抑郁症患者脑源性神经营养因子Va166Met多态性与血清浓度的关系

目的 探讨脑源性神经营养因子(BDNF)基因Va166Met多态性与抑郁症之间的关系以及Va166Met多态性是否影响血清BDNF浓度.方法 对76例未经药物治疗的抑郁症患者和50例正常人,用限制性片段长度多态性方法分析Va166Met多态性,采用酶联吸附反应方法对血清BDNF浓度进行检测.结果 (1)抑郁症患者血清BDNF浓度(24.7±12.7)ng/ml显著低于正常对照组(36.6±16.4)pg/ml,差异有统计学意义(P＜0.01);(2)抑郁症组和对照组之间的Va166Met多态性位点的等位基因频率和基因型分布差异无统计学意义(P＞0.05);(3)在押郁症组和对照组,Val/Met+Met/Met基因型组与Val/Val基因型相比,血清BDNF浓度差异无统计学意义(P＞0.05).结论 抑郁症患者存在较低的血清BDNF水平,BDNF基因Val66Met多态性与抑郁症之间无相关性,Va166Met多态性对血清BDNF水平浓度无明显影响.     

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。     

脑源性神经营养因子与抑郁症

神经营养因子是神经元网络形成和可塑性的重要调节因子,以脑源性神经营养因子(BDNF)最受关注。抗抑郁治疗通过提高BDNF表达来促进神经元可塑性,从而取得疗效。本文从临床前研究、临床研究和基因多态性等方面对BDNF与抑郁症作一综述。     

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...     

脑源性神经营养因子和抑郁症

抑郁症是以显著而持久的情绪低落或心境改变为主要特征的一组精神疾病。其高发病率、致死率、高疾病负担已引起社会各界的关注。然而,由于其发病机制的不详,患者很难获得完全治愈的机会。近年来,国内外研究者发现脑源性神经营养因子可能参与抑郁症的发病和治疗过程。脑源性神经营养因子(Brain-derived neurotrophic factor,BD-NF)在中枢神经系统及周围神经系统的多种神经元均有分布,尤以海马和皮层含量最高。其基因定位于11p13,酪氨酸激酶受体B(tyrosine kinase receptor,TrkB)是其特异性受体,当BDNF与TrkB结合时,受体分子二聚化,其多…     

脑源性神经营养因子与抑郁症的研究进展

海马结构和功能的改变涉及抑郁症的病理生理学过程，海马脑源性神经营养因子表达下调与海马结构和功能的改变密切相关，促进细胞凋亡可能参与慢性应激损伤海马。抗抑郁剂通过调节脑源性神经营养因子的表达逆转海马损伤而发挥治疗作用。     

脑源性神经营养因子基因Val66Met多态性与重性抑郁障碍患者认知功能的关系

目的:探讨脑源性神经营养因子(BDNF)基因Val66Met多态性与重性抑郁障碍认知功能的关系。方法:对100例重性抑郁障碍患者进行认知功能测验和事件相关电位P300检查,同时检测BDNF基因多态性。结果:Val/Val基因型患者大部分认知测验成绩优于Met/Met基因型,差异均有统计学意义(P均<0.01);Met/Met基因型患者P3潜伏期(LATP3)长于Val/Val基因型[分别(304.3±11.8)ms和(293.3±15.7)ms],P3波幅(AMPP3)低于Val/Val基因型[分别(5.9±1.9)μV和(7.4±2.1)μV],差异均有统计学意义(P<0.05或P<0.01)。结论:BDNF基因Val66Met多态性可能与重性抑郁障碍患者认知功能损害有关。     

血清脑源性神经营养因子水平及其基因多态性与首发老年抑郁症认知功能的关系

目的 探求血清脑源性神经营养因子（BDNF）水平及其基因多态性与老年首发抑郁症患 者认知功能障碍的关系。方法 前瞻性连续纳入2014 年4 月至2016 年1 月首都医科大学附属北京安定 医院门诊或住院的60 岁及以上老年首发抑郁症患者。采用汉密尔顿抑郁量表（HAMD-17）、言语流畅性 测验、连线测验A-B、Stroop字色测试和威斯康星卡片分类测试对患者进行抑郁症严重程度及认知功能 的评定,采集患者静脉血测定血清BDNF水平,并提取DNA,测定BDNF rs6265 基因单核苷酸多态性位 点。结果 共80 例老年抑郁症患者纳入本研究。BDNF rs6265 基因型与抑郁障碍严重程度无关（均P＞ 0.05）。HAMD-17 总分与言语流畅性测验、WCST持续性错误数呈负相关（r=-0.239、-0.226,均P＜ 0.05）。 rs6265 VAL/MET 基因型的连线测验A-B 表现较VAL/VAL 基因型差［（62.0±18.9）分比（48.3±18.6）分］, 差异有统计学意义（P＜ 0.05）。血清BDNF水平与认知功能之间无相关性（均P ＞ 0.05）,与HAMD-17 评 分呈负相关（r=-0.23,P＜ 0.05）。结论 BDNF rs6265 基因多态性与老年抑郁症患者认知功能损害相关, 而与BDNF 水平无显著关联,提示BDNF 可能通过其他机制影响老年抑郁症认知功能。     

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。     

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.     

Val66Met polymorphism association with serum BDNF and inflammatory biomarkers in major depression

Objectives: Current evidence supports participation of neurotrophic and inflammatory factors in the pathogenesis of major depressive disorder (MDD). Some studies reported an association between the Val66Met polymorphism (rs6265) of brain-derived neurotrophic factor (BDNF) gene with MDD and peripheral BDNF levels. However, no previous studies have examined the association of this polymorphism with inflammation. The present study assessed the association of the Val66Met polymorphism with serum levels of BDNF and inflammatory markers among depressed outpatients.

Methods: All participants (n?=?73) met DSM-IV criteria for a unipolar depressive episode. The serum levels of BDNF and inflammatory biomarkers (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) were compared between individuals presenting with at least one Met allele (Met-carriers) and those homozygous for the Val allele.

Results: In our sample (84.9% female, mean age 52.4?±?10.3 years), 24.7% (n?=?18) were Met-carriers. After Bonferroni correction, the Met allele was significantly associated with higher BDNF and lower TNF-α. These associations persisted after adjusting for potential confounders.

Conclusions: The pattern of low BDNF and high inflammation in MDD may be influenced by the Val66Met polymorphism. The association of a polymorphism in the BDNF gene with inflammatory markers in addition to BDNF levels suggests an interaction between these systems.     

精神分裂症脑源性神经营养因子和海马结构改变的关联

精神分裂症是一种严重精神病,以幻觉、思维及行为紊乱和社会功能退化为特征,患病率为1％,给个人、家庭及社会带来极大负担。精神分裂症的研究涉及遗传、神经生化、病理生理、影像学等多个领域,但其确切病因及病理机制目前仍不明确。脑影像学研究表明,精神分裂症患者存在大脑结构异常,主要表现为侧脑室扩大和脑体积减小。     

Brain-derived neurotrophic factor Val66Met polymorphism and dexamethasone/CRH test results in depressed patients

Data suggest that both neurotrophic and hypothalamic-pituitary-adrenocortical (HPA) systems are involved in the pathophysiology of depression. The aim of the present study was to investigate whether the non-conservative brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has an impact on HPA axis activity in depressed patients. At admission, the dexamethasone/CRH (DEX/CRH) test was performed in 187 drug-free in-patients suffering from major depression or depressed state of bipolar disorder (DSM-IV criteria). Moreover, genotyping of BDNF Val66Met polymorphism was carried out using the fluorescence resonance energy transfer method (FRET). Homozygous carriers of the Met/Met genotype showed a significantly higher HPA axis activity during the DEX/CRH test than patients carrying the Val/Val or Val/Met genotype (ACTH, cortisol). Our results further contribute to the hypothesized association between HPA axis dysregulation and reduced neuroplasticity in depression and are consistent with the assumption that BDNF is a stress-responsive intercellular messenger modifying HPA axis activity.     

Brain derived neurotrophic factor Val66Met polymorphism, the five factor model of personality and hippocampal volume: Implications for depressive illness

Altered hippocampal volume, the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and neuroticism have each been implicated in the etiology of psychiatric disorders, especially depression. However, the relationship between these variables is not well understood. Here, we determined the effects of the BDNF Val66met polymorphism on the five-factor personality dimensions (assessed using the NEO-FFI), trait depression (assessed with the DASS-21) in a cross-sectional cohort of 467 healthy volunteers. A large matched subset of this cohort was also assessed for grey matter volume of the hippocampus and contiguous temporal cortical regions using magnetic resonance imaging. In Met carriers, elevations in neuroticism and trait depression and stress were associated with lower mean hippocampal volume, but there were no such associations in Val homozygotes. Trait depression, in particular, was found to moderate the effects of BDNF genotypes on hippocampal volume. Met carriers with high trait depression showed a reduction in grey matter volume of the mean hippocampus compared with Val homozygotes. These findings suggest that even in otherwise healthy subjects, trait depression may contribute to the susceptibility of Met carriers to hippocampal grey matter loss.     

