. https://doi.org/10.3389/fpsyt.2018.00648PMid:30564151 PMCid:PMC6288374
