Dissosiyatif Kimlik Bozukluğu Olan Bireylerde Tiyol-Disülfid Dengesi

Abstract

Amaç: Bu çalışmanın amacı, Dissosiyatif Kimlik Bozukluğu (DKB) tanılı bireylerde tiyol-disülfid homeostazı (TDH) parametrelerini değerlendirerek oksidatif stres düzeylerinde bozulma olup olmadığını araştırmak ve bu biyolojik değişikliklerin DKB ile ilişkisini incelemektir. Materyal ve Metod: DSM-5 kriterlerine göre DKB tanısı konan 56 hasta ile herhangi bir psikiyatrik bozukluğu bulunmayan 43 sağlıklı gönüllü çalışmaya dahil edilmiştir. Katılımcılardan 12 saatlik açlık sonrası kan örnek-leri alınarak tiyol-disülfid homeostazı parametreleri ölçülmüştür. Ölçümler kolorimetrik yöntemle gerçek-leştirilmiş, toplam tiyol, doğal tiyol ve disülfid düzeyleri ile bunların oranları hesaplanmıştır. Katılımcılara Dissosiyatif Yaşantılar Ölçeği (DYÖ) ve Çocukluk Çağı Travmaları Ölçeği (ÇÇTÖ) uygulanmıştır. Veriler istatistik-sel olarak bağımsız gruplar t testi, Mann-Whitney U testi, ki-kare testi ve korelasyon analizleri kullanılarak değerlendirilmiştir. Bulgular: DKB grubunda toplam tiyol (p<0.001) ve disülfid düzeyleri (p<0.001) ile disülfid/toplam tiyol oranları (p=0.02), sağlıklı kontrol grubuna göre istatistiksel olarak anlamlı derecede düşüktü. Doğal ti-yol/toplam tiyol oranı ise DKB grubunda kontrol grubuna kıyasla anlamlı derecede yüksekti (p=0.02). Kore-lasyon analizlerinde ise DKB grubunda TDH parametreleri ile DYÖ ve ÇÇTÖ skorları arasında anlamlı bir ilişki saptanmamıştır. Sonuç: Bu çalışma, DKB tanılı bireylerde tiyol-disülfid homeostazının bozulduğunu göstermektedir. Toplam tiyol düzeylerindeki düşüş, antioksidan kapasitede azalma olduğunu düşündürürken, disülfid düzeylerinin de düşük bulunması redoks sisteminin yeterince aktive olamadığını düşündürmektedir. Bulgular, DKB’nin biyolojik temelini anlamada tiyol-disülfid homeostazı dengesinin potansiyel bir biyobelirteç olabileceğini göstermekte olup, daha geniş örneklemlerle yapılacak çalışmalarla desteklenmesi gerekmektedir.

Keywords

• Dissosiyatif Kimlik Bozukluğu
• Tiyol-Disülfid Homeostazı
• Oksidatif Stres

Thiol-Disulfide Balance in Patients with Dissociative Identity Disorder

Abstract

Background: This study aimed to evaluate thiol-disulfide homeostasis (TDH) parameters in individuals diag-nosed with Dissociative Identity Disorder (DID) to investigate whether there is a disruption in oxidative stress levels and to examine the relationship of these biological changes with DID. Materials and Methods: Fifty-six patients diagnosed with DID according to DSM-5 criteria and 43 healthy volunteers without any psychiatric disorders were included in the study. After 12 hours of fasting, blood samples were collected from all participants to measure TDH parameters. Measurements were performed using a colorimetric method, and total thiol, native thiol, disulfide levels, and their ratios were calculated. Participants were also assessed with the Dissociative Experiences Scale (DES) and the Childhood Trauma Questionnaire (CTQ). Data were analyzed statistically using independent samples t-test, Mann-Whitney U test, chi-square test, and correlation analyses. Results: In the DID group, total thiol (p<0.001), disulfide levels (p<0.001), and disulfide/total thiol ratios (p=0.02) were significantly lower compared to the healthy control group. In contrast, the native thiol/total thiol ratio was significantly higher in the DID group than in the control group (p=0.02). However, correla-tion analyses revealed no significant relationship between TDH parameters and DES or CTQ scores within the DID group. Conclusions: This study demonstrates that thiol-disulfide homeostasis is disrupted in individuals with DID. The decrease in total thiol levels indicates reduced antioxidant capacity, while the concomitant decrease in disulfide levels suggests insufficient activation of the redox system. The results highlight the potential of thiol-disulfide homeostasis balance as a biomarker in understanding the biological basis of DID and unders-core the need for further studies with larger samples to support these findings.

