BDNF RESPONSE TO ANTIDEPRESSANT TREATMENTS
A current hypothesis holds that depression results from stress-
induced loss of dendrites and synapses in the hippocampus, along
with an increase in these microstructures in the amygdala;
antidepressant treatments act by stimulating dendritic
arborization and new synapse formation in the hippocampus
(Tardito et al, 2006; Pittenger and Duman, 2008).

Brain-derived neurotrophic factor (BDNF) is a protein the effects
of which support existing neurons as well as promote the growth
and differentiation of new neurons and synapses. BDNF is
upregulated in animal models of antidepressant action. What
happens in humans? To what extent might BDNF be implicated in the
antidepressant mechanisms?

It is generally stated that serum BDNF is low in depressed
subjects and increases with improvement of mood (Post, 2007).
This is in line with the neuroplasticity hypothesis of
antidepressant action. However, recent evidence suggest that the
situation is not so simple. This body of literature is briefly
summarized.

RESULTS OBEDIENT TO THE HYPOTHESIS:
1. Yoshimura et al (2007) examined serum BDNF in 42 depressed
patients. They found that patients with higher baseline severity
of depression had lower BDNF levels, and that BDNF levels rose
after 4 and 8 weeks of treatment with either paroxetine or
milnacipran.

2. Piccinni et al (2008) studied 15 depressed patients at
baseline and after 1, 3, 6, and 12 months of antidepressant
treatment. Relative to healthy controls, serum BDNF levels in
patients were significantly lower only at the baseline
assessment.

DOES BDNF BEHAVE CONTRARIWISE IN MEN?
Huang et al (2008) studied 111 patients (82% female) with major
depression and 107 healthy controls (61% female). They found
that, relative to controls, serum BDNF was decreased in depressed
women but not in depressed men. Four weeks of antidepressant use
(n=79) was associated with an increase in serum BDNF, especially
in women. Increased BDNF levels were associated with
antidepressant response only in women.

INDIVIDUAL ANTIDEPRESSANTS THROW A SPANNER IN THE WORKS:
1. Hellweg et al (2008) studied depressed patients who received
amitriptyline (n=20) or paroxetine (n=20) for 5 weeks. Serum BDNF
decreased by 12% with paroxetine but increased by 13% with
amitriptyline. BDNF levels were unrelated to antidepressant
response.

2. Matrisciano et al (2008) studied 21 depressed patients and 20
healthy controls at baseline and, again, after 5 weeks and 6
months. As expected, baseline serum BDNF levels were lower in
patients than in controls; and improvement in HAM-D ratings was
associated with increased BDNF levels. Sertraline increased BDNF
levels at 5 weeks; the effect persisted at 6 months. However,
venlafaxine increased BDNF levels only at the 6-month assessment,
and escitalopram did not increase BDNF levels at all.

CONCLUSIONS
Serum BDNF is decreased in depressed patients; it rises with
antidepressant treatment or with recovery from depression.
However, these results are not as clear in men as they are in
women; and the results may be influenced by the specific
antidepressant that is prescribed. The implication is that serum
BDNF may not be a good marker of antidepressant action; or even
that BDNF may play less of a role in antidepressant mechanisms
than hypothesized.

COMMENTS
The small subsample sizes in some studies could explain the
nonsignificance of some of the results; nevertheless, future
studies should control for gender and antidepressant type in the
analyses.

REFERENCES
Hellweg R, Ziegenhorn A, Heuser I, Deuschle M. Serum
concentrations of nerve growth factor and brain-derived
neurotrophic factor in depressed patients before and after
antidepressant treatment. Pharmacopsychiatry 2008; 41: 66-71.

Huang TL, Lee CT, Liu YL. Serum brain-derived neurotrophic factor
levels in patients with major depression: effects of
antidepressants. J Psychiatr Res 2008; 42: 521-525.

Matrisciano F, Bonaccorso S, Ricciardi A, Scaccianoce S,
Panaccione I, Wang L et al. Changes in BDNF serum levels in
patients with major depression disorder (MDD) after 6 months
treatment with sertraline, escitalopram, or venlafaxine. J
Psychiatr Res 2008 May 27. [Epub ahead of print].

Piccinni A, Marazziti D, Catena M, Domenici L, Del Debbio A,
Bianchi C et al. Plasma and serum brain-derived neurotrophic
factor (BDNF) in depressed patients during 1 year of
antidepressant treatments. J Affect Disord 2008; 105: 279-283.

Pittenger C, Duman RS. Stress, depression, and neuroplasticity: a
convergence of mechanisms. Neuropsychopharmacology Reviews 2008;
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Post RM. Role of BDNF in bipolar and unipolar disorder: clinical
and theoretical implications. J Psychiatr Res 2007; 41: 979-990.

Tardito D, Perez J, Tiraboschi E, Musazzi L, Racagni G, Popoli M.
Signaling pathways regulating gene expression, neuroplasticity,
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critical overview. Pharmacological Reviews 2006; 58: 115-134.

Yoshimura R, Mitoma M, Sugita A, Hori H, Okamoto T, Umene W et
al. Effects of paroxetine or milnacipran on serum brain-derived
neurotrophic factor in depressed patients. Prog
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Article by Dr C Andrade MD