Download PDF
Pharmacopsychiatry 2009; 42(1): 23-28
DOI: 10.1055/s-0028-1085442
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Insulin-like Growth Factor-I (IGF-I) Serum Concentrations in Depressed Patients: Relationship to Saliva Cortisol and Changes during Antidepressant Treatment

B. Weber-Hamann 1 , W. F. Blum 2 , 3 , J. Kratzsch 4 , M. Gilles 1 , I. Heuser 1 , 5 , M. Deuschle 1
  • 1Central Institute of Mental Health, Mannheim, Germany
  • 2Lilly Research Laboratories, Eli Lilly & Co., Bad Homburg, Germany
  • 3University Children's Hospital, Giessen, Germany
  • 4Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Germany
  • 5Department of Psychiatry and Psychotherapy, Charité, Campus Benjamin Franklin, Berlin, Germany
Further Information

Publication History

received 28.03.2008 revised 07.07.2008

accepted 09.07.2008

Publication Date:
19 January 2009 (online)

Also available at
    Permissions and Reprints

Abstract

Introduction: The present study was designed to test the hypothesis that total and free insulin-like growth factor-I (IGF-I) serum concentrations in depressed patients are related to hypothalamus-pituitary-adrenal (HPA) system activity and show a longitudinal decline in patients responding to treatment as well as to declining HPA system activity.

Methods: We measured total and free IGF-I as well as IGF-binding protein-3 in 77 depressed patients after wash-out of pre-medication and again after 28 or 35 days of treatment with paroxetine or amitriptyline.

Results: Total but not free IGF-I serum concentrations are related to saliva cortisol concentrations in drug-free depressed patients. In responders to both amitriptyline and paroxetine, total IGF-I serum concentrations declined during treatment.

Discussion: Our findings show IGF-I to be related to HPA system activity and to decline in responders to treatment while serum concentrations of the biologically active free IGF-I are neither related to HPA system activity nor do they change during the course of treatment. Our data do not support the hypothesis that free IGF-I may play a major role in physical disturbances in depressed patients.