Keywords

• Dissociative Identity Disorder
• Thiol-Disulfide Homeostasis
• Oxidative Stress

References

1. 1. American Psychiatric Association. Dissociative Disorders. S Schultz, E Kuhl, ed, Diagnostic and Statistical Manual of Mental Disorders Fifth Edition, American Psychiatric Publishing, Wash-ington, 2013; 328–345.
2. 2. Simone Reinders AAT, Willemsen AT, Vos HP, den Boer JA, Ni-jenhuis ER. Fact or factitious? A psychobiological study of au-thentic and simulated dissociative identity states. PloS one. 2012; 7(6), e39279.
3. 3. Merckelbach H, Lynn SJ, Lilienfeld SO. Vissia and co-workers claim that DID is trauma-based. But how strong is their evi-dence?. Acta Psychiatrica Scandinavica,. 2016; 134(6).
4. 4. Vissia EM, Giesen ME, Chalavi S, Nijenhuis ER, Draijer N, Brand BL, et al. Is it trauma‐or fantasy‐based? Comparing dissociative identity disorder, post‐traumatic stress disorder, simulators, and controls. Acta Psychiatrica Scandinavica. 2016; 134(2), 111-128.
5. 5. Tutkun H, Yargıç Lİ, Şar V. Dissociative identity disorder: Clinical investigation of 20 cases from Turkey. Dissociation 1995; 8:3-9.
6. 6. Şar V, Dorahy MJ, Krüger C. Revisiting the etiological aspects of dissociative identity disorder: a biopsychosocial perspective. Psychol Res Behav Manag. 2017; 10:137-46.
7. 7. Şar V. Dissosiyatif Bozukluklar, Karamustafalıoğlu O, ed. Temel ve Klinik Psikiyatri Güneş Tıp Kitabevi, İstanbul 2017; 453-460
8. 8. Lynn SJ, Lilienfeld SO, Merckelbach H, Giesbrecht T, McNally RJ, Loftus EF, et al. The trauma model of dissociation: inconvenient truths and stubborn fictions. Psychological bulletin, 2014; 140(3), 896–910. https://doi.org/10.1037/a0035570

