Is serum BDNF concentration a peripheral marker of depression? Molecular Psych.2014.July.


Neurotrophin hypothesis of depression was originally formulated in 1997 by Duman, Heninger and Nestler. Stress induced aberrations in neural plasticity is thought to result in depression. This is reflected in lower BDNF . Antidepressants increase the BDNF levels and correct this aberration. In 2002 , low BDNF was shown in depressed patients (Karege et al. 2002). In 2003, an increase in BDNF with antidepressant treatment was demonstrated (Shimizu et al 2003). Meta analysis have  confirmed these observations.

Molendijk  et al report current state of knowledge by a new meta analysis . From 55  studies, they  extracted 124 between-group effect- size estimates and 55 correlation coefficients.


Antidepressant-free depressed patients had lower BDNF concentrations as compared with healthy controls (d=  0.71, 95% CI = -0.89 to  -0.53).  Heathy controls and antidepressant treated groups did not differ in BDNF levels. Higher symptom severity was associated with a lower BDNF levels in untreated patients. 

Differences were still significant after correcting for publication bias.

The effects sizes are smaller than previous analysis , mainly due to  adjusting for between-study heterogeneity and publication bias.

This analysis confirms that  altered serum BDNF concentrations are peripheral manifestations of depression.  Authors raise the possibility that BDNF  cab  used  as a treatment biomarker helping us to predict the outcomes.  Another interesting question: What is the difference between pro and mature BDNF as it is thought that they have opposing actions. Would the ratio tell us more about depression or  treatment response ?

 Summary of the article: 

Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484).

Molendijk ML, Spinhoven P, Polak M, Bus BA, Penninx BW, Elzinga BM. Mol Psychiatry. 2014 Jul;19(7):791-800.

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