Cognitive functions and serum levels of brain-derived neurotrophic factor in patients with major depressive disorder

Objective

We assessed major cognitive domains in major depressive disorder (MDD) compared to a healthy control group using neurocognitive tests. We hypothesized that lower serum brain-derived neurotrophic factor (BDNF) levels would be associated with poorer neurocognitive performance in patients with major depression and that these associations would be shown in healthy controls as well.

Method

Executive functions, sustaining and focusing of attention, memory functions, and verbal fluency were assessed in this study using the Trail-Making Test (TMT), Stroop Color Word Interference Test-TBAG Form (SCWT), Wisconsin Card Sorting Test (WCST), Test of Variables of Attention (TOVA), Auditory Consonant Trigram test (ACTT), Digit Span subtest of the Wechsler Memory Scale (DST), Rey Auditory Verbal Learning Test (RAVLT), and Controlled Oral Word Association Test (COWAT).

Results

The MDD group showed significantly poorer performance than the control group in cognitive functions; they also had lower levels of BDNF than the control group. However, there was no correlation between cognitive performances and BDNF levels except in the TMT, Part B.

Conclusions

The current understanding of the importance of neurocognitive assessment and related biological markers in depression is improving. Further studies with larger sample sizes evaluating neurocognitive functions with molecular analyses of BDNF levels may reveal a novel marker for predicting and monitoring neurocognitive deficits in depression.     

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.     

Decreased levels of brain-derived neurotrophic factor in the remitted state of unipolar depressive disorder

Hasselbalch BJ, Knorr U, Bennike B, Hasselbalch SG, Greisen Søndergaard MH, Vedel Kessing L. Decreased levels of brain‐derived neurotrophic factor in the remitted state of unipolar depressive disorder. Objective: Decreased levels of peripheral brain‐derived neurotrophic factor (BDNF) have been associated with depression. It is uncertain whether abnormally low levels of BDNF in blood are present beyond the depressive state and whether levels of BDNF are associated with the course of clinical illness. Method: Whole‐blood BDNF levels were measured in blood samples from patients with unipolar disorder in a sustained state of clinical remission and in a healthy control group. Participants were recruited via Danish registers, a method that benefits from the opportunity to obtain well‐matched community‐based samples as well as providing a high diagnostic validity of the patient sample. Results: A total of 85 patients and 50 controls were included in the study. In multiple linear regression analyses, including the covariates age, gender, 17‐item Hamilton Depression Rating Scale scores, body‐mass index, education, smoking and physical exercise, patients with unipolar depressive disorder had decreased levels of BDNF compared to healthy control individuals [B = ?7.4, 95% CI (?11.2, ?3.7), = 0.21 P < 0.001]. No association between course of clinical illness and BDNF levels was present. Conclusion: Whole‐blood BDNF levels seem to be decreased in patients remitted from unipolar depressive disorder, suggesting that neurotrophic changes may exist beyond the depressive state.     

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。     

Association between serum brain-derived neurotrophic factor and plasma interleukin-6 in major depressive disorder with melancholic features

Inflammatory processes as well as attenuation of brain-derived neurotrophic factor (BDNF) availability are involved in the pathophysiology of major depressive disorder (MDD). Although it is generally presumed that these two systems interact negatively in the brain, preclinical and human in vitro studies have shown synergistic rather than antagonistic interactions in the periphery. We therefore examined the association between serum levels of BDNF and plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in patients with MDD (n = 1070) and non-depressed controls (n = 379) from the Netherlands Study of Depression and Anxiety. We used multiple regression analyses with serum BDNF as the dependent variable and we specifically tested the presence of BDNF–cytokine associations in DSM-IV-assigned melancholic MDD patients, identified by the Inventory of Depressive Symptomatology. After adjustment for sociodemographics, sampling variability, lifestyle indicators, somatic diseases and medication use, BDNF levels were predicted by the interaction between MDD diagnosis and IL-6 (p-interaction = .006). Stratified analyses showed that BDNF levels are indeed positively associated with IL-6 levels in MDD patients (β = .07, p = .02), but not in non-depressed controls (β = −.07, p = .23). When further stratified for melancholic and non-melancholic MDD (p-interaction = .005), IL-6 emerged as a robust positive predictor of BDNF only in the melancholic sample (β = .21, p = .01), wherein serum BDNF levels were accordingly enhanced. Post-hoc exploratory analyses verified an accentuated positive association of BDNF levels with leucocyte counts in melancholia. No significant associations emerged between BDNF and TNF-α. Overall, our cross-sectional approach may have disclosed an allostatic, BDNF-inducing component of peripheral immunity and/or an immunotrophic function of peripheral BDNF. Both scenarios may warrant further exploration, as they could inform new research concepts towards immune-based antidepressive treatment strategies.     

