TELOMERE LENGTH AS A MARKER OF SUICIDAL RISK IN SCHIZOPHRENIA



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Abstract

Schizophrenia and suicidal behavior are associated with shortening of telomere length. The aim of the study was to compare the content (pg/µg) of the telomeric repeat in DNA isolated from peripheral blood cells in three groups of subjects: patients with schizophrenia and a history of suicide, patients with schizophrenia without suicide, and healthy control volunteers.

Material and methods

47 patients with schizophrenia with suicidal behavior, 47 patients without self-destructive tendencies and 47 healthy control volunteers were examined clinically and for the content of telomere repeat in the DNA of blood leukocytes matched by sex and age.

Results

Analysis of the determination of the telomere repeat (TR) content in DNA indicates a statistically significant increase in telomere length in the series: patients with schizophrenia and suicides - patients with schizophrenia without suicides - healthy controls (225 vs 224 vs 255; p = 0.024). The same trend is observed for the concentration of mitochondrial DNA (mtDNA) (257 vs 262 vs 272; p = 0.012).

Conclusions: first established the phenomenon of telomere shortening in schizophrenia associated with suicidal risk. Telomere length corresponds to the parameters of a biological marker - an objectively measured indicator of normal or pathological processes, but its validity still needs to be verified with an assessment of its sensitivity, specificity, positive and negative predictive value. It is premature to consider telomere length as a predictive indicator of suicidal risk.

About the authors

Natalia V. Zakharova

State budgetary institution of health care of the city of Moscow “Psychiatric Hospital no. 1 Named after N.A. Alexeev of the Department of Health of Moscow ”

Author for correspondence.
Email: nataliza80@gmail.com
ORCID iD: 0000-0001-7507-327X

Head of the Laboratory for Fundamental Research Methods of the Scientific Research Center of Neuropsychiatry, PKB No. 1, Ph.D

 

