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Background We investigated the relationship between a brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) and the clinical response of patients with major depressive disorder to selective serotonin reuptake inhibitors (SSRIs; here, paroxetine and sertraline). In addition, serum BDNF levels in these patients were considered together with the clinical response. Methods A total of 132 patients who met the DSM-IV criteria for major depressive disorder were enrolled in the study. 54 of these patients were male and 78 were female (age range, 20–74 years; mean ± S.D., 51 ± 15). The patients' clinical improvement was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17) before (T0) and at 8 weeks after the administration of SSRI treatment (T8). Patients with at least a 50% decrease in the HAMD-17 score were classified as responders. Results No correlation was observed between the BDNF Val66Met polymorphism and response to SSRIs or between the BDNF Val66Met polymorphism and serum BDNF levels at T0. An inverse correlation was found between serum BDNF levels and HAMD-17 scores at T0. Conclusions These results suggest that the BDNF Val66Met polymorphism is independent of both the response to SSRI treatment and serum BDNF levels. The findings in the present study reconfirm that the serum BDNF level is a state biomarker for depression.

Only two-thirds of depressive patients respond to antidepressant treatment. Recently, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we examined the effects of various atypical antipsychotic drugs as adjuvant to antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenaline reuptake inhibitors, tricyclic antidepressants and mood stabilizers, on plasma BDNF levels in refractory depressed patients. Forty-five patients who met the DSM-IV criteria for major depressive disorder (n=31) or bipolar disorder (10 with bipolar I, 4 with bipolar II) were enrolled in the study. Twenty-one were male and 24 were female, and their ages ranged from 28 to 71 (mean+/-SD=49+/-12) years. Plasma BDNF levels were measured using a sandwich ELISA. The plasma BDNF levels in responders (those showing a decline in HAM-D scores of 50% or more) were significantly increased 4weeks after the administration of each atypical antipsychotic drug, while the levels in non-responders were not changed. Furthermore, there was a significant correlation between the changes in HAM-D scores and the changes in plasma BDNF levels. These results suggest that adding an atypical antipsychotic drug to ongoing treatment with an antidepressant or mood stabilizer is useful and well-tolerated for refractory depressed patients, and the efficacy of atypical antipsychotics as an adjuvant might involve an increase of plasma BDNF levels.

In the present study, we compared plasma levels of interleukin-6 (IL-6), tumor necrosis factor-alpha(TNFalpha), and brain-derived neurotrophic factor (BDNF) among selective serotonin reuptake inhibitor (SSRI)- or serotonin noradrenaline reuptake inhibitor (SNRI)-responsive depressed patients (n=31), SSRI- or SNRI-refractory depressed patients (n=20), and healthy controls (n=30). The plasma levels of IL-6 and TNF-alpha were significantly higher in depressed patients than in healthy controls. Treatment with antidepressants significantly reduced plasma levels of IL-6 and TNF-alpha. In addition, the plasma IL-6 level, but not the plasma TNF-alpha level, was higher in SSRI-refractory than SSRI-responsive depressed patients, and higher in SNRI-refractory than SNRI-responsive depressed patients. On the other hand, the plasma BDNF level was significantly lower in depressed patients than in healthy controls, whereas no difference was found in plasma BDNF levels between SSRI-responsive and -refractory depressed patients or between SNRI-responsive and -refractory depressed patients. These results suggest that higher plasma IL-6 activity is associated with the refractoriness of depression, and plasma IL-6 levels might be a predictor for response to SSRIs or SNRI.

Depression is a risk factor for coronary heart disease (CHD). It has been demonstrated that there is a potential role of nitric oxide (NO) in the relationship between depression and CHD risk as well as an effect of antidepressants on NO production. This study included 40 in- or outpatients in our university hospital who met the DSM-IV-TR criteria for major depressive disorder (M/F: 15/25, age: 47+/-19 years) and 30 age- and sex-matched healthy controls (M/F: 10/20, age: 45+/-15 years), and also examined the effects of the antidepressants on the plasma NOx levels in depressed patients. The baseline plasma NOx levels were significantly lower in the whole depressed group than in the control group (p