References

  • 1 Bang P, Degerblad M, Thoren M. et al . Insulin-like growth factor (IGF) I and II and IGF binding protein (IGFBP) 1, 2 and 3 in serum from patients with Cushing's syndrome.  Acta Endocrinol (Copenh). 1993;  128 397-404
    PubMedGoogle Scholar
  • 2 Blum WF, Albertsson-Wikland K, Rosberg S. et al . Serum levels of insulin-like growth factor 1 and IGF binding protein 3 reflect spontaneous growth hormone secretion.  J Clin Endocrinol Metab. 1993;  76 1610-1616
    CrossrefPubMedGoogle Scholar
  • 3 Blum WF, Breier BH. Radioimmunoassays for IGFs and IGFBPs.  Growth Regul. 1994;  4 ((Suppl 1)) 11-19
    PubMedGoogle Scholar
  • 4 Blum WF, Ranke MB, Kietzmann K. et al . A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency.  J Clin Endocrinol Metab. 1990;  70 1292-1298
    CrossrefPubMedGoogle Scholar
  • 5 Bunn RC, Fowlkes JL. Insulin-like growth factor binding protein proteolysis.  Trends Endocrin Metab. 2003;  14 176-181
    PubMedGoogle Scholar
  • 6 Contreras F, Navarro MA, Menchon JM. Growth hormone response to growth hormone releasing hormone in nondelusional and delusional depression and healthy controls.  Psychological Medicine. 1996;  26 301-307
    PubMedGoogle Scholar
  • 7 Deijen JB, Boer H de, Veen EA van der. Cognitive changes during growth hormone replacement in adult men.  Psychoneuroendocrinology. 1998;  23 45-55
    CrossrefPubMedGoogle Scholar
  • 8 Deuschle M, Blum WF, Strasburger CJ. et al . Insulin-like growth factor-I plasma concentrations are increased in depressed patients.  Psychoneuroendocrinology. 1997;  22 493-503
    CrossrefPubMedGoogle Scholar
  • 9 Deuschle M, Hamann B, Meichel C. et al . Antidepressive treatment with amitriptyline and paroxetine: effects on saliva cortisol concentrations.  J Clin Psychopharmacol. 2003;  23 201-205
    CrossrefPubMedGoogle Scholar
  • 10 Deuschle M, Krumm B, Bindeballe N. et al . Open-label non-randomized versus double-blind randomized antidepressive treatment: what are the advantages of clinical decision over randomization.  Pharmacopsychiatry. 2004;  37 299-302
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Deuschle M, Luppa P, Hamann B. et al . Increased concentration of corticostreroid-binding globulin due to antidepressant treatment with amitriptyline, but not paroxetine.  J Psychiatr Res. 2003;  37 85-87
    CrossrefPubMedGoogle Scholar
  • 12 Franz B, Buysse DJ, Cherry CR. et al . Insulin-like growth factor 1 and growth hormone binding protein in depression: a preliminary communication.  J Psychiatric Res. 1999;  33 121-127
    CrossrefPubMedGoogle Scholar
  • 13 Henn FA, Vollmayr B. Neurogenesis and depression: etiology or epiphenomenon?.  Biol Psychiatry. 2004;  56 146-150
    CrossrefPubMedGoogle Scholar
  • 14 Hoshaw BA, Malberg JE, Lucki I. Central administration of IGF-I and BDNF leads to long-lasting antidepressant-like effects.  Brain Res. 2005;  1037 204-208
    CrossrefPubMedGoogle Scholar
  • 15 Janssen JA, Stolk RP, Pols HA. et al . Serum free IGF-I, total IGF-I, IGFBP-1 and IGFBP-3 levels in an elderly population: relation to age and sex steroid levels.  J Clin Endocrinol Metab. 1998;  48 471-478
    PubMedGoogle Scholar
  • 16 Janssen JA, Jacobs ML, Derkx FH. et al . Free and total insulin-like growth factor (IGF-I), IGF binding protein-1 (IGFBP-1), and IGFBP-3 and their relationships to the presence of diabetic retinopathy and glomerular hyperfiltration in insulin-dependent diabetes mellitus.  J Clin Endocrinol Metab. 1997;  82 2809-2815
    CrossrefPubMedGoogle Scholar
  • 17 Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions.  Endocr Rev. 1995;  16 3-34
    CrossrefPubMedGoogle Scholar
  • 18 Kopf D, Wesphal S, Luley CW. et al . Lipid metabolism and insulin resistance in depressed patients: significance of weight, hypercortisolism and antidepressant treatment.  J Clin Psychopharmacol. 2004;  24 527-531
    PubMedGoogle Scholar
  • 19 LeRoith D. The insulin-like growth factor system.  Experimental Diab Res. 2003;  4 205-212
    PubMedGoogle Scholar
  • 20 Lesch KP, Rupprecht R, Müller U. et al . Insulin-like growth factor I in depressed patients and controls.  Acta Psychiatrica Scandinavica. 1988;  78 684-688
    CrossrefPubMedGoogle Scholar
  • 21 Lesch KP, Laux G, Erb A. et al . Growth hormone (GH) and prolactin responses after GH-releasing hormone in major depressive disorder: relationship to somatomedin C levels and dexamethasone suppressibility of cortisol.  Psychoneuroendocrinology. 1988;  13 255-263
    CrossrefPubMedGoogle Scholar
