An Emerging Role of Leptin in Clinical Psychiatry

  • T. Pollmächer
Conference paper
Part of the Research and Perspectives in Endocrine Interactions book series (RPEI)


Early in the 20th century changes in appetite and weight had already been recognized as important features of severe psychiatric disorders. The present chapter reviews recent evidence suggesting that the fat cell-derived hormone leptin is pathophysiologically involved in these changes. Moreover, data are discussed supporting the speculation that leptin, which is now recognized to be a cytokine-like peptide involved in many aspects of brain function such as neurodevelopment, neuronal survival and various aspects of behavior and cognition, plays a patho-physiological role in behavioral and cognitive changes observed in psychiatric patients and, in particular, in anorexia nervosa and schizophrenia.


Anorexia Nervosa Antipsychotic Drug Bulimia Nervosa Severe Psychiatric Disorder Increase Motor Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Allison DB, Fontaine KR, Heo M, Mentore JL, Cappelleri JC, Chandler LP, Weiden PJ, Cheskin LJ (1999a) The distribution of body mass index among individuals with and without schizophrenia. J Clin Psychiat 60:215–220CrossRefGoogle Scholar
  2. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ (1999b) Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiat 156:1686–1996PubMedGoogle Scholar
  3. Auwerx J, Staels B (1998) Leptin. Lancet 351:737–742PubMedCrossRefGoogle Scholar
  4. Beumont PJ, Arthur B, Russell JD, Touyz SW (1994) Excessive physical activity in dieting disorder patients: proposals for a supervised exercise program. Intl J Eat Disord 15:21–36CrossRefGoogle Scholar
  5. Brömel T, Blum WF, Ziegler A, Schulz E, Bender M, Fleischhaker C, Remschmidt H, Krieg JC, Hebebrand J (1998) Serum leptin levels increase rapidly after initiation of clozapine therapy. Mol Psychiat 3:76–80CrossRefGoogle Scholar
  6. Bukanan R (2000) Schizophrenia: introduction and overview. In: Sadock B, Sadock V (eds) Comprehensive textbook of psychiatry. Lippincott Williams & Wilkins, New York, pp 1096–1109Google Scholar
  7. Bustillo JR, Buchanan RW, Irish D, Breier A (1996) Differential effect of clozapine on weight: a controlled study. Am J Psychiat 153:817–819PubMedGoogle Scholar
  8. Devuyst O, Lambert M, Rodhain J, Lefebvre C, Coche E (1993) Haematological changes and infectious complications in anorexia nervosa: a case-control study. Q J Med 86:791–799PubMedGoogle Scholar
  9. Dicou E, Attoub S, Gressens P (2001) Neuroprotective effects of leptin in vivo and in vitro. Neuroreport 12:3947–3951PubMedCrossRefGoogle Scholar
  10. Eder U, Mangweth B, Ebenbichler C, Weiss E, Hofer A, Hummer M, Kemmler G, Lechleitner M, Fleischhacker WW (2001) Association of olanzapine-induced weight gain with an increase in body fat. Am J Psychiat 158:1719–1722PubMedCrossRefGoogle Scholar
  11. Esler M, Vaz M, Collier G, Nestel P, Jennings G, Kaye D, Seals D, Lambert G (1998) Leptin in human plasma is derived in part from the brain, and cleared by the kidneys. Lancet 351(9106):879PubMedCrossRefGoogle Scholar
  12. Exner C, Hebebrand J, Remschmidt H, Wewetzer C, Ziegler A, Herpertz S, Schweiger U, Blum WF, Preibisch G, Heldmaier G, Klingenspor M (2000) Leptin suppresses semi-starvation induced hyperactivity in rats: implications for anorexia nervosa. Mol Psychiat 5:476–481CrossRefGoogle Scholar
  13. Fantuzzi G, Faggioni R (2000) Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukocyte Biol 68:437–446PubMedGoogle Scholar
  14. Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O’Rahilly S (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 341:879–884PubMedCrossRefGoogle Scholar
  15. Hebebrand J, Ballauff A, Hinney A, Herpertz S, Köpp W, Wewetzer C, Ziegler A, Blum WF, Remschmidt H (1999) Die gewichtsregulation im rahmen der Anorexia nervosa unter besonderer berücksichtigung der leptinsekretion. Nervenarzt 70:31–40PubMedCrossRefGoogle Scholar
  16. Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, Lubina JA, Patane J, Self B, Hunt P, McCamish M (1999) Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 282:1568–1575PubMedCrossRefGoogle Scholar
  17. Hinze-Selch D, Schuld A, Kraus T, Kühn M, Uhr M, Haack M, Pollmächer T (2000) Effects of antidepressants on weight and on the plasma levels of leptin, TNF-α and soluble TNF receptors: a longitudinal study in patients treated with amitriptyline or paroxetine. Neuropsychopharmacology 23(1):13–19PubMedCrossRefGoogle Scholar
  18. Jalenques I, Tauveron I, Albuisson E, Audy V, Fleury-Duhamel N, Codert A (1996) Weight gain as a predictor of long-term clozapine efficiency. Clin Drug Invest 12:16–25CrossRefGoogle Scholar
