The 5-HTTLPR polymorphism, platelet serotonin transporter activity and platelet serotonin content in underweight and weight-recovered females with anorexia nervosa

  • Stefan EhrlichEmail author
  • Leonora Franke
  • Susann Scherag
  • Roland Burghardt
  • Regina Schott
  • Nora Schneider
  • Simone Brockhaus
  • Jakob Hein
  • Ralf Uebelhack
  • Ulrike Lehmkuhl
Original Paper


Serotonin (5-HT) pathways play an important role in the pathophysiology of anorexia nervosa (AN). In this study, we investigated functional characteristics of the platelet 5-HT transporter and platelet 5-HT content in AN patients at various stages of their illness in comparison to healthy control woman (HCW) controlling for the 5-HTTLPR deletion/insertion polymorphism and other confounding variables. Fasting blood samples of 58 acutely underweight AN patients (acAN, BMI = 15.2 ± 1.4), 26 AN patients of the initial acAN sample after short-term/partial weight restoration (BMI = 17.3 ± 0.9), 36 weight-recovered AN patients (recAN, BMI = 20.7 ± 2.2) and 58 HCW (BMI = 21.6 ± 2.0) were assessed for kinetic characteristics of platelet 5-HT uptake (V max, K m) and platelet 5-HT content. Plasma leptin served as an indicator of malnutrition. Mean V max and K m values were significantly higher in recAN subjects in comparison to HCW (2.05 ± 0.62 vs. 1.66 ± 0.40 nmol 5-HT/109 platelets min and 432 ± 215 vs. 315 ± 136 nmol, respectively) but there were no differences in platelet 5-HT content (464.8 ± 210.6 vs. 472.0 ± 162.2 ng 5-HT/109 platelets). 5-HT parameters in acAN patients and HCW were similar. 5-HTTLPR variants were not related to 5-HT platelet variables. In the longitudinal part of the study we found significantly increased 5-HT content but unchanged 5-HT uptake in AN patients after short-term/partial weight restoration. Our results highlight the importance of malnutrition for the interpretation of abnormalities in neurotransmitter systems in AN. Changes in platelet 5-HT transporter activity were related to the stage of the illness but not to 5-HTTLPR genotype. Increased V max and K m in recovered AN patients might mirror adaptive modulations of the 5-HT system.


Anorexia nervosa Serotonin transporter Platelet 5-HTTLPR deletion/insertion polymorphism Leptin 



The authors would like to thank I. Kamenzky for excellent technical assistance, D. Weiss, M.D. for help with the biochemical assessments and J.V. Merle as well as A. Oskamp for help with the patient recruitment. Funding for this study was provided by the Charité Research Fund and the German Research Fund (DFG, personal grant to SE).

Conflict of interest statement

All authors declare that they have no conflicts of interest.


  1. 1.
    Amstein R, Fetkovska N, Buhler FR (1990) Age, platelet serotonin kinetics and 5HT2-receptor blockade in essential hypertension. J Hum Hypertens 4:441–444PubMedGoogle Scholar
  2. 2.
    Anderson IM, Parry-Billings M, Newsholme EA, Fairburn CG, Cowen PJ (1990) Dieting reduces plasma tryptophan and alters brain 5-HT function in women. Psychol Med 20:785–791CrossRefPubMedGoogle Scholar
  3. 3.
    Askenazy F, Candito M, Caci H, Myquel M, Chambon P, Darcourt G, Puech AJ (1998) Whole blood serotonin content, tryptophan concentrations, and impulsivity in anorexia nervosa. Biol Psychiatry 43:188–195CrossRefPubMedGoogle Scholar
  4. 4.
    Attia E, Wolk S, Cooper T, Glasofer D, Walsh BT (2005) Plasma tryptophan during weight restoration in patients with anorexia nervosa. Biol Psychiatry 57:674–678CrossRefPubMedGoogle Scholar
  5. 5.
