The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study

Recent studies suggested a role of brain-derived neurotrophic factor (BDNF) in depression. While BDNF levels are lower in depressed patients, antidepressant treatment increases serum BDNF levels of depressed patients. Our study aims to test the effect of chronic venlafaxine treatment on serum BDNF levels in patients with a major depressive disorder. Ten patients diagnosed as major depressive disorder according to DSM-IV are included in the study. Two of the patients had their first episode and were drug-naive, the other eight patients were drug-free for at least 4 weeks. The severity of depression was assessed with Hamilton Depression Rating Scale (HDRS). The control group consisted of ten age- and sex-matched subjects without any psychiatric disorder. Blood samples were collected at the baseline and after 12 weeks of antidepressant treatment (during remission). At the baseline the mean serum BDNF level was 17.9+/-9.1 ng/ml and the mean HDRS score was 23.2+/-4.6. Serum BDNF levels of the study group were significantly lower than in the control group (31.6+/-8.6 ng/ml). 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. From the baseline to the remission after 12 weeks of treatment, the increase in serum BDNF level and the decrease in HDRS score were statistically significant, respectively. When we compared the serum BDNF level of depressed patients at remission to that of the controls, there was no statistically significant difference. This study shows that venlafaxine treatment of depression improves serum BDNF level which may be considered as a nonspecific peripheral marker of depression.     

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.     

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.     

抑郁症患者血清脑源性神经营养因子水平及其相关因素

目的 探讨抑郁症患者血清脑源性神经营养因子水平及其相关因素,为防治抑郁症提供重要依据.方法 采用酶联免疫吸附法和汉密尔顿抑郁量表分别测定40例抑郁症患者(患者组)的血清BDNF水平和抑郁严重程度,并与49名正常者(对照组)进行对比分析.结果 患者组治疗前血清BDNF水平明显降低,与对照组比较差异有统计学意义(P＜0.01).患者组治疗8周末血清BDNF水平明显升高,HAMD总分明显降低,与治疗前比较差异有统计学意义(P＜0.05).患者组治疗前后血清BDNF水平与性别及年龄均呈负相关,差异具有统计学意义(P＜0.05),与受教育程度、病程及HAMD总分比较无统计学意义(P＞0.05).结论 抑郁症患者存在血清BDNF水平的下降,抗抑郁治疗可改善抑郁症状,并显著提高血清BDNF水平.     

Partial normalization of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode

We had previously reported decreased serum brain-derived neurotrophic factor (BDNF) levels in depressed patients. In the present study, we tested the hypothesis that antidepressant treatment would normalize serum BDNF levels, at least in a subgroup of patients. Major depressed patients (15 females and 11 males) diagnosed according to DSM-IV criteria and healthy controls (13 females and 13 males) participated in this study. Serum BDNF was assayed with the ELISA method for depressed and remitted patients and the severity of depression was evaluated with the Montgomery-Asberg Depression Rating Scale. An analysis of variance showed that treatment had an effect [F(1, 24) = 4.46, p = 0.045] on the normalization of serum BDNF levels. We also found a correlation between the severity of depression (r = 0.51, p = 0.008), the pretreatment BDNF levels (r = 0.62, p = 0.001) and the difference in serum BDNF levels after antidepressant treatment. These results suggest that antidepressant treatment has a positive effect on serum BDNF levels and support the hypothesis of neurotrophic factor involvement in affective disorders.     

The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment

Neurotrophic factors are critical regulators of the formation and plasticity of neuronal networks. Brain-derived neurotrophic factor (BDNF) is abundant in the brain and periphery, and is found in both human serum and plasma. Animal studies have demonstrated that stress reduces BDNF expression or activity in the hippocampus and that this reduction can be prevented by treatment with antidepressant drugs. A similar change in BDNF activity occurs in the brain of patients with major depression disorder (MDD). Recently, clinical studies have indicated that serum or plasma BDNF levels are decreased in untreated MDD patients. Antidepressant treatment for at least four weeks can restore the decreased BDNF function up to the normal value. Therefore, MDD is associated with impaired neuronal plasticity. Suicidal behavior can be a consequence of severe impaired neuronal plasticity in the brain. Antidepressant treatment promotes increased BDNF activity as well as several forms of neuronal plasticity, including neurogenesis, synaptogenesis and neuronal maturation. BDNF could also play an important role in the modulation of neuronal networks. Such a neuronal plastic change can positively influence mood or recover depressed mood. These alterations of BDNF levels or neuronal plasticity in MDD patients before and after antidepressant treatment can be measured through the examination of serum or plasma BDNF concentrations. BDNF levels can therefore be useful markers for clinical response or improvement of depressive symptoms, but they are not diagnostic markers of major depression.     

