Individual differences in neural correlates of fear conditioning as a function of 5-HTTLPR and stressful life events

Fear learning is a crucial process in the pathogeneses of psychiatric disorders, which highlights the need to identify specific factors contributing to interindividual variation. We hypothesized variation in the serotonin transporter gene (5-HTTLPR) and stressful life events (SLEs) to be associated...

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Published inSocial cognitive and affective neuroscience Vol. 8; no. 3; pp. 318 - 325
Main Authors Klucken, Tim, Alexander, Nina, Schweckendiek, Jan, Merz, Christian J., Kagerer, Sabine, Osinsky, Roman, Walter, Bertram, Vaitl, Dieter, Hennig, Juergen, Stark, Rudolf
Format Journal Article
LanguageEnglish
Published England Oxford University Press 01.03.2013
Subjects
Adult
Brain - blood supply
Brain - pathology
Brain Mapping
Conditioning, Classical - physiology
DNA Mutational Analysis
Fear - psychology
Female
Galvanic Skin Response - genetics
Genotype
Humans
Image Processing, Computer-Assisted
Individuality
Life Change Events
Magnetic Resonance Imaging
Male
Original
Oxygen - blood
Serotonin Plasma Membrane Transport Proteins - genetics
Stress, Psychological - genetics
Stress, Psychological - pathology
Stress, Psychological - psychology
Young Adult
amygdala
imaging genetics
classical conditioning
5-HTTLPR
fear
Online AccessGet full text
ISSN1749-5016
1749-5024
1749-5024
DOI10.1093/scan/nss005