    Bailer UF, Frank GK, Henry SE, Price JC, Meltzer CC, Becker C, Ziolko SK, Mathis CA, Wagner A, Barbarich-Marsteller NC, Putnam K, Kaye WH (2007) Serotonin transporter binding after recovery from eating disorders. Psychopharmacology (Berl) 195:315–324CrossRefGoogle Scholar
  6. 6.
    Blundell JE, Lawton CL, Halford JC (1995) Serotonin, eating behavior, and fat intake. Obes Res 3(Suppl 4):471S–476SPubMedGoogle Scholar
  7. 7.
    Brewerton TD, Jimerson DC (1996) Studies of serotonin function in anorexia nervosa. Psychiatry Res 62:31–42CrossRefPubMedGoogle Scholar
  8. 8.
    Bruce KR, Steiger H, Ng Ying Kin NM, Israel M (2006) Reduced platelet [3H]paroxetine binding in anorexia nervosa: relationship to eating symptoms and personality pathology. Psychiatry Res 142:225–232CrossRefPubMedGoogle Scholar
  9. 9.
    Bulik CM, Epstein LH, McKee M, Kaye W (1991) Drug use in women with bulimia and anorexia nervosa. NIDA Res Monogr 105:462–463Google Scholar
  10. 10.
    Camacho A, Dimsdale JE (2000) Platelets and psychiatry: lessons learned from old and new studies. Psychosom Med 62:326–336PubMedGoogle Scholar
  11. 11.
    De Villard R, Flachaire E, Laujin A, Maillet J, Revol O, Charles S, Mamelle JC, Renaud B, Quincy C (1991) Platelet serotonin concentration in children under 5 years of age. Pediatrie 46:813–816PubMedGoogle Scholar
  12. 12.
    Demitrack MA, Heyes MP, Altemus M, Pigott TA, Gold PW (1995) Cerebrospinal fluid levels of kynurenine pathway metabolites in patients with eating disorders: relation to clinical and biochemical variable. Biol Psychiatry 37:512–520CrossRefPubMedGoogle Scholar
  13. 13.
    Ehrlich S, Franke L, Schneider N, Salbach-Andrae H, Schott R, Craciun EM, Pfeiffer E, Uebelhack R, Lehmkuhl U (2009) Aromatic amino acids in weight-recovered females with anorexia nervosa. Int J Eat Disord 42:166–172CrossRefPubMedGoogle Scholar
  14. 14.
    Ehrlich S, Franke L, Schott R, Salbach-Andrae H, Pfeiffer E, Lehmkuhl U, Uebelhack R (2008) Platelet monoamine oxidase activity in underweight and weight-recovered females with anorexia nervosa. Pharmacopsychiatry 41:226–231CrossRefPubMedGoogle Scholar
  15. 15.
    Fernstrom JD, Fernstrom MH (2007) Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain. J Nutr 137:1539S–1547S discussion 1548SPubMedGoogle Scholar
  16. 16.
    Fichter M, Quadflieg N (1999) SIAB. Strukturiertes Inventar für Anorektische und Bulimische Essstörungen nach DSM-IV und ICD-10. Huber, BernGoogle Scholar
  17. 17.
    Fichter M, Quadflieg N (2001) The structured interview for anorexic and bulimic disorders for DSM-IV and ICD-10 (SIAB-EX): reliability and validity. Eur Psychiatry 16:38–48CrossRefPubMedGoogle Scholar
  18. 18.
    Frank GK, Kaye WH, Meltzer CC, Price JC, Greer P, McConaha C, Skovira K (2002) Reduced 5-HT2A receptor binding after recovery from anorexia nervosa. Biol Psychiatry 52:896–906CrossRefPubMedGoogle Scholar
  19. 19.
    Franke GH (2002) SCL-90-R. Symptom-Checkliste von L.R. Derogatis—Deutsche Version. Beltz Test GMBH, GöttingenGoogle Scholar
  20. 20.
    Franke L, Schewe HJ, Muller B, Campman V, Kitzrow W, Uebelhack R, Berghofer A, Muller-Oerlinghausen B (2000) Serotonergic platelet variables in unmedicated patients suffering from major depression and healthy subjects: relationship between 5HT content and 5HT uptake. Life Sci 67:301–305CrossRefPubMedGoogle Scholar
  21. 21.