Serum BDNF levels before treatment predict SSRI response in depression

Objectives

The “neurotrophin hypothesis” of depression posits a role of brain-derived neurotrophic factor (BDNF) in depression, although it is unknown whether BDNF is more involved in the etiology of depression or in the mechanism of action of antidepressants. It is also unknown whether pre-treatment serum BDNF levels predict antidepressant response.

Methods

Thirty un-medicated depressed subjects were treated with escitalopram (N = 16) or sertraline (N = 14) for 8 weeks. Twenty-five of the depressed subjects completed 8 weeks of antidepressant treatment and had analyzable data. Twenty-eight healthy controls were also studied. Serum for BDNF assay was obtained at baseline in all subjects and after 8 weeks of treatment in the depressed subjects. Depression ratings were obtained at baseline and after 8 weeks of treatment in the depressed subjects.

Results

Pre-treatment BDNF levels were lower in the depressed subjects than the controls (p = 0.001) but were not significantly correlated with pre-treatment depression severity. Depression ratings improved with SSRI treatment (p < 0.001), and BDNF levels increased with treatment (p = 0.005). Changes in BDNF levels were not significantly correlated with changes in depression ratings. However, pre-treatment BDNF levels were directly correlated with antidepressant responses (p < 0.01), and “Responders” to treatment (≥ 50% improvement in depression ratings) had higher pre-treatment BDNF levels than did “Non-responders” (p < 0.05).

Conclusions

These results confirm low serum BDNF levels in un-medicated depressed subjects and confirm antidepressant-induced increases in BDNF levels, but they suggest that antidepressants do not work simply by correcting BDNF insufficiency. Rather, these findings are consistent with a permissive or facilitatory role of BDNF in the mechanism of action of antidepressants.     

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.     

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.     

Serum brain-derived neurotrophic factor levels in patients with major depression: effects of antidepressants

This study tried to investigate the relationships between serum brain-derived neurotrophic factor (BDNF) protein levels and major depressive patients and discuss the effects of antidepressants on the serum BDNF protein levels. A total of 218 participants, including 111 patients with major depression (91 women) and 107 healthy controls (65 women), were recruited in this study. Serum BDNF protein levels were measured using an ELISA kit. Psychiatric diagnoses were made according to DSM-IV criteria. Severity of major depression was assessed by the 17-item Hamilton Depression Rating Scale. Using analysis of covariance with age adjustment, there were significantly low serum BDNF protein levels in depressive patients than healthy controls in women (F=7.530, p=0.007), but not in men. Additionally, changes in serum BDNF protein levels were significantly increased in 79 patients taking antidepressants during a period of 4 weeks (t=2.116, p=0.038), especially in 61 women (t=2.542, p=0.014). Age-adjusted ANCOVA revealed no significant differences in serum BDNF protein levels between 58 responders and 21 non-responders (F=0.008, P=0.928). In responders, there were significantly increased changes in serum BDNF protein levels in 44 women (t=2.501, p=0.016), but not in 14 men (t=-0.767, p=0.457). These analytical results suggest that low serum BDNF may play an important role in depressive women and antidepressant treatment significantly increase serum BDNF. However, further studies of larger populations are necessary to confirm these results and further elucidate the effects of different classes of antidepressants on serum BDNF protein levels.     

抑郁症患者治疗前后血清脑源性神经营养因子水平变化及相关因素分析

目的 探讨抑郁症患者血清脑源性神经营养因子(BDNF)水平及其变化与负性生活事件、抑郁症发病及治疗效应的关系.方法 采用横断面的病例-对照及前瞻性自身对照设计.对所有抑郁症患者给予抗抑郁治疗(包括抗抑郁药和改良电抽搐治疗),并随访治疗8周;采用酶联免疫吸附法测定63例抑郁症患者(抑郁症组)治疗前和治疗第2,4,8周末及80名正常对照(以下简称对照组)血清BDNF水平,并评定汉密尔顿抑郁量表(HAMD)和生活事件量表.结果 抑郁症组治疗前血清BDNF水平[(24±14)μg/L]显著低于对照组[(36±15)μg/L](t=-4.863,P=0.000),并与病前1年负性生活事件刺激值、治疗前HAMD总分均显著负相关(r=-0.331,P=0.008;r=-0.343,P=0.006),而后两者有相互正相关(r=0.292,P=0.020);治疗第2周末血清BDNF水平仍显著低于对照绢(t=-5.990,P=0.000),并与其抑郁症状严重度平行负相关(r=-0.269,P=0.033),且其血清BDNF增加率与HAMD减分率平行正相关(r=0.252,P=0.047);治疗第4,8周末血清BDNF水平均显著高于治疗前(经ISD检验,P=0.000;P=0.005),与对照组的差异均无统计学意义(P均＞0.05).治疗第2,4,8周末HAMD总分渐减并均低于治疗前(P均=0.001),且其HAMD平均减分率渐升(分别为40%,66%和74%).结论血清BDNF低下与负性生活事件、抑郁症发病密切相关,血清BDNF升高可能为抗抑郁治疗临床疗效的重要指标之一.     

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.     

Low serum levels of brain-derived neurotrophic factor in patients with schizophrenia do not elevate after antipsychotic treatment

Brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the etiology of schizophrenia. There is a line of evidence that disruption of neurotrophins could play a role in the etiology of schizophrenia, and antipsychotics show their effect by altering levels of neurotrophins. The aim of this study was to evaluate the effect of antipsychotics on serum BDNF levels and their relationship with the symptoms in patients with schizophrenia. Twenty-two schizophrenia patients were enrolled in the study. The control group consisted of 22 age- and sex-matched physically and mentally healthy volunteers (7 male, 15 female). Serum BDNF levels and the positive and negative syndrome scale (PANSS) scores were recorded at baseline and after 6 weeks of treatment. Serum BDNF levels were also recorded in the control group. Schizophrenia patients who failed to meet 30% improvement in PANSS score were excluded from the study. The baseline serum BDNF levels of schizophrenia patients were lower than those of controls (t = 4.56; df = 21; p < 0.001). There was no correlation between serum BDNF levels and PANSS scores in patients with schizophrenia (p > 0.05). Although PANSS (for positive symptoms p < 0.001, for negative symptoms p < 0.001) and general psychopathology (t = 20.9; df = 22; p < 0.001) scores improved significantly after 6 weeks of antipsychotic treatment; there was no change in BDNF levels in patients' serum (p > 0.05). Our results support the view that BDNF would be associated with schizophrenia. However, we could not conclude that treatment with antipsychotics alters serum BDNF levels in patients with schizophrenia.     

Serum Ghrelin and Leptin Levels in Patients with Depression and the Effects of Treatment

Objective

Ghrelin and leptin, appetite-regulating hormones, play a role in mood regulation. Current data about the relation between leptin/ghrelin and depression are still controversial. This study aimed to investigate serum leptin and ghrelin levels in patients with depression and the effects of treatment on these levels.

Methods

Serum ghrelin and leptin levels were measured before and after treatment with antidepressant drugs and/or electroconvulsive therapy in 28 patients with depression and once in 21 healthy controls.

Results

Serum ghrelin levels of the patients were high in the pre-treatment. After the treatment, ghrelin levels were not different from those of the controls. We found no difference in serum levels of leptin between the patients and controls and no change with treatment. body mass index of the patients increased after the treatment especially in the drug-treated group.

Conclusion

The present study found increased serum ghrelin levels in depressive patients and normalization with improving of depression but no alteration in leptin levels.     

Serum brain-derived neurotrophic factor level is reduced in antidepressant-free patients with late-life depression

Abstract

Objectives. The aim of the present study is to investigate serum BDNF levels in older depressed patients as compared to healthy elderly controls. Methods. Twenty-nine elderly subjects with major depression and 42 healthy older adults were enrolled to this study. All depressed patients were antidepressant-free for at least 1 month prior clinical and laboratorial assessments. Serum BDNF levels were determined by sandwich ELISA. Results. BDNF levels were lower in elderly depressed patients as compared to controls (P=0.034). Patients with late-onset depression had the lowest BDNF level (median 478.5, interquartile range 373.5–740.9 pg/l) when compared to early-onset depression (median 620.7, interquartile range 366.1–971.9 pg/l) and healthy controls (median 711.3, interquartile range 534.7–1181.0 pg/l) (P<0.03). Conclusions. Reduced serum BDNF level may be a state marker of late-life depression in non-medicated elderly patients. Our findings provide further evidences that reduced neurotrophic support may have an important role in the physiopathology of late-life depression.     

