Plasma brain-derived neurotrophic factor as a peripheral marker for the action mechanism of antidepressants

Numerous studies have demonstrated that depression is associated with a decreased expression of brain-derived neurotrophic factor (BDNF). BDNF shows antidepressant-like effects in animal models. Therefore, we tested the hypothesis that BDNF might be a peripheral marker for the mechanism of action of antidepressant agents in humans. Thirty-two patients meeting the DSM-IV criteria for major depressive disorder and 50 normal control subjects were recruited for this study. Plasma BDNF levels and Hamilton Depression Rating Scales were measured at baseline and 6 weeks after antidepressant administration. At baseline, the mean plasma BDNF level was lower in the depressive patients (698.1 +/- 537.7 pg/ml) than in the control subjects (830.7 +/- 624.8 pg/ml), although the difference was not statistically significant (p = 0.33). The plasma BDNF levels in depressive patients significantly increased from 698.1 +/- 537.7 to 1,028.9 +/- 744.5 after 6 weeks of antidepressant treatment (p = 0.01). Moreover, plasma BDNF levels were significantly increased after 6 weeks of treatment in the responder group, while there was no statistically significant change in the unresponsive group. These results suggest that the therapeutic response after antidepressant administration might be attributable to the increase in BDNF levels. BDNF may play a critical role in the action mechanism of antidepressant drugs. Further studies with a larger number of subjects are needed to verify these findings.     

Effects of fluoxetine and venlafaxine on serum brain derived neurotrophic factor levels in depressed patients

Background

Several studies demonstrated that depressed patients had low serum BDNF levels which correlated with the severity of their depression, and antidepressant treatment increases levels of serum BDNF in depressed patients. It was speculated that agents acting on both noradrenergic and serotonergic transporters might have a greater influence on BDNF levels. The aim of our study was to determine effects of venlafaxine vs. fluoxetine on serum BDNF levels in depressive patients.

Methods

Forty-three patients diagnosed as major depressive disorder according to DSM-IV are included in the study. Forty-three patients were randomized to take fluoxetine (22 cases) or venlafaxine (21 cases). Serum levels of BDNF were measured by ELISA at baseline and 6 weeks after the start of treatment.

Results

Baseline levels of BDNF were not significantly different between the patient group and the controls. But male patients and the male controls showed statistical differences with respect to baseline BDNF levels. BDNF levels of the patient group did not change with treatment. Yet, the increase of BDNF levels was close to statistically significant in the fluoxetine group, whereas not significant in the venlafaxine group. There were no significant differences in baseline and 6th week BDNF levels between the responders and the non-responders.

Conclusion

Further studies controlling for a wide variety of confounding variables are needed, which may help to reach a clear conclusion about the potential of BDNF as a biomarker for depression or as a predictor of antidepressant efficacy.     

Effect of treatment on serum brain–derived neurotrophic factor levels in depressed patients

Researchers have reported that serum brain–derived neurotrophic factor (sBDNF) of drug–free depressed patients are lower than those of healthy controls and proposed that low sBDNF levels might reflect failure of neuronal plasticity in depression. In this study, we compared sBDNF levels of depressed patients (n = 28) before and after 8 weeks of antidepressant treatment, with those of healthy controls (n = 18) to test the hypothesis that initially low sBDNF levels of drug–free depressed patients will increase parallel with their clinical response to antidepressant treatment. The severity of depression and response to treatment were assessed with Hamilton Rating Scale for Depression (HAM–D). sBDNF was assayed with the sandwich ELISA method. Baseline sBDNF levels of patients (mean, 20.8 ng/ml; [S.D., 6.7]) were significantly lower than those of controls (mean, 26.8 ng/ml; [S.D., 9.3]; p = 0.015), and were negatively correlated with HAM–D scores (r = –0.49, p = 0.007). After 8 weeks of treatment, sBDNF levels of patients had increased significantly (mean, 33.3 ng/ml; [S.D., 9.9]; p < 0.001) and no longer differed from those of controls. These results support the hypothesis that BDNF might play a critical role in the pathophysiology of major depressive disorder and successful antidepressant treatment increases the attenuated BDNF levels in depressed patients.     

Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine

Recent studies have implicated brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression and the activity of antidepressant drugs. Serum BDNF levels are lower in depressed patients, and increase in response to antidepressant medication. However, how BDNF responds to different classes of antidepressant drugs is unknown. We assessed serum BDNF levels in 21 patients with major depressive episode treated with sertraline, escitalopram, or venlafaxine and 20 healthy controls. Serum samples were collected between 10 a.m. and 12 p.m. at baseline, 5 weeks, and 6 months of treatment. BDNF levels were measured via immunoassay. The severity of symptoms and response to treatment were assessed by the Hamilton rating scales for depression (HRSD). Baseline serum BDNF levels were significantly lower in depressed patients compared to controls. Sertraline increased BDNF levels after 5 weeks and 6 months of treatment. Venlafaxine increased BDNF levels only after 6 months. Escitalopram did not affect BDNF levels at either time point. A significant negative association was found between percentage increase in BDNF levels and percentage decreased in HRSD scores after 6 months of treatment. In conclusion, these results suggest that different antidepressant drugs have variable effects on serum BDNF levels. This is true even though the three different drugs were equally effective in relieving symptoms of depression and anxiety.     

Reboxetine combination in treatment-resistant depression to selective serotonin reuptake inhibitors

INTRODUCTION: Treatment-resistant depression is a relatively common clinical occurrence: between 60-70% of depressive patients fail to achieve total remission to the initial treatment with selective serotonin reuptake inhibitors (SSRI). METHODS: In this prospective 12-week open-label study, we evaluated the effectiveness of the addition of reboxetine to 141 outpatients diagnosed with major depressive disorder, according to DSM-IV-TR criteria, who were partial responders or non-responders over a period of 6 weeks, to previous treatment in monotherapy with SSRI. Evaluation of antidepressant efficacy was carried out through the application of the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impressions-Global Improvement Scale (CGI-I). Data were analyzed on an intent-to-treat basis, using the last-observation-carried-forward method. RESULTS: Mean score on the HDRS at baseline was 26.24+/-7.21, falling to 13.96+/-8.00 in week 12 (mean decrease of 46.79%; p<0.0001) The percentages of responders (HDRS total score > or =50%) and patients considered as benefiting from complete remission (HDRS score < or =10) at 12 weeks were 50.4% and 34.5%, respectively. By the end of the treatment, a mean decrease in CGI-I score of 1.88 points was obtained (41.14% of reduction; p<0.0001), and 77% of the patients were evaluated as improved (CGI-I score <4). Nervousness was the adverse effect most frequently reported (5.21%), followed by dryness of mouth (4.38%), and insomnia (3.56%). CONCLUSION: The results of this study suggest that the combination strategy with reboxetine appears to be a potentially useful tool in cases of SSRI-resistant depression.     

Serum brain-derived neurotrophic factor level in dysthymia: a comparative study with major depressive disorder

In this present work, it is aimed to demonstrate BDNF serum concentrations in patients with dysthymia and to compare them with BDNF serum concentrations in patients with major depressive disorder and healthy subjects. The study was carried out in Celal Bayar University Hospital, Manisa, Turkey. Seventeen patients with dysthymia, 24 patients with major depressive disorder and 26 subjects without any psychiatric diagnosis and any psychiatric treatment were included in the study. The severity of depression was assessed with 17-item HAM-D. All subjects were asked to give their written consent. Blood samples were collected at baseline. Serum BDNF was kept at -70 degrees C before testing, and assayed with an ELISA Kit (Promega; Madison, WI, USA), after dilution with the Block and Sample solution provided with the kit. The data were subjected to the analysis of variance. The BDNF serum concentrations of the dysthymia group (mean=28.9+/-9.2 ng/ml) were significantly higher than that of the major depressive disorder group (21.2+/-11.3 ng/ml) (p=0.002), and it was not different from the level of the control group (31.4+/-8.8 ng/ml). BDNF serum concentrations and HAM-D score did not have any significant correlation in the dysthymia and major depression groups (r=-0.276, p=0.086). The low level of BDNF in patients with dysthymic disorder seems to point out that BDNF changes in mood disorders are state-dependent and vary according to the severity of depressive episodes.     

No change between the serum brain-derived neurotrophic factor in female patients with anorexia nervosa before and after partial weight recovery

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family. Several lines of evidence indicate that BDNF plays a role in the pathophysiology of eating disorders (ED). We found that serum BDNF levels in patients with ED were significantly lower than in normal controls. The aim of this longitudinal study was to compare serum BDNF levels in patients with anorexia nervosa (AN) before (n=13, initial mean body mass index (BMI)=14.2 kg/m(2)+/-0.7) and after partial recovery (mean BMI=16.2 kg/m(2)+/-1.7, mean weight gain 5.0 kg+/-2.0), with age-matched normal control subjects (n=17, mean BMI=20.4 kg/m(2)+/-1.5). METHODS: Eating related psychopathology and depressive symptoms were evaluated before and after partial weight recovery, using the Eating Disorder Inventory-2 (EDI-2) and the 17-item Hamilton Depression Rating Scale (HDRS). Serum BDNF levels were measured using a sandwich enzyme-linked immunosorbent assay. RESULTS: Serum BDNF levels with the AN patients (14.5+/-4.4 ng/ml) were significantly (p<0.01) lower than in control subjects (22.1+/-8.9 ng/ml). There were no significant differences in serum BDNF levels between the patients with AN before (14.5+/-4.4 ng/ml) and after (17.2+/-6.9 ng/ml) partial weight recovery. In all subjects, there was a positive correlation (r=0.5, p<0.01) between the baseline BDNF levels and the EDI-2 scores (n=30). Furthermore, in all subjects there was a positive correlation (r=0.4, p<0.05) between the BDNF levels and the BMI. CONCLUSIONS: Serum BDNF levels did not change after partial weight recovery in AN patients. Our results suggest that an alteration of the serum BDNF in AN patients is not due to changes in body weight. Thus, other possible mechanisms that could be related to low serum BDNF levels in AN patients should be evaluated.     

Efficacy of electroconvulsive therapy is associated with changing blood levels of homovanillic acid and brain-derived neurotrophic factor (BDNF) in refractory depressed patients: a pilot study

Electroconvulsive therapy (ECT) is effective for patients with antidepressant medication-resistant depression. However, the mechanisms of ECT's effectiveness for treating depression are not fully understood. We therefore investigated ECT's effects on blood levels of brain-derived neurotrophic factor (BDNF), catecholamine metabolites, and nitric oxide (NO) in 18 treatment-refractory depressed patients. Serum BDNF levels increased significantly following ECT in responders to ECT (before ECT: 8.0+/-9.7 ng/mL; five weeks after start of ECT: 15.1+/-11.1 ng/mL), whereas BDNF levels in non-responders were unchanged (before ECT: 11.5+/-11.0 ng/mL; five weeks after start of ECT: 9.4+/-7.5 ng/mL). Furthermore, the plasma HVA levels, but not MHPG levels, were significantly reduced after ECT (before ECT: 8.5+/-1.9 ng/mL; five weeks after start of ECT: 5.8+/-2.2 ng/mL). This latter finding occurred in parallel with the improvement of depressive symptoms in all patients. These results suggest that the mechanisms underlying ECT's effect on refractory depression may be related to dopaminergic neurons and BDNF.     

Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients

Brain-derived neurotrophic factor (BDNF) is an important member of the neurotrophin family of growth factors, abundant in the brain and periphery. Researchers have reported that serum BDNF levels in drug-free depressed patients are lower than those of healthy controls, and have proposed that these low levels might reflect a failure of neuronal plasticity in depression. In the present study, we investigated the effects of paroxetine, an SSRI, and milnacipran, an SNRI, on serum BDNF levels in depressed patients. Serum levels of BDNF were measured by ELISA before, 4 weeks, and 8 weeks after the start of treatment with antidepressants. Forty-two patients were randomly administered paroxetine (21 cases) or milnacipran (21 cases). A negative correlation was found between serum BDNF levels and baseline Ham-D scores. The response and remission rates for each drug were not significantly different. Serum BDNF levels in responders were significantly increased 2.6- and 1.8-fold 8 weeks after treatment with paroxetine or milnacipran, respectively. These results suggest that both drugs improve the depressive state by increasing BDNF levels.     

广泛性焦虑障碍治疗前后血清脑源性神经营养因子水平的变化

目的研究广泛性焦虑障碍(generalized anxiety disorder,GAD)患者血清脑源性神经营养因子(brain derived neurotrophic factor,BDNF)水平的特点及其治疗变化。方法收集GAD患者及正常对照者各40名,采用帕罗西汀片有效治疗量治疗12周,治疗前后采用汉密尔顿焦虑量表(Hamilton Anxiety Scale,HAMA)进行疗效评估,采用ELISA法测定血清BDNF的浓度并与对照组比较。结果治疗前GAD患者的血清BDNF水平[(26.03±10.52)ng/mL]低于对照组[(43.27±10.28)ng/mL],治疗后GAD患者血清BDNF水平[(35.85±11.96)ng/mL]较治疗前升高,但仍低于正常对照组,其差异均有统计学意义(P均<0.05);治疗后GAD显效患者[(39.43±12.35)ng/mL]与对照组血清BDNF水平的差异无统计学意义(P>0.05);基线时,GAD患者血清BDNF水平与HAMA量表总分、精神性焦虑因子分呈负相关(P<0.05),与躯体性焦虑因子分的相关没有统计学意义(P>0.05);治疗后,GAD患者血清BDNF水平的变化与HAMA总分、躯体性焦虑因子分、精神性焦虑因子分变化均呈负相关(P均<0.05)。结论血清BDNF水平可能是GAD的状态性指标之一。     

Substance P serum levels are increased in major depression: preliminary results.

BACKGROUND: Substance P (SP) is thought to have an impact in the pathophysiology of depression and the mechanism of action of antidepressant drugs. The aim of this study was to analyze the serum SP levels in healthy control subjects and in depressed patients before and after antidepressant treatments. METHODS: Twenty-three patients with major depression and 33 control subjects participated in the study. Using an enzyme immunoassay, the SP serum levels were determined in patients at baseline (before treatment) and after 2 and 4 weeks of antidepressant therapy. Determinations of SP in control subjects were carried out twice, at baseline and after 4 weeks. RESULTS: The mean baseline SP serum concentration was significantly higher in depressed patients as compared with control subjects (p <.001). Repeated measurements in control subjects showed that SP remains relatively constant over a period of 4 weeks. Although in depressed patients there was no overall change in the mean SP levels between baseline and 4 weeks' treatment, 37% of them exhibited a decrease of SP (15%-50%), which can be correlated to a better drug response than an increase in SP concentration after treatment (p =.001). CONCLUSIONS: Our data show that serum SP levels are increased in a proportion of patients with major depression and might thus indicate a subgroup of the disorder in which neuropeptides have a key position. Future studies are needed to clarify whether the observed SP decrease in treatment responders can be attributed to a specific class of drugs.     

Brain-derived neurotrophic factor and subcallosal deep brain stimulation for refractory depression

Objectives. Subcallosal cingulate (SCC) deep brain stimulation (DBS) is a promising experimental treatment for treatment-resistant depression (TRD). Given the role of brain-derived neurotrophic factor (BDNF) in neuroplasticity and antidepressant efficacy, we examined the effect of SCC-DBS on serum BDNF in TRD. Methods. Four patients with TRD underwent SCC-DBS treatment. Following a double-blind stimulus optimization phase of 3 months, patients received continuous stimulation in an open label fashion for 6 months. Clinical improvement in depressive symptoms was evaluated bi-weekly for 6 months using the Hamilton Depression Rating Scale (HDRS). Mature serum BDNF levels were measured before and 9–12 months after surgery. Results. Three patients responded to SCC-DBS: two showed full clinical response (50% reduction in HDRS scores) and one had partial response (35% reduction in HDRS scores) at the clinical endpoint. Interestingly, all four patients showed reduction in serum BDNF concentration from pre-DBS baseline. Conclusions. SCC-DBS for TRD may be associated with decreased levels of serum BDNF. Longitudinal studies with multiple measurements in a larger sample are required to determine the role of BDNF as a biomarker of SCC-DBS antidepressant efficacy.     

The clinical response to total sleep deprivation and recovery sleep in geriatric depression: potential indicators of antidepressant treatment outcome

The clinical response to antidepressant treatment in late-life depression is often delayed and highly variable. Better indicators of antidepressant efficacy are needed early in the course of treatment, so that augmentation strategies or alternative treatments may be initiated. The goal of this study was to evaluate whether the change in the Hamilton depression rating scale (HDRS) after 36 h of total sleep deprivation (TSD) and recovery sleep predicted clinical outcome after 12 weeks of antidepressant treatment, and whether greater predictive value was observed in certain aspects of depressive symptomology. Fifteen elderly patients diagnosed with major depression underwent combined treatment with an initial 36 hours of TSD and a 12-week trial with the antidepressant paroxetine. Six HDRS subscores were evaluated with respect to how the changes after TSD and after one night of recovery sleep correlated with HDRS scores after 12 weeks of treatment. A significant correlation was obtained between the change in the core depressive symptomology subscale from baseline to recovery sleep and the HDRS score at 12 weeks, but the correlation was not significant when evaluating the change from baseline to TSD. These results indicate that the decrease in symptoms after recovery sleep compared with baseline levels (indicating the persistence of the antidepressant response), rather than the symptom reduction after TSD, has greater predictive value with respect to treatment outcome.     

Low plasma BDNF is associated with suicidal behavior in major depression

Brain-derived neurotrophic factor (BDNF), the most abundant neurotrophin in the brain, has a known association with the pathophysiology of anxiety and depression. However, the role of BDNF in suicide has not been well investigated to date. This study examined plasma BDNF levels in 32 major depressive disorder (MDD) patients who had recently attempted suicide, 32 non-suicidal MDD patients, and 30 normal controls. The lethality of the suicide attempt was measured using the Risk-Rescue Rating (RRR) and Lethality Suicide Attempt Rating Scale (LSARS). The severity of depression was measured with the Hamilton Depression Rating Scale (HDRS). Plasma BDNF levels were measured by enzyme linked immunosorbent assay. BDNF levels were significantly lower in suicidal MDD patients (430.5+/-397.0 pg/ml) than non-suicidal MDD patients (875.80+/-663.02 pg/ml) or normal controls (889.4+/-611.3 pg/ml) (F=6.682, p=0.002). The most suitable cut-off point of BDNF level between suicidal depression and non-suicidal depression groups was 444.58 pg/ml. At this cut-off point, the sensitivity=68.7%, specificity=78.1%, positive predictive value=75.9%, and negative predictive value=71.4%. However, there was no significant difference in BDNF levels between the depressive control and normal control groups (p=0.996). LSARS and RRR did not reveal any significant correlations with BDNF levels in suicidal patients. In addition, BDNF levels were not different between fatal and non-fatal suicide attempts. These results suggest that reduction of plasma BDNF level is related to suicidal behavior in major depression and that BDNF level may be a biological marker of suicidal depression.     

Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo.

BACKGROUND: Most examinations of the clinical efficacy of drugs used to treat depression pool subjects across gender and age groups. This investigation compared these patient subpopulations on the basis of remission and response rates associated with venlafaxine and selective serotonin reuptake inhibitor (SSRI) treatment. METHOD: A meta-analysis of original data from 8 comparable double-blind, active-controlled, randomized clinical trials (4 also placebo-controlled) was conducted. Antidepressant efficacy was assessed for patients (N = 2,045) aged 18 to 83 years (subgroups: < or = 40, 41-54, 55-64, and > or = 65 years) who met DSM-III-R criteria for major depression or DSM-IV criteria for major depressive disorder and were randomly assigned to receive venlafaxine (immediate release, N = 474; extended release, N = 377), one of several SSRIs (N = 748), or placebo (N = 446) for up to 8 weeks. Symptoms of depression were assessed using the Hamilton Rating Scale for Depression (HAM-D). Remission was defined as a HAM-D-17 score < or = 7, response was defined as > or = 50% decrease in HAM-D-21 score, and absence of depressed mood was defined as a HAM-D depressed mood item score of 0. RESULTS: We detected no significant age-by-treatment, gender-by-treatment, or age-by-gender-by-treatment interactions; men and women of different ages within a given antidepressant treatment group exhibited similar rates of remission, response, and absence of depressed mood. Regardless of age or gender, remission rates during venlafaxine therapy were significantly higher than during SSRI therapy (remission rates at week 8: venlafaxine, 40%-55% vs. SSRI, 31%-37%; p < .05). Regardless of patient age or gender, onset of remission was more rapid with venlafaxine than with SSRI treatment. By contrast, rates of absence of depressed mood with venlafaxine (34%-42%) and SSRIs (31%-37%) did not differ significantly and tended to be similar for all patient subgroups. CONCLUSION: These data suggest that men and women have comparable responses to SSRIs and venlafaxine across various age groups. Moreover, patients exhibited a more rapid onset and a greater likelihood of remission with venlafaxine therapy than with SSRI therapy regardless of age or gender.     

High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and easily tolerated method of altering cortical physiology. To date, numerous open and sham controlled clinical trials have explored the antidepressant potential of rTMS. In the present study, we investigated clinical trials of high-frequency rTMS (20 Hz) for treatment of refractory depression, and also examined the effect of rTMS on plasma levels of catecholamine metabolites and brain-derived neurotropic factor (BDNF). METHODS: Twenty-six depressed inpatients who met the DSM-IV criteria for major depressive disorder and had failed to respond to treatment with at least two antidepressant drugs given at adequate doses (above 150 mg/day in an equivalent dose of imipramine) and durations (at least 4 weeks for each drug) were enrolled in this study. Eleven were males, 15 females. The ages of the subjects ranged from 19 to 78 years old (mean +/- SD = 52.9 +/- 17.8). All patients were administered left prefrontal 20 Hz rTMS at 80 % MT (total 800 pulses a day) over ten daily sessions. The plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were analyzed by high-performance liquid chromatography. The plasma levels of BDNF were also measured with the sandwich ELISA method. RESULTS: The mean 17-item Hamilton Rating Scale for Depression (Ham-D) score of 20.5 +/- 5.2 before rTMS was significantly decreased to 15.6 +/- 7.3 after rTMS. Nine of 26 patients (35 %) demonstrated some improvement (Ham-D > or = 25 %) by rTMS. The levels of plasma MHPG, but not those of HVA, were significantly reduced after rTMS treatment, and a negative correlation was observed between the change in plasma MHPG levels and the change in scores of agitation. In addition, the plasma levels of BDNF were significantly increased by 23 % in responders and partial responders, but not in nonresponders, after rTMS treatment, and a trend for association was found between the changes in Ham-D scores and changes in plasma BDNF levels in all patients after rTMS treatment. CONCLUSION: These results suggest that rTMS treatment brings about some improvement in refractory depression, especially for symptoms such as agitation, by influencing MHPG and BDNF, which is in accordance with previous reports showing that BDNF was increased by various antidepressants treatments.     

Serum brain-derived neurotrophic factor (BDNF) levels in patients with panic disorder: as a biological predictor of response to group cognitive behavioral therapy

Little is known about biological predictors of treatment response in panic disorder. Our previous studies show that the brain-derived neurotrophic factor (BDNF) may play a role in the pathophysiology of major depressive disorders and eating disorders. Assuming that BDNF may be implicated in the putative common etiologies of depression and anxiety, the authors examined serum BDNF levels of the patients with panic disorder, and its correlation with therapeutic response to group cognitive behavioral therapy (CBT). Group CBT (10 consecutive 1 h weekly sessions) was administered to the patients with panic disorder after consulting the panic outpatient special service. Before treatment, serum concentrations of BDNF and total cholesterol were measured. After treatment, we defined response to therapy as a 40% reduction from baseline on Panic Disorder Severity Scale (PDSS) score as described by [Barlow, D.H., Gorman, J.M., Shear, M.K., Woods, S.W., 2000. Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial. JAMA. 283, 2529-2536]. There were 26 good responders and 16 poor responders. 31 age- and sex-matched healthy normal control subjects were also recruited in this study. The serum BDNF levels of the patients with poor response (25.9 ng/ml [S.D. 8.7]) were significantly lower than those of the patients with good response (33.7 ng/ml [S.D. 7.5]). However, there were no significant differences in both groups of the patients, compared to the normal controls (29.1 ng/ml [S.D. 7.1]). No significant differences of other variables including total cholesterol levels before treatment were detected between good responders and poor responders. These results suggested that BDNF might contribute to therapeutic response of panic disorder. A potential link between an increased risk of secondary depression and BDNF remains to be investigated in the future.     

Decreased serum brain-derived neurotrophic factor levels in major depressed patients

Recent findings with animal models have suggested a possible role for brain-derived neurotrophic factor (BDNF) in depression. We have therefore hypothesized that depression could be characterized by low levels of serum BDNF. Major depressed patients (15F + 15M) diagnosed according to DSM-IV criteria and healthy controls (15F + 15M) participated in the study. Serum BDNF was assayed with the ELISA method and the severity of depression was evaluated with Montgomery-Asberg-Depression Rating Scale (MADRS). BDNF levels were significantly lower in patients than in controls: 22.6 +/- 3 and 26.5 +/- 7 ng/ml (t-test = 2.7; d.f. = 58; P < 0.01). They were negatively correlated to the MADRS scores (r = -0.55; P < 0.02). Female patients were more depressed and released less BDNF than men. Analysis of covariance (MADRS and gender as independent variable vs. BDNF as dependent variable) indicated that depression severity mainly accounted for the negative correlation. These results suggest that major depression is characterized by low serum BDNF levels and support the hypothesis of neurotrophic factor involvement in affective disorders.     

脑源性神经营养因子Val66Met功能基因多态性与抗抑郁剂疗效

目的：探讨脑源性神经营养因子（BDNF）Val66Met功能基因多态性与抗抑郁剂临床疗效的相关性。方法：302例抑郁症患者给予抗抑郁剂治疗8周。于治疗前和治疗2、4、6、8周后采用汉密尔顿抑郁量表（HAMD）评定抑郁严重程度和疗效。以治疗后HAMD总分≤7分为临床痊愈,将302例患者分为痊愈组160例和未痊愈组142例,抽取患者静脉血,采用Illumina GoldenGate定制芯片分析BDNFVal66Met基因多态性并进行基因分型。结果：痊愈组基因型分布A/A31例（19.4%）、A/G92例（57.5%）和G/G37例（23.1%）,未痊愈组分别为28例（19.7%）、78例（54.9%）和36例（25.4%）（χ2=0.054,P=0.817）;痊愈组等位基因频率分布A154例（48.1%）和G166例（51.9%）,未痊愈组分别为134例（47.2%）和150例（52.8%）（χ2=0.247,P=0.884）。3种BDNFVal66Met基因型患者间在性别、年龄、受教育年限、病程、发病次数、有无精神疾病家族史、HAMD基线及减分率上差异均无统计学意义（P均〉0.05）。结论：BDNFVal66Met基因多态性不是影响抗抑郁剂治疗近期疗效的主要因素。