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 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.     

Investigation of serum BDNF levels in drug-naive patients with schizophrenia

The role of brain-derived neurotrophic factor (BDNF) is to promote and modulate the neuronal responses across neurotransmitter systems in the brain. Therefore, abnormal BDNF signaling may be associated with the pathophysiology of schizophrenia. Decreased BDNF levels in the brain and the serum of patients with psychotic disorders have been reported. In the present study, we assessed serum BDNF levels in a group of 14 drug-naive first-episode patients with schizophrenia (FEP), compared to 15 healthy controls. The serum BDNF levels in the sample of FEP patients was significantly reduced compared to normal controls (23.92+/-5.99 ng/ml vs. 30.0+/-8.43 ng/ml, F=5.01, df=1, p=.034). Negative correlations were shown between serum BDNF levels of the patients and the PANSS Positive and Negative subscale scores. Our findings indicate that BDNF levels at the onset of schizophrenia may reflect associated pathophysiological processes as well as the severity of positive and negative psychotic symptoms.     

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.     

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.     

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.     

Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity.

BACKGROUND: Recent reports have suggested a role for brain-derived neurotrophic factor (BDNF) in psychiatric disorders. Decreased serum BDNF levels have been reported in major depression, but the cause of this decrease has not yet been investigated. The goal of this study was to assess blood BDNF and a platelet activation index, PF4. METHODS: Forty-three drug-free patients (27 female, 16 male) diagnosed with major depression and 35 healthy control subjects (18 female, 17 male) were assessed for plasma, serum, and blood BDNF content. Brain-derived neurotrophic factor and PF4 were assayed with enzyme-linked immunosorbent assay methods, and severity of depression was evaluated with the Montgomery-Asberg Depression Rating Scale. RESULTS: Serum and plasma BDNF levels were decreased in depressed patients compared with control subjects. In whole blood, BDNF levels were unaltered in the depressed subjects compared with control subjects. The serum/blood BDNF ratio was lower in patients with major depression. Increased plasma but not serum PF4 levels were observed in depressed subjects compared with control subjects. CONCLUSIONS: Our results suggest that an alteration of serum or plasma BDNF is not due to the change in blood BDNF but rather is probably related to mechanisms of BDNF release. Secretion of BDNF seems to be independent of platelet reactivity; other mechanisms are therefore probably involved and need to be elucidated.     

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.     

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.     

Decreased serum semicarbazide sensitive aminooxidase (SSAO) activity in patients with major depression

Semicarbazide sensitive aminooxidase (SSAO) is known to interplay with monoamine oxidases (MAO) and several antidepressants. Taking into account the monoamine hypothesis concerning the pathophysiology of depression, the aim of the present pilot study was to evaluate serum SSAO activity in depressed patients. A total of 21 inpatients with major depression and 41 healthy controls were studied. Serum SSAO activity was determined by HPLC on days 1, 5 and 10 of inpatient treatment. At baseline without medication including antidepressants, highly depressed patients (MADRS score>or=30) had significantly decreased serum SSAO activity (mean 385+/-161 mU/l) when compared to healthy controls (mean 526+/-141 mU/l; p=0.003). This SSAO decrease was less pronounced at day 5 and day 10 under an antidepressive drug regime. Decreased serum SSAO activity was observed in patients with major depression, especially in those with high MADRS scores. The present results support the hypothesis of dysfunctional monoaminergic metabolism in the pathogenesis of depressive disorders. The disputable association between depression and monoamine metabolism requires further investigation, particularly with regard to SSAO activity and medication status.     

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.     

