Neuroendocrine and Molecular Interactions in Eating Disorders

Öz

There are three basic pillars for the development of eating disorders: genetic predisposition, neuro-endocrine-molecular changes in the brain and metabolic response to it. As a result of neuroendocrine research, a close relationship has been found between neuroendocrine functions and symptom domains of psychiatric disorders such as eating disorders and mood disorders. Certain hormones, neurotransmitters and other molecules which might have effect on the basis of eating disorders can be listed as estrogen, serotonin, leptin, ghreline, alpha-melanocyte stimulating hormone, cholecystokinin, dopamine, noradrenaline, brain-derived neurotropic factor, agouti-related protein, neuropeptide-Y, opioids and their receptors, thiamine, zinc, omega-3 acids. In this review, main neuroendocrine-molecular changes and interactions that occur in the eating disorders have been discussed.

Anahtar Kelimeler

• Eating disorders, anorexia nervosa, neuroendocrine functions

Yeme Bozukluklarında Nöroendokrin ve Moleküler Etkileşimler

Öz

Yeme bozukluklarının gelişiminde üç temel ayağın bulunduğu söylenebilir: genetik yatkınlık, beyindeki nöroendokrin-moleküler değişimler ve metabolizmanın buna yanıtı. Nöroendokrin araştırmalar sonucunda nöroendokrin işlevler ile yeme bozuklukları ve duygudurum bozuklukları gibi psikiyatrik hastalıkların belirti kümeleri arasında yakın bir ilişki olduğu saptanmıştır. Yeme bozukluklarının temelinde etkisi olduğu varsayılan bazı hormonlar, nörotransmitterler ve diğer moleküller östrojen, serotonin, leptin, ghrelin, alfa-melanosit uyarıcı hormon, kolesistokinin, dopamin, noradrenalin, beyin kaynaklı nörotrofik faktör, agouti-ilişkili protein, nöropeptid-Y, opioidler ve reseptörleri, tiyamin, çinko, omega-3 yağ asitleridir. Bu derlemede yeme bozukluklarında ortaya çıkan ana nöroendokrin-moleküler değişimler ve etkileşimler ele alınmıştır.

Anahtar Kelimeler

• Yeme bozuklukları, anoreksiya nervoza, nöroendokrin işlevler

Kaynakça

1. Sofuoğlu S. Psikiyatrik bozukluklarda nöroendokrin değişiklikler. Türkiye Klinikleri Tıp Bilimleri Dergisi 1985; 5:27-32. Tarım Ö. Endosistemik etkileşimler. Güncel Pediatri 2004; 2:120-123.
2. Öztürk O, Ulu şahin A. Ruh Sağlığı ve Bozuklukları, 11. Baskı, Ankara, 2008.
3. Kim YR, Kim JH, Kim MJ, Tresure J. Differential methylation of the oxytocin receptor gene in patients with anorexia nervosa: a pilot study. PloS One 2014; 9:e886673.
4. Kaye W. Eating disorders: hope despite mortal risk. Am J Psychiatry 2009; 166:1309-1311.
5. Neumarker KJ. Mortality and sudden death in anorexia nervosa. Int J Eat Disord 1997; 21:205-212.
6. Halmi KA. Eating disorders: In Comprehensive Textbook of Psychiatry, Volume II (Eds BJ Sadock, VA Sadock):. Philadelphia, Lippincott Williams & Wilkins ,2000.
7. Marcus MD, Wildes JE. Eating disorders. In: Goldman's Cecil Medicine. 24th ed. (Eds L Goldman, AI Schafer AI):226. Philadelphia, PA: Elsevier Saunders, 2011.
8. Treasure J, Claudino AM, Zucker N. Eating disorders. Lancet. 2010; 375:583-593.

