1) To study the predicitve value of fear acquisition and extinction mechanisms on treatment outcome in anxiety disordered patients. 2) To study pathological fear acquisition and extinction in anxiety disorders: what are the differences in…
ID
Source
Brief title
Condition
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint measures of change indices are: State Trait Anxiety Inventory
(state subscale) and Disorder specific ratings. Physiological (skin conductance
response and electromyograhy) and self-reported (Visual analogue scales)
measures are used to measure speed of fear acquisition, fear extinction and
context learning. Various polymorphisms will be genotyped: serotonine (5HTTLPR,
5-HTR1A), dopamine (COMT Val158Met, DAT), cannabinoïd (CB1 rs2180619 en CB1
rs1049353) and glutamergic polymorfisms (SLC1A1/EAAC1 rs3780412, rs301430).
Promising newly detected polymorphisms available through the literature will be
tested as well.
Secondary outcome
Secondary objectives: several questionnaires and neuropsychological tests (see
section 3.8 and 4.4 of the research protocol) were added to be able to control
for possible modulating effects on fear conditioning, such as: depresion,
memory function and life-events.
Background summary
Anxiety disorders are among the most prevalent psychiatric disorders, with
substantial genetic involvement. Dysfunctional fear acquisition and extinction
mechanisms are postulated to underlie anxiety disorders. Fear acquisition and
extinction are extremely suitable to systematically study in the laboratory
using classical fear conditioning paradigms. These paradigms can be extended
using contextual cues that signal safety or threat. Previous research in
healthy participants indicated that participants who were unable to learn the
association between a fearful conditioned stimulus and context, displayed
higher trait anxiety than persons who learn to differentiate between contextual
cues of threat and safety. Next step is to investigate pathological fear
acquisition and extinction mechanisms in patients with anxiety disorders, and
to investigate the predictive value of these mechanisms on treatment outcome.
State of the art treatment of anxiety disorders is exposure with response
prevention (ERP), a behavioral treatment in which anxiety extinction mechanisms
are at the core of the procedure. The exact relationship between speed of fear
acquisition -and extinction and subsequent treatment effect in patients with
anxiety disorders is unclear.
Several genetic polymorphisms seem to be involved in dysfunctional fear
conditioning, extinction and the development of anxiety disorders. Most genetic
mechanisms related to fear acquisition and extinction have been investigated
using animal models, and to date few studies have investigated relationships
between genetic polymorphisms, fear acquisition and extinction mechanisms and
outcome in anxiety disordered patients. Therefore, it seems highly worthwhile
to study the relationship between genetic polymorphisms, fear acquisition and
extinction mechanisms and treatment outcome in anxiety disorder patients.
Study objective
1) To study the predicitve value of fear acquisition and extinction mechanisms
on treatment outcome in anxiety disordered patients.
2) To study pathological fear acquisition and extinction in anxiety disorders:
what are the differences in conditioning mechanisms between patients with
anxiety disorders and healthy controls.
3) To study the genetic underpinnings of fear acquisition and extinction. To
study the second objective, associations are studied between genetic
polymorphisms involved in dopamine, glutamate, neuronal growth and serotonin
pathways, and speed of fear acquisition/ extinction in patients with anxiety
disorders versus healthy controls.
4) To explore relationships between genotype, fear acquisition and extinction
and treatment outcome; is a mediational versus a liability model likely? To
study the third objective, results from objectives 1 and 2 are combined with
model fitting procedures (using mplus) to test the most likely model to explain
the relationship between genetic factors, speed of fear acquisition and
extinction and treatment change.
Study design
250 patients with lifetime anxiety disorders are included in the study. With
respect to some of the research questions tested they are compared with
respectively 60 helathy controls (conditioning task 1) and 150 healthy controls
(conditioningtask 2, see METC protocol nr. NL31689.041.10). Patients are
recruited at the Academic Anxiety outpatient clinics Altrecht (AAA). Part of
the standars procedure at the AAA, is the assessment of standardized
qualitative and quantitative measures of (general and disease specific) anxiety
in all patients. These measurements are being assessed at pre-treatment, post
treatment and 6 months after completing treatment to gain insight into the
treatment effects. Beside these questionnaires that are part of the
standardized care, several questionnaires and neuropsychological tests are
being assessed primary for the present study. These will measure factors that
may interfere with conditioning mechanisms (like memory). Further, two tasks
are performed in a (virtual) computerized environment to assess fear
acquisition and extinction using several contextual cues, in a
quasi-experimental design. Lastly, in all participants blood is drawn by a
trained research assistent (or in case of refusal buccal swabs are collected)
to collect DNA using standardized procedures.
Study burden and risks
All participants are asked to visit the department of experimental psychology
once for a period of three hours and forty minutes. Participants will possibly
experience minor discomfort during the fear conditioning tasks, since shock
administration is involved. No health risks are associated with the study.
Heidelberglaan 1
Utrecht 3508 TC
NL
Heidelberglaan 1
Utrecht 3508 TC
NL
Listed location countries
Age
Inclusion criteria
a. Patients with a lifetime diagnosis of the following disorders as a primary diagnosis: Panic disorder with or without agoraphobia, social anxiety disorder, specific phobia, generalized anxiety disorder, post-traumatic stress disorder and obsessive compulsive disorder.
b. Males and females between 18 and 65 years old.
c. Command of the Dutch language (i.e. ability to understand procedures and questionnaires).
d. Normal or corrected normal vision.;The inclusion criteria for the healthy controls participating in conditioning task 1 are the same as described above, with the exception of criterium a.
Exclusion criteria
a. Current comorbid severe psychiatric disorder in the past 6 months: i.e. severe major depressive disorder (BDI * 30), bipolar disorder, psychotic disorder.
b. Lifetime history of substance dependence, or substance abuse within the last three months.
c. Mental retardation (IQ < 80)
d. History of any physical disease which may confound the results of the study according to the investigator, like brain damage.
e. Hearing/ vision problems
f. Current use of antipsychotic medication;The inclusion criteria for the healthy controls participating in conditioning task 1 are the same as described above.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL35780.041.11 |