    Franke L, Schewe HJ, Uebelhack R, Berghofer A, Muller-Oerlinghausen B (2003) Platelet-5HT uptake and gastrointestinal symptoms in patients suffering from major depression. Life Sci 74:521–531CrossRefPubMedGoogle Scholar
  22. 22.
    Gonda X, Fountoulakis KN, Juhasz G, Rihmer Z, Lazary J, Laszik A, Akiskal HS, Bagdy G (2009) Association of the s allele of the 5-HTTLPR with neuroticism-related traits and temperaments in a psychiatrically healthy population. Eur Arch Psychiatry Clin Neurosci 259:106–113CrossRefPubMedGoogle Scholar
  23. 23.
    Gorwood P (2004) Eating disorders, serotonin transporter polymorphisms and potential treatment response. Am J Pharmacogenomics 4:9–17CrossRefPubMedGoogle Scholar
  24. 24.
    Halbreich U, Rojansky N, Zander KJ, Barkai A (1991) Influence of age, sex and diurnal variability on imipramine receptor binding and serotonin uptake in platelets of normal subjects. J Psychiatr Res 25:7–18CrossRefPubMedGoogle Scholar
  25. 25.
    Hassanyeh F, Marshall EF (1991) Measures of serotonin metabolism in anorexia nervosa. Acta Psychiatr Scand 84:561–563CrossRefPubMedGoogle Scholar
  26. 26.
    Hebebrand J, Muller TD, Holtkamp K, Herpertz-Dahlmann B (2007) The role of leptin in anorexia nervosa: clinical implications. Mol Psychiatry 12:23–35CrossRefPubMedGoogle Scholar
  27. 27.
    Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, Lesch KP (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem 66:2621–2624CrossRefPubMedGoogle Scholar
  28. 28.
    Hrdina PD, Bakish D, Ravindran A, Chudzik J, Cavazzoni P, Lapierre YD (1997) Platelet serotonergic indices in major depression: up-regulation of 5-HT2A receptors unchanged by antidepressant treatment. Psychiatry Res 66:73–85CrossRefPubMedGoogle Scholar
  29. 29.
    Huether G, Zhou D, Schmidt S, Wiltfang J, Ruther E (1997) Long-term food restriction down-regulates the density of serotonin transporters in the rat frontal cortex. Biol Psychiatry 41:1174–1180CrossRefPubMedGoogle Scholar
  30. 30.
    Jahng JW, Kim JG, Kim HJ, Kim BT, Kang DW, Lee JH (2007) Chronic food restriction in young rats results in depression- and anxiety-like behaviors with decreased expression of serotonin reuptake transporter. Brain Res 1150:100–107CrossRefPubMedGoogle Scholar
  31. 31.
    Kaye W (2008) Neurobiology of anorexia and bulimia nervosa. Physiol Behav 94:121–135CrossRefPubMedGoogle Scholar
  32. 32.
    Kaye WH, Ebert MH, Raleigh M, Lake R (1984) Abnormalities in CNS monoamine metabolism in anorexia nervosa. Arch Gen Psychiatry 41:350–355PubMedGoogle Scholar
  33. 33.
    Kaye WH, Frank GK, Bailer UF, Henry SE, Meltzer CC, Price JC, Mathis CA, Wagner A (2005) Serotonin alterations in anorexia and bulimia nervosa: new insights from imaging studies. Physiol Behav 85:73–81CrossRefPubMedGoogle Scholar
  34. 34.
    Kromeyer-Hauschild K, Wabitsch M, Kunze D, Geller D, Geiss HC, Hesse V, von Hippel A, Jaeger U, Johnsen D, Korte W, Menner K, Müller G, Müller JM, Niemann-Pilatus A, Remer T, Schaefer F, Wittchen H-U, Zabransky S, Zellner K, Ziegler A, Hebebrand J (2001) Perzentile für den Body Mass Index für das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben. Monatsschrift für Kinderheilkunde 149:807–818Google Scholar
  35. 35.
