Çağatay UĞUR, Mehmet SERTÇELİK, ÖZDEN ŞÜKRAN ÜNERİ, Gülser DİNÇ ŞENSES, Ebru SEKMEN, Esra SOLMAZ

DEHB ve otizm spektrum bozukluğu olan çocuklarda serum ürotensin-II düzeylerinin değerlendirilmesi

Amaç: Ürotensin-II (U-II), bilinen en etkin vazokonstrüktörlerden biridir. Beyin kan akımında oluşturduğu etkilerden dolayı nöropsikiyatrik hastalıkların gelişiminde rol oynadığı düşünülmektedir. Otizm spektrum bozukluğu (OSB) ve dikkat eksikliği hiperaktivite bozukluğu (DEHB) çocukluk çağında sık görülen ve etiyolojileri halen tam olarak bilinemeyen nöropsikiyatrik hastalıklardır. Bu çalışmada OSB ve DEHB'li çocukların serum U-II düzeylerinin değerlendirilmesi ve sağlıklı kontrollerle karşılaştırılması amaçlanmıştır. Yöntem: Ankara Çocuk Hematoloji ve Onkoloji Eğitim ve Araştırma Hastanesi, Çocuk ve Ergen Psikiyatrisi Polikliniği'ne başvuranlar arasından, DSM-5 tanı ölçütlerine göre DEHB ve OSB tanısı konan ve en az bir aydır ilaç kullanmayan 4-12 yaşları arasında 60'ar çocuk ile sağlıklı 59 çocuk çalışmaya alınmıştır. Katılımcılara Okul Çağı Çocukları için Duygulanım Bozuklukları ve Şizofreni Görüşmesi uygulanmıştır. On iki saat açlık sonrası venöz kan örnekleri alınarak ELİSA yöntemi ile serum U-II düzeyi belirlenmiştir. Analizler için SPSS 16.0 kullanılmış, anlamlılık düzeyi p

Evaluation of serum urotensin-II levels of children with ADHD and autism spectrum disorder

Objective: Urotensin-II (U-II) is one of the most vasoconstrictive substrates for the mammals. Lately, this substrate is thought to be responsible for developing of the neuropsychiatric disorders, by causing an abnormal brain bloodstream situation. Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are frequently seen disorders in childhood and their etiologies are remain unclear. This study evaluated the serum urotensin-II levels of children with ASD and ADHD and compared with healthy subjects' urotensin-II levels. Methods: Total of 179 children between age of 4-12, 60 of them diagnosed with ADHD and 60 of children with ASD, according to the DSM-5 criteria and both had no treatment for at least a month and 59 of healthy subjects whom they all admitted to the Ankara Pediatric Hematology-Oncology Training and Research Hospital were included. Schedule for Affective Disorders and Schizophrenia for School-Age Children, a semi-structured interview, was applied to all subjects. Venous samples of the participants were given after a-12 hours starvation. Serum U-II levels were analyzed by the use of ELISA kits. SPSS 16.0 was used for analysis and p<0.05 was accepted as significance level. Results: U-II levels of children with ASD were found higher than that of ADHD and healthy groups. There was also a positive correlation between U-II levels and autism behavior checklist scores. Discussion: Higher U-II levels and its levels' correlation with symptom severity of disorder are thought to be a responsible factor that could play a role in ASD etiology. Further studies with larger sample size could be useful to investigate the role of UII in the etiology and treatment research of ASD.