9. Allison KC, Stunkard AJ, Their SL. Overcoming the Night Eating Syndrome: A Step-By-Step Guide to Breaking the Cycle. Oakland, CA, New Harbinger, 2004.
10. Tunçbilek E. Obesite genetik bir hastalık mıdır? Çocuk Sağlığı ve Hastalıkları Dergisi 2005; 48:101-108.
11. Pinel JP, Assanand S, Lehman DR, Hunger, eating and ill health. Am Psychol 2000; 55:1105-1116.
12. Janas-Kozik M, Zejda J, Stochel M, Brozek G, Janas A, Jelonek I. Orthorexia- a new diagnosis? Psychiatr Pol. 2012; 46:441
13. Annagür BB, Bozkurt Zincir S. Anoreksiya nervozada hormonal değişimler. Düşünen Adam Psikiyatri ve Nörolojik Bilimler Dergisi 2012; 25:63-69.
14. Morimoto Y, Oishi T, Hanasaki N, et al. Interrelations among amenorrhea, serum gonadotropins and body weight in anorexia nervosa. Endocrinol Jpn 1980; 27:191-200.
15. Vigersky RA, Loriaux DL, Andersen AE, Lipsett MB. Anorexia nervosa: behavioural and hypothalamic aspects. Clin Endocrinol Metab1976; 5:517-535.
16. Lipton MA, DiMascio A, Killam KF. Psychopharmacology: A Generation and Progress. Raven Press. New York, 1981.
17. Chrousos GP, Torpy DJ, Gold PW. Interactions between the hypothalamic- pituitary-adrenal axis and the female reproductive system: clinical implications. Ann Intern Med 1998; 129:229-240.
18. Krueger F, Parasuraman R, Iyengar V, Thornburg M, Weel J, Lin M et al. Oxytocin receptor genetic variation promotes human trust behavior. Front Hum Neurosci 2012; 6:4.
19. Kumsta R, Hummel E, Chen FS, Heinrichs M. Epigenetic regulation of the oxytocin receptor gene: implications for behavioral neuroscience. Front Neurosci 2013; 7:83.
20. Young JK. Anorexia nervosa and estrogen: current status of the hypothesis. Neurosci Biobehav Rev 2010; 34:1195-1200. Coşkun A. Yeme bozukluklarında moleküler mekanizmalar. Bilim ve Teknik 2012; 2:58-62.
21. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000; 404:661–671.
22. Kaye WH. Neuropeptide abnormalities in anorexia nervosa. Psychiatry Res 1996; 62:65-74.
23. Bailer UF, Kaye WH. A review of neuropeptide and neuroendocrine dysregulation in anorexia and bulimia nervosa. Curr Drug Targets CNS Neurol Disord 2003; 2:53-59.
24. Sinha MK. Human leptin: the hormone of adipose tissue. Eur J Endocrinol 1997; 136:461-464.
25. Ostlund RE, Yang JW, Klein S, Gingerich R. Relation between plasma leptin concentration and body fat, gender, diet, age and metabolic covariates. J Clin Endocrinol Metab 1996; 81:3909-3913.
26. Eckert ED, Pomeroy C, Raymond N, Kohler PF, Thuras P, Bowers CY. Leptin in anorexia nervosa. J Clin Endocrinol Metab 1998; 83:791-795.
27. Burghardt PR, Love TM, Stohler CS, Hodgkinson C, Shen PH, Enoch MA et al. Leptin regulates dopamine responses to sustained stress in humans. J Neurosci 2012; 32:15369-15376.
28. Coleman DL. Obese and diabetes: Two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 1978; 14:141-148.
29. McConway MG, Johnson D, Kelly A, Griffin D, Smith J, Wallace AM. Differences in circulating concentrations of total, free and bound leptin relate to gender and body composition in adult humans. Ann Clin Biochem 2000; 37:717-723.
30. Misra M, Miller KK, Cord J, Prabhakaran R, Herzog DB. Relationships between serum adipokines, insulin levels, and bone density in girls with anorexia nervosa. J Clin Endocrinol Metab 2007; 92:2046–2052.
31. Nogueira JP, Maraninchi M, Lorec AM, Corroller AB, Nicolay A et al. Specific adipocytokines profiles in patients with hyperactive and/or binge/purge form of anorexia nervosa. Eur J Clin Nutr 2010; 64:840–844.
32. Vink T, Hinney A, van Elburg AA, van Goozen SH, Sandkuijl LA. Association between an agouti-related protein gene polymorphism and anorexia nervosa. Mol Psychiatry 2001; 6:325–328.
33. Byerly MS, Swanson R, Wei Z, Seldin MM, McCulloh PS, et al. A Central Role for C1q/TNF-Related Protein 13 (CTRP13) in Modulating Food Intake and Body Weight. PLoS ONE 2013; 8:e62862.
