Relationships between trait and state anxiety and the central benzodiazepine receptor: a PET study

Relationships between trait and state anxiety and the central benzodiazepine receptor: a PET study The central benzodiazepine receptor (cBZr) has long been implicated in anxiety disorders on the basis of: (i) the well‐known anxiolytic and anxiogenic properties of cBZr agonists and inverse agonists, respectively; (ii) a possibly reduced sensitivity to benzodiazepines in anxious subjects; and (iii) a putative endogenous ligand. Thus, two main hypothesis have been advanced, namely changes in the concentration or properties of the latter, and changes in the GABAA complex conformation, which contains the cBZr. Neither postmortem studies nor appropriate animal models are available to investigate these ideas. We have used positron emission tomography (PET) to measure both the density and affinity of the cBZr in multiple brain regions in unmedicated patients and age‐ and sex‐matched healthy volunteers, and have looked for differences between groups as well as correlations between cBZr parameters and state and trait anxiety scores. We studied 10 unmedicated patients (sex ratio 1 : 1; mean age: 39 years), prospectively recruited using DSM III‐R criteria, and 10 age‐ and gender‐matched healthy unmedicated volunteers. Thanks to a PET procedure using two successive administrations of 11C‐flumazenil (at high and low specific radioactivity) and previously validated by us, we estimated the Bmax, Kd and bound : free (B/F) ratios in 11 neocortical areas and in the cerebellum. Before and after the PET session, anxiety scores from Spielberger’s and Covi’s scales were obtained. There was no statistically significant difference in Bmax, Kd or B/F‐values between the two groups for any region. Across the two groups, there were only a few marginally significant anxiety‐score–PET correlations, suggesting chance findings. This is the first fully quantitative study to report on the relationships between cBZr parameters and anxiety. Using two independent approaches (i.e. group comparison and across‐group correlations), we found no evidence for a link between anxiety trait or state and the cBZr in neocortex or cerebellum in this sample. These findings, if confirmed by studies on larger samples, have implications for the pharmacotherapy of anxiety disorders, and will need to be considered when designing new neurobiological models of anxiety. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

Relationships between trait and state anxiety and the central benzodiazepine receptor: a PET study

Loading next page...
 
/lp/wiley/relationships-between-trait-and-state-anxiety-and-the-central-ZQoHsDDNwK
Publisher
Wiley
Copyright
Copyright © 1999 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
DOI
10.1046/j.1460-9568.1999.00556.x
Publisher site
See Article on Publisher Site

Abstract

The central benzodiazepine receptor (cBZr) has long been implicated in anxiety disorders on the basis of: (i) the well‐known anxiolytic and anxiogenic properties of cBZr agonists and inverse agonists, respectively; (ii) a possibly reduced sensitivity to benzodiazepines in anxious subjects; and (iii) a putative endogenous ligand. Thus, two main hypothesis have been advanced, namely changes in the concentration or properties of the latter, and changes in the GABAA complex conformation, which contains the cBZr. Neither postmortem studies nor appropriate animal models are available to investigate these ideas. We have used positron emission tomography (PET) to measure both the density and affinity of the cBZr in multiple brain regions in unmedicated patients and age‐ and sex‐matched healthy volunteers, and have looked for differences between groups as well as correlations between cBZr parameters and state and trait anxiety scores. We studied 10 unmedicated patients (sex ratio 1 : 1; mean age: 39 years), prospectively recruited using DSM III‐R criteria, and 10 age‐ and gender‐matched healthy unmedicated volunteers. Thanks to a PET procedure using two successive administrations of 11C‐flumazenil (at high and low specific radioactivity) and previously validated by us, we estimated the Bmax, Kd and bound : free (B/F) ratios in 11 neocortical areas and in the cerebellum. Before and after the PET session, anxiety scores from Spielberger’s and Covi’s scales were obtained. There was no statistically significant difference in Bmax, Kd or B/F‐values between the two groups for any region. Across the two groups, there were only a few marginally significant anxiety‐score–PET correlations, suggesting chance findings. This is the first fully quantitative study to report on the relationships between cBZr parameters and anxiety. Using two independent approaches (i.e. group comparison and across‐group correlations), we found no evidence for a link between anxiety trait or state and the cBZr in neocortex or cerebellum in this sample. These findings, if confirmed by studies on larger samples, have implications for the pharmacotherapy of anxiety disorders, and will need to be considered when designing new neurobiological models of anxiety.

Journal

European Journal of NeuroscienceWiley

Published: Apr 1, 1999

References

  • Increased urinary output of tribuline in generalised anxiety disorder.
    Clow, Clow; Glover, Glover; Sandler, Sandler; Tiller, Tiller
  • The amygdala and emotion.
    Gallagher, Gallagher; Chiba, Chiba
  • The relationship between benzodiazepine receptor sensitivity and neuroticism.
    Glue, Glue; Wilson, Wilson; Coupland, Coupland; Ball, Ball; Nutt, Nutt
  • Reduced benzodiazepine binding in panic disorders measured by iomazenil and SPECT.
    Kaschka, Kaschka; Feistel, Feistel; Ebert, Ebert
  • Benzodiazepine receptors in rat brain.
    Squires, Squires; Braestrup, Braestrup

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off