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Theories of specific phobias consider classical conditioning as a central mechanism in the pathogenesis and maintenance of the disorder. Although the neuronal network underlying human fear conditioning is understood in considerable detail, no study to date has examined the neuronal correlates of fear conditioning directly in patients with specific phobias. Using functional magnet resonance imaging (fMRI) we investigated conditioned responses using phobia-relevant and non-phobia-relevant unconditioned stimuli in patients with specific phobias (n=15) and healthy controls (n=14) by means of a differential picture-picture conditioning paradigm: three neutral geometric figures (conditioned stimuli) were followed by either pictures of spiders, highly aversive scenes or household items (unconditioned stimuli), respectively. Enhanced activations within the fear network (medial prefrontal cortex, anterior cingulate cortex, amygdala, insula and thalamus) were observed in response to the phobia-related conditioned stimulus. Further, spider phobic subjects displayed higher amygdala activation in response to the phobia-related conditioned stimulus than to the non-phobia-related conditioned stimulus. Moreover, no differences between patients and healthy controls emerged regarding the non-phobia-related conditioned stimulus. The results imply that learned phobic fear is based on exaggerated responses in structures belonging to the fear network and emphasize the importance of the amygdala in the processing of phobic fear. Further, altered responding of the fear network in patients was only observed in response to the phobia-related conditioned stimulus but not to the non-phobia-related conditioned stimulus indicating no differences in general conditionability between patients with specific phobias and healthy controls.
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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.
Erkunden
Team
- Vaitl (2)
Eintragsart
Sprache
- Englisch (2)
Thema
- Fear/*psychology
- Adult (2)
- Animals (1)
- Arousal (1)
- Brain/blood supply/pathology (1)
- Brain Mapping (1)
- Conditioning, Classical/*physiology (1)
- DNA Mutational Analysis (1)
- Electric Conductivity (1)
- Emotions (1)
- Female (2)
- Galvanic Skin Response/genetics (1)
- Genotype (1)
- Humans (2)
- Image Processing, Computer-Assisted (1)
- *Individuality (1)
- Learning/*physiology (1)
- Life Change Events (1)
- Magnetic Resonance Imaging (1)
- Male (2)
- Oxygen/blood (1)
- Phobic Disorders/*psychology (1)
- Reference Values (1)
- Serotonin Plasma Membrane Transport Proteins/*genetics (1)
- Skin Physiological Phenomena (1)
- *Spiders (1)
- *Stress, Psychological/genetics/pathology/psychology (1)
- Young Adult (2)