34. Wei Z, Peterson JM, Wong GW. Metabolic regulation by C1q/TNFrelated protein-13 (CTRP13): activation OF AMP-activated protein kinase and suppression of fatty acid-induced JNK signaling. J Biol Chem 2011; 286:15652–15665.
35. Loos RJ, Bouchard C. Obesity-is it a genetic disorder? J Intern Med 2003; 254:401-425.
36. Farooqi IS, Keogh JM, Yeo GSH, Lank EJ, Cheetham T, O’Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 2003; 348:1085-1095.
37. Branson R, Potoczna N, Kral JG, Lentes KU, Hoehe MR, Horber FF. Binge eating as a major phenotype of melanocortin 4 receptor gene mutations. N Engl J Med 2003; 348:1096-1103.
38. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402:656-660.
39. Tschöp M, Smiley D, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407:908-913.
40. Gregory JW, Greene SA, Jung RT, Scrimgeour CM, Rennie MJ. Metabolic effects of growth hormone treatment: an early predictor of growth hormone response? Arch Dis Child 1993; 68:205-209.
41. Yiş U, Öztürk Y, Büyükgebiz B. Ghrelin: enerji metabolizmasının düzenlenmesinde yeni bir hormon. Çocuk Sağlığı ve Hastalıkları Dergisi 2005; 48:196-201.
42. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K et al. A role for ghrelin in the central regulation of feeding. Nature 2001; 409:194-198.
43. De Ambrogi M, Volpe S, Tamanini C. Ghrelin: central and peripheral effects of a novel peptydil hormone. Med Sci Monit 2003; 9:217-224.
44. Hewson AK, Dickson SL. Systemic administration of ghrelin induces Fos and Egr-1 proteins in the hypothalamic arcuate nucleus of fasted and fed rats, J Neuroendocrinol 2000; 12:1047-1049.
45. Pichika R, Buchsbaum MS, Bailer U, Hoh C, Decastro A, Buchsbaum BR et al. Serotonin transporter binding after recovery from bulimia nervosa. Int J Eat Disord 2012; 45:345-352.
46. Marco EM, Romero-Zerbo SY, Viveros MP, Bermudez-Silva FJ. The role of the endocannabinoid system in eating disorders: pharmacological implications. Behav Pharmacol 2012; 23:526-536.
47. Obarzanek E, Lesem MD, Jimerson DC. Resting metabolic rate of anorexia nervosa patients during weight gain. Am J Clin Nutr 1994; 60:666-675.
48. Altemus M, Hetherington MM, Flood M, Licinio J, Nelson ML, Bernat AS, Gold PW. Decrease in resting metabolic rate during abstinence from bulimic behavior. Am J Psychiatry 1991; 148:1071-1072.
49. Hashizume K, Suzuki S, Komatsu A, Hiramatsu K, Mori J, Yamazaki M et al. Administration of recombinant human growth hormone normalizes GH-IGF1 axis and improves malnutrition-related disorders in patients with anorexia nervosa. Endocr J 2007; 54:319-327.
50. Gianotti L, Broglio F, Aimaretti G, Arvat E, Colombo S, Di Summa M et al. Low IGF-I levels are often uncoupled with elevated GH levels in catabolic conditions. J Endocrinol Invest 1998; 21:115-121.
51. Grinspoon S, Baum H, Lee K, Anderson E, Herzog D, Klibanski A. Effects of short-term recombinant human insulin-like growth factor-I administration on bone turnover in osteopenic women with anorexia nervosa. J Clin Endocrinol Metab 1996; 81:3864-3870.
52. Maury E, Ramsey KM, Bass J. Circadian rhythms and metabolic syndrome: from experimental genetics to human disease. Circ Res 2010; 106:447-462.
53. Jing MY, Sun JY, Weng XY. Insights on zinc regulation of food intake and macronutrient selection. Biol Trace Elem Res 2007; 115:187-194. Semra Bozkurt Zincir, Uzm.Dr., Erenköy Ruh ve Sinir Hastalıkları Eğitim ve Araştırma Hastanesi, İstanbul. Yazışma Adresi/Correspondence: Semra Bozkurt Zincir, Erenköy Ruh ve Sinir Hastalıkları Eğitim ve Araştırma Hastanesi, İstanbul, Turkey. E-mail: [e-mail] Yazarlar bu makale ile ilgili herhangi bir çıkar çatışması bildirmemiştir. The authors reported no conflict of interest related to this article. Çevrimiçi adresi / Available online at: www.cappsy.org/archives/vol6/no4/ Çevrimiçi yayım / Published online 10 March/Mart 10, 2014; doi: 10.5455/cap.20140225100233