Childhood trauma and platelet brain-derived neurotrophic factor (BDNF) after a three month follow-up in patients with major depressive disorder

A large amount of brain-derived neurotrophic factor (BDNF) is stored in the human platelets and only small amounts of it circulate in the plasma. However, a few studies have focused on platelet BDNF in patients with major depressive disorder (MDD) and childhood trauma. Our study population consisted of 105 MDD patients and 50 healthy controls. We used the mini-international neuropsychiatric interview (M.I.N.I.), the early trauma inventory self report-short form (ETISR-SF), as well as measured serum, plasma, and platelet BDNF at baseline, 1 month, and 3 month periods. There was a significant association between childhood trauma and platelet BDNF at baseline, 1 month, and 3 months, after adjusting for age, gender, education, body mass index, severity of depression, anxiety, alcohol consumption, and current stress. Conversely, plasma and serum BDNF did not have a significant association with childhood trauma. MDD patients revealed significantly higher levels of platelet BDNF in those with childhood trauma than in those without (t = 2.4, p = 0.018), and platelet BDNF was significantly higher in cases with sexual abuse on post-hoc analysis (p = 0.042). However, no significant differences were found in healthy controls, according to whether or not they had experienced childhood trauma. Platelet BDNF showed a significant correlation with severity of childhood trauma at baseline (r = 0.25, p = 0.012) and at 3 months (r = 0.38, p = 0.003) in MDD. In conclusion, platelet BDNF was significantly higher in MDD patients with childhood trauma than in those without, and it was correlated with severity of trauma.     

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.     

抑郁症患者自杀行为与血清脑源性神经营养因子水平的关系

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之间的关系.方法:采用酶联吸附反应方法对有自杀行为的21例抑郁症患者(自杀组)、无自杀行为的52例抑郁症患者(非自杀组)以及80例正常人(对照组)血清的BDNF进行检测,应用汉密尔顿抑郁量表(HAMD)对抑郁症患者的抑郁症状进行评定. 结果:抑郁症患者...     

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.     

脑源性神经营养因子基因多态性与重性抑郁障碍认知功能的关系

目的 探讨脑源性神经营养因子(BDNF)基因Va166Met多态性与重性抑郁障碍认知功能的关系.方法 以100例重性抑郁障碍患者(患者组)与100名健康志愿者(对照组)为研究对象,采用1组神经心理学检测评估认知功能,并检测BDNF基因多态性;分别按照总智商(FIQ)、威斯康星卡片分类测验改良版(M-WCST)分类数、正确数、持续错误数、河内塔测试(TOH)计划时间、执行时间及总分的测验成绩由好到差排序,将患者组分为组1(成绩前50例,认知功能较好的患者)和组2(成绩后50例,认知功能较差的患者),检测组1与组2 BDNF基因型频率分布.结果 (1)对照组:除数字广度外,其他神经心理学测验成绩在BDNF基因型间的差异均无统计学意义(P>0.05).(2)患者组:中国修订韦氏成人智力量表(WAIS-RC)FIQ[(102.1±11.5)分vs(92.5±10.2)分]、M-WCST分类数[(5.6±1.7)分vs(2.9±1.2)分]和正确数[(36.5±6.0)分vs(26.8±5.6)分]、TOH总分[(50.8±9.6)分vs(40.4±9.3)分]及各项测验成绩,连线测验(TMT)A耗时数和B耗时数的成绩在患者组Val/Val基因型均优于Met/Met基因型,差异有统计学意义(P均<0.01).(3)组1Met/Met基因型频率分布显著低于组2,差异均有统计学意义(P均<0.01);除FIQ和TOH执行时间外,其他各项组1 Val/Val基因型频率显著高于组2,差异有统计学意义(P均<0.05).结论 BDNF基因Va166Met多态性与重性抑郁障碍患者认知功能损害可能有关.

Abstract：

objective To investigate relationship between brain-derived neurotrophic factor (BDNF)gene Va166Met polymorphism and cognitive function in patients with major depressive disorder.Methods One hundred patients with major depressive disorder and 100 healthy volunteers were included.The cognitive function was assessed by a series of neuropsychology tests,and BDNF gene polymorphism was detected.Results (1)In control group,the achievements of all neuropsychology tests except for digit span were not significantly different among ones with different BDNF genotypes(P>0.05).(2)In patient group,the achievements of neuropsychology tests such as WAIS-RC(102.1±1 1.5 vs.92.5±10.2),M-WCST(5.6±1.7 vs.2.9±1.2,36.5±6.0 vs.26.8±5.6),TOH(50.8±9.6 vs.40.4±9.3),time for TMT-A and TMT-B,were significantly better in ones with Val/Val genotype than in ones with Met/Met genotype(P≤0.01).(3)The Val/Val genotype frequency in patients with better cognitive function was higher than that in patients with worse cognitive function,while Met/Met genotype frequency was in the opposite direction(P<0.05 or P<0.01).Conclusion The BDNF gene Va166Met polymorphism is possibly correlated with impairment of cognitive function in patients with major depressive disorder.     

