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
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
3
Blum WF, Breier BH.
Radioimmunoassays for IGFs and IGFBPs.
Growth Regul.
1994;
4
((Suppl 1))
11-19
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
5
Bunn RC, Fowlkes JL.
Insulin-like growth factor binding protein proteolysis.
Trends Endocrin Metab.
2003;
14
176-181
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
7
Deijen JB, Boer H de, Veen EA van der.
Cognitive changes during growth hormone replacement in adult men.
Psychoneuroendocrinology.
1998;
23
45-55
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
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
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
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
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
13
Henn FA, Vollmayr B.
Neurogenesis and depression: etiology or epiphenomenon?.
Biol Psychiatry.
2004;
56
146-150
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
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
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
17
Jones JI, Clemmons DR.
Insulin-like growth factors and their binding proteins: biological actions.
Endocr Rev.
1995;
16
3-34
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
19
LeRoith D.
The insulin-like growth factor system.
Experimental Diab Res.
2003;
4
205-212
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
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
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
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
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)
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
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
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
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
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
30
Schneider HJ, Pagotto U, Stalla GK.
Central effects of somatotropic system.
Eur J Endocrinology.
2003;
149
377-392
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
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
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
34
Takahashi M, Sawayama E, Sawayama T. et al .
Reversible paroxetine-induced symptomatic hypothyroidism.
Pharmacopsychiatry.
2007;
40
201-202
35
Thissen JP, Ketelslegers JM, Underwood LE.
Nutritional regulation of the insulin-like growth factors.
Endocrinology Review.
1994;
15
80-101
36
Tichomirowa MA, Keck ME, Schneider HJ. et al .
Endocrine disturbances in depression.
J Endocrinol Invest.
2005;
28
89-99
37
Wajchenberg BL, Liberman B, Giannella ND. et al .
Growth hormone axis in Cushing's syndrome.
Horm Res.
1996;
45
99-107
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
39
Watson S, Porter RJ, Young AH.
Effect of hydrocortisone on the pituitary response to growth hormone releasing hormone.
Psychopharmacology.
2000;
152
40-46
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
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
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
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