Serum Concentrations of Nerve Growth Factor and Brain-Derived Neurotrophic Factor in Depressed Patients before and after Antidepressant Treatment

 

 Buy Article Permissions and Reprints

Abstract

Introduction: Stress, glucocorticoids and anti-depressant treatment have been found to mod-ulate the expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Recent research suggests that serum BDNF concentration is reduced in depression and that successful antidepressant treatment leads to an increase in serum BDNF concentration.

Methods: We studied depressed patients re-ceiving a standardized antidepressant treat-ment with either 150 mg amitriptyline (n=20) or 40 mg paroxetine (n=20) for 36 days in a prospective design. Changes in the concentrations of serum neurotrophins and salivary cortisol in response to antidepressant treatment were assessed.

Results: Independent of clinical efficacy there was a significant ‘treatment’ by ‘medication’ interaction effect on BDNF serum concentrations that indicated a decline of BDNF by 12% in paroxetine-treated patients while there was an increase by 13% in amitriptyline-treated patients. Neither antidepressant altered NGF concentrations. The changes in cortisol and neurotrophin concentrations were not related.

Discussion: Changes in BDNF serum concentrations as a result of antidepressant therapy depend on the antidepressant instead of being a general characteristic of response to antidepressant treatment.

References

• 1 Aloe L, Bracci-Laudiero L, Alleva E, Lambiase A, Micera A, Tirassa P. Emotional stress induced by parachute jumping enhances blood nerve growth factor levels and the distribution of nerve growth factor receptors in lymphocytes.  Proc Natl Acad Sci USA. 1994;  91 10440-10444
  CrossrefPubMedGoogle Scholar
• 2 Altar CA, Whitehead RE, Chen R, Wortwein G, Madsen TM. Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain.  Biol Psychiatry. 2003;  54 703-709
  CrossrefPubMedGoogle Scholar
• 3 Angelucci F, Aloe L, Jimenez-Vasquez P, Mathe AA. Lithium treatment alters brain concentrations of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor in a rat model of depression.  Int J Neuropsychopharmacol. 2003;  6 225-231
  PubMedGoogle Scholar
• 4 Aydemir C, Yalcin ES, Aksaray S. et al . Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women.  Prog Neuropsychopharmacol Biol Psychiatry. 2006;  30 1256-1260
  CrossrefPubMedGoogle Scholar
• 5 Aydemir O, Deveci A, Taneli F. The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study.  Prog Neuropsychopharmacol Biol Psychiatry. 2005;  29 261-265
  CrossrefPubMedGoogle Scholar
• 6 Bonini S, Lambiase A, Bonini S. et al . Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma.  Proc Natl Acad Sci USA. 1996;  93 10955-10960
  CrossrefPubMedGoogle Scholar
• 7 Carroll BJ, Cassidy F, Naftolowitz D. et al . Pathophysiology of hypercortisolism in depression.  Acta Psychiatr Scand. 2007;  ((Suppl)) 90-103
  CrossrefPubMedGoogle Scholar
• 8 Chao HM, Sakai RR, Ma LY, MacEwen BS. Adrenal steroid regulation of neurotrophic factor expression in the rat hippocampus.  Endocrinology. 1998;  139 3112-3118
  CrossrefPubMedGoogle Scholar
• 9 Foubert G De, Carney SL, Robinson CS. et al . Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment.  Neuroscience. 2004;  128 597-604
  CrossrefPubMedGoogle Scholar
• 10 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
• 11 Dias BG, Banerjee SB, Duman RS, Vaidya VA. Differential regulation of brain derived neurotrophic factor transcripts by antidepressant treatments in the adult rat brain.  Neuropharmacology. 2003;  45 553-563
  CrossrefPubMedGoogle Scholar
• 12 Duman RS. Depression: a case of neuronal life and death?.  Biol Psychiatry. 2004;  56 140-145
  CrossrefPubMedGoogle Scholar
• 13 Duman RS, Monteggia LM. A Neurotrophic model for stress-related mood disorders.  Biol Psychiatry. 2006;  59 1116-1127
  CrossrefPubMedGoogle Scholar
• 14 Foreman PJ, Taglialatela G, Angelucci L, Turner CP, Perez-Polo JR. Nerve growth factor and p75NGFR factor receptor mRNA change in rodent CNS following stress activation of the hypothalamo-pituitary-adrenocortical axis.  J Neurosci Res. 1993;  36 10-18
  CrossrefPubMedGoogle Scholar
• 15 Gervasoni N, Aubry JM, Bondolfi G. et al . Partial normalization of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode.  Neuropsychobiology. 2005;  51 234-238
  CrossrefPubMedGoogle Scholar
