脑源性神经营养因子血清浓度与双相障碍关系横断面研究

背景近年来发现,脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）的血清浓度与双相障碍症状关系的研究结果不一致。目的检验BDNF血清浓度与双相障碍的关系,并讨论双相障碍家族史在两者关系中的作用。方法检测了228例双相障碍患者和153名健康对照者的BDNF血清浓度,采用杨氏躁狂量表和汉密尔顿抑郁量表（17项）评估患者的躁狂或抑郁症状,将杨氏躁狂量表评分≥20分定义为躁狂发作,共计85例;将汉密尔顿抑郁量表评分≥17分定义为抑郁发作,共计14例;将杨氏躁狂量表评分〈20分并且汉密尔顿抑郁量表评分〈17分定义为缓解期,共计129例。结果患者组平均（标准差）BDNF血清浓度低于健康对照组[18．75（8．98）ng／d比23．72（5．60）．g／ml,t=6．09,P〈0．001】,且各个亚组（躁狂组、抑郁组和缓解期组）与健康对照组BDNF血清浓度的差异均有统计学意义。躁狂发作期与缓解期之间的BDNF血清浓度差异有统计学意义,其余各亚组间的差异无统计学意义。在多元线性回归模型中控制各个因素后,发现仅有杨氏躁狂量表评分与BDNF血清浓度呈正相关（标准回归系数=0．17,P=0．011）。结论双相障碍患者的BDNF血清浓度低于健康对照组,BDNF血清浓度与躁狂症状存在正相关,与是否存在家族史并不相关。     

脑梗死后认知功能障碍患者血清BDNF水平及氟西汀的治疗作用

目的探讨脑梗死后认知功能障碍与血清BDNF的关系,观察氟西汀对血清BDNF和认知功能的影响。方法应用ELISA法检测血清BDNF水平,比较脑梗死后认知功能障碍组患者和认知功能正常组患者血清BDNF水平。将脑梗死后认知功能障碍组患者按照有无接受氟西汀治疗随机分为对照组和氟西汀组,观察两组治疗前后血清BDNF水平及MMSE分值的变化。分析血清BDNF与MMSE分值的相关性。结果脑梗死后认知功能障碍组患者血清BDNF水平低于认知功能正常组;对照组治疗前、后MMSE分值及血清BDNF水平无明显变化;氟西汀治疗组治疗后MMSE分值及血清BDNF水平均较治疗前升高;氟西汀治疗组治疗后MMSE分值及血清BDNF水平均较对照组治疗后升高;脑梗死后认知功能障碍患者MMSE分值与血清BDNF水平呈正相关。结论脑梗死后认知功能障碍的发生和程度与血清BDNF水平有关,氟西汀能改善脑梗死后认知功能患者的认知功能,并可能部分是通过增加血清BDNF来实现的。     

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。     

伴自杀未遂双相障碍患者的血清脑源性神经营养因子水平

目的 分析伴自杀未遂的双相障碍（BD）患者与不伴自杀未遂患者及健康人群间血清BDNF水平的差异,探讨BDNF在预防BD患者自杀中的作用.方法 采用DSM-IV轴Ⅰ障碍用临床定式检查（患者版）（SCID-I/P）对临床诊断为心境障碍的患者进行评佑.纳入111例BD患者（26例有自杀未遂史）及41例健康对照.使用汉密尔顿抑郁量表（HAMD-17）及杨氏躁狂量表（YMRS）评估患者症状严重程度;使用酶联免疫吸附测定法测定所有研究对象的血清BDNF水平.结果 伴自杀未遂的BD患者血清BDNF水平（13.8±7.4） ng/ml显著低于无自杀未遂患者（18.7±11.9） ng/ml及健康对照组（26.0±12.9）ng/ml（F=9.371,P＜0.01）;伴自杀未遂的BD患者抑郁发作次数显著多于不伴自杀未遂患者,在控制抑郁发作次数后,两组间血清BDNF水平差异消失（P=0.236）;伴自杀未遂的BD患者血清BDNF水平和抑郁发作次数有相关性的倾向（r=-0.388,P=0.068）,与HAMD-17得分呈负相关（r=-0.585,P＜0.01）.结论 本研究提示BDNF在BD及BD患者自杀未遂的病理生理机制中起重要作用;伴自杀未遂的BD患者血清BDNF水平可能与抑郁发作次数、抑郁严重程度相关;通过有效治疗来提高BDNF水平可能通过减少抑郁发作次数,降低抑郁严重程度来降低自杀风险.     

阿托伐他汀钙治疗急性脑梗死的疗效及对血清BDNF水平的影响

目的 探讨阿托伐他汀钙治疗急性脑梗死的疗效及对血清脑源性神经营养因子(BDNF)水平的影响.方法 选取首次发病的急性脑梗死患者126例,随机分为治疗组和对照组,2组均常规治疗,治疗组同时加用阿托伐他汀钙治疗.分别在治疗前、治疗后6个月采用美国国立卫生院卒中量表(NIHSS)评价患者的神经功能缺损状况,日常生活活动能力量表(ADL)评价患者的活动能力,并采用双抗体夹心酶联免疫吸附法检测血清BDNF水平.结果 治疗6个月以后,2组NIHSS评分均明显降低(P＜0.05),且治疗组明显高于对照组(P＜0.05);2组ADL评分均明显升高(P＜0.05),且治疗组显著高于对照组(P＜0.05);治疗组和对照组血清BDNF含量均明显升高(P＜0.05),且治疗组的血清BDNF含量比对照组升高的更多(P＜0.05).结论 阿托伐他汀钙可明显提高血清BDNF水平,改善急性脑梗死患者的神经功能和日常活动能力.     

Tourette's综合征患者血清脑源性神经营养因子表达水平对照研究

目的 探讨Tourette's综合征(TS)患者血清脑源性神经营养因子水平.方法 用ELISA法检测31例TS患者和29例年龄性别相匹配的正常人血清中BDNF含量.结果 TS组血清BDNF含量显著低于正常对照组[(14.26±10.69)ng/ml vs(23.34±6.86)ng/ml,P=0.001].结论 BDNF表达的下调可能是导致TS神经退行性改变的细胞分子机制之一.     

神经病理性疼痛患者血清BDNF,5-HT水平

目的 研究神经病理性疼痛(NP)患者的血清脑源性神经营养因子(BDNF)和5-羟色胺(5-HT)水平变化及其焦虑、抑郁状况,探索NP可能的生化机制和临床心理特征.方法 在精神专科医院门诊和综合医院神经科门诊收集NP患者(NP组)35例,同期收集健康对照者(对照组)42人,进行血清采集和量表评定,用ELISA法测其血清BDNF和5-HT浓度,采用疼痛视觉模拟评分法(VAS)、Zung抑郁自评量表(SDS)和Zung焦虑自评量表(SAS)评估研究对象的疼痛强度、抑郁和焦虑水平.结果 NP组BDNF血清浓度显著低于对照组,差异有统计学意义(t=2.157,P=0.034),两组5-HT血清浓度的差异无统计学意义(t=-0.315,P=0.754);对照组BDNF与5-HT血清浓度呈正相关(r=0.461,P=0.004).VAS与5-HT浓度呈负相关(r=-0.326,P=0.021);NP组SDS、SAS评分均高于对照组(t=2.058,P=0.039;t=2.568,P=0.011),VAS分与SAS及SDS评分均呈正相关(r=0.502,P=0;r=0.346,P=0.018);SDS分、SAS分与BDNF、5-HT浓度水平均无相关性.结论 BDNF可能在神经病理性疼痛发生的生化机制中起一定作用;NP患者的焦虑、抑郁症状明显,但主要表现为疼痛感所致的继发性状态,与NP的生化机制无相关性.     

Tourettes综合征患对照研究术者血清脑源性神经营养因子表达水平

目的探讨Touretteg综合征（TS）患者血清脑源性神经营养因子水平。方法用ELISA法检测31例TS患者和29例年龄性别相匹配的正常人血清中BDNF含量。结果TS组血清BDNF含量显著低于正常对照纽[（14．26&#177;10．69）ng／mlvs（23．34&#177;6．86）ng／ml,P=0．001]。结论BDNF表达的下调可能是导致TS神经退行性改变的细胞分子机制之一。     

BDNF及其受体TrkB在实验性癫痫中的作用及意义探讨

目的检测大鼠杏仁核点燃癫痫后不同脑区脑源性神经营养因子（BDNF）及其受体TrkB的表达与定位。方法建立大鼠杏仁核点燃癫痫模型，应用免疫组化方法观察点燃鼠不同脑区不同点燃时程BDNF及TrkB的表达及含量。结果点燃后大鼠颞叶及海马BDNF随着点燃次数的增加而升高，并持续至点燃后49d;TrkB的表达也随着点燃次数的增加而升高，并持续至点燃后7d（改变同BDNF），点燃1周后表达逐渐减少，至点燃后7周时基本恢复正常。结论BDNF及TrkB直接参与癫痫的发生与发展，早期具有保护作用，但随着表达的进一步增加，又促进癫痫的发生发展，并一定程度上促进了癫痫发作后的神经细胞凋亡及脑损伤过程。     

Serum levels of brain-derived neurotrophic factor in patients with internet use disorder

Internet use disorder (IUD) is characterised by excessive internet gaming use and has temporarily been conceptualised as a behavioural addiction. Since brain-derived neurotrophic factor (BDNF) has been hypothesised to be involved in the development and maintenance of addictive disorders, we investigated BDNF expression in IUD. We measured BDNF serum levels in male patients with IUD (n=11) and individually matched healthy controls (n=10). There was no significant difference in BDNF serum levels of patients with IUD in comparison to control subjects. Serum levels of BDNF were not correlated with severity of IUD or clinical and demographic variables in our study. These preliminary findings possibly suggest a different underlying pathophysiology in IUD compared to addictive disorders. Thus, further studies are needed to clarify, whether IUD represents an addictive spectrum disorder, an impulse control disorder or finally an individual diagnostic entity that overlaps with both disease categories.     

Serum concentrations of brain-derived neurotrophic factor in patients with gender identity disorder

Gender Identity Disorder (GID) is characterized by a strong and persistent cross-gender identification that affects different aspects of behavior. Brain-derived neurotrophic factor (BDNF) plays a critical role in neurodevelopment and neuroplasticity. Altered BDNF-signaling is thought to contribute to the pathogenesis of psychiatric disordersand is related to traumatic life events. To examine serum BDNF levels, we compared one group of DSM-IV GID patients (n = 45) and one healthy control group (n = 66). Serum BDNF levels were significantly decreased in GID patients (p = 0.013). This data support the hypothesis that the reduction found in serum BDNF levels in GID patients may be related to the psychological abuse that transsexuals are exposed during their life.     

共患学习障碍的注意缺陷多动障碍儿童脑源性神经营养因子与5-羟色胺的关联性研究

目的 探讨脑源性神经营养因子(BDNF)与血清5-羟色胺(5-HT)在伴学习障碍(LD)的注意缺陷多动障碍(ADHD)患儿中的作用及关系. 方法 选择河南省精神卫生中心门诊及病房自2011年1月至2011年10月收治的ADHD患儿40例,其中伴LD患儿15例,不伴LD患儿25例,选择同期健康体检儿童25例作为正常对照组,比较3组受试者血清BDNF、5-HT的水平并分析ADHD伴LD组患儿血清BDNF及5-HT水平的相关性. 结果 ADHD伴LD组、ADHD不伴LD组及正常对照组BDNF水平依次降低,差异有统计学意义(P＜0.05);与ADHD伴LD组比较,ADHD不伴LD组及正常对照组5-HT水平升高,差异有统计学意义(P＜0.05);ADHD伴LD组患儿血清BDNF、5-HT水平呈负相关关系(r=-0.084,P=0.004). 结论 伴LD的ADHD患儿中存在BDNF及5-HT异常,二者可能相互作用共同参与ADHD的病理过程.     

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.     

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.     

Plasma brain-derived neurotrophic factor concentrations in children and adolescents

Background

Brain-derived neurotrophic factor (BDNF) is a mediator of neuronal plasticity influencing learning, memory and cognitive behavior. The aim of this study is to assess plasma BDNF variations according to pubertal status.

Methods

A total of 110 subjects were included in the study. Blood samples were collected after overnight fasting. Plasma BDNF concentrations were measured by enzyme-linked immunosorbent assay. Gonadotrophins, sex steroids, and IGF-1 were also assessed.

Results

BDNF was positively correlated with platelet count and negatively associated with both BMI and age. BDNF levels in pubertal males were significantly lower than prepubertal males and both prepubertal and pubertal females.

Conclusions

Plasma BDNF levels seem to be influenced by hormonal status. We demonstrate that parameters such as age or gender have a specific impact on stored and circulating BDNF blood levels and platelets remain the most important predictor of their concentration. Further studies are necessary to better understand the role of this neurotrophin in pubertal development.     

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.