Study of the association between oxytocin receptor gene polymorphism, childhood adversity and negative symptoms of schizophrenia

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Is known that the neurohormone oxytocin plays an important role in the pathogenesis of mental illness, and also models the relationship between stress factors, especially those acting in the early stages of development, and the development of mental disorders. Based on these data, we investigated the effects of the interaction of the environmental factor, which was considered the adversity of childhood (ND) and the oxytocin receptor (OXTR) genotypes in the polymorphic sites rs4686302 and rs7632287, on the severity of negative symptoms of schizophrenia. The study involved 592 patients with schizophrenia (headings F20. according to ICD-10). Information about the presence of ND was obtained from case histories and patient interviews. Analysis of covariance (GML) was used for statistical data processing; in post-hoc pairwise comparison, Tukey’s test was used. A significant effect of the interaction between ND and OXTR gene polymorphism rs7632287(G/A) on the severity of negative symptoms in patients with schizophrenia was revealed. In patients without ND, polymorphisms did not have a significant effect on the studied phenotype. Thus, our study showed for the first time that the rs7632287(G/A) polymorphism and ND have a mutual effect on the severity of negative symptoms of schizophrenia.

Full Text

Restricted Access

About the authors

T. V. Lezheiko

Mental Health Research Center

Author for correspondence.
Email: Lezheiko@list.ru
Russian Federation, Moscow, 115522