• 16 Gonul AS, Akdeniz F, Taneli F, Donat O, Eker C, Vahip S. Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients.  Eur Arch Psychiatry Clin Neurosci. 2005;  255 381-386
  CrossrefPubMedGoogle Scholar
• 17 Groves JO. Is it time to reassess the BDNF hypothesis of depression?.  Mol Psychiatry. 2007;  12 1079-1088
  CrossrefPubMedGoogle Scholar
• 18 Guaiana G, Barbui C, Hotopf M. Amitriptyline versus other types of pharmacotherapy for depression.  Cochrane Database Syst Rev. 2003;  CD004186
  PubMedGoogle Scholar
• 19 Hadjiconstantinou M, MacGuire L, Duchemin AM, Laskowski B, Kiecolt-Glaser J, Glaser R. Changes in plasma nerve growth factor levels in older adults associated with chronic stress.  J Neuroimmunol. 2001;  116 102-106
  CrossrefPubMedGoogle Scholar
• 20 Hellweg R, Gericke CA, Jendroska K, Hartung HD, Cervos-Navarro J. NGF content in the cerebral cortex of non-demented patients with amyloid-plaques and in symptomatic Alzheimer's disease.  Int J Dev Neurosci. 1998;  16 787-794
  PubMedGoogle Scholar
• 21 Hellweg R, Hock C, Hartung HD. An improved rapid and highly sensitive enzyme immunoassay for nerve growth factor.  Technique J Methods Cell Mol Biol. 1989;  1 43-49
  PubMedGoogle Scholar
• 22 Hellweg R, Lang UE, Nagel M, Baumgartner A. Subchronic treatment with lithium increases nerve growth factor content in distinct brain regions of adult rats.  Mol Psychiatry. 2002;  7 604-608
  CrossrefPubMedGoogle Scholar
• 23 Hellweg R, Arnim CA von, Buchner M, Huber R, Riepe MW. Neuroprotection and neuronal dysfunction upon repetitive inhibition of oxidative phosphorylation.  Exp Neurol. 2003;  183 346-354
  CrossrefPubMedGoogle Scholar
• 24 Hellweg R, Richthofen S von, Anders D. et al . The time course of nerve growth factor content in different neuropsychiatric diseases - a unifying hypothesis.  J Neural Transm. 1998;  105 871-903
  CrossrefPubMedGoogle Scholar
• 25 Hellweg R, Zueger M, Fink K, Hörtnagl H, Gass P. Olfactory bulbectomy in mice leads to increased BDNF levels and decreased serotonin turnover in depression-related brain areas.  Neurobiol Dis. 2007;  25 1-7
  CrossrefPubMedGoogle Scholar
• 26 Holoubek G, Nöldner M, Treiber K, Müller WE. Effect of chronic antidepressant treatment on ß-receptor coupled signal transduction cascade. Which effect matters most?.  Pharmacopsychiatry. 2004;  37 113-119
  Article in Thieme ConnectPubMedGoogle Scholar
• 27 Holsboer F. Stress, hypercortisolism and corticosteroid receptors in depression: implications for therapy.  J Affect Disord. 2001;  62 77-91
  PubMedGoogle Scholar
• 28 Huang TL, Lee CT, Liu YL. Serum brain-derived neurotrophic factor levels in patients with major depression: Effects of antidepressants.  J Psychiatr Res. 2007;  , (in press)
  PubMedGoogle Scholar
• 29 Jacobsen JP, Mørk A. The effect of escitalopram, desipramine, electroconvulsive seizures and lithium on brain-derived neurotrophic factor mRNA and protein expression in the rat brain and the correlation to 5-HT and 5-HIAA levels.  Brain Res. 2004;  1024 183-192
  CrossrefPubMedGoogle Scholar
• 30 Karege F, Bondolfi G, Gervasoni N, Schwald M, Aubry JM, Bertschy G. Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity.  Biol Psych. 2005;  57 1068-1072
  CrossrefPubMedGoogle Scholar
• 31 Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM. Decreased serum brain-derived neurotrophic factor levels in major depressed patients.  Psychiatry Res. 2002;  109 143-148
  CrossrefPubMedGoogle Scholar
• 32 Lang UE, Anders D, Danker-Hopfe H, Hellweg R. Measurement of nerve growth factor serum concentration in a psychologically stressful situation in men.  Stress. 2004;  7 39-42
  CrossrefPubMedGoogle Scholar
• 33 Lang UE, Bajbouj M, Gallinat J, Hellweg R. Brain-derived neurotrophic factor serum concentrations in depressive patients during vagus nerve stimulation and repetitive transcranial magnetic stimulation.  Psychopharmacology (Berl). 2006;  187 56-59
  CrossrefPubMedGoogle Scholar
• 34 Lang UE, Gallinat J, Danker-Hopfe H, Bajbouj M, Hellweg R. Nerve growth factor serum concentrations in healthy human volunteers: physiological variance and stability.  Neurosci Lett. 2003;  344 13-16
  CrossrefPubMedGoogle Scholar
• 35 Lang UE, Jockers-Scherubl MC, Hellweg R. State of the art of the neurotrophin hypothesis in psychiatric disorders: implications and limitations.  J Neural Transm. 2004;  111 387-411
  CrossrefPubMedGoogle Scholar
• 36 Lopez-Munoz F, Alamo C, Rubio G, Garcia-Garcia P, Pardo A. Reboxetine combination in treatment-resistant depression to selective serotonin reuptake inhibitors.  Pharmacopsychiatry. 2007;  40 14-19