    Leibowitz SF (1990) The role of serotonin in eating disorders. Drugs 39(Suppl 3):33–48CrossRefPubMedGoogle Scholar
  36. 36.
    Lesch KP, Wolozin BL, Murphy DL, Reiderer P (1993) Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem 60:2319–2322CrossRefPubMedGoogle Scholar
  37. 37.
    McBride PA, Anderson GM, Khait VD, Sunday SR, Halmi KA (1991) Serotonergic responsivity in eating disorders. Psychopharmacol Bull 27:365–372PubMedGoogle Scholar
  38. 38.
    Melke J, Westberg L, Landen M, Sundblad C, Eriksson O, Baghei F, Rosmond R, Eriksson E, Ekman A (2003) Serotonin transporter gene polymorphisms and platelet [3H] paroxetine binding in premenstrual dysphoria. Psychoneuroendocrinology 28:446–458CrossRefPubMedGoogle Scholar
  39. 39.
    Mellerup E, Bennike B, Bolwig T, Dam H, Hasholt L, Jorgensen MB, Plenge P, Sorensen SA (2001) Platelet serotonin transporters and the transporter gene in control subjects, unipolar patients and bipolar patients. Acta Psychiatr Scand 103:229–233CrossRefPubMedGoogle Scholar
  40. 40.
    Monteleone P, Brambilla F, Bortolotti F, La Rocca A, Maj M (1998) Prolactin response to d-fenfluramine is blunted in people with anorexia nervosa. Br J Psychiatry 172:439–442CrossRefPubMedGoogle Scholar
  41. 41.
    Murphy DL, Lerner A, Rudnick G, Lesch KP (2004) Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol Interv 4:109–123CrossRefPubMedGoogle Scholar
  42. 42.
    Patkar AA, Berrettini WH, Mannelli P, Gopalakrishnan R, Hoehe MR, Bilal L, Weinstein S, Vergare MJ (2004) Relationship between serotonin transporter gene polymorphisms and platelet serotonin transporter sites among African-American cocaine-dependent individuals and healthy volunteers. Psychiatr Genet 14:25–32CrossRefPubMedGoogle Scholar
  43. 43.
    Pauli-Pott U, Friedel S, Hinney A, Hebebrand J (2009) Serotonin transporter gene polymorphism (5-HTTLPR), environmental conditions, and developing negative emotionality and fear in early childhood. J Neural Transm 116:503–512CrossRefPubMedGoogle Scholar
  44. 44.
    Pivac N, Nedic G, Mustapic M, Babic A, Stipcevic T, Borovecki F, Hajnsek S, Muck-Seler D (2009) The lack of genotype-phenotype relationship between platelet serotonin concentration and serotonin transporter gene promoter polymorphism in healthy subjects. Neurosci Lett 462:45–48CrossRefPubMedGoogle Scholar
  45. 45.
    Preuss UW, Soyka M, Bahlmann M, Wenzel K, Behrens S, de Jonge S, Kruger M, Bondy B (2000) Serotonin transporter gene regulatory region polymorphism (5-HTTLPR), [3H]paroxetine binding in healthy control subjects and alcohol-dependent patients and their relationships to impulsivity. Psychiatry Res 96:51–61CrossRefPubMedGoogle Scholar
  46. 46.
    Ramacciotti CE, Coli E, Paoli R, Marazziti D, Dell’Osso L (2003) Serotonergic activity measured by platelet [3H]paroxetine binding in patients with eating disorders. Psychiatry Res 118:33–38CrossRefPubMedGoogle Scholar
  47. 47.
    Rathner G, Waldherr K (1997) Eating Disorder Inventory-2. Eine deutschsprachige Validierung mit Normen für weibliche und männliche Jugendliche. Z Klin Psychol Psychiatr Psychother 45:157–182Google Scholar
  48. 48.