V. A. Mikhailova

Mental Health Research Center

Email: Lezheiko@list.ru
Russian Federation, Moscow, 115522

M. V. Gabaeva

Mental Health Research Center

Email: Lezheiko@list.ru
Russian Federation, Moscow, 115522

V. E. Golimbet

Mental Health Research Center

Email: Lezheiko@list.ru
Russian Federation, Moscow, 115522

References

  1. Radua J., Ramella-Cravaro V., Ioannidis J.P.A. et al. What causes psychosis? Аn umbrella review of risk and protective factors // World Psychiatry. 2018. V. 17. № 1. P. 49–66. https://doi.org/10.1002 /wps.20490
  2. Robinson N., Bergen S.E. Environmental risk factors for schizophrenia and bipolar disorder and their relationship to genetic risk: Current knowledge and future directions // Front. Genetics. 2021. V. 12. https://doi.org/10.3389/fgene.2021.686666
  3. Harvey P.D., Deckler E., Jarskog F.et al. Predictors of social functioning in patients with higher and lower levels of reduced emotional experience: Social cognition, social competence, and symptom severity // Schizophrenia Res. 2019. V. 206. P. 271–276. https://doi.org/10.1016/j.schres. 2018.11.005
  4. Mäki P., Veijola J., Jones P.B. et .al. Predictors of schizophrenia // British Med. Bull. 2005. V. 9. P. 73–74. https://doi.org/10.1093/bmb/ldh046
  5. Reichenberg A. The assessment of neuropsychological functioning in schizophrenia // Dialogues in Clin. Neuroscience. 2010. V. 12. № 3. P. 383–392. https://doi.org/10.31887/DCNS.2010.12.3
  6. Feldman R., Monakhov M., Pratt M. et al. Oxytocin pathway genes: Evolutionary ancient system impacting on human affiliation, sociality, and psychopathology // Biol.Psychiatry. 2016. V. 79. № 3. P. 174–184. https://doi.org/10.1016/j.biopsych.2015.08.008
  7. Marsh N., Marsh A.A., Lee M.R. et al. Oxytocin and the neurobiology of prosocial behavior // Neuroscientist. 2021. V. 27. № 6. P. 604–619. https://doi.org/10.1177/1073858420960111
  8. Strauss G.P., Chapman H.C., Keller W.R. et al. Endogenous oxytocin levels are associated with impaired social cognition and neurocognition in schizophrenia // J. Psychiatric Res. 2019. V. 12. P. 38–43. https://doi.org/0.1016/j.jpsychires.2019.02.017
  9. Ettinger U., Hurlemann R., Chan R.C.K. Oxytocin and schizophrenia spectrum disorders // Curr. Topics in Behavioral Neurosciences. 2018. V. 35. P. 515–527. https://doi.org/10.1007/7854_2017_27
  10. Malhi G.S., Das P., Outhred T. et al. Interactions of OXTR rs53576 and emotional trauma on hippocampal volumes and perceived social support in adolescent girls // Psychoneuroendocrinology. 2020. V. 115. https://doi.org/10.1016/j.psyneuen.2020.104635
  11. Zheng S., Masuda T., Matsunaga M. et al. Oxytocin receptor gene (OXTR) and childhood adversity influence trust // Psychoneuroendocrinology. 2020. V. 121. https://doi.org/10.1016/j.psyneuen.2020.104840
  12. Zwicker A., Denovan-Wright E.M., Uher R. Gene-environment interplay in the etiology of psychosis // Psychol. Medicine. 2018. V. 48. № 12. P. 1925–1936. https://doi.org/10.1017/S003329171700383X
  13. Montag C., Brockmann E.M., Bayerl M. et al. Oxytocin and oxytocin receptor gene polymorphisms and risk for schizophrenia: A case-control study // World J. Biol. Psychiatry. 2013. V. 14. № 7. P. 500–508. https://doi.org/10.3109/15622975.2012.677547
  14. Mongan D., Ramesar M., Föcking M. et al. Role of inflammation in the pathogenesis of schizophrenia: A review of the evidence, proposed mechanisms and implications for treatment // Early Interv. Psychiatry. 2020. V. 14. № 4. P. 385–397. https://doi.org/10.1111/eip.12859
  15. Womersley J.S., Hemmings S.M.J., Ziegler C. et al. Childhood emotional neglect and oxytocin receptor variants: Аssociation with limbic brain volumes // World J. Biol. Psychiatry. 2020. V. 21. № 7. P. 513–528. https://doi.org/110.1080/15622975.2019.1584331
  16. Михайлова В.А., Лежейко Т.В., Колесина Н.Ю., Голимбет В.Е. Исследование связи между генами окситоцинэргической системы, перинатальными осложнениями и формированием межличностных отношений у больных шизофренией // Журнал неврол. и психиатрии м. С.С. Корсакова. 2021. T. 121. № 10. C. 95–100. https://doi.org/10.17116/jnevro202112110195
  17. Veras A.B., Getz M., Froemke R.C. et al. Rare missense coding variants in oxytocin receptor (OXTR) in schizophrenia cases are associated with early trauma exposure, cognition and emotional processing // Psychiatric Res. 2018. V. 97. P. 58–64. https://doi.org/10.1016/j.jpsychires.2017.11.011
  18. Campbell D.B, Datta D., Jones S.T. et al. Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder // J. of Neurodevelopmental Disorders. 2011. V. 3. № 2. P. 101–112. https://doi.org/10.1007/s11689-010-9071-2
  19. Walum H., Lichtenstein P., Neiderhiser J.M. et al.Variation in the oxytocin receptor gene is associated with pair-bonding and social behavior // Biol. Psychiatry. 2012. V. 71. № 5. P. 419–426. https://doi.org/10.1016/j.biopsych.2011.09.002
  20. Wu N, Li Z., Su Y. The association between oxytocin receptor gene polymorphism (OXTR) and trait empathy // J. of Affective Disorders. 2012. V. 138. № 3. P. 468–472. https://doi.org/10.1016/j.jad.2012.01.009
  21. Hovey D., Lindstedt M., Zettergren A. et al. Antisocial behavior and polymorphisms in the oxytocin receptor gene: Findings in two independent samples // Mol. Psychiatry. 2016. V. 21. №7. P. 983–938. https://doi.org/10.1038/mp.2015.144
  22. LoParo D., Waldman I.D. The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: A meta-analysis // Mol. Psychiatry. 2015. V. 20. № 5. P. 640–646. https://doi.org//10.1038/mp.2014.77
  23. Westberg L., Henningsson S., Zettergren A. et al. Variation in the oxytocin receptor gene is associated with face recognition and its neural correlates // Front. Behav, Neurosci. 2016. V. 10. https://doi.org/10.3389/fnbeh.2016.00178
  24. Kalmakis K.A., Chandler G.E. Adverse childhood experiences: Towards a clear conceptual meaning // J. Adv. Nursing. 2014. V. 70. № 7. P. 1489–1501. https://doi.org/10.1111/jan.12329
  25. Reichl C., Kaess M., Fuchs A. et al. Childhood adversity and parenting behavior: The role of oxytocin receptor gene polymorphisms // Neural Transmission. 2019. V. 126. № 6. P. 777–787. https://doi.org/10.1007/s00702-019-02009-9
  26. Popovic D., Schmitt A., Kaurani L. et al. Childhood trauma in schizophrenia: Current findings and research perspectives // Front. Neurosci. 2019. V. 13. P. 274. https://doi.org/10.3389/fnins.2019.00274
  27. Kogan S.M., Bae D., Cho J. et al. Childhood adversity, socioeconomic instability, oxytocin-receptor-gene methylation, and romantic-relationship support among young african american men // Psychol. Sci. 2019. V. 30. № 8. P. 1234–1244. https://doi.org/0.1177/0956797619854735
  28. Алфимова М.В., Коровайцева Г.И., Габаева М.В. и др. Генетический полиморфизм цитокинов ИЛ-1β, ИЛ-4 и TNF-α как фактор, модулирующий влияние невзгод детства на симптоматику шизофрении // Журн. неврол. и психиатрии им. С.С. Корсакова. 2022. T. 122. № 9. C. 110–117. https://doi.org/10.17116/jnevro202212209111023.
  29. Kalyouncu T., Ozbaran B., Kose S. et al. Variation in the oxytocin receptor gene is associated with social cognition and ADHD // J. of Attention Disorders. 2019. V. 23. № 7. P. 702–711. https://doi.org/10.1177/1087054717706757
  30. Meyer M., Jurek B., Alfonso-Prieto M. et al. Structure-function relationships of the disease-linked A218T oxytocin receptor variant // Mol. Psychiatry. 2022. V. 27. № 2. P. 907–917. https://doi.org/10.1038/s41380-021-01241-8
  31. Chang S.C., Glymour M.M., Rewak M. et al. Are genetic variations in OXTR, AVPR1A, and CD38 genes important to social integration? Results from two large U.S. cohorts // Psychoneuroendocrinology. 2014. V. 39. P. 257–268. https://doi.org/10.1016/j.psyneuen. 2013.09.024
  32. Kohlhoff J., Cibralic S., Hawes D.J. et al. Oxytocin receptor gene (OXTR) polymorphisms and social, emotional and behavioral functioning in children and adolescents: A systematic narrative review // Neuroscience & Biobehavioral Reviews. 2022. V. 135. P. 104573. https://doi.org/10.1016/j.neubiorev.2022.104573
  33. Bey K., Campos-Martin R., Klawohn J. et al. Hypermethylation of the oxytocin receptor gene (OXTR) in obsessive-compulsive disorder: Further evidence for a biomarker of disease and treatment response // Epigenetics. 2022. V. 17. № 6. P. 642–652. https://doi.org/10.1080/15592294.2021.1943864
  34. Muros N.I., García A.S., Forner C. et al. Facial affect recognition by patients with schizophrenia using human avatars // J. Clin. Medicine. 2021. V. 28. № 9. https://doi.org/10.3390/jcm10091904

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Russian Academy of Sciences