  Article in Thieme ConnectPubMedGoogle Scholar
• 37 Mackin P, Gallagher P, Watson S, Young AH, Ferrier IN. Changes in brain-derived neurotrophic factor following treatment with mifepristone in bipolar disorder and schizophrenia.  Aust N Z J Psychiatry. 2007;  41 321-326
  CrossrefPubMedGoogle Scholar
• 38 Malberg JE, Eisch AJ, Nestler EJ, Duman RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus.  J Neurosci. 2000;  20 9104-9110
  PubMedGoogle Scholar
• 39 Nibuya M, Morinobu S, Duman RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments.  J Neurosci. 1995;  15 7539-7547
  PubMedGoogle Scholar
• 40 Nockher WA, Renz H. Neurotrophins in clinical diagnostics: pathophysiology and laboratory investigation.  Clin Chim Acta. 2005;  352 49-74
  CrossrefPubMedGoogle Scholar
• 41 Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ. Transport of brain-derived neurotrophic factor across the blood-brain barrier.  Neuropharmacology. 1998;  37 1553-1561
  CrossrefPubMedGoogle Scholar
• 42 Pan W, Banks WA, Kastin AJ. Permeability of the blood-brain barrier to neurotrophins.  Brain Res. 1998;  788 87-94
  CrossrefPubMedGoogle Scholar
• 43 Radka SF, Holst PA, Fritsche M, Altar CA. Presence of brain-derived neurotrophic factor in brain and human and rat but not mouse serum detected by a sensitive and specific immunoassay.  Brain Res. 1996;  709 122-130
  CrossrefPubMedGoogle Scholar
• 44 Ridder S, Chourbaji S, Hellweg R. et al . Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions.  J Neurosci. 2005;  25 6243-6250
  CrossrefPubMedGoogle Scholar
• 45 Russo-Neustadt A, Beard RC, Cotman CW. Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression.  Neuropsychopharmacology. 1999;  21 679-682
  CrossrefPubMedGoogle Scholar
• 46 Russo-Neustadt AA, Alejandre H, Garcia C, Ivy AS, Chen MJ. Hippocampal brain-derived neurotrophic factor expression following treatment with reboxetine, citalopram, and physical exercise.  Neuropsychopharmacology. 2004;  29 2189-2199
  CrossrefPubMedGoogle Scholar
• 47 Schinder AF, Poo M. The neurotrophin hypothesis for synaptic plasticity.  Trends Neurosci. 2000;  23 639-645
  PubMedGoogle Scholar
• 48 Schulte-Herbrüggen O, Chourbaji S, Müller H. Differential regulation of nerve growth factor and brain-derived neurotrophic factor in a mouse model of learned helplessness.  Exp Neurol. 2006;  202 404-409
  CrossrefPubMedGoogle Scholar
• 49 Schulte-Herbrüggen O, Hellweg R, Chourbaji S. et al . Differential regulation of neurotrophins and serotonergic function in mice with genetically reduced glucocorticoid receptor expression.  Exp Neurol. 2007;  204 307-316
  CrossrefPubMedGoogle Scholar
• 50 Shimizu E, Hashimoto K, Okamura N. et al . Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants.  Biol Psychiatry. 2003;  54 70-75
  CrossrefPubMedGoogle Scholar
• 51 Staats R, Stoll P, Zingler D, Virchow JC, Lommatzsch M. Regulation of brain-derived neurotrophic factor (BDNF) during sleep apnoea treatment.  Thorax. 2005;  60 688-692
  CrossrefPubMedGoogle Scholar
• 52 Ueyama T, Kawai Y, Nemoto K, Sekimoto M, Tone S, Senba E. Immobilization stress reduced the expression of neurotrophins and their receptors in the rat brain.  Neurosci Res. 1997;  28 103-110
  CrossrefPubMedGoogle Scholar
• 53 Richthofen S von, Lang UE, Hellweg R. Effects of different kinds of acute stress on nerve growth factor content in rat brain.  Brain Res. 2003;  987 207-213
  CrossrefPubMedGoogle Scholar
• 54 Yehuda R, Teicher MH, Trestman RL, Levengood RA, Siever LJ. Cortisol regulation in posttraumatic stress disorder and major depression: a chronobiological analysis.  Biol Psychiatry. 1996;  40 79-88
  CrossrefPubMedGoogle Scholar
• 55 Yukimasa T, Yoshimura R, Tamagawa A. et al . High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors.  Pharmacopsychiatry. 2006;  39 52-59
  Article in Thieme ConnectPubMedGoogle Scholar
• 56 Ziegenhorn AA, Schulte-Herbrüggen O, Danker-Hopfe H. et al . Serum neurotrophins-A study on the time course and influencing factors in a large old age sample.  Neurobiol Aging. 2007;  28 1436-1445
  CrossrefPubMedGoogle Scholar

1 These authors contributed equally to the work presented here

Correspondence

R. HellwegMD 

Department of Psychiatry

Charité- Universitätsmedizin Berlin

Campus Benjamin Franklin

Eschenallee 3

14050 Berlin

Germany

Phone: +49/30/8445 87 86

Fax: +49/30/8445 83 41

Email: rainer.hellweg@charite.de