BDNF gene polymorphism (Val66Met) predicts amygdala and anterior hippocampus responses to emotional faces in anxious and depressed adolescents.
BDNF gene polymorphism (Val66Met) predicts amygdala and anterior hippocampus responses to emotional faces in anxious and depressed adolescents.
复制标题
DOI：
10.1016/j.neuroimage.2009.11.026
复制
发表时间：
2010-11-15
期刊：
影响因子：
5.7
通讯作者：
Ernst, Monique
中科院分区：
文献类型：
--
作者：
Lau, Jennifer Y. F.;Goldman, David;Buzas, Beata;Hodgkinson, Colin;Leibenluft, Ellen;Nelson, Eric;Sankin, Lindsey;Pine, Daniel S.;Ernst, Monique
关键词：
人脑源性神经营养因子 (BDNF) 基因的多态性在密码子 66 (Val66Met) 处产生缬氨酸到蛋氨酸的取代，可能通过影响大脑回路功能而与成人焦虑和情绪障碍相关。尚未在焦虑和抑郁的青少年中探索 BDNF 基因变异与大脑活动之间的关联。目前的研究调查了患有焦虑症和/或重度抑郁症（MDD）的青少年以及健康青少年的 BDNF 基因型与杏仁核-海马对情绪刺激的反应之间的关联。 27 名患有严重受损的当前焦虑症和/或 MDD 的未接受药物治疗的患者和 31 名健康青少年，在收集杏仁核和海马体的功能磁共振成像数据期间，对他们对恐惧、愤怒、中性和快乐面部表情的恐惧进行了年龄、性别和智商匹配。使用重复测量方差分析模型分析左右杏仁核和海马反应，其中诊断（患者、健康）和基因型（Met 携带者、Val/Val 纯合子）作为组间因素，面部表情（恐惧、愤怒、中性、快乐）作为受试者内因素。诊断和基因型诊断相互作用的显着影响（F's>4，p's<.05）表征了杏仁核和前海马区域的激活。研究发现，患者的激活程度高于健康青少年。重要的是，这些过度激活是由 BDNF 基因型调节的：Met 携带者在情绪面孔上表现出比仅在 Val/Val 纯合子患者中更大的神经反应。这些数据首先证明了 BDNF 基因变异对青少年焦虑和抑郁的神经相关因素的贡献。早期的“基因-大脑”联系可能为情感障碍神经功能障碍的长期模式奠定基础。
A polymorphism of the human Brain Derived Neurotrophic Factor (BDNF) gene that produces a valine-to-methionine substitution at codon 66 (Val66Met), is linked to adult anxiety and mood disorders, possibly through effects on brain circuitry function. Associations between BDNF gene variants and brain activity have not been explored in anxious and depressed adolescents. The current study investigated the association between BDNF genotype and amygdala-hippocampal responses to emotional stimuli in adolescents with anxiety disorders and/or major depressive disorder (MDD) and in healthy adolescents. Twenty-seven unmedicated patients with acutely-impairing current anxiety disorders and/or MDD and 31 healthy adolescents, matched on age, gender and IQ, rated their fear of fearful, angry, neutral and happy facial expressions during collection of fMRI data on the amygdala and hippocampus. Left and right amygdala and hippocampal responses were analyzed using Repeated-measures Analyses of Variance models, with Diagnosis (patients, healthy) and Genotype (Met-carriers, Val/Val homozygotes) as between-group factors and facial expression (fearful, angry, neutral, happy) as a within-subject factor. Significant effects of Diagnosis and Diagnosis-by-Genotype interactions (F’s>4, p’s<.05) characterized activations in amygdala and anterior hippocampal regions. Greater activations in patients than healthy adolescents were found. Critically, these hyperactivations were modulated by BDNF genotype: Met-carriers showed greater neural responses of emotional faces than Val/Val homozygotes in patients only. These data are first to demonstrate the contribution of BDNF gene variants to the neural correlates of adolescent anxiety and depression. Early “gene-brain” linkages may lay the foundation for longer-term patterns of neural dysfunction in affective disorders.
登录
查看更多内容
影响因子：
10.6
作者：
Kaufman, J;Yang, BZ;Gelernter, J
通讯作者：
Gelernter, J
影响因子：
--
作者：
Beesdo, Katja;Lau, Jennifer Y. F.;Guyer, Amanda E.;McClure-Tone, Erin B.;Monk, Christopher S.;Nelson, Eric E.;Fromm, Stephen J.;Goldwin, Michelle A.;Wittchen, Hans-Ulrich;Leibenluft, Ellen;Erns, Monique;Pine, Daniel S.
通讯作者：
Pine, Daniel S.
影响因子：
10.6
作者：
Davidson, RJ
通讯作者：
Davidson, RJ
影响因子：
17.7
作者：
Callicott, JH;Mattay, VS;Weinberger, DR
通讯作者：
Weinberger, DR
影响因子：
17.7
作者：
Arbelle, S;Benjamin, J;Ebstein, RP
通讯作者：
Ebstein, RP