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. 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.

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.