Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) levels in post-mortem brain tissue from patients with depression compared to healthy individuals - a proof of concept study

Eur Psychiatry. 2017 Oct:46:65-71. doi: 10.1016/j.eurpsy.2017.06.009. Epub 2017 Jul 11.

Abstract

The neurotrophic factors (NTF) hypothesis of depression was postulated nearly a decade ago and is nowadays widely acknowledged. Previous reports suggest that cerebral concentrations of NTF may be reduced in suicide victims who received minimal or no antidepressant pharmacotherapy. Recent evidence suggests that antidepressant treatment may improve or normalise cerebral concentrations of neurotrophic factors. Therefore, we examined the concentration of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) in different brain regions (cortex, cingulate gyrus, thalamus, hippocampus, putamen and nucleus caudatus) of 21 individuals - 7 patients of which 4 patients with major depressive disorder (MDD) and overall age 86.8±5 years who received antidepressant pharmacotherapy (selective serotonin re-uptake inhibitors [SSRI]; tricyclic antidepressants [TCA]), 3 patients with MDD without antidepressant treatment and overall age 84.3±5 years versus 14 unaffected subjects at age 70.3±13.8. We detected significant elevation of BDNF (parietal cortex) and NT3 (parietal, temporal and occipital cortex, cingulate gyrus, thalamus, putamen and nucleus caudatus regions) in MDD patients who received antidepressant medication compared to MDD untreated patients and controls. Moreover, we detected a significant decrease of NT3 levels in the parietal cortex of patients suffering from MDD non-treated patients without treatment compared to healthy individuals. Although the limited statistical power due to the small sample size in this proof of concept study corroborates data from previous studies, which show that treatment with antidepressants mediates alterations in neuroplasticity via the action of NTF. However, more research using post-mortem brain tissue with larger samples needs to be carried out as well as longitudinal studies to further verify these results.

Keywords: Affective disorders; Antidepressants; Depression; Molecular biology; Psychiatry; Psychopharmacology.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Autopsy
  • Brain / drug effects
  • Brain / metabolism*
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Case-Control Studies
  • Depression / drug therapy
  • Depression / metabolism*
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nerve Growth Factors / metabolism*
  • Neuronal Plasticity / drug effects
  • Neurotrophin 3 / metabolism*
  • Proof of Concept Study*
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Suicide

Substances

  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • NTF3 protein, human
  • Nerve Growth Factors
  • Neurotrophin 3
  • Serotonin Uptake Inhibitors
  • BDNF protein, human