Early-life stress, the endocannabinoid system, and fear memory extinctio

Phase 2

Completed

Conditions: Post Traumatic Stress Disorder
Trauma-related Anxiety Disorder
10002861

Registration Number: NL-OMON50765

Lead Sponsor: Radboud Universitair Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 96

Inclusion Criteria

In each substudy, in order to be eligible to participate in this study, a
participant must meet all of the following criteria:

For both groups:

* Healthy volunteers between 18 and 45 years of age.
* Predominant right-handedness.
* For substudy 2 only: History of taking cannabis.

For ELS group:

* Meet the criteria for ELS as measured using the self-report questionnaire
*Maltreatment and Abuse Chronology of Exposure Scale (MACE-X)*. There are 10
subscales in MACE-X, the criterion for each subscale is listed below.
* In the emotional neglect subscale, the cut-off is 2 items out of 5.
* In the parental non-verbal abuse subscale, the cut-off is 4 out of 6.
* In the parental physical maltreatment subscale, the cut-off is 4 items.
* In the parental verbal abuse subscale, the cut-off is 3 items out of 4.
* In the sexual abuse subscale, the cut-off is 2 items out of 7.
* In the witnessing interparental violence subscale, the cut-off is 2 items out
of 5.
* In the peer verbal abuse subscale, the cut-off is 4 items out of 5.
* In the peer physical bullying subscale, the cut-off is 2 items out of 5.
* In the physical neglect, the cut-off is 2 items out of 5.
* In the witnessing violence to siblings subscale, the cut-off is 1 items out
of 4.
We will include people a) who meet the criterion on any single subscale, while
only counting items under age of ten, or b) who meet the criteria on multiple
subscales regardless of age, when the sum of percentages of the cut-offs
reached below the age of ten for each of these subscales equals or exceeds 100.
For instance, if a potential participant scores 2 item on the sexual abuse
subscale, of which 1 is below the age of 10, and scores 5 on the verbal abuse
subscale, of which 3 are below the age of ten, then this participant would be
included because (1/2) *100 + (3/4) *100 <= 125.
* For Non-ELS group: We aim to recruit participants in the control group with
no experiences of ELS. The MACE-X has six subscales which are indicate severe
childhood maltreatment: Emotional Neglect, Parental Nonverbal Emotional Abuse,
Parental Physical Maltreatment, Parental Verbal Abuse, Sexual Abuse, or
Witnessing Interparental Violence. The criterion for each of these subscales is
listed below.
* In the emotional neglect subscale, the cut-off is 2 items out of 5.
* In the parental non-verbal abuse subscale, the cut-off is 4 out of 6.
* In the parental physical maltreatment subscale, the cut-off is 4 items.
* In the parental verbal abuse subscale, the cut-off is 3 items out of 4.
* In the sexual abuse subscale, the cut-off is 2 items out of 7.
* In the witnessing interparental violence subscale, the cut-off is 2 items out
of 5.
And four subscales which are less relevant to severe childhood maltreatment.
The criterion for each of these subscales is listed below.
* In the peer verbal abuse subscale, the cut-off is 4 items out of 5.
* In the peer physical bullying subscale, the cut-off is 2 items out of 5.
* In the physical neglect, the cut-off is 2 items out of 5.
* In the witnessing violence to siblings subscale, the cut-off is 1 items out
of 4
We will include people into the control group who a) score 0 on the six
subscales most relevant to severe childhood maltreatment (SCM) listed above,
and b) score below the cut-off o

Exclusion Criteria

In each study, a potential subject who meets any of the following criteria will
be excluded from participation in this study:

For both groups:

* Body mass index lower than 18.5 or higher than 30.
* Abnormal hearing or (uncorrected) vision.
* Average use of psychotropic medication or recreational drugs weekly or more.
* Habitual smoking, i.e. more than a package of cigarettes per week and a
self-reported
inability or unease to cease smoking for 24 hours prior to testing.
* Use of psychotropic medication, or of recreational drugs over a period of one
week prior to each test session, and use of alcohol within the last 24 hours
before each measurement.
* Regular use of corticosteroids.
* Current psychiatric treatment. (e.g., severe depression, anorexia nervosa,
severe mood disorders, mania, schizophrenia or borderline personality disorder)
* Current neurological treatment.
* Current endocrine treatment. (e.g., phechromocytoma, hyperthyroidism,
Cushing*s syndrome)
* Contraindication for systemic hydrocortisone (e.g., ulcus ventriculi, ulcus
duodeni, certain infections, and eye problems that point toward a risk
(closed-angle) glaucoma).
* History of repeated (more than once) of autonomic failure (e.g., vasovagal
reflex syncope).
* Contraindications for MRI scanning (e.g., pacemaker, implanted metal parts,
deep brain stimulation, claustrophobia)
* Metal objects in or around the body (braces, pacemaker, metal fragments,
hearing devices).
* Use of medication that may interact with hydrocortisone (study 1) or THC
(study 2). E.g., for Hydrocortisone, e.g., taking taking mifepristone within
one week before and during the study period is reason for exclusion. For THC,
taking rifampicin, ketoconazole, and omeprazole will not be allowed within one
week before and during the study period.
* Cognitive impairment (MMSE < 26)
* Pregnancy
* Night shift work
* Known enhanced risk of using THC or hydrocortisone

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>autonomic nervous system measurement (skin conductance, heart rate, and pupil<br /><br>dilation responses) and subjective scores on 5-point scale to rate the<br /><br>expectancy of the appearance of the unconditioned stimuli (USs) to<br /><br>fear-conditioned stimuli one day after extinction (i.e., safety learning).</p><br>

Secondary Outcome Measures