Orkun AYDIN, CUMHUR TAŞ, Pınar Unal AYDIN, Fikret Poyraz ÇÖKMÜŞ, AYŞEN ESEN DANACI

Şizofreni hastalarının anneleri ile sağlıklı kontrollerin yürütücü işlev, sosyal biliş ve plazma oksitosin düzeylerinin karşılaştırılması: Yeni bir endofenotip arayışı

Amaç: Şizofrenide hem tanıya yardımcı, hem de tedaviye yanıt ile işlevselliği yordayıcı bazı endofenotipler bulunmuştur. Günümüze kadar yapılan çalışmalarda biyokimyasal bir endofenotip bulunmamıştır. Endofenotip olarak değerlendirilen yürütücü işlev, sosyal biliş gibi değişkenler ile yapılan çalışmalarda farklı sonuçlar elde edilmiştir. Oksitosin, şizofreni hastalarında yapılan çalışmalarda eksikliği saptanan ve tedavide etkili olabileceği düşünülen bir hormondur. Oksitosin hormonu ile yapılan herhangi bir endofenotip çalışmasıtır. Hem yeni bir endofenotip belirleme, hem de önceden saptanmış endofenotipleri sınama amacını güden çalışmamızda şizofreni hastalarının anneleri odak noktamız olmuştur. Yöntem: Şizofreni hastalarının sağlıklı anneleri ve sağlıklı kontroller çalışmaya alınmış olup tüm deneklere Gözlerden Zihin Okuma Testi, Wisconsin Kart Eşleme Testi, Wechsler Yetişkinler için Zeka Ölçeği sözcük dağarcığı alt testi uygulanmış ve plazma oksitosin düzeyleri biyokimyasal olarak analiz edilmiştir. Sonuçlar: Çalışmanın sonuçları incelendiğinde, şizofreni hastalarının anneleri ile sağlıklı kontroller arasında plazma oksitosin düzeyi açısından anlamlı farklılık olduğu gözlenmiştir. Plazma oksitosin düzeyinin düşüklüğü, şizofreni hastalarının anneleri ile sağlıklı kontrol grubunu birbirinden ayırt etmede tek anlamlı değişken olarak saptanmıştır. Yürütücü işlevleri değerlendiren Wisconsin Kart Eşleme Testi ve sosyal bilişi değerlendiren Gözlerden Zihin Okuma Testi sonuçları incelendiğinde şizofreni hastalarının anneleri ile sağlıklı kontroller arasında bir fark saptanmamıştır. Tartışma: Oksitosin hormonu şizofreni hastalığı için yeni bir endofenotip olabilir. Bu konuda yapılacak yeni endofenotip belirleme çalışmalarına gerek vardır.

The comparison of executive functions, social cognition and plasma oxytocin level between mothers' of schizophrenia patients and healthy control: searching for a new endophenotype

Objective: Previous studies documented that there were a variety of endophenotypes that helped to diagnose as well as to predict functionality and treatment response. There is little, if any research that focused on investigating biochemical endophenotypes. Besides, the studies that include executive functions and social cognition, which were accepted as endophenotypes, have different results. In studies involving schizophrenia patients, the deficiency of oxytocin was found to be the most important hormone that would affect the treatment process. However, there have been no endophenotype studies that investigated the role of oxytocin hormone in the treatment process of schizophrenia patients. The purpose of the present study was twofold: (a) to detect new endophenotypes, and (b) to test endophenotypes that were previously found by focusing on the schizophrenia patients' mothers. Methods: The participants were the healthy mothers of schizophrenia patients and healthy control group. They took the Reading the Mind in the Eyes Test, Wisconsin Card Sorting Test, and Wechsler Adult Intelligence Scale vocabulary subtest, respectively. In addition, participants' blood samples were collected to include the level of plasma oxytocin as a biochemical in the data analyses. Results: Results revealed that there was a significant difference in plasma oxytocin levels for the healthy mother's of schizophrenia patients and the healthy control group. Low level of plasma oxytocin level was found to be the only significant factor that differentiates the patients' mothers and the healty control group. When the results of the Reading the Mind in the Eyes Test that measures executive functions, and the Wisconsin Card Sorting Test that measures social cognition were analyzed, no significant differences were found between the groups. Discussion: Our findings showed that oxytocin hormone could be a new endophenotype for schizophrenia. However, there is still a need for studies that focus on the investigation of detecting new endopheno types.