9. 9. Dalenberg CJ, Brand BL, Loewenstein RJ, Gleaves DH, Dorahy MJ, Cardeña E, et al. Reality versus fantasy: reply to Lynn et al. (2014). Psychol Bull. 2014; 140(3):911-20. doi: 10.1037/a0036685. PMID: 24773506.
10. 10. Wolf EJ, Rasmusson AM, Mitchell KS, Logue MW, Baldwin CT, Miller MW. A Genome‐Wide Association Study of Clinical Symp-toms of Dissociation in a Trauma‐exposed Sample. Depress Anxi-ety. 2014 ;31(4):352-60.
11. 11. Vermetten E, Spiegel D. Trauma and Dissociation: Implications for Borderline Personality Disorder. Curr Psychiatry Rep. 2014;16(2): 434.
12. 12. Hagenaars MA, Oitzl M, Roelofs K. Updating Freeze: Aligning Animal And Human Research. Neurosci Biobehav Rev. 2014;47:165-76.
13. 13. Krause-Utz A, Frost R, Winter D, Elzinga BM. Dissociation and Alterations in Brain Function and Structure: Implications for Borderline Personality Disorder. Curr Psychiatry Rep. 2017; 19(1):6.
14. 14. Nemeroff CB. Paradise Lost: The Neurobiological And Clinical Consequences Of Child Abuse And Neglect. Neuron 2016;89(5):892- 909.
15. 15. Kabadayi Sahin E, Turan G, Neselioglu S, Can SS, Atagun MI. Thiol-disulphide homeostasis in patients with general anxiety disorder and panic disorder. Dusunen Adam Journal of Psychiatry and Neurological Sciences. 2019; 32(4), 289.
16. 16. Yılmaz ÖF, Kartal F, Kartalcı Ş. "Obsesif kompulsif bozukluğu olan olgularda dinamik tiyol/disülfit dengesi ve oksidatif metaboliz-manın değerlendirilmesi." Turkish J Clinical Psychiatry 2023; 26:300-308.
17. 17. Emekdar G, Tas Hİ, Sehitoglu H. İlk Atak Major Depresyon Has-talarında İnflamasyon ve Oksidatif Stres Belirteçleri ile Tedavi Yanıtı İlişkisinin İncelenmesi: Bir İzlem Çalışması. Türk Psikiyatri Dergisi 2023; 34(2):89−99
18. 18. Ng F, Berk M, Dea O, Bush AI. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. The in-ternational journal of neuropsychopharmacology, 2008; 11(6), 851–876. https://doi.org/10.1017/S1461145707008401
19. 19. Erel O, Neselioglu S. A novel and automated assay for thi-ol/disulphide homeostasis. Clinical biochemistry. 2014; 47(18), 326-32.
20. 20. Ergin Tuncay M, Atagun MI, Erel, O. Thiol disulfide homeostasis in psychiatric disorders: A comprehensive review. Progress in neuro-psychopharmacology & biological psychiatry. 2023; 123, 110719. https://doi.org/10.1016/j.pnpbp.2023.110719
21. 21. Erel Ö. Erdoğan S. Thiol-disulfide homeostasis: an integrated approach with biochemical and clinical aspects. Turkish journal of medical sciences, 2020; 50(SI-2), 1728–38. https://doi.org/10.3906/sag-2003-64
22. 22. Topcuoglu C, Bakirhan A, Yilmaz FM, Neselioglu S, Erel O, Sahiner SY. Thiol/disulfide homeostasis in untreated schizophrenia pa-tients. Psychiatry research, 22017; 51, 212–6. https://doi.org/10.1016/j.psychres.2017.02.016
23. 23. Kotan VO, Yilmaz FM, Neselioglu S, Erel O, Okay IT, Kiral S. Thi-ol/disulphide homeostasis in men with heroin addiction. Dusu-nen Adam Journal of Psychiatry and Neurological Sciences, 2017; 30(2), 95.
24. 24. Cingi Yirün M, Ünal K, Yirün O, Kiliç OHT, Erel Ö. Thiol/disulphide homeostasis in manic episode and remission phases of bipolar disorder. Nordic journal of psychiatry, 2018; 72(8), 572-7.
25. 25. Kilicarslan T, Sahan E, Kirik F, Guler EM, Kurtulmus A, Yildiz FBP, et al. The relation of optical coherence tomography findings with oxidative stress parameters in patients with bipolar disor-der and unaffected first-degree relatives. Journal of Affective Disorders, 296, 283-290.
26. 26. Erzin, G, Kotan V. O, Topçuoğlu C, Özkaya G, Erel, Ö, Yüksel RN, et al. Thiol/disulphide homeostasis in bipolar disorder. Psychiatry research, 2018; 261,237-42.
27. 27. Karaaslan Ö, Hacımusalar Y, Bal C, Ercan M. Evaluation of thi-ol/disulfide homeostasis in patients with a first episode of major depressive disorder. Med Sci Discov. 2019; 6(1):1-7
