Serum levels of brain-derived neurotrophic factor in major depressive disorder: state–trait issues, clinical features and pharmacological treatment

Abstract

Recent evidence supports ‘the neurotrophin hypothesis of depression' in its prediction that brain-derived neurotrophic factor (BDNF) is involved in depression. However, some key questions remain unanswered, including whether abnormalities in BDNF persist beyond the clinical state of depression, whether BDNF levels are related to the clinical features of depression and whether distinct antidepressants affect BDNF levels equally. We addressed these questions and investigated serum BDNF levels in 962 depressed patients, 700 fully remitted persons (⩾6 months) and 382 healthy controls. We found serum BDNF levels to be low in antidepressant-free depressed patients relative to controls (P=0.007) and to depressed patients who were treated with an antidepressant (P=0.001). BDNF levels of fully remitted persons (whether unmedicated or treated with an antidepressant) were comparable to those of controls. Analyzing the sample of antidepressant-free depressed patients showed that BDNF levels were unrelated to the core clinical features of depression such as its severity or first versus a recurrent episode. The antidepressant associated upregulation of serum BDNF in depressed patients was confined to selective serotonin reuptake inhibitors (SSRIs) (P=0.003) and St John's wort (P=0.03). Our results suggest that low serum levels of BDNF are a state abnormality that is evident during depression and normalizes during remission. Increases in serum levels of BDNF during antidepressant treatment appear to be confined to some antidepressants and do not parallel clinical characteristics, such as the severity of depressive symptoms.

Changes of Serum Concentrations of Brain-Derived Neurotrophic Factor (BDNF) during Treatment with Venlafaxine and Mirtazapine: Role of Medication and Response to Treatment

“…In line with a recent meta-analysis [ 14 ] , an epidemiological study (n = 962) found serum BDNF to be low in currently depressed subjects and to be normalized in remission, while antidepressants were diff erentially related to serum BDNF (St. John's wort > SSRI > venlafaxine > TCA > mirtazapine) [ 15 ] . Thus, antidepressants may diff er in their ability to induce BDNF.…”

“…While there is evidence that diff erent classes of antidepressants differentially infl uence hypothalamus-pituitary-adrenal (HPA) axis parameters in humans [ 31 , 32 ] , there is only limited information on changes in BDNF serum concentrations after administration of diff erent antidepressants. Both, cross-sectional epidemiological [ 15 ] as well as longitudinal studies support the hypothesis that antidepressants have heterogeneous eff ects on serum BDNF [ 16 , 17 , 23 ] . Only few studies considered response to treatment to play a role in antidepressants' eff ects on serum BDNF.…”

Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin

“…In turn, chronic administration of sertraline increases hippocampal BDNF mRNA levels in rats [9]. Similarly, SSRI-induced increases in serum BDNF levels have been detected in depressed patients [32]. Furthermore, SERT heterozygous null mice subjected to poor maternal care show elevated hippocampal BDNF mRNA levels relative to wild type controls undergoing identical experimental procedures [33].…”

Epigenetic regulation of BDNF expression according to antidepressant response

“…1 The neurotrophin hypothesis of depression postulates that stress and depression are associated with decreased BDNF expression that can be reversed by antidepressant treatment. 2 The goal of the present study was to investigate the effect of antidepressant treatment on the epigenetic regulation of BDNF in major depressive disorder (MDD).The BDNF gene has distinct splice variants, each one regulated by a specific promoter region, that determine tissue-specific regulation of expression. 3 Of these variants, BDNF-IV is the most commonly studied and its expression changes have been associated with behavioural phenotypes, psychiatric disorders and epigenetic modifications.…”

“…1 The neurotrophin hypothesis of depression postulates that stress and depression are associated with decreased BDNF expression that can be reversed by antidepressant treatment. 2 The goal of the present study was to investigate the effect of antidepressant treatment on the epigenetic regulation of BDNF in major depressive disorder (MDD).…”