Symptom Provocation in Specific Phobia Affects the Substance P Neurokinin-1 Receptor System

doi:10.1016/j.biopsych.2006.07.003

Biological Psychiatry

Volume 61, Issue 8, 15 April 2007, Pages 1002-1006

https://doi.org/10.1016/j.biopsych.2006.07.003 Get rights and content

Background

Animal studies demonstrate that stress and negative affect enhance the release of the neuropeptide substance P (SP), which binds to the neurokinin 1 (NK1) receptor. This positron emission tomography (PET) study evaluated how the activity in the SP-NK1 receptor system in the amygdala was affected by fear provocation in subjects with specific phobia.

Methods

Sixteen adult women with DSM-IV–defined specific phobia for either snakes or spiders but not both viewed pictures of feared and non-feared animals while being PET-scanned for 60 min with the highly specific NK1 receptor antagonist [¹¹C]GR205171 as the labeled PET tracer.

Results

The uptake of the labeled NK1 receptor antagonist was significantly reduced in the right amygdala during phobic stimulation. In the left amygdala no significant differences were found between phobic and non-phobic conditions. There was a negative correlation in the right, but not left, amygdala between subjective anxiety ratings and NK1 tracer binding.

Conclusions

Fear provocation affects the SP-NK1 receptor system in the right amygdala. This reflects reduced NK1 receptor availability during fear and could mirror an increased release of endogenous substance P.

Section snippets

Subjects

Sixteen female subjects (mean age = 22.75, SD = 4.12, range = 19–34) fulfilling the DSM-IV (American Psychiatric Association 1994) criteria for specific spider or snake phobia but not both were included in the study. Screening included web-based Swedish versions (Fredrikson 1983) of the Snake Anxiety Questionnaire (SNAQ, 0–30 points) and Spider Phobia Questionnaire (SPQ, 0–31 points) (Klorman et al. 1974), telephone questioning, clinical interview, and a snake- and spider-fear symptom

Behavioral Measures

State anxiety ratings confirmed significant anxiety differences resulting from exposure to the phobic and non-phobic pictures: 68 ± 11.2 and 29 ± 6.7, respectively [t(15) = 10.97; p < .0001].

Brain Imaging Data Measures

The Patlak analysis demonstrated lower slope values during the visual fear provocation as compared with the non-phobic stimulation. The ratios between the slope values for the two conditions differed significantly from 1 in the right [t(15) = 2.30; p < .05] but not the left amygdala [t(15) = .63; ns] (

Discussion

This is the first in vivo study demonstrating emotional modulation of the human SP-NK1 receptor system. Specifically, fear provocation in individuals with specific phobia resulted in fewer available NK1 receptors. This is consistent with an increased endogenous SP release occupying the NK1 receptors, thus preventing the [¹¹C]-labeled NK1 antagonist from binding. We conclude that, similar to animals (cf. Kramer et al 1998, Santarelli et al 2001), negative affect alter activity in the SP-NK1

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Original articleSymptom Provocation in Specific Phobia Affects the Substance P Neurokinin-1 Receptor System

Background

Methods

Results

Conclusions

Section snippets

Subjects

Behavioral Measures

Brain Imaging Data Measures

Discussion

Physiol Behav

Neuropharmacology

Neurosci Lett

Eur Neuropsychopharmacol

Pharmacol Biochem Behav

Biol Psychiatry

Regul Pept

Pharmacol Ther

Neuropeptides

Biol Psychiatry

Behavior Therapy

Behav Brain Res

Brain Res

Biol Psychiatry

Neuron

Biol Psychiatry

Biol Psychiatry

Brain Res

Eur Neuropsychopharmacol

Eur J Pharmacol

Neuropsychopharmacology

Diagnostic and Statistical Manual of Mental Disorders

Amygdala response in patients with acute PTSD to masked and unmasked emotional facial expressions

Am J Psychiatry

Original article
Symptom Provocation in Specific Phobia Affects the Substance P Neurokinin-1 Receptor System