  19. Kalra SP, Dube MG, Pu S, Xu B, Horvath TL, Kalra PS (1999) Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocrine Rev 20:68–100CrossRefGoogle Scholar
  20. Karsenty G (2001) Leptin controls bone formation through a hypothalamic relay. Recent Prog Horm Res 56:401–415PubMedCrossRefGoogle Scholar
  21. Köpp W, Blum WF, von Prittwitz S, Ziegler A, Lubbert H, Emons G, Herzog W, Herpertz S, Deter HC, Remschmidt H, Hebebrand J (1997) Low leptin levels predict amenorrhea in underweight and eating disordered females. Mol Psychiat 2:335–340CrossRefGoogle Scholar
  22. Köpp W, Blum WF, Ziegler A, Mathiak K, Lubbert H, Herpertz S, Deter HC, Hebebrand J (1998) Serum leptin and body weight in females with anorexia and bulimia nervosa. Horm Metab Res 30:272–275PubMedCrossRefGoogle Scholar
  23. Kraepelin E (1901) Einführung in die psychiatrische klinik. Dreissig Vorlesungen. Barth Verlag, LeipzigGoogle Scholar
  24. Kraus T, Haack M, Schuld A, Hinze-Selch D, Kühn M, Uhr M, Pollmächer T (1999) Body weight and leptin plasma levels during treatment with antipsychotic drugs. Am J Psychiat 156:312–314PubMedGoogle Scholar
  25. Kraus T, Haack M, Schuld A, Hinze-Selch D, Pollmächer T (2001) Low leptin levels but normal body mass indices in patients with depression or schizophrenia. Neuroendocrinology 73:243–247PubMedCrossRefGoogle Scholar
  26. Kraus T, Zimmermann U, Schuld A, Haack M, Hinze-Selch D, Pollmächer T (2001) Zur pathophysiologie der gewichtsregulation im rahmen der thérapie mit Psychopharmaka. Fortschritte der Neurologie-Psychiatrie 69:116–137PubMedCrossRefGoogle Scholar
  27. Kraus T, Haack M, Schuld A, Hinze-Selch D, Koethe D, Pollmächer T (2002) Body weight, the tumor necrosis factor system and leptin production during treatment with mirtazapine or venlafaxine. Pharmacopsychiatry, in press.Google Scholar
  28. Lieberman JA (1999) Is schizophrenia a neurodegenerative disorder? A clinical and neurobiological perspective. Biol Psychiat 46:729–739PubMedCrossRefGoogle Scholar
  29. Maier W, Lichtermann D, Rietschel M, Held T, Falkai P, Wagner M, Schwab S (1999) [Genetics of schizophrenic disorders. New concepts and findings]. Nervenarzt 70:955–969PubMedCrossRefGoogle Scholar
  30. Masuzaki H, Ogawa Y, Hosoda K, Miyawaki T, Hanaoka I, Hiraoka J, Yasuno A, Nishimura H, Yoshimasa Y, Nishi S, Nakao K (1997) Glucocorticoid regulation of leptin synthesis and secretion in humans: elevated plasma leptin levels in Cushing’s syndrome. J Clin Endocrin Metab 82:2542–2547CrossRefGoogle Scholar
  31. Meltzer HY, Lee MA, Ranjan R (1994) Recent advances in the pharmacotherapy of schizophrenia. Acta Psychiatr Scand 384:95–101CrossRefGoogle Scholar
  32. Morimoto T, Yamamoto Y, Yamatodani A (2001) Brain histamine and feeding behavior. Behav Brain Res 124:145–150PubMedCrossRefGoogle Scholar
  33. Newcomer JW, Selke G, Melson AK, Gross J, Vogler GP, Dagogo-Jack S (1998) Dose-dependent cortisol-induced increases in plasma leptin concentration in healthy humans. Arch Gen Psychiat 55:995–1000PubMedCrossRefGoogle Scholar
  34. Pickar D (1995) Prospects for pharmacotherapy of schizophrenia. Lancet 345:557–562PubMedCrossRefGoogle Scholar
  35. Pollmächer T (2002) Treatment of schizophrenia. In: Smelser NJ, Balters PB (eds) International Encyclopedia of the social and behavioral sciences. Pergamon, Kidlington, pp 13546–13552Google Scholar
  36. Rayner DV, Trayhurn P (2001) Regulation of leptin production: sympathetic nervous system interactions. J Mol Med 79:8–20PubMedCrossRefGoogle Scholar
  37. Schafroth U, Godang K, Ueland T, Bollerslev J (2001) Leptin response to endogenous acute stress is independent of pituitary function. Eur J Endocrinol 145:295–301PubMedCrossRefGoogle Scholar
  38. Shanley LJ, Irving AJ, Harvey J (2001) Leptin enhances NMDA receptor function and modulates hippocampal synaptic plasticity. J Neuroscience 21(24):RC186Google Scholar
  39. Sinton CM, Fitch TE, Gershenfeld HK (1999) The effects of leptin on REM sleep and slow wave delta in rats are reversed by food deprivation. J Sleep Res 8:197–203PubMedCrossRefGoogle Scholar
  40. Steppan CM, Swick AG (1999) A role for leptin in brain development. Biochem Biophys Res Commun 256:600–602PubMedCrossRefGoogle Scholar
  41. Wauters M, Considine RV, Van Gaal LF (2000) Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol 143:293–311PubMedCrossRefGoogle Scholar
  42. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • T. Pollmächer
    • 1
  1. 1.Max Planck Institute of PsychiatryMunichGermany

Personalised recommendations