Genetic variation in brain-derived neurotrophic factor and human fear conditioning

被引:66
作者
Hajcak, G. [1 ]
Castille, C. [1 ]
Olvet, D. M. [1 ]
Dunning, J. P. [1 ]
Roohi, J. [2 ]
Hatchwell, E. [2 ,3 ]
机构
[1] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Dept Genet, Stony Brook, NY 11794 USA
[3] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA
关键词
Anxiety; BDNF; fear; fear-potentiated startle; generalization; startle; FACTOR VAL66MET POLYMORPHISM; ACTIVITY-DEPENDENT SECRETION; LONG-TERM POTENTIATION; SYNAPTIC-TRANSMISSION; HUMAN-MEMORY; AMYGDALA; STARTLE; BDNF; CONSOLIDATION; EXTINCTION;
D O I
10.1111/j.1601-183X.2008.00447.x
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Brain-derived neurotrophic factor (BDNF) has been implicated in hippocampal-dependent learning processes, and carriers of the Met allele of the Val66Met BDNF genotype are characterized by reduced hippocampal structure and function. Recent nonhuman animal work suggests that BDNF is also crucial for amygdala-dependent associative learning. The present study sought to examine fear conditioning as a function of the BDNF polymorphism. Fifty-seven participants were genotyped for the BDNF polymorphism and took part in a differential-conditioning paradigm. Participants were shocked following a particular conditioned stimulus (CS+) and were also presented with stimuli that ranged in perceptual similarity to the CS+ (20, 40 or 60% smaller or larger than the CS+). The eye blink component of the startle response was measured to quantify fear conditioning; post-task shock likelihood ratings for each stimulus were also obtained. All participants reported that shock likelihood varied with perceptual similarity to the CS+ and showed potentiated startle in response to CS +/- 20% stimuli. However, only the Val/Val group had potentiated startle responses to the CS+. Met allele carrying individuals were characterized by deficient fear conditioning - evidenced by an attenuated startle response to CS+ stimuli. Variation in the BDNF genotype appears related to abnormal fear conditioning, consistent with nonhuman animal work on the importance of BDNF in amygdala-dependent associative learning. The relation between genetic variation in BDNF and amygdala-dependent associative learning deficits is discussed in terms of potential mechanisms of risk for psychopathology.
引用
收藏
页码:80 / 85
页数:6
相关论文
共 45 条
[1]   Contextual fear-potentiated startle conditioning in humans: Replication and extension [J].
Ameli, R ;
Ip, C ;
Grillon, C .
PSYCHOPHYSIOLOGY, 2001, 38 (03) :383-390
[2]   CONDITIONED FEAR AS REVEALED BY MAGNITUDE OF STARTLE RESPONSE TO AN AUDITORY STIMULUS [J].
BROWN, JS ;
KALISH, HI ;
FARBER, IE .
JOURNAL OF EXPERIMENTAL PSYCHOLOGY, 1951, 41 (05) :317-328
[3]   Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior [J].
Chen, Zhe-Yu ;
Jing, Deqiang ;
Bath, Kevin G. ;
Ieraci, Alessandro ;
Khan, Tanvir ;
Siao, Chia-Jen ;
Herrera, Daniel G. ;
Toth, Miklos ;
Yang, Chingwen ;
McEwen, Bruce S. ;
Hempstead, Barbara L. ;
Lee, Francis S. .
SCIENCE, 2006, 314 (5796) :140-143
[4]   Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons [J].
Chen, ZY ;
Patel, PD ;
Sant, G ;
Meng, CX ;
Teng, KK ;
Hempstead, BL ;
Lee, FS .
JOURNAL OF NEUROSCIENCE, 2004, 24 (18) :4401-4411
[5]   Amygdala BDNF signaling is required for consolidation but not encoding of extinction [J].
Chhatwal, Jasmeer P. ;
Stanek-Rattiner, Lisa ;
Davis, Michael ;
Ressler, Kerry J. .
NATURE NEUROSCIENCE, 2006, 9 (07) :870-872
[6]  
Conner JM, 1997, J NEUROSCI, V17, P2295
[7]  
Davis M., 1984, P287
[8]   FEAR-POTENTIATED STARTLE - A NEURAL AND PHARMACOLOGICAL ANALYSIS [J].
DAVIS, M ;
FALLS, WA ;
CAMPEAU, S ;
KIM, M .
BEHAVIOURAL BRAIN RESEARCH, 1993, 58 (1-2) :175-198
[9]   Neural systems involved in fear and anxiety measured with fear-potentiated startle [J].
Davis, Michael .
AMERICAN PSYCHOLOGIST, 2006, 61 (08) :741-756
[10]   Association between BDNF Val66Met genotype and episodic memory [J].
Dempster, E ;
Toulopoulou, T ;
McDonald, C ;
Bramon, E ;
Walshe, M ;
Filbey, F ;
Wickham, H ;
Sham, PC ;
Murray, RM ;
Collier, DA .
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2005, 134B (01) :73-75