PDF

___

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth ed., Text Revision. Washington, DC: American Psychiatric Association, 2000.
2. Schaefer GB, Mendelsohn NJ. Professional Practice and Guidelines Committee: Clinical genetics evaluation in identifying the etiology of autism spectrum disorders. Genet Med 2008; 10:301- 305.
3. Rice C. Prevalence of Autism Spectrum Disorders: Autism and Developmental Disabilities Monitoring Network, United States, 2006. Morbidity and Mortality Weekly Report. Surveillance Summaries. Volume 58, p.10. Centers for Disease Control and Prevention, 2009.
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth ed., Washington, DC: American Psychiatric Association, 1994.
5. Biederman J, Faraone SV. Attention-deficit hyperactivity disorder. Lancet 2005; 366:237-248.
6. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 2007; 164:942-948.
7. Cohly HH, Panja A. Immunological findings in autism. Int Rev Neurobiol 2005; 71:317-341.
8. Ross BM, McKenzie I, Glen I, Bennett CPW. Increased levels of ethane, a non-invasive marker of n-3 fatty acid oxidation, in breath of children with attention deficit hyperactivity disorder. Nutr Neurosci 2003; 6:277-281.
9. Onan D, Hannan RD, Thomas WG. Urotensin II: The old kid in town. Trends Endocrinol Metab 2004; 15:175-182.
10. Coulouarn Y, Jégou S, Tostivint H, Vaudry H, Lihrmann I. Cloning, sequence analysis and tissue distribution of the mouse and rat urotensin II precursors. FEBS Lett 1999; 457:28-32.
11. Sturm H, Fernell E, Gillberg C. Autism spectrum disorders in children with normal intellectual levels: associated impairments and subgroups. Dev Med Child Neurol 2004; 46:444-447.
12. McDonald J, Batuwangala M, Lambert DG. Role of urotensin II and its receptor in health and disease. J Anesth 2007; 21:378-389.
13. Ong KL, Lam KS, Cheung BM. Urotensin II: Its function in health and its role in disease. Cardiovasc Drugs Ther 2005; 19:65-75.
14. Gartlon J, Parker F, David C, Harrison DC, Douglas SA, Ashmeade TE, et al. Central effects of urotensin-II following ICV administration in rats. Psychopharmacology 2001; 155:426-433.
15. Matsushita M, Shichiri M, Imai T, Iwashina M, Tanaka H, Takasu N, et al. Co-expression of urotensin-II and its receptor (GPR14) in human cardiovascular and renal tissue. J Hypertens 2001; 19:2185-2190.
16. Totsune K, Takahashi K, Arihara Z, Sone M, Satoh F, Ito S, et al. Role of urotensin II in patients on dialysis. Lancet 2001; 358:810-811.
17. Bulbul F, Alpak G, Unal A, Copoglu US, Orkmez M, Virit O, et al. New molecule in the etiology of schizophrenia: Urotensin II. Psychiatry Clin Neurosci 2014; 68:133-136.
18. Kawaguchi Y, Ono T, Kudo M, Kushikata T, Hashiba E, Yoshida H, et al. The effects of benzodiazepines on urotensin II-stimulated norepinephrine release from rat cerebrocortical slices. AnesthAnalg 2009; 108:1177-1181.
19. Cabanlit M, Wills S, Goines P, Ashwood P, Van de Water J. Brain-specific autoantibodies in the plasma of subjects with autistic spectrum disorder. Ann N Y AcadSci 2007; 1107:92-103.
20. Ban Y, Watanabe T, Suguro T, Matsuyama TA, Iso Y, Sakai T, et al. Increased plasma urotensinII and carotid atherosclerosis are associated with vascular dementia. J Atheroscler Thromb 2009; 16:179-187.
21. Müller N, Myint AM, Schwarz MJ. Inflammation in schizophrenia. Adv Protein Chem 2012; 88:49.
22. Selek S, Savas HA, Gergerlioglu HS, Bulut M, Yilmaz HR. Oxidative imbalance in adult attention deficit/hyperactivity disorder. Biol Psychol 2008; 79:256-259.
23. James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH, et al. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet 2006; 141:947-956.