Russian Federation

Lidia V. Bravve

Email: bravve95@yandex.ru
Russian Federation

Galina S. Mamedova

Email: gsh.mamedova@yandex.ru

Maria A. Kaydan

Email: kaydan.maria@yandex.ru

Elisaveta S. Ershova

Email: es-ershova@rambler.ru

Andrey V. Martynov

Email: avlamar@mail.ru

Natalia N. Veiko

Email: satelit32006@yandex.ru

Kostyuk V. Svetlana

Email: svet-vk@yandex.ru

References

  1. Nordentoft M. et al. OPUS study: suicidal behaviour, suicidal ideation and hopelessness among patients with first-episode psychosis. One-year follow-up of a randomised controlled trial // Br. J. Psychiatry Suppl. 2002. Vol. 43. P. s98–s106.
  2. Saha S., Chant D., McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? // Arch. Gen. Psychiatry. 2007. Vol. 64, № 10. P. 1123–1131.
  3. Moussaoui D., El Hamaoui Y. Faculty Opinions recommendation of A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? // Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature. 2008.
  4. Luhr R. et al. Trends in sepsis mortality over time in randomised sepsis trials: a systematic literature review and meta-analysis of mortality in the control arm, 2002–2016 // Critical Care. 2019. Vol. 23, № 1.
  5. Hor K., Taylor M. Suicide and schizophrenia: a systematic review of rates and risk factors // J. Psychopharmacol. 2010. Vol. 24, № 4 Suppl. P. 81–90.
  6. Roy A., Pompili M. Management of schizophrenia with suicide risk // Psychiatr. Clin. North Am. 2009. Vol. 32, № 4. P. 863–883.
  7. Pompili M., Fiorillo A. Preventing Suicide in Patients with Mental Disorders. MDPI, 2020. 148 p.
  8. Sadek J. A Clinician’s Guide to Suicide Risk Assessment and Management. Springer, 2018. 113 p.
  9. Agerbo E. High Income, Employment, Postgraduate Education, and Marriage // Archives of General Psychiatry. 2007. Vol. 64, № 12. P. 1377.
  10. Healy D. et al. Mortality in schizophrenia and related psychoses: data from two cohorts, 1875–1924 and 1994–2010 // BMJ Open. 2012. Vol. 2, № 5. P. e001810.
  11. Montross L.P., Zisook S., Kasckow J. Suicide Among Patients with Schizophrenia: A Consideration of Risk and Protective Factors // Annals of Clinical Psychiatry. 2005. Vol. 17, № 3. P. 173–182.
  12. Kasckow J., Felmet K., Zisook S. Managing Suicide Risk in Patients with Schizophrenia // CNS Drugs. 2011. Vol. 25, № 2. P. 129–143.
  13. Thong J.Y. et al. Suicide in psychiatric patients: case-control study in Singapore // Aust. N. Z. J. Psychiatry. 2008. Vol. 42, № 6. P. 509–519.
  14. Hunt I.M. et al. Suicide in recently discharged psychiatric patients: a case-control study // Psychological Medicine. 2009. Vol. 39, № 3. P. 443–449.
  15. Miles C.P. Conditions predisposing to suicide: a review // J. Nerv. Ment. Dis. 1977. Vol. 164, № 4. P. 231–246.
  16. Kirkpatrick B. et al. Is schizophrenia a syndrome of accelerated aging? // Schizophr. Bull. 2008. Vol. 34, № 6. P. 1024–1032.
  17. Shivakumar V. et al. Do schizophrenia patients age early? // Asian J. Psychiatr. 2014. Vol. 10. P. 3–9.
  18. Okusaga O.O. Accelerated aging in schizophrenia patients: the potential role of oxidative stress // Aging Dis. 2014. Vol. 5, № 4. P. 256–262.
  19. Polho G.B. et al. Leukocyte telomere length in patients with schizophrenia: A meta-analysis // Schizophr. Res. 2015. Vol. 165, № 2-3. P. 195–200.
  20. Papanastasiou E., Gaughran F., Smith S. Schizophrenia as segmental progeria // J. R. Soc. Med. 2011. Vol. 104, № 11. P. 475–484.
  21. Savolainen K. et al. History of mental disorders and leukocyte telomere length in late adulthood: the Helsinki Birth Cohort Study (HBCS) // J. Psychiatr. Res. 2012. Vol. 46, № 10. P. 1346–1353.
  22. de Leon J., Diaz F.J. A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors // Schizophr. Res. 2005. Vol. 76, № 2-3. P. 135–157.
  23. Mittal D. et al. Healthcare providers’ attitudes toward persons with schizophrenia // Psychiatr. Rehabil. J. 2014. Vol. 37, № 4. P. 297–303.
  24. Eitan E., Hutchison E.R., Mattson M.P. Telomere shortening in neurological disorders: an abundance of unanswered questions // Trends Neurosci. 2014. Vol. 37, № 5. P. 256–263.
  25. Cifuentes-Rojas C., Shippen D.E. Telomerase regulation // Mutat. Res. 2012. Vol. 730, № 1-2. P. 20–27.
  26. Kawanishi S., Oikawa S. Mechanism of telomere shortening by oxidative stress // Ann. N. Y. Acad. Sci. 2004. Vol. 1019. P. 278–284.
  27. Hossein Fatemi S. The Molecular Basis of Autism. Springer, 2015. 437 p.
  28. Kim J.-H. et al. The relationship between leukocyte mitochondrial DNA copy number and telomere length in community-dwelling elderly women // PLoS One. 2013. Vol. 8, № 6. P. e67227.
  29. Li Z. et al. Association of telomere length and mitochondrial DNA copy number with risperidone treatment response in first-episode antipsychotic-naïve schizophrenia // Sci. Rep. 2015. Vol. 5. P. 18553.
  30. Fernandez-Egea E. et al. Telomere length and pulse pressure in newly diagnosed, antipsychotic-naive patients with nonaffective psychosis // Schizophr. Bull. 2009. Vol. 35, № 2. P. 437–442.
  31. Kao H.-T. et al. Rapid telomere erosion in schizophrenia // Mol. Psychiatry. 2008. Vol. 13, № 2. P. 118–119.
  32. Nieratschker V. et al. Longer telomere length in patients with schizophrenia // Schizophr. Res. 2013. Vol. 149, № 1-3. P. 116–120.
  33. Mansour H. et al. Does telomere length mediate associations between inbreeding and increased risk for bipolar I disorder and schizophrenia? // Psychiatry Res. 2011. Vol. 188, № 1. P. 129–132.
  34. Zhang D. et al. Cerebellar telomere length and psychiatric disorders // Behav. Genet. 2010. Vol. 40, № 2. P. 250–254.
