Journal ArticleDOI
Serotonin Transporter Genetic Variation and the Response of the Human Amygdala
Ahmad R. Hariri,Venkata S. Mattay,Alessandro Tessitore,Bhaskar Kolachana,Francesco Fera,David Goldman,Michael F. Egan,Daniel R. Weinberger +7 more
TLDR
Genetically driven variation in the response of brain regions underlying human emotional behavior is demonstrated and differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.Abstract:
A functional polymorphism in the promoter region of the human serotonin transporter gene (SLC6A4) has been associated with several dimensions of neuroticism and psychopathology, especially anxiety traits, but the predictive value of this genotype against these complex behaviors has been inconsistent. Serotonin [5- hydroxytryptamine, (5-HT)] function influences normal fear as well as pathological anxiety, behaviors critically dependent on the amygdala in animal models and in clinical studies. We now report that individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter polymorphism, which has been associated with reduced 5-HTT expression and function and increased fear and anxiety-related behaviors, exhibit greater amygdala neuronal activity, as assessed by BOLD functional magnetic resonance imaging, in response to fearful stimuli compared with individuals homozygous for the long allele. These results demonstrate genetically driven variation in the response of brain regions underlying human emotional behavior and suggest that differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.read more
Citations
More filters
Journal ArticleDOI
Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene
Avshalom Caspi,Karen Sugden,Terrie E. Moffitt,Alan Taylor,Ian W. Craig,Hona Lee Harrington,Joseph L. McClay,Jonathan Mill,Judy Martin,Antony W. Braithwaite,Richie Poulton +10 more
TL;DR: Evidence of a gene-by-environment interaction is provided, in which an individual's response to environmental insults is moderated by his or her genetic makeup.
Journal ArticleDOI
The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function
Michael F. Egan,Masami Kojima,Masami Kojima,Joseph H. Callicott,Terry E. Goldberg,Bhaskar Kolachana,Alessandro Bertolino,Eugene Zaitsev,Bert Gold,David Goldman,Michael Dean,Bai Lu,Daniel R. Weinberger +12 more
TL;DR: A role is demonstrated for BDNF and its val/met polymorphism in human memory and hippocampal function and it is suggested val/ met exerts these effects by impacting intracellular trafficking and activity-dependent secretion of BDNF.
Journal ArticleDOI
Beyond Diathesis Stress: Differential Susceptibility to Environmental Influences.
Jay Belsky,Michael Pluess +1 more
TL;DR: Evidence consistent with the proposition that individuals differ in plasticity is reviewed, and multiple instances in which specific genes function less like "vulnerability factors" and more like "plasticity factors," thereby rendering some individuals more malleable or susceptible than others to both negative and positive environmental influences.
Journal ArticleDOI
5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression
Lukas Pezawas,Andreas Meyer-Lindenberg,Emily M. Drabant,Beth A. Verchinski,Karen E. Munoz,Bhaskar Kolachana,Michael F. Egan,Venkata S. Mattay,Ahmad R. Hariri,Daniel R. Weinberger +9 more
TL;DR: Morphometrical analyses showed reduced gray matter volume in short-allele carriers in limbic regions critical for processing of negative emotion, particularly perigenual cingulate and amygdala, and relative uncoupling of this circuit.
Journal ArticleDOI
The brain basis of emotion: A meta-analytic review
TL;DR: A meta-analytic summary of the neuroimaging literature on human emotion finds little evidence that discrete emotion categories can be consistently and specifically localized to distinct brain regions, and finds evidence that is consistent with a psychological constructionist approach to the mind.
References
More filters
Journal ArticleDOI
Neurophysiological investigation of the basis of the fMRI signal
TL;DR: These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses.
Journal ArticleDOI
Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region
Klaus-Peter Lesch,D. Bengel,Armin Heils,Sue Z. Sabol,Benjamin D. Greenberg,Susanne Petri,Jonathan Benjamin,Clemens R. Müller,Dean H. Hamer,Dennis L. Murphy +9 more
TL;DR: The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5HTT expression and 5HT uptake in lymphoblasts as discussed by the authors, which is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs.
The Emotional Brain
TL;DR: In The Emotional Brain, Joseph LeDoux investigates the origins of human emotions and explains that many exist as part of complex neural systems that evolved to enable us to survive.
Journal ArticleDOI
The amygdala: vigilance and emotion
Michael Davis,Paul J. Whalen +1 more
TL;DR: A review of available studies examining the human amygdala covers both lesion and electrical stimulation studies as well as the most recent functional neuroimaging studies, and attempts to integrate basic information on normal amygdala function with the current understanding of psychiatric disorders, including pathological anxiety.
Journal ArticleDOI
Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia.
Michael F. Egan,Terry E. Goldberg,Bhaskar Kolachana,Joseph H. Callicott,C.M. Mazzanti,Richard E. Straub,David Goldman,Daniel R. Weinberger +7 more
TL;DR: The data suggest that the COMT Val allele, because it increases prefrontal dopamine catabolism, impairs prefrontal cognition and physiology, and by this mechanism slightly increases risk for schizophrenia.