Neural and Pharmacological Correlates of Intrusions in Patients With Posttraumatic Stress Disorder

There is evidence that glucocorticoids have an impact on intrusive memories in patients with posttraumatic stress disorder (PTSD). Hydrocortisone impairs intrusive memory retrieval whereas dexamethasone should strengthen intrusions in PTSD. We, the investigators, want to investigate (1) the effect of these two glucocorticoids on traumatic memories and (2) assess the neural correlates using the script-driven imagery paradigm in the functional magnetic resonance imaging (fMRI) scanner. We hypothesize that intrusive memories are less intensive under hydrocortisone-administration and more intense under dexamethasone-administration comparing both to a placebo-condition. Regarding the neural activation pattern we expect higher activation in the hydrocortisone condition in the amygdala, the hippocampus and the medial prefrontal cortex compared to the placebo-condition and less activation in the dexamethasone-condition compared to the placebo-condition.

Study Overview

• Status: Completed
• Conditions: Posttraumatic Stress Disorder
• Intervention / Treatment: Drug: Placebo; Drug: 10 mg HydrocortisoneHöchst; Drug: Dexamethasone

Detailed Description

There is evidence that glucocorticoids have an impact on intrusive memories in patients with posttraumatic stress disorder (PTSD). Hydrocortisone impairs intrusive memory retrieval whereas dexamethasone should strengthen intrusions in PTSD. We, the investigators, want to investigate (1) the effect of these two glucocorticoids on traumatic memories and (2) assess the neural correlates using the script-driven imagery paradigm in the functional magnetic resonance imaging (fMRI) scanner. Therefore an individual trauma-and an individual neutral -script is assessed from each participant, recorded and replayed during fMRI-scanning. We hypothesize that intrusive memories are less intense under hydrocortisone-administration and more intense under dexamethasone-administration comparing both to a placebo-condition. Regarding the neural activation pattern we expect higher activation in the hydrocortisone condition in the amygdala, the hippocampus and the medial prefrontal cortex compared to the placebo-condition and less activation in the dexamethasone-condition compared to the placebo-condition.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Baden Württemberg6
    • Mannheim, Baden Württemberg6, Germany, 68159
      • Central Institute of Mental Health, Dep. of Psychosomatic and Psychotherapeutic Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age: 18-45
• Female
• Posttraumatic Stress Disorder assessed by the Structured Clinical Interview (SKID-I)
• Intrusive memories (Impact of Events Scale - Revised [IES-R] intrusion scale > 7)

Exclusion Criteria:

• • Lifetime diagnosis schizophrenia according to Diagnostic and Statistical Manual, Fourth Edition (DSM-IV)

  • Mental retardation
  • Body mass index < 16.5
  • Current drug and alcohol abuse and addiction
  • Life-threatening self-injurious behavior in the last 4 months
  • Suicide attempt with the strong intention to die in the last 4 months.
  • Following diseases in anamnesis: stomach ulcera or intestinal ulcera, pancreatitis, corticoid-induced psychosis, severe osteoporosis, severe hyper-tension, heart failure, myasthenia gravis, asthma bronchiale, glaucoma, cataract, diabetes mellitus, herpes simples, herpes zoster (viremic phase), renal transplantation.
  • Any pretreatment with hydrocortisone in the last 4 weeks prior to the first administration of Investigational Medicinal Product.
  • Following current medication: cardiac glycosides, saluretics, antidiabetics, cumarin-derivatives, rifampicine, phenytoine, barbiturates, primidone, non-steroidal anti-inflammatory drug (NSAID), salicylate and indometacine, atropine, praziquantel, chloroquine, hydroxychloroquine, mefloquine, somatropine, protireline, cyclosporine, non-depolarising muscle relaxants.
  • Pregnancy or lactation period
  • Inadequate birth control
  • Shift working
  • Intercontinental travel within 2 weeks prior to enrollment (to avoid jet-lag)
  • History of hypersensitivity to investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
  • No subject will be allowed to enrol in this trial more than once.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydrocortisone, fMRI, Intrusions; 10 mg Hydrocortisone are administered one hour before the fMRI experiment. We use the script-driven imagery paradigm to induce intrusive memories during fMRI scanning.	Drug: 10 mg HydrocortisoneHöchst; 10 mg Hydrocortisone Höchst are administered one hour before fMRI scanning; Other Names: HydrocortisoneHöchst
Experimental: Dexamethasone, fMRI, Intrusions; 2 mg Dexamethasone are administered at 10 pm the day before the fMRI experiment. (DEX-Test). We use the script-driven imaging paradigm to induce intrusive memories during fMRI-scanning.	Drug: Dexamethasone; 2 mg Dexamethasone are administered at 10 pm the day before the fMRI experiment.
Experimental: Placebo, fMRI, Intrusions; Placebo is administered one hour before the fMRI experiment. We use the script-driven imaging paradigm to induce intrusive memories during fMRI-scanning in patients with posttraumatic stress disorder.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Neural activation pattern of intrusive memories in patients with posttraumatic stress disorder under administration of hydrocortisone, dexamethasone and placebo.	May 2010-Sept 2011

Secondary Outcome Measures

Outcome Measure	Time Frame
Intensity of intrusions under the administration of hydrocortisone, dexamethasone and placebo.	may 2010-Sept. 2011

Collaborators and Investigators

• Sponsor: Central Institute of Mental Health, Mannheim
• Investigators: Principal Investigator: Christian Schmahl, MD, Central Institute of Mental Health, Dep. of Psychosomatic and Psychotherapeutic Medicine

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: April 20, 2010
• First Submitted That Met QC Criteria: April 20, 2010
• First Posted (Estimate): April 21, 2010

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 28, 2017
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: fMRI; Posttraumatic Stress Disorder; Traumatic Memories
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Trauma and Stressor Related Disorders; Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: GC-fMRI-PTSD; GC-fMRI-PTSD-2010 (Other Identifier: Intern)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO