Improving Therapeutic Learning for PTSD

Improving Therapeutic Learning for PTSD

The proposed project seeks to demonstrate the engagement of post-exposure dopamine neurotransmission and downstream acute reorganization of dopaminergic resting-state neural networks as a means of increasing consolidation of extinction memories formed during analogue exposure therapy in adult women with PTSD. Participants will include 120 women aged 21-50 with a current diagnosis of PTSD related to physical or sexual assault, English speaking, and medically healthy. Participants will complete the stages of the study across 2-3 days, depending on participant need.

Specific Aim 1: Test the degree to which exogeneous manipulations of dopamine neurotransmission affect exposure therapy learning across multiple indices. Hypothesis: L-DOPA will decrease measures of fear responding across indices.

Specific Aim 2: Test the degree to which post-exposure functional connectivity within dopaminergic neural networks mediates the effect of dopaminergic manipulation on fear responding after exposure therapy. Hypothesis: L-DOPA will predict enhanced post-exposure dopaminergic functional connectivity, which in turn predicts decrease fear recall.

Inclusion Criteria:

• Current diagnosis of PTSD where the index traumatic event includes physical or sexual assault
• English speaking
• Medically healthy

Exclusion Criteria:

• internal ferromagnetic objects (such as electronic devices, surgical implants, shrapnel, etc.)
• major medical disorders (such as cancer)
• psychotic disorders
• neurocognitive disorders
• developmental disorders
• pregnancy
• breastfeeding
• use of Monoamine oxidase inhibitors (MAO-I) in past two weeks is exclusionary

Additional Exclusion Criteria at UT-Austin:

• heart disease
• hepatic impairment
• peptic ulcer disease
• COPD
• prescription medications that may interact with L-DOPA will not be permitted during a predetermined wash-out period

Due to safety concerns, participants with these conditions will be ineligible to participate:

• Claustrophobia, or the inability to lie still in a confined space
• Major medical disorders (e.g., HIV, cancer)
• Magnetic metallic implants (such as screws, pins, shrapnel remnants, aneurysm clips, artificial heart valves, inner ear (cochlear) implants, artificial joints, and vascular stents), as these may heat, pull, or twist in the strong magnetic field of the MRI scanner
• Electronic or magnetic implants, such as pacemakers, as these may stop working
• Permanent makeup or tattoos with metallic dyes
• A positive pregnancy test (for females), since the effect of strong magnetic fields and L-Dopa on the developing fetus remains unknown and inconclusive. (all female participants of childbearing potential will have a pregnancy test on the day of the MRI scan. Participants who test positive would be notified of this positive result)
• A self-reported history of loss of consciousness (greater than 30 minutes)
• Physical disabilities that prohibit task performance (such as blindness or deafness)
• Psychotic disorders (e.g., schizophrenia)
• Any other condition that the investigator believes might put the participant at risk

Due to their effects on image quality, participants with the following MAY be ineligible to participate per Principal Investigator's judgment:

• Medications which may affect image quality (e.g., water pills)
• Nonremovable dental implants, such as braces or upper permanent retainers, as these will distort the MRI images we collect (note: filings, crowns, and silver or gold teeth are OK)
• Any other condition, medication, or implant that the investigator believes would degrade image quality or render data unusable