Depression,antidepressants, and plasma DBH

Plasma levels of dopamine-β-hydroxylase (DBH) were determined in 16 unmedicated patients with major depressive episodes (nonpsychotic) and in an equal number of normal subjects, before and after 4 weeks of treatment with tricyclic antidepressants. Some eight patients were treated with amitriptyline, and the remainder received desipramine. The controls remained medication free during the entire experimental period. Degrees of depression were quantified before and after treatment with the Hamilton Rating Scale of Depression (HRSD). There were no significant differences between the depressed patients and the controls on levels of DBH. Similarly, there were no within-group, pre-posttreatment differences on the enzyme levels in either group. Pre-and posttreatment HRSD scores did not correlate with corresponding plasma DBH levels. Plasma levels of amitriptyline, nortriptyline (product of amitriptyline in the body), and desipramine at the end of 4 weeks of treatment also failed to correlate with the enzyme levels.     

alpha1-acid glycoprotein in late-life depression: relationship to medical burden and genetics

Serum alphal-acid glycoprotein (AAG) concentrations were examined in relationship to age, medical burden, depression, and mental status in elderly control (n = 19, mean age = 72.1 +/- 6.8 years) and depressed (n = 58, mean age = 71.9 +/- 7.1 years) subjects. DNA was analyzed for allelic variants of the AGP1 (ORM1) gene in both groups. Depressed subjects' AAG serum levels were measured at baseline and after 6 weeks of antidepressant treatment. Before treatment, depressed subjects had significantly higher serum AAG concentrations than nondepressed controls (t49.2 = -3.48, P = .0011). Pretreatment AAG levels also correlated with degree of medical burden, measured by the Cumulative Illness Rating Scale-Geriatrics (r = 0.28, P = .0303), but not with age, depression severity, or cognitive scores. There was no significant difference between responders and nonresponders on changes in AAG levels from baseline to week 6. Frequency differences in ORM1 allelic variants apparently did not influence increased AAG concentrations in depressed patients.     

Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women

Neuroplastic processes are thought to be involved in the pathophysiology of many psychiatric disorders, including major depression. It has been hypothesized that the brain-derived neurotrophic factor (BNDF), a key factor in neuroplasticity, is associated with depressive disorders. Our study evaluated the pre- and post-treatment levels of BDNF in a group of depressed patients and compared them with healthy controls. In order to exclude the effects of gender on neuroplasticity, our study group was restricted to women exclusively and consisted of 20 depressive patients and 20 healthy controls, with similar age and educational level distribution. Blood samples were collected before the treatment and on the sixth week of the treatment with 10 mg S-citalopram. The pre-treatment BDNF levels of the depressed patients were found to be lower than those of the healthy subjects. During the sixth week, the BDNF levels of depressive patients were significantly higher than the pre-treatment levels but similar to those of control subjects. These findings suggest that BDNF level may be an important factor in the etiopathogenesis of depression and may have a role in the action mechanism of antidepressant drugs.     

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.     

Substance P in serum and cerebrospinal fluid of depressed patients: no effect of antidepressant treatment

The neuropeptide substance P (SP) and its receptor, the neurokinin receptor-1 (NK-1), have been associated with some aspects of the pathophysiology of depression. There is limited information available about the effects of antidepressant treatment on serum and cerebrospinal fluid (CSF) concentrations of SP. We measured serum levels of SP in 78 depressed patients after a 6-day medication washout period, as well as after 14 and 35 days of antidepressant treatment with either paroxetine or amitriptyline. In 11 patients, SP was determined in CSF both before and after treatment. Eleven healthy male subjects served as controls. Baseline SP concentrations were independent of age, gender and severity of depression. Neither the total group nor subgroups showed significant differences in SP serum concentrations. SP concentrations in CSF did not change significantly in the patients during treatment, but there was a trend for an increase in paroxetine-treated patients. Serum SP concentrations were not related to treatment response or the class of antidepressant administered. Our data do not support the hypothesis that changes in SP levels in serum or CSF are related to antidepressant response.