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Abstract Fear learning is a crucial process in the pathogeneses of psychiatric disorders, which highlights the need to identify specific factors contributing to interindividual variation. We hypothesized variation in the serotonin transporter gene (5-HTTLPR) and stressful life events (SLEs) to be associated with neural correlates of fear conditioning in a sample of healthy male adults (n = 47). Subjects were exposed to a differential fear conditioning paradigm after being preselected regarding 5-HTTLPR genotype and SLEs. Individual differences in brain activity as measured by functional magnetic resonance imaging (fMRI), skin conductance responses and preference ratings were assessed. We report significant variation in neural correlates of fear conditioning as a function of 5-HTTLPR genotype. Specifically, the conditioned stimulus (CS+) elicited elevated activity within the fear-network (amygdala, insula, thalamus, occipital cortex) in subjects carrying two copies of the 5-HTTLPR S′ allele. Moreover, our results revealed preliminary evidence for a significant gene-by-environment interaction, such as homozygous carriers of the 5-HTTLPR S′ allele with a history of SLEs demonstrated elevated reactivity to the CS+ in the occipital cortex and the insula. Our findings contribute to the current debate on 5-HTTLPR x SLEs interaction by investigating crucial alterations on an intermediate phenotype level which may convey an elevated vulnerability for the development of psychopathology.
AbstractList Fear learning is a crucial process in the pathogeneses of psychiatric disorders, which highlights the need to identify specific factors contributing to interindividual variation. We hypothesized variation in the serotonin transporter gene (5-HTTLPR) and stressful life events (SLEs) to be associated with neural correlates of fear conditioning in a sample of healthy male adults (n = 47). Subjects were exposed to a differential fear conditioning paradigm after being preselected regarding 5-HTTLPR genotype and SLEs. Individual differences in brain activity as measured by functional magnetic resonance imaging (fMRI), skin conductance responses and preference ratings were assessed. We report significant variation in neural correlates of fear conditioning as a function of 5-HTTLPR genotype. Specifically, the conditioned stimulus (CS(+)) elicited elevated activity within the fear-network (amygdala, insula, thalamus, occipital cortex) in subjects carrying two copies of the 5-HTTLPR S' allele. Moreover, our results revealed preliminary evidence for a significant gene-by-environment interaction, such as homozygous carriers of the 5-HTTLPR S' allele with a history of SLEs demonstrated elevated reactivity to the CS(+) in the occipital cortex and the insula. Our findings contribute to the current debate on 5-HTTLPR x SLEs interaction by investigating crucial alterations on an intermediate phenotype level which may convey an elevated vulnerability for the development of psychopathology.Fear learning is a crucial process in the pathogeneses of psychiatric disorders, which highlights the need to identify specific factors contributing to interindividual variation. We hypothesized variation in the serotonin transporter gene (5-HTTLPR) and stressful life events (SLEs) to be associated with neural correlates of fear conditioning in a sample of healthy male adults (n = 47). Subjects were exposed to a differential fear conditioning paradigm after being preselected regarding 5-HTTLPR genotype and SLEs. Individual differences in brain activity as measured by functional magnetic resonance imaging (fMRI), skin conductance responses and preference ratings were assessed. We report significant variation in neural correlates of fear conditioning as a function of 5-HTTLPR genotype. Specifically, the conditioned stimulus (CS(+)) elicited elevated activity within the fear-network (amygdala, insula, thalamus, occipital cortex) in subjects carrying two copies of the 5-HTTLPR S' allele. Moreover, our results revealed preliminary evidence for a significant gene-by-environment interaction, such as homozygous carriers of the 5-HTTLPR S' allele with a history of SLEs demonstrated elevated reactivity to the CS(+) in the occipital cortex and the insula. Our findings contribute to the current debate on 5-HTTLPR x SLEs interaction by investigating crucial alterations on an intermediate phenotype level which may convey an elevated vulnerability for the development of psychopathology.
Fear learning is a crucial process in the pathogeneses of psychiatric disorders, which highlights the need to identify specific factors contributing to interindividual variation. We hypothesized variation in the serotonin transporter gene (5-HTTLPR) and stressful life events (SLEs) to be associated with neural correlates of fear conditioning in a sample of healthy male adults ( n  = 47). Subjects were exposed to a differential fear conditioning paradigm after being preselected regarding 5-HTTLPR genotype and SLEs. Individual differences in brain activity as measured by functional magnetic resonance imaging (fMRI), skin conductance responses and preference ratings were assessed. We report significant variation in neural correlates of fear conditioning as a function of 5-HTTLPR genotype. Specifically, the conditioned stimulus (CS + ) elicited elevated activity within the fear-network (amygdala, insula, thalamus, occipital cortex) in subjects carrying two copies of the 5-HTTLPR S′ allele. Moreover, our results revealed preliminary evidence for a significant gene-by-environment interaction, such as homozygous carriers of the 5-HTTLPR S′ allele with a history of SLEs demonstrated elevated reactivity to the CS + in the occipital cortex and the insula. Our findings contribute to the current debate on 5-HTTLPR x SLEs interaction by investigating crucial alterations on an intermediate phenotype level which may convey an elevated vulnerability for the development of psychopathology.
Fear learning is a crucial process in the pathogeneses of psychiatric disorders, which highlights the need to identify specific factors contributing to interindividual variation. We hypothesized variation in the serotonin transporter gene (5-HTTLPR) and stressful life events (SLEs) to be associated with neural correlates of fear conditioning in a sample of healthy male adults (n = 47). Subjects were exposed to a differential fear conditioning paradigm after being preselected regarding 5-HTTLPR genotype and SLEs. Individual differences in brain activity as measured by functional magnetic resonance imaging (fMRI), skin conductance responses and preference ratings were assessed. We report significant variation in neural correlates of fear conditioning as a function of 5-HTTLPR genotype. Specifically, the conditioned stimulus (CS+) elicited elevated activity within the fear-network (amygdala, insula, thalamus, occipital cortex) in subjects carrying two copies of the 5-HTTLPR S′ allele. Moreover, our results revealed preliminary evidence for a significant gene-by-environment interaction, such as homozygous carriers of the 5-HTTLPR S′ allele with a history of SLEs demonstrated elevated reactivity to the CS+ in the occipital cortex and the insula. Our findings contribute to the current debate on 5-HTTLPR x SLEs interaction by investigating crucial alterations on an intermediate phenotype level which may convey an elevated vulnerability for the development of psychopathology.
Author Schweckendiek, Jan
Alexander, Nina
Kagerer, Sabine
Merz, Christian J.
Vaitl, Dieter
Hennig, Juergen
Osinsky, Roman
Klucken, Tim
Stark, Rudolf
Walter, Bertram
AuthorAffiliation 1 Bender Institute of Neuroimaging, Justus Liebig University Giessen, 35394 Giessen, 2 Department of Biological Psychology, Technical University of Dresden, 01069 Dresden, 3 Department of Cognitive Psychology, Ruhr-University Bochum, 44780 Bochum, 4 Department of Psychology I, University of Wuerzburg, 97070 Würzburg and 5 Department of Psychobiology and Behavioral Medicine, Justus Liebig University Giessen, 35394 Giessen
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/22258800$$D View this record in MEDLINE/PubMed
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Copyright The Author(s) (2012). Published by Oxford University Press. 2012
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ISSN 1749-5016
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IsDoiOpenAccess true
IsOpenAccess true
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Issue 3
Keywords amygdala
imaging genetics
classical conditioning
5-HTTLPR
fear
Language English
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These authors contributed equally to this work.
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Snippet Fear learning is a crucial process in the pathogeneses of psychiatric disorders, which highlights the need to identify specific factors contributing to...
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StartPage 318
SubjectTerms Adult
Brain - blood supply
Brain - pathology
Brain Mapping
Conditioning, Classical - physiology
DNA Mutational Analysis
Fear - psychology
Female
Galvanic Skin Response - genetics
Genotype
Humans
Image Processing, Computer-Assisted
Individuality
Life Change Events
Magnetic Resonance Imaging
Male
Original
Oxygen - blood
Serotonin Plasma Membrane Transport Proteins - genetics
Stress, Psychological - genetics
Stress, Psychological - pathology
Stress, Psychological - psychology
Young Adult
Title Individual differences in neural correlates of fear conditioning as a function of 5-HTTLPR and stressful life events
URI https://www.ncbi.nlm.nih.gov/pubmed/22258800
https://www.proquest.com/docview/3171558203
https://www.proquest.com/docview/1317407607
https://www.proquest.com/docview/1551631795
https://pubmed.ncbi.nlm.nih.gov/PMC3594727
Volume 8
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