24. Gökler B, Ünal F, Pehlivantürk B, Kültür EÇ, Akdemir D, Taner Y. Reliability and validity of Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version. Turk J Child Adolesc Ment Health 2004; 11:109-116.
25. Conners CK. Conners' Rating Scales-Revised technical manual. North Tonawanda, NY: MultiHealth Systems, 1997.
26. Kaner S, Buyukozturk S, Iseri E, Ak A, Ozaydın L. Conners' Parent Rating Scale Long Form-Revised: factor structure, reliability and validity studies. Turk J Child AdolescMent Health 2011; 18:45- 58.
27. Kaner S, Buyukozturk S, Iseri E, Ak A, Ozaydın L. The validity and reliability study of the Turkish version of Conners' Teacher rating scale-revised (CTRS-R). World Psychiatric Association Congress (12-16 July 2006, İstanbul), Complete Text Book, 2006, p.12-16, İstanbul, Turkey.
28. Aman MG, Singh NN, Stewart AW, Field CJ. Psychometric characteristics of the Aberrant Behavior Checklist. Am J Mental Deficiency 1985; 89:492-502.
29. Aman MG, Singh NN, Turbott SH. Reliability of the Aberrant Behavior Checklist and the effect of variations in instructions. Am J Mental Deficiency 1987; 92:237-240.
30. Karabekiroglu K, Aman MG. Validity of the aberrant behavior checklist in a clinical sample of toddlers. Child Psychiatry Hum Dev 2009; 40:99-110.
31. Schopler E, Reichler RJ, Rochen Renner B. The Childhood Autism Rating Scale (CARS). Eleventh ed., Western Psychological Services, 2007.
32. Robert J, Reichler RJ, Rochen Renner B. Practice DVD on Using the CARS. Western Psychological Services, 1988.
33. Mesibov G, Schopler E, Schaffer B, Michal N. Use of childhood autism rating scale with autistic adolescents and adults. J Am Acad Child Adolesc Psychiatry 1989; 28:538-541.
34. Gassologlu Sİ, Baykara B, Avcil S, Demiral Y. Çocukluk Otizmi Derecelendirme Ölçeği Türkçe Formunun geçerlik ve güvenilirlik çalışması. Turk Psikiyatri Derg 2016; 27:1-9.
35. Krug DA, Arick JR, Almond PA. Autism Screening Instrument for Educational Planning. Second ed., Austin, Texas: Pro-ed Inc., 1993.
37. Malaspina D, Harkavy-Friedman J, Corcoran C, Mujica-Parodi L, Printz D, Gorman JM, et al. Resting neural activity distinguishes subgroups of schizophrenia patients. Biol Psychiatry 2004; 56:931-937.
38. Haijma SV, Van Haren N, Cahn W, Koolschijn PC, Hulshoff Pol HE, Kahn RS. Brain volumes in schizophrenia: A meta-analysis in over 18000 subjects. Schizophr Bull 2013; 39:1129-1138.
39. Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL, et al. Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry 2004; 9:684-697.
40. Tosic M, Ott J, Barral S, Bovet P, Deppen P, Gheorghita F, et al. Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene. Am J Hum Genet 2006; 79:586-592.
41. Ozcan ME, Gulec M, Ozerol E, Polat R, Akyol O. Antioxidant enzyme activities and oxidative stress in affective disorders. Int Clin Psychopharmacol 2004; 19:89-95.
42. Brown NC, Andreazza AC, Young LT. An updated meta-analysis of oxidative stress markers in bipolar disorder. Psychiatry Res 2014; 218:61-68.
43. Emerit J, Edeas M, Bricaire F. Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 2004; 58:39-46.
44. Lu N, Yu HY, Wang R, Zhu YC. Central reactive oxygen species mediate cardiovascular effects of urotensin II in spontaneously hypertensive rat. Sheng Li Xue Bao 2012; 64:142-148.
45. Chauhan A, Chauhan V. Oxidative stress in autism. Pathophysiology 2006; 13:171-181.
46. Pardo CA, Vargas DL, Zimmerman AW. Immunity, neuroglia and neuroinflammation in autism. Int Rev Psychiatry 2005; 17:485-495.
47. Rossignol DA, Frye RE. A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Mol Psychiatry 2012; 17:389-401.
48. Mackness B, Durrington PN, Mackness MI. Review. Human serum paraoxonase. Gen Pharmacol 1998; 31:329-336.