    Rausch JL, Johnson ME, Li J, Hutcheson J, Carr BM, Corley KM, Gowans AB, Smith J (2005) Serotonin transport kinetics correlated between human platelets and brain synaptosomes. Psychopharmacology (Berl) 180:391–398CrossRefGoogle Scholar
  49. 49.
    Roggenbach J, Muller-Oerlinghausen B, Franke L, Uebelhack R, Blank S, Ahrens B (2007) Peripheral serotonergic markers in acutely suicidal patients. 1. Comparison of serotonergic platelet measures between suicidal individuals, nonsuicidal patients with major depression and healthy subjects. J Neural Transm 114:479–487CrossRefPubMedGoogle Scholar
  50. 50.
    Roy A, Everett D, Pickar D, Paul SM (1987) Platelet tritiated imipramine binding and serotonin uptake in depressed patients and controls. Relationship to plasma cortisol levels before and after dexamethasone administration. Arch Gen Psychiatry 44:320–327PubMedGoogle Scholar
  51. 51.
    Steiger H, Richardson J, Israel M, Ng Ying Kin NM, Bruce K, Mansour S, Marie Parent A (2005) Reduced density of platelet-binding sites for [3H]paroxetine in remitted bulimic women. Neuropsychopharmacology 30:1028–1032CrossRefPubMedGoogle Scholar
  52. 52.
    Uebelhack R, Franke L, Herold N, Plotkin M, Amthauer H, Felix R (2006) Brain and platelet serotonin transporter in humans-correlation between [123I]-ADAM SPECT and serotonergic measurements in platelets. Neurosci Lett 406:153–158CrossRefPubMedGoogle Scholar
  53. 53.
    Weizman R, Carmi M, Tyano S, Apter A, Rehavi M (1986) High affinity [3H]imipramine binding and serotonin uptake to platelets of adolescent females suffering from anorexia nervosa. Life Sci 38:1235–1242CrossRefPubMedGoogle Scholar
  54. 54.
    Wihlback AC, Sundstrom-Poromaa I, Allard P, Mjorndal T, Spigset O, Backstrom T (2001) Influence of postmenopausal hormone replacement therapy on platelet serotonin uptake site and serotonin 2A receptor binding. Obstet Gynecol 98:450–457CrossRefPubMedGoogle Scholar
  55. 55.
    Wihlback AC, Sundstrom Poromaa I, Bixo M, Allard P, Mjorndal T, Spigset O (2004) Influence of menstrual cycle on platelet serotonin uptake site and serotonin2A receptor binding. Psychoneuroendocrinology 29:757–766CrossRefPubMedGoogle Scholar
  56. 56.
    Zemishlany Z, Modai I, Apter A, Jerushalmy Z, Samuel E, Tyano S (1987) Serotonin (5-HT) uptake by blood platelets in anorexia nervosa. Acta Psychiatr Scand 75:127–130CrossRefPubMedGoogle Scholar
  57. 57.
    Zhang F, Chen Y, Heiman M, Dimarchi R (2005) Leptin: structure, function and biology. Vitam Horm 71:345–372CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Stefan Ehrlich
    • 1
    • 2
    • 4
    Email author
  • Leonora Franke
    • 2
  • Susann Scherag
    • 3
  • Roland Burghardt
    • 1
  • Regina Schott
    • 1
  • Nora Schneider
    • 1
  • Simone Brockhaus
    • 1
  • Jakob Hein
    • 2
  • Ralf Uebelhack
    • 2
  • Ulrike Lehmkuhl
    • 1
  1. 1.Department of Child and Adolescent Psychiatry, Psychosomatics and PsychotherapyCharité, Universitätsmedizin Berlin, CVKBerlinGermany
  2. 2.Department of Psychiatry and PsychotherapyCharité, Universitätsmedizin Berlin, CCMBerlinGermany
  3. 3.Department of Child and Adolescent PsychiatryUniversity of Duisburg-EssenEssenGermany
  4. 4.Department of Psychiatry, Harvard Medical School, Massachusetts General HospitalAthinoula A. Martinos Center for Biomedical ImagingCharlestownUSA

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