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1. Brüne M. Textbook of Evolutionary Psychiatry and Psychosomatic Medicine. First ed., UK, 2008.
2. Ulas? H, Tas?lıca S, Alptekin K. S?izofrenide no? rofizyolojik ve no? rokognitif genetik belirleyicilerin (endofenotip) yeri. Klin Psikiyatr Derg 2008; 11:9- 12.
3. Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003; 160:636-645.
4. Louchart-de la Chapelle S, Nkam I, Houy E, Belmont A, Menard JF, Roussignol AC, et al. A concordance study of three electrophysiological measures in schizophrenia. Am J Psychiatry 2005; 162:466-474.
5. Thibaut F, Boutros NN, Jarema M, Oranje B, Hasan A, Daskalakis ZJ, et al. Criteria for biomarkers and endophenotypes of schizophrenia part I: Neurophysiology. World J Biol Psychiatry 2015; 16:280-290.
6. Arfken CL, Carney S, Boutros NN. Translating biological parameters into clinically useful diagnostic tests. Curr Psychiatry Rep 2009; 11:320- 323.
7. Light GA, Swerdlow NR, Rissling AJ, Radant A, Sugar CA, Sprock J, et al. Characterization of neurophysiologic and neurocognitive biomarkers for use in genomic and clinical outcome studies of schizophrenia. PLoS One 2012; 7:(7),e39434.
8. Swerdlow NR, Gur RE, Braff DL. Consortium on the genetics of schizophrenia (COGS) assessment of endophenotypes for schizophrenia. Schizophr Res 2015; 163:9-16.
9. Allen AJ, Griss ME, Folley BS, Hawkins KA, Pearlson GD. Endophenotypes in schizophrenia: a selective review. Schizophr Res 2009; 109:24- 37.
10. Stöber G, Ben-Shachar D, Cardon M, Falkai P, Fonteh AN, Gawlik M, et al. Schizophrenia: from the brain to peripheral markers. World J Biol Psychiatry 2009; 10:127-155.
11. Snitz BE, MacDonald AW, Carter CS. Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. Schizophr Bull 2006; 32(1):179-194.
12. Kalkstein S, Hurford I, Gur RC. Neurocognition in schizophrenia. Curr Top Behav Neurosci 2010; 4:373-390.
13. Chen WJ, Liu SK, Chang CJ. Sustained attention deficit and schizotypal personality features in non psychotic relatives of schizophrenic patients. Am J Psychiatry 1998; 155:1214-1220.
14. Laurent A, Biloa-Tang M, Bougerol T. Executive/ attentional performance and measures of schizotypy in patient with schizophrenia and their non psychotic first-degree relatives. Schizophr Res 2000; 46:269-283.
15. Sitskoorn MM, AlemanA, Ebisch SJ. Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis. Schizophr Res 2004; 71:285- 295.
16. Barrantes-Vidal N, Aguilera M, Campanera S. Working memory in siblings of schizophrenia patients. Schizophr Res 2007; 95:70-75.
17. Kelly, J, Swanson L. Additional forebrain regions projecting to the posterior pituitary: preoptic region, bed nucleus of the stria terminalis, and zona incerta. Brain Res 1980; 197(1):1-9.
18. Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC. Oxytocin improves "mind-reading" in humans. Biol Psychiatry 2007; 61(6):731-733.
19. Guastella AJ, Carson DS, Dadds MR, Mitchell PB, Cox RE. Does oxytocin influence the early detection of angry and happy faces? Psychoneuroendocrinology 2009; 34(2):220-225.
20. Fischer-Shofty M, Shamay-Tsoory SG, Harari H, Levkovitz Y. The effect of intranasal administration of oxytocin on fear recognition. Neuropsychologia 2010; 48(1):179-184.
21. Perez-Rodriguez MM, Mahon K, Russo M, Ungar AK, Burdick KE. Oxytocin and social cognition in affective and psychotic disorders. Eur Neuropsychopharmacol 2015; 25(2):265-282.
22. Onwumere J, Grice S, Kuipers E. Delivering cognitive-B behavioural family interventions for schizophrenia. Aust Psychol 2016; 51(1):52-61.