  35. Malaspina D. et al. Telomere length, family history, and paternal age in schizophrenia // Mol Genet Genomic Med. 2014. Vol. 2, № 4. P. 326–331.
  36. Darrow S.M. et al. The Association Between Psychiatric Disorders and Telomere Length: A Meta-Analysis Involving 14,827 Persons // Psychosom. Med. 2016. Vol. 78, № 7. P. 776–787.
  37. Otsuka I. et al. Aberrant telomere length and mitochondrial DNA copy number in suicide completers // Sci. Rep. 2017. Vol. 7, № 1. P. 3176.
  38. Kim H. et al. Association between telomere length and completed suicide observed in 71 suicide victims - Preliminary findings // J. Psychosom. Res. 2019. Vol. 120. P. 8–11.
  39. Kay S.R., Fiszbein A., Opler L.A. The positive and negative syndrome scale (PANSS) for schizophrenia // Schizophr. Bull. 1987. Vol. 13, № 2. P. 261–276.
  40. Andreasen N.C. et al. Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs // Biol. Psychiatry. 2010. Vol. 67, № 3. P. 255–262.
  41. Cassidy R.M. et al. Risk Factors for Suicidality in Patients With Schizophrenia: A Systematic Review, Meta-analysis, and Meta-regression of 96 Studies // Schizophr. Bull. 2018. Vol. 44, № 4. P. 787–797.
  42. Hert M.D. et al. Risk factors for suicide in young people suffering from schizophrenia: a long-term follow-up study // Schizophrenia Research. 2001. Vol. 47, № 2-3. P. 127–134.
  43. Modestin J., Zarro I., Waldvogel D. A Study of Suicide in Schizophrenic In-patients // British Journal of Psychiatry. 1992. Vol. 160, № 3. P. 398–401.
  44. Pinikahana J., Happell B., Keks N.A. Suicide and schizophrenia: a review of literature for the decade (1990-1999) and implications for mental health nursing // Issues Ment. Health Nurs. 2003. Vol. 24, № 1. P. 27–43.
  45. Siris S.G. Suicide and schizophrenia // J. Psychopharmacol. 2001. Vol. 15, № 2. P. 127–135.
  46. Pompili M. et al. Suicide risk in schizophrenia: learning from the past to change the future // Annals of General Psychiatry. 2007. Vol. 6, № 1.
  47. Altamura A.C. et al. Clinical variables related to suicide attempts in schizophrenic patients: a retrospective study // Schizophrenia Research. 2003. Vol. 60, № 1. P. 47–55.
  48. Mauri M.C. et al. Suicide attempts in schizophrenic patients: Clinical variables // Asian Journal of Psychiatry. 2013. Vol. 6, № 5. P. 421–427.
  49. Bousman C.A. et al. Negative Symptoms of Psychosis Correlate with Gene Expression of the Wnt/β-Catenin Signaling Pathway in Peripheral Blood // Psychiatry J. 2013. Vol. 2013. P. 852930.
  50. Porton B. et al. Telomerase levels in schizophrenia: a preliminary study // Schizophr. Res. 2008. Vol. 106, № 2-3. P. 242–247.
  51. Rizvi S., Raza S.T., Mahdi F. Telomere length variations in aging and age-related diseases // Curr. Aging Sci. 2014. Vol. 7, № 3. P. 161–167.
  52. Bošković M. et al. Oxidative stress in schizophrenia // Curr. Neuropharmacol. 2011. Vol. 9, № 2. P. 301–312.
  53. Hoffmeyer K. et al. Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells // Science. 2012. Vol. 336, № 6088. P. 1549–1554.
  54. Stower H. Telomeres: stem cells, cancer and telomerase linked by WNT // Nature reviews. Genetics. 2012. Vol. 13, № 8. P. 521.
  55. Beaulieu J.-M., Gainetdinov R.R. The physiology, signaling, and pharmacology of dopamine receptors // Pharmacol. Rev. 2011. Vol. 63, № 1. P. 182–217.
  56. Emamian E.S. et al. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia // Nat. Genet. 2004. Vol. 36, № 2. P. 131–137.
  57. Li X., Jope R.S. Is glycogen synthase kinase-3 a central modulator in mood regulation? // Neuropsychopharmacology. 2010. Vol. 35, № 11. P. 2143–2154.
  58. Yu W.-Y. et al. Short telomeres in patients with chronic schizophrenia who show a poor response to treatment // J. Psychiatry Neurosci. 2008. Vol. 33, № 3. P. 244–247.
  59. Kota L.N. et al. Shortened telomere in unremitted schizophrenia // Psychiatry Clin. Neurosci. 2015. Vol. 69, № 5. P. 292–297.
  60. Weischer M., Bojesen S.E., Nordestgaard B.G. Telomere shortening unrelated to smoking, body weight, physical activity, and alcohol intake: 4,576 general population individuals with repeat measurements 10 years apart // PLoS Genet. 2014. Vol. 10, № 3. P. e1004191.
  61. Emanuela F. et al. Inflammation as a Link between Obesity and Metabolic Syndrome // J. Nutr. Metab. 2012. Vol. 2012. P. 476380.
  62. Roberts C.K., Sindhu K.K. Oxidative stress and metabolic syndrome // Life Sci. 2009. Vol. 84, № 21-22. P. 705–712.
  63. Leykin I., Mayer R., Shinitzky M. Short and long term immunosuppressive effects of clozapine and haloperidol // Immunopharmacology. 1997. Vol. 37, № 1. P. 75–86.
  64. Müller N., Myint A.-M., Schwarz M.J. Inflammation in schizophrenia // Adv. Protein Chem. Struct. Biol. 2012. Vol. 88. P. 49–68.
  65. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework // Clin. Pharmacol. Ther. 2001. Vol. 69, № 3. P. 89–95.
  66. First M.B. et al. Clinical Applications of Neuroimaging in Psychiatric Disorders // American Journal of Psychiatry. 2018. Vol. 175, № 9. P. 915–916.
  67. Kimura M. et al. Offspring’s leukocyte telomere length, paternal age, and telomere elongation in sperm // PLoS Genet. 2008. Vol. 4, № 2. P. e37.
  68. Prescott J. et al. Paternal age at birth is associated with offspring leukocyte telomere length in the nurses’ health study // Hum. Reprod. 2012. Vol. 27, № 12. P. 3622–3631.

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Copyright (c) Zakharova N.V., Bravve L.V., Mamedova G.S., Kaydan M.A., Ershova E.S., Martynov A.V., Veiko N.N., Svetlana K.V.

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