Effects of tryptophan depletion on serum levels of brain-derived neurotrophic factor in unmedicated patients with remitted depression and healthy subjects

OBJECTIVE: Data suggest the involvement of serotonergic and neurotrophic systems in major depressive disorder. To investigate their potential interaction, the authors studied changes in serum levels of brain-derived neurotrophic factor (BDNF) during tryptophan depletion and sham depletion in unmedicated patients with remitted major depressive disorder and in a group of healthy comparison subjects. METHOD: Twenty-seven patients with remitted major depressive disorder and 20 healthy subjects underwent tryptophan depletion and sham depletion in a randomized, placebo-controlled, double-blind crossover study. Serum BDNF concentrations and plasma tryptophan concentrations as well as behavioral assessments were obtained. RESULTS: During tryptophan depletion, BDNF levels increased in healthy volunteers. By contrast, patients with remitted major depressive disorder were unable to mount this presumed compensatory response, and BDNF levels remained low in these patients. CONCLUSIONS: The results further substantiate the potential role of BDNF in major depressive disorder.     

利培酮对精神分裂症首次发病患者血清脑源性神经营养因子水平的影响

目的：探讨利培酮对首发精神分裂症患者血清脑源性神经营养因子（BDNF）水平的影响。方法：采用酶联免疫吸附法测定40例首发精神分裂症患者（患者组）在给予利培酮治疗前和治疗8周后的血清BDNF水平,并与40名正常人（正常对照组）的血清BDNF水平进行比较。结果：治疗前患者组血清BDNF水平显著低于正常对照组（P〈0．05）,治疗8周,患者组血清BDNF水平较治疗前明显升高（P〈0．01）;与正常对照组差异无统计学意义（P〉0．05）。患者组中有阳性家族史者（8例）与阴性家族史者（32例）之间血清BDNF水平差异无统计学意义（P〉0．05）。患者组治疗前后血清BDNF水平与阳性与阴性症状量表评分（r=0．283,r=0．09;P〉0．05）无显著相关;两组血清BDNF水平与年龄（r=-0．142,r=-0．122;P〉0．05）、体质量指数（r=-0．112,r=0．039;P〉0．05）均无显著相关。结论：首发精神分裂症患者可能存在血清BDNF水平低下,利培酮治疗可提高其血清BDNF水平。     

Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients

Neurotrophic factors regulate neuronal development as well as synaptic plasticity, and their impairment is often implicated as a cause of schizophrenia. Among various neurotrophic molecules, brain-derived neurotrophic factor (BDNF) levels have been found to be increased in the corticolimbic regions of patients’ brains. In the present study, we assessed peripheral BDNF levels in whole blood as well as in the serum of two independent groups of schizophrenic patients (n=34 in each group) and healthy volunteers (n=35 and n=27, respectively). BDNF protein levels in fresh serum and blood of the patients and volunteers were measured using a two-site enzyme immunoassay and correlated with the number and decay of platelets. In addition to the studies of patients and volunteers, neuroleptic effects on BDNF levels were assessed by administering haloperidol to adult rats for 2 weeks or 5 months. The major findings were as follows: BDNF levels were significantly reduced in the serum of schizophrenic patients (P<0.005, Mann–Whitney U-test) but not in their whole blood. Antipsychotic dose did not correlate with serum BDNF levels. Moreover, chronic administration of haloperidol failed to decrease serum BDNF levels in adult rats. Abnormal levels of BDNF are evident not only in the brain of schizophrenic patients, but also in their peripheral blood. The BDNF reduction in serum but not in whole blood suggests a potential deficit in neurotrophic factor release in patients with schizophrenia.     

晚发性抑郁症患者血浆脑源性神经营养因子水平与认知功能

目的 探讨晚发性抑郁症患者血浆脑源性神经营养因子(BDNF)水平与抑郁症发病及认知功能之间的关系.方法 采用酶联免疫吸附法测定34例未经治疗的晚发性抑郁症患者(患者组)和32名正常对照(对照组)血浆BDNF水平;对患者组及对照组进行17项汉密尔顿抑郁量表( HAMD17)评估及神经心理学测试;对患者组的血浆BDNF水平及HAMD17总分与认知功能进行Pearson相关分析.结果 患者组治疗前的神经认知测试成绩显著差于对照组(P＜0.01);患者组的血浆BDNF水平[(3.24±2.67) μg/L]低于对照组[(6.71±3.16)μg/L,P＜0.01].血浆BDNF水平与各项认知成绩、HAMD17总分值均无显著相关性(P＞0.05).结论 部分晚发性抑郁症患者存在认知功能广泛受损;血浆BDNF水平低下与晚发性抑郁症发病密切相关,与认知功能可能无直接相关性.     

脑出血患者血清脑源性神经营养因子与痴呆的相关性分析

目的 探讨脑出血患者血清脑源性神经营养因子(BDNF)与痴呆的相关性.方法 选取180例脑出血患者,出院后6个月根据认知功能评分分为血管性认知功能障碍组(VCI)60例,其中血管性痴呆组(VD)22例,非痴呆型血管性认知功能障碍组(VCIND)38例;对照组为无认知障碍者120例.入院后及出院后6个月采用酶联免疫吸附法...     

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.