Serum brain-derived neurotrophic factor and glucocorticoid receptor levels in lymphocytes as markers of antidepressant response in major depressive patients: A pilot study

• Published in: Psychiatry research 2011-09, Vol.189 (2), p.239-245
• Main Authors: Rojas, Paulina Soledad, Fritsch, Rosemarie, Rojas, Romina Andrea, Jara, Pablo, Fiedler, Jenny Lucy
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Analysis of Variance; Antidepressive Agents, Second-Generation - pharmacology; Antidepressive Agents, Second-Generation - therapeutic use; Biological and medical sciences; Biomarkers; Brain-Derived Neurotrophic Factor - blood; Cortisol; CREB-Binding Protein - metabolism; Cyclohexanols - pharmacology; Cyclohexanols - therapeutic use; Depression; Depressive Disorder, Major - blood; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - pathology; Early improvement; Female; Follow-Up Studies; Humans; Hydrocortisone - blood; Lymphocytes; Lymphocytes - drug effects; Lymphocytes - metabolism; Major depression; Male; Medical sciences; Middle Aged; Mood disorders; Neuropharmacology; Neurotrophins; Pharmacology. Drug treatments; Pilot Projects; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Receptors, Glucocorticoid - metabolism; Time Factors; Venlafaxine; Venlafaxine Hydrochloride
• ISSN: 0165-1781; 1872-7123
• DOI: 10.1016/j.psychres.2011.04.032

Abstract Depressive patients often have altered cortisol secretion, an effect that likely derives from impaired activity of the glucocorticoid receptor (GR), the main regulator of the hypothalamus–pituitary–adrenal (HPA) axis. Glucocorticoids reduce the levels of brain-derived neurotrophic factor (BDNF), a downstream target of antidepressants. Antidepressants promote the transcriptional activity of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), a regulator of BDNF expression. To identify potential biomarkers for the onset of antidepressant action in depressive patients, GR and phospho-CREB (pCREB) levels in lymphocytes and serum BDNF levels were repeatedly measured during the course of antidepressant treatment. Thirty-four depressed outpatients (10 male and 24 female) were treated with venlafaxine (75 mg/day), and individuals exhibiting a 50% reduction in their baseline 17-Item Hamilton Depression Rating Scale score by the 6th week of treatment were considered responders. Responders showed an early improvement in parallel with a rise in BDNF levels during the first two weeks of treatment. Non-responders showed increased GR levels by the third week and reduced serum BDNF by the sixth week of treatment. In contrast, venlafaxine did not affect levels of pCREB. We conclude that levels of BDNF in serum and GR levels in lymphocytes may represent biomarkers that could be used to predict responses to venlafaxine treatment.