23. Sharif F, Maryam S, Arash M. Effect of a psychoeducational intervention for family members on caregiver burdens and psychiatric symptoms in patients with schizophrenia in Shiraz, Iran. BMC Psychiatry 2012; 12(1):48-57.
24. Cassidy H, O'Callaghan N. Efficacy of a psychoeducational intervention in improving relatives' knowledge about schizophrenia and reducing rehospitalisation. Eur Psychiatry 2001; 16:446-450.
25. Bartz JA, Zaki J, Ochsner KN, Bolger N, Kolevzon A, Ludwig N, et al. Effects of oxytocin on recollections of maternal care and closeness. Proc Natl Acad Sci U S A 2010; 107:21371-21375.
26. First RL, Spitzer M, Gibbon JBW. Structured Clinical Interview for DSM-IV-TR Axis I DisordersResearch Version, Patient Edition (SCID-I/P). First ed., New York, 2002.
27. Husarova VM, Lakatosova S, Pivovarciova A, Babinska K, Bakos J, Durdiakova J, et al. Plasma oxytocin in children with autism and its correlations with behavioral parameters in children and parents. Psychiatry Investig 2016; 13(2):174-183.
28. Goldman M, Marlow-O'Connor M, Torres I, Carter CS. Diminished plasma oxytocin in schizophrenic patients with neuroendocrine dysfunction and emotional deficits. Schizophr Res 2008; 98(1):247-255.
29. Ovla HD, Taşdelen B. Aykırı değer yönetimi. Mersin Üniv Tıp Fak Der 2012; 5(3):64-67.
30. Wechsler D. Wechsler Adult Intelligence ScaleFourth Edition (WAIS- IV). TX: NCS Pearson, San Antonio, 2008.
31. Krull KR, Scott JG, Sherer M. Estimation of premorbid intelligence from combined performance and demographic variables. Clin Neuropsychol 1995; 9:83-88.
32. Yıldırım EA, Kas?ar M, Gu? du? k M. Go? zlerden Zihin Okuma Testi'nin Tu? rkc?e gu? venirlik c?alıs?ması. Turk Psikiyatri Derg 2001; 22:177-186.
33. Clarke D. Cambridge International AS and A Level Psychology Revision Guide. First ed., London: Hodder Education Press, 2013, p.87-96.
34. Heaton R. Wisconsin Card Sorting Test Manual. Psychological Assessment Resources, Odessa: FL, 1981.
35. Karakas? S, Irak M, Ersezgin O?U. Wisconsin kart es?leme testi (WCST) ve Stroop testi TBAG formu puanlarının test ic?i ve testler-arası ilis?kileri. 10. Ulusal Psikoloji Kongresi (Eylül 1998, Ankara) Özet Kitabı, 1998, s.44, Ankara.
36. Szeto A, McCabe PM, Nation DA, Tabak BA, Rossetti MA, McCullough ME, et al. Evaluation of enzyme immunoassay and radioimmunoassay methods of the measurement of plasma oxytocin. Psychosom Med 2011; 73(5):393.
37. Pentaraki A, Toulopoulou T, Stefanis NC, Stahl D, Kaliora SC, Roukas D, et al. Theory of mind as a potential endophenotype of schizophrenia: Understanding mental states from the eyes in families with schizophrenia. Schizophr Res 2008; 102:188.
38. Baron-Cohen S, Wheelwright S, Hill J, Raste Y, Plumb I. The "Reading the Mind in the Eyes" test revised version: A study with normal adults, and adults with Asperger syndrome or high-functioning autism. J Child Psychol Psychiatry 2001; 42(2):241-251.
39. Herpertz SC, Bertsch K. Oxytocin effects on brain functioning in humans. Biol Psychiatry 2016; 79(8):631-632.
40. Davis MC, Lee J, Horan WP, Clarke AD, McGee MR, Green MF et al. Effects of single dose intranasal oxytocin on social cognition in schizophrenia. Schizophr Res 2013; 147:393-397.
41. Woolley J, Chuang B, Lam O, Lai W, O'Donovan A, Rankin K, et al. Oxytocin administration enhances controlled social cognition in patients with schizophrenia. Psychoneuroendocrinology 2014; 47:116-125.
42. Bakermans KM, Van IM. Sniffing around oxytocin: review and meta analyses of trials in healthy and clinical groups with implications for pharmacotherapy. Transl Psychiatry 2013; 3:258.