28. 28. Asoğlu M, Kilicaslan F, Beginoğlu Ö, Fedai Ü, Akil Ö, Çelik H, et al. Thiol/disulphide homeostasis as a new oxidative stress marker in untreated patients with generalized anxiety disorder. Alpha Psy-chiatry 2018; 19:143-9.
29. 29. Kurhan F, Alp HH. Investigation of Thiol/Disulfide Balance and Oxidative DNA Damage in Patients Experiencing Avalanche Disas-ter and with a Diagnosis of Post-Traumatic Stress Disorder. Alpha Psychiatry. 2021; 22(3):123-129. doi: 10.5455/apd.10091. PMID: 36425441; PMCID: PMC9590662.
30. 30. Perković MN, Milković L, Uzun S, Mimica N, Pivac N, Waeg G, et al. Association of Lipid Peroxidation Product 4-Hydroxynonenal with Post-Traumatic Stress Disorder. Biomolecules. 2021;11(9):1365. doi: 10.3390/biom11091365. PMID: 34572578; PMCID: PMC8469760.
31. 31. Oroian BA, Ciobica A, Timofte D, Stefanescu C, Serban IL. New Metabolic, Digestive, and Oxidative Stress-Related Manifesta-tions Associated with Posttraumatic Stress Disorder. Oxid Med Cell Longev. 2021; 5599265. doi: 10.1155/2021/5599265. PMID: 34966477; PMCID: PMC8712172.
32. 32. Karanikas E, Daskalakis NP, Agorastos A. Oxidative Dysregulation in Early Life Stress and Posttraumatic Stress Disorder: A Compre-hensive Review. Brain Sci. 2021; 11(6):723. doi: 10.3390/brainsci11060723. PMID: 34072322; PMCID: PMC8228973..
33. 33. Atli A, Bulut M, Bez Y, Kaplan İ, Özdemir PG, et al. Altered lipid peroxidation markers are related to post-traumatic stress disor-der (PTSD) and not trauma itself in earthquake survivors. Eur Arch Psychiatry Clin Neurosci. 2016; 266(4):329-36. doi: 10.1007/s00406-015-0638-5.
34. 34. Tezcan E, Atmaca M, Kuloglu M, Ustundag B. Free radicals in patients with post-traumatic stress disorder. Eur Arch Psychiatry Clin Neurosci. 2003; 253(2):89-91. doi: 10.1007/s00406-003-0413-x. PMID: 12799747..
35. 35. Steullet P, Cabungcal JH, Monin A, Dwir D, O'Donnell P, Cuenod M, et al. Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A "central hub" in schizophrenia patho-physiology? Schizophr Res. 2016; 176(1):41-51. doi: 10.1016/j.schres.2014.06.021. Epub 2014 Jul 5. PMID: 25000913; PMCID: PMC4282982..
36. 36. Şar V, Öztürk PE, İkikardeş E. Çocukluk çağı ruhsal travma ölçeğinin Türkçe uyarlamasının geçerlilik ve güvenilirliği. Journal of Medical Sciences. 2012;32(4):1054-63.
37. 37. Bernstein DP, Fink L, Handelsman L, Foote J, Lovejoy M, Wenzel K, et al. Initial reliability and validity of a new retrospective measure of child abuse and neglect. The American journal of psychiatry, 1994; 151(8), 1132–36. https://doi.org/10.1176/ajp.151.8.1132
38. 38. Terawaki H, Terada T, Ogura M, Era S, Hosoya T. Büyük Doğu Japonya depreminden sonra oksidatif stresin yükselmesi. Clin Exp Nephrol. 2012; 16(5):816–817. 10.1007/s10157-012-0668-5
39. 39. Beğinoğlu Ö, Asoğlu M, Sabuncu E, Çelik H. Evaluation of Thi-ol/Disulfide Interrelation in Major Depressive Disorder. Alpha psychiatry, 2023; 24(6), 283–87. https://doi.org/10.5152/alphapsychiatry.2023.231277
40. 40. Kulaksizoglu B, Kulaksizoglu S. Thiol/disulfide homeostasis in schizophrenic patients. Neurochemical Journal, 2018; 12, 102-06.
41. 41. Guler EM, Kurtulmus A, Gul AZ, Kocyigit A, Kirpinar I. Oxidative stress and schizophrenia: A comparative cross-sectional study of multiple oxidative markers in patients and their first-degree rel-atives. International journal of clinical practice, 2012; 75(11), e14711. https://doi.org/10.1111/ijcp.14711
42. 42. Gul H, Oner O. Neurobiology and Brain Imaging Studies of Disso-ciative Disorders-Dissosiyatif Bozuklukların Nörobiyolojisi ve Beyin Görüntüleme Çalışmaları. Turkiye Klinikleri J Psychiatry-Special Topics 2017;10(3):177-8