Progress in Neuro-Psychopharmacology and Biological Psychiatry
The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study
Introduction
In recent years, the biological basis of depression has been an important focus of research. Besides the monoamine theory which is assumed to be involved, several studies have implicated a major role for intracellular pathways regulating neuroplasticity and neurodegeneration in the aetiology of mood disorders (Popoli et al., 2002). In this hypothesis, as a result of stress, neuronal atrophy, and decreased neurogenesis, depression occurs, and by stimulating intracellular pathways, antidepressants lead to an up-regulation of cAMP response element binding (CREB) protein and to an increase in the expression of neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF).
BDNF is important for maintaining synaptic function and neural plasticity (D'Sa and Duman, 2002). Serum BDNF levels are decreased in depressed and untreated patients, and the severity of depression negatively correlates with BDNF levels (Shimizu et al., 2003). Moreover, antidepressant treatment increases serum BDNF levels and it is positively correlated with medication response (Shimizu et al., 2003). In this respect, selective serotonine (5-HT) (SSRI) and norepinephrine (NE) (SNRI) reuptake inhibitors, monoamine oxidase inhibitors, and electroconvulsive therapy (ECT) have been found to up-regulate BDNF; whereas other classes of psychotropic drugs do not influence BDNF expression levels (Duman, 2004). Atypical antipsychotics are being studied in combination with antidepressants for increasing BDNF levels in hippocampus (Duman, 2004). Furthermore, BDNF itself is sufficient to produce an antidepressant response (Duman, 2004).
In vitro studies revealed that chronically administered antidepressant treatment induces an up-regulation in serum BDNF levels in rat brain (Popoli et al., 2002). When focused on other regulatory neurochemicals, it is still undetermined whether other neurotrophic factors (such as GDNF, FGF2) are functionally relevant in depressed patients under treatment (Duman, 2004). Thus, a decrease in serum BDNF levels in depression with an ability to respond to an antidepressant treatment may make BDNF become a marker for depression.
Most of the antidepressant studies showing the up-regulation in BDNF levels in depression are done in vitro, post mortem, or in rodents. Antidepressant treatment blocks the down-regulation of neurogenesis that is caused by stress (Malberg and Duman, 2003). Increased BDNF expression in response to antidepressant treatment has been shown with different classes of antidepressants such as SSRIs (fluoxetine, fluvoxamine, and sertraline), selective NE reuptake inhibitors (desipramine), and dual aminergic reuptake inhibitors (imipramine, milnacipran) (Duman et al., 2000, Popoli et al., 2002). In another study, chronic venlafaxine treatment did not influence CREB mRNA levels and reduced levels of phosphorylated CREB protein in the cortex (Nibuya et al., 1996).
On the other hand, data on BDNF levels in depressed patients and their response to antidepressant treatment are insufficient. Karege et al. (2002) pointed out to low levels of BDNF in patients with a major depressive disorder when compared to control subjects, and to a negative correlation between depression severity and serum BDNF levels. Shimizu et al. (2003) compared serum BDNF levels of drug-naive and treated patients with major depressive disorder and found that the serum BDNF level was lower in the drug-naive group than in the treated group and normal control group. In another study, the effect of antidepressant treatment on serum BDNF levels was studied by Gonul et al. (2003). They found that antidepressant treatment for 8 weeks in patients with major depressive disorder significantly increases serum BDNF levels, in comparison to healthy subjects.
Venlafaxine is a dual-action antidepressant with high rates of remission achievement in major depression (Rudolph, 2002). Even though it was suggested that venlafaxine administration did not affect serum BDNF levels in rat hippocampus (Nibuya et al., 1996), data on the effect of venlafaxine treatment on serum BDNF levels in depressed patients are missing. In this study we aimed to test the effect of chronic antidepressant treatment on serum BDNF level in patients with a major depressive disorder, compared to sex- and age-matched healthy control subjects.
Section snippets
Method
This study was carried out in Celal Bayar University Hospital, Manisa, Turkey.
Results
Table 1 shows demographic and clinical characteristics of both the major depressive disorder and the control groups. At the baseline, the mean serum BDNF level was 17.9±9.1 ng/ml and mean HDRS score was 23.2±4.6. Serum BDNF level of the patient group was significantly lower than in the control group (Z=−2.64, p=0.007). At the end of the study, the mean serum BDNF level was 34.6±7.1 ng/ml whereas the mean HDRS score was 8.2±3.9 in the major depressive disorder group. In Fig. 1, before- and
Discussion
In this work, the effect of long-term treatment of major depressive disorder with an antidepressant (venlafaxine) on serum BDNF level was studied. As a result it is shown that chronic venlafaxine treatment significantly increases serum BDNF levels in patients with major depressive disorder and improves to the level of control subjects. To our knowledge, this is the first follow-up study with a specific antidepressant drug treatment in patients with major depressive disorder to report the
Conclusion
These findings reveal that serum BDNF level in major depressive disorder may be considered as a nonspecific peripheral marker that can respond to antidepressant treatment. This study is carried out in a relatively small group of patients. These results should be repeated in wider groups of patients. Furthermore, to determine the significance of BDNF in depression, serum BDNF levels should be measured and monitored in various patient groups such as treatment-resistant depressed patients or
Acknowledgement
The authors wish to thank to Wyeth Turkey who partially supported this study by financing laboratory kits.
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