Serum brain-derived neurotrophic factor level in relation to illness severity and episode duration in patients with major depression

BackgroundSince there are few data on the possible association between BDNF levels and characteristics of major depression, the present study assesses brain-derived neurotrophic factor (BDNF) levels in three drug-free patient samples, and explores whether episode duration, and severity correlate with serum BDNF levels.MethodSerum BDNF levels were measured in 42 drug-free patients with major depression. The duration of the index episode and the presence of psychotic features were assessed with the Schedule for Affective Disorders and Schizophrenia, and the severity of depression was measured with the 17-item Hamilton Rating Scale for Depression. The sample was divided into three groups: severely depressed inpatients without psychotic features, severely depressed inpatients with psychotic features, and moderately depressed outpatients.ResultsMean serum BDNF level in the total sample was 18.0 ± 2.8 ng/ml, with no significant difference between the three patient samples (F = 1.80, df = 2, p = 0.18). Mean serum BDNF level was significantly lower in patients with an index episode over one year, compared with patients who had a shorter index episode (F = 4.90, df = 1, p = 0.033).ConclusionThese data show that patients with a long index episode have significantly lower serum BDNF levels. We found no influence of the presence of psychotic features and severity of depression on serum BDNF levels.     

Decreased levels of serum brain-derived neurotrophic factor in both depressed and euthymic patients with unipolar depression and in euthymic patients with bipolar I and II disorders

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) has been proposed as a candidate molecule in the pathophysiology of major depressive disorder (MDD) and bipolar disorders (BD). Reduced levels of peripheral BDNF have been found in drug-free MDD patients, in drug-treated depressed or manic patients with BD type I (BD-I), but not in drug-treated euthymic BD-I individuals. No study has been done in patients with BD type II (BD-II). Moreover, the influence of Axis I psychiatric comorbidity on circulating BDNF in affective patients has never been evaluated. Therefore, in the present study, we aimed: (i) to confirm previous findings on peripheral BDNF in MDD and BD-I patients; (ii) to assess whether changes in circulating BDNF occur also in patients with BD-II; and (iii) to exclude the possibility that comorbid psychiatric disorders exerted an effect on BDNF levels in affective patients. METHODS: We measured serum BDNF concentrations by an enzyme-linked immunosorbent assay method in 85 subjects, including 24 euthymic patients with unipolar depression (UD), 17 euthymic patients with BD-I, 11 euthymic patients with BD-II, 11 UD patients with a current major depressive episode and 22 drug-free healthy controls. At the time of the study, 15 patients were drug-treated; the remaining ones were drug-free for at least four weeks. RESULTS: Compared to healthy controls, serum BDNF concentrations were significantly reduced in all the patient groups (F(4,80) = 3.840, p = 0.006) with no significant difference among them. Drug treatments and comorbid psychiatric disorders had no effect on lowered circulating BDNF levels in affective patients. CONCLUSIONS: Present results confirm previous independent findings of reduced circulating BDNF in patients with MDD and report, for the first time, decreased serum BDNF levels in euthymic patients with UD, BD-I and BD-II, independently from drug treatment status and concomitant Axis I psychiatric disorders.     

Association of low serum BDNF with depression in patients with Parkinson's disease

ObjectiveIncreasing evidence shows that brain-derived neurotrophic factor (BDNF) plays a critical role in the development of depression and the mechanisms of antidepressant. Parkinson disease (PD) is associated with depression and decreased BDNF. The aim of the present study was to examine the association of BDNF with depression in PD, which has not been investigated.MethodsWe recruited 96 PD patients with (n = 46) and without depression (n = 50) and 102 healthy controls and measured the serum BDNF levels in both groups. Zung Self-Rating Depression Scale (SDS) was administered for the severity of depression and Hoehn-Yahr staging scale for motor abilities in PD patients.ResultsSerum BDNF levels were significantly lower in PD patients than healthy controls (p < 0.01). Also serum BDNF levels were significantly decreased in PD patients with than without depression (p < 0.01). BDNF levels were negatively associated with SDS in both PD patients with and without depression (both p < 0.01). Multiple regression analysis confirmed that in either PD with or without depression group, BDNF was an independent contributor to SDS (both p < 0.05).ConclusionsOur findings suggest that decreased serum BDNF may be involved in the pathophysiology of depression in PD patients.     

抑郁症自杀未遂患者血清脑源性神经营养因子水平的变化

目的探讨血清脑源性神经营养因子（BDNF）水平与抑郁症患者自杀行为的关系。方法采用酶联免疫分析实验测定抑郁症自杀未遂患者（36例）、无自杀行为患者（55例）及36名正常对照血清BDNF水平,对抑郁症患者以汉密尔顿抑郁量表（HAMD）评定抑郁症状,以自杀意念自评量表（SIOSS）评定自杀意念的强烈程度。结果抑郁症患者组血清BDNF水平低于正常对照组（P〈0．01）。自杀未遂组血清BDNF水平低于无自杀组及正常对照组（P〈0．01）。自杀未遂组HAMD总分和SIOSS总分高于无自杀组。抑郁症患者血清BDNF水平与SIOSS总分呈负相关。结论抑郁症患者存在血清BDNF降低,BDNF水平可能是自杀倾向行为的生物学标志。     

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.     

Reduced serum levels of brain-derived neurotrophic factor in adult male patients with autism

BACKGROUND: The precise mechanisms underlying the pathophysiology of autism are currently unknown. Given the key role of brain-derived neurotrophic factor (BDNF) in brain development, we hypothesized that BDNF may play a role in the pathophysiology of autism. In this study, we studied whether serum levels of BDNF are altered in patients with autism. METHODS: We measured serum levels of BDNF in 18 adult male patients with autism and 18 age-matched healthy male control subjects. RESULTS: The serum levels of BDNF in patients with autism (25.6+/-2.15 ng/ml (mean+/-S.D.)) were significantly (z = -4.42, p < 0.001) lower than those of normal controls (61.6+/-10.9 ng/ml (mean+/-S.D.)). Nevertheless, we found no correlations between BDNF levels and clinical variables in autistic patients. CONCLUSIONS: This study suggests that reduced BDNF levels may play a role in the pathophysiology of autism.     

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.     

Reduced serum BDNF levels in schizophrenic patients on clozapine or typical antipsychotics

Neurotrophic factors regulate neuronal development and synaptic plasticity, possibly playing a role in the pathophysiology of schizophrenia and other psychiatric disorders. Decreased brain-derived neurotrophic factor (BDNF) levels have been found in brains and in the serum of schizophrenic patients, but results are inconsistent. Also, clozapine may upregulate brain BDNF expression. In the present study, we assessed serum BDNF immunoreactivity in 44 schizophrenic patients (20 on clozapine and 24 on typical antipsychotics) and in 25 healthy volunteers. Serum BDNF levels were measured using an enzyme immunoassay. Healthy controls showed significantly higher levels of BDNF compared to the whole group of schizophrenic patients (p<0.001) as well as to the subgroups on typical antipsychotics and clozapine (p<0.001). Serum BDNF values for controls were 168.8+/-26.3pg/ml, for the clozapine group were 125.4+/-44.5pg/ml and for the group on typicals were 101.3+/-51.6pg/ml. BDNF values from patients on clozapine were non-significantly higher than values from patients on typical antipsychotics (p=0.09). Serum BDNF was strongly and positively correlated with clozapine dose (r=0.643; p=0.002) but not with other demographic characteristics. These results reinforce previous findings of reduced serum BDNF levels in schizophrenic patients and suggest a differential effect of clozapine compared to typical antipsychotics on such levels.     

Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF

Neurotrophic factors have been investigated in relation to depression. The aim of the present study was to widen this focus to sortilin, a receptor involved in neurotrophic signalling. The serum sortilin level was investigated in 152 individuals with depression and 216 control individuals, and eight genetic markers located within the SORT1 gene were successfully analysed for association with depression. Genotyping was performed using the Sequenom MassARRAY platform. All the individuals returned a questionnaire and participated in a semi-structured diagnostic interview. Sortilin levels were measured by immunoassay, and potential determinants of the serum sortilin level were assessed by generalized linear models. Serum levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were measured in previous studies. We identified a significant increase of serum sortilin levels in depressed individuals compared with controls (P=0.0002) and significant positive correlation between serum sortilin levels and the corresponding levels of BDNF and VEGF. None of the genotyped SNPs were associated with depression. Additional analyses showed that the serum sortilin level was influenced by several other factors. Alcohol intake and body mass index, as well as depression, serum BDNF and serum VEGF were identified as predictors of serum sortilin levels in our final multivariate model. In conclusion, the results suggest a role of circulating sortilin in depression which may relate to altered activity of neurotrophic factors.