  • 22 Magiakou MA, Mastorakos G, Gomez MT. et al . Suppressed spontaneous and stimulated growth hormone secretion in patients with Cushing’s disease before and after surgical cure.  J Clin Endocrinol Metab. 1994;  78 131-137
    CrossrefPubMedGoogle Scholar
  • 23 Mahajan T, Crown A, Checkley S. et al . Atypical depression in growth hormone deficient adults, and the beneficial effects of growth hormone treatment on depression and quality of life.  Eur J Endocrinology. 2004;  151 325-332
    CrossrefPubMedGoogle Scholar
  • 24 Malberg JE, Platt B, Rizzo SJ. et al . Increasing the levels of insulin-like growth factor-I by an IGF binding protein inhibitor produces anxiolytic and antidepressant-like effects.  Neuropsychopharmacology. 2007 Mar 7;  , (epub ahead of print)
    PubMedGoogle Scholar
  • 25 MacMillan CV, Bradley C, Gibney J. et al . Psychological effects of withdrawal of growth hormone therapy from adults with growth hormone deficiency.  Clin Endocrinology. 2003;  59 467-475
    PubMedGoogle Scholar
  • 26 Nam SY, Lee EJ, Kim KR. et al . Effect of obesity on total and free insulin-like growth factor (IGF)-1 and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone.  Int J Obes Relat Metab Disord. 1997;  21 355-359
    CrossrefPubMedGoogle Scholar
  • 27 Nass R, Thorner MO. Impact of GH-cortisol ratio on the age-dependent changes in body composition.  Growth Horm IGF Res. 2002;  12 147-161
    CrossrefPubMedGoogle Scholar
  • 28 Rosmond R, Dallman MF, Bjorntorp P. Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities.  J Clin Endocrinol Metab. 1998;  83 1853-1859
    CrossrefPubMedGoogle Scholar
  • 29 Rupprecht R, Rupprecht C, Rupprecht M. et al . Effect of glucocorticoids on the regulation of the hypothalamic-pituitary-somatotropic system in depression.  J Affective Disord. 1989;  17 9-16
    CrossrefPubMedGoogle Scholar
  • 30 Schneider HJ, Pagotto U, Stalla GK. Central effects of somatotropic system.  Eur J Endocrinology. 2003;  149 377-392
    CrossrefPubMedGoogle Scholar
  • 31 Siever LJ, Trestman RL, Coccaro EF. The growth hormone response to clonidine in acute and remitted depressed male patients.  Neuropsychopharmacology. 1992;  6 165-177
    PubMedGoogle Scholar
  • 32 Smink JJ, Gresnigt MG, Hamers N. et al . Short-term glucocorticoid treatment of prepubertal mice decreases growth and IGF-I expression in the growth plate.  J Endocrinol. 2003;  177 381-388
    CrossrefPubMedGoogle Scholar
  • 33 Stewart PM, Toogood AA, Tomlinson JW. Growth hormone, insulin-like growth factor-I and the cortisol-cortisone shuttle.  Horm Res. 2001;  56 ((Suppl 1)) 1-6
    PubMedGoogle Scholar
  • 34 Takahashi M, Sawayama E, Sawayama T. et al . Reversible paroxetine-induced symptomatic hypothyroidism.  Pharmacopsychiatry. 2007;  40 201-202
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Thissen JP, Ketelslegers JM, Underwood LE. Nutritional regulation of the insulin-like growth factors.  Endocrinology Review. 1994;  15 80-101
    CrossrefPubMedGoogle Scholar
  • 36 Tichomirowa MA, Keck ME, Schneider HJ. et al . Endocrine disturbances in depression.  J Endocrinol Invest. 2005;  28 89-99
    PubMedGoogle Scholar
  • 37 Wajchenberg BL, Liberman B, Giannella ND. et al . Growth hormone axis in Cushing's syndrome.  Horm Res. 1996;  45 99-107
    PubMedGoogle Scholar
  • 38 Wakeno M, Okugawa G, Takekita Y. et al . Delirium associated with paroxetine in an elderly depressive patient: a case report.  Pharmacopsychiatry. 2007;  40 199-200
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Watson S, Porter RJ, Young AH. Effect of hydrocortisone on the pituitary response to growth hormone releasing hormone.  Psychopharmacology. 2000;  152 40-46
    CrossrefPubMedGoogle Scholar
  • 40 Weber-Hamann B, Hentschel F, Kniest A. et al . Hypercortisolemic depression is associated with increased intra-abdominal fat.  Psychosom Med. 2002;  64 274-277
    PubMedGoogle Scholar
  • 41 Zenker S, Haverkamp F, Klingmüller D. Growth hormone deficiency in pituitary disease: relationship to depression, apathy and somatic complaints.  Eur J Endocrinology. 2002;  147 165-171
    PubMedGoogle Scholar
  • 42 Zhou X, Loke KY, Pillai CC. et al . IGFs and IGF- binding proteins in short children with steroid-dependent nephrotic syndrome on chronic glucocorticoids: changes with 1 year exogenous GH.  Eur J Endocrinol. 2001;  144 237-243
    CrossrefPubMedGoogle Scholar

Correspondence

B. Weber-HamannMD 

Central Institute of Mental Health

J5

68159 Mannheim

Germany

Phone: +49/621/1703 23 21

Fax: +49/621/1703 23 25

Email: bettina.hamann@zi-mannheim.de

      >