中老年抑郁症患者执行功能障碍及其与血清脑源性神经营养因子的关系

目的探讨中老年抑郁症患者执行功能及其与血清脑源性神经营养因子(BDNF)的关系,为了解中老年抑郁症患者执行功能及生化指标的变化提供理论基础。方法选取2014年6月-2015年1月在贵州医科大学附属医院心理科住院的、符合《精神障碍诊断与统计手册(第4版)》(DSM-IV)抑郁症诊断标准的中老年住院患者78例(抑郁组),并于同期选取贵州医科大学附属医院职工、心理科患者家属80例(对照组),根据抑郁自评量表(SDS)评分将抑郁组分为轻中度抑郁组和重度抑郁组。采用执行功能行为评定量表成人版自评问卷(BRIEF-A)评定抑郁组和正常对照组的执行功能,包括行为管理指数(BRI)和元认知指数(MI)。采用生物素双抗体夹心酶联免疫吸附法(ELISA)测定BDNF水平。结果抑郁组BRIEF-A总评分、BRI、MI及各因子评分均高于正常对照组(P均0.01);重度抑郁组的抑制、转移、工作记忆因子评分与轻中度抑郁组差异无统计学意义(P均0.05),而BRIEF-A总评分及其他因子评分均高于轻中度抑郁组(P均0.05)。中老年抑郁组BDNF水平低于正常对照组,重度抑郁组BDNF水平低于轻中度抑郁组(P均0.05)。执行功能总评分及各因子评分与BDNF水平的相关均无统计学意义(P均0.05)。结论与正常中老年人相比,中老年抑郁症患者执行功能明显受损,中老年抑郁组患者BDNF水平较低,且随抑郁程度加重而下降。抑郁症患者的执行功能和BDNF水平无明显相关性。     

弥漫性轴索损伤BDNF及其Val66Met基因多态性与认知功能的相关性研究

目的探讨弥漫性轴索损伤（DAI）（Ⅱ型）患者伤后1个月血清脑源性神经营养因子（BDNF）水平及其Val66Met基因多态性与认知功能的关系。 方法选取晋江市医院神经外科自2015年8月至2020年8月收治的106例DAI（Ⅱ型）患者为病例组,选择同期来本院体检的105名健康体检者为对照组,采用第二版洛文斯顿作业疗法认知量表（LOTCA）、蒙特利尔评估量表中文版（MoCA）分别评估对照组和病例组伤后1个月时的认知功能;采用酶联免疫吸附试验测定2组研究对象的血清BDNF水平;聚合酶链反应-限制性片段长度多态性分析BDNF Val66Met基因多态性;多元逐步回归法分析病例组整体认知功能与BDNF及BDNF Val66Met基因多态性的相关性。 结果病例组伤后1个月相同基因亚型血清BDNF浓度均低于对照组,差异有统计学意义（P<0.05）;病例组Val/Val亚型血清BDNF浓度高于Val/Met、Met/Met亚型,差异有统计学意义（P<0.05）,而Val/Met和Met/Met亚型血清BDNF浓度比较差异无统计学意义（P>0.05）。病例组患者3种基因亚型伤后1个月的LOTCA和MoCA评分均低于对照组,差异有统计学意义（P<0.05）;病例组Val/Val亚型评分高于Val/Met、Met/Met评分,差异有统计学意义（P<0.05）,而Val/Met和Met/Met亚型评分比较,差异无统计学意义（P>0.05）。DAI（Ⅱ型）整体认知水平与BDNF Val66Met基因多态性、BDNF浓度具有线性回归关系（F=11.417,P<0.001）,其具有一定的相关性（|β|=0.966、0.877;r=0.569、0.579）。 结论BDNF可影响DAI认知功能,其BDNF Val66Met基因多态性可能是影响DAI认知功能的风险因素之一。     

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.