• Change in PTSD Symptoms as Measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) [ Time Frame: Baseline, Week 5, Week 10, 3 month follow up ]
  The CAPS is the gold standard in PTSD assessment. It is a 30-item structured interview used for current (past week or month) and lifetime diagnosis of PTSD. The CAPS was designed to be administered by clinicians and clinical researchers who have a working knowledge of PTSD. The full interview takes 45-60 minutes to administer. Scores range from 0 to 80 with higher values represent a worse outcome.
• Change in Depressive Symptoms as Measured by the Hamilton Rating Scale for Depression (HRSD). [ Time Frame: Baseline, Week 5, Week 10, 3 month follow up ]
  The Hamilton Rating Scale for Depression is a 17-item instrument that was designed to measure frequency and intensity of depressive symptoms in individuals with major depressive disorder. Ratings are made using either a five- or a three-point scale, yielding total scores from 0 to 61, with higher values represent a worse outcome.

• Change from baseline to post treatment and 3 month follow up on severity of PTSD symptoms [ Time Frame: Baseline, Week 5, Week 10, 3 month follow up ]
  We will use the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). The CAPS-5 is a 30-item structured interview that can be used to determine current (past month) diagnosis of PTSD, to make lifetime diagnosis of PTSD, and to assess PTSD symptoms over the past wee
• Change from baseline to post treatment and 3 month follow up on severity of depressive symptoms [ Time Frame: Baseline, Week 5, Week 10, 3 month follow up ]
  We will use the The Hamilton Rating Scale for Depression (HRSD),[1] also called the Hamilton Depression Rating Scale (HDRS), abbreviated HAM-D, is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. The patient is rated by a clinician on 17 to 29 items (depending on version) scored either on a 3-point or 5-point Likert-type scale.

Approximately half of the individuals with posttraumatic stress disorder (PTSD) present with major depressive disorder (MDD). Compared to PTSD alone, patients with comorbid PTSD-MDD demonstrate greater distress and poorer treatment outcome. Functional magnetic resonance imaging (fMRI) show that relative to PTSD alone, PTSD-MDD is associated with decreased resting state functional connectivity (rs-FC) in both fear- and reward-processing circuits. In addition, our data suggest that Prolonged Exposure (PE), first-line PTSD treatment, may successfully target impairments in the fear circuits, but not in the reward circuits, which may explain the treatment-refractory quality of PTSD-MDD.

The goal of this pilot study is to test the feasibility, safety and initial efficacy of an integrated therapeutic approach targeting both fear and reward impairments in PTSD-MDD patients. Specifically, the investigators will examine a combination treatment with PE, shown to effectively address fear circuitry deficits, and Pramipexole, a dopamine agonist, shown to increase reward circuit function and to have promise in treating depression but not previously studied in PTSD. The central hypothesis is that combined PE/Pramipexole will a) improve PTSD and depressive symptoms in PTSD-MDD patients, and b) increase functional connectivity of fear and reward pathways as measured by fMRI rs-FC. In this pilot study, 15 adults aged 18-60 years with PTSD-MDD will receive combined 10-week of PE and Pramipexole up to the maximum dose of 4mg a day. Clinical assessment will be conducted at baseline, week 5, post treatment and at 3-month follow up. Behaviorally assessments including the probabilistic reward task (PRT) and attention allocation tasks, and fMRI scans for resting state functional connectivity (rs-FC) will be conducted at baseline and end of treatment.

• PTSD
• MDD

Inclusion Criteria:

1. Males or females between the ages of 18 and 60
2. Current DSM-V diagnosis of PTSD comorbid with MDD
3. CAPS-5 ≥ 25, and 17-item HRSD ≥ 17
4. Able to give consent, fluent in English

Exclusion Criteria:

1. Prior or current diagnosis with traumatic brain injury, bipolar disorder, psychotic disorder, gambling or impulse control disorders, or dementia
2. History of psychosis, psychotic disorder, mania or bipolar disorder
3. Severe substance use disorder excluding nicotine (i.e., nicotine use disorder and mild-moderate alcohol/cannabis use disorder are accepted)
4. Individuals at risk for suicide based on history and current mental state. BDI-II suicide item > 2 or CGI-Severity baseline score of 7.
5. Treatment with antidepressants or other psychotropic medication in the past 4 weeks (or 6 weeks for fluoxetine; an exception will be made for zolpidem used intermittently for sleep).
6. Pregnancy or plans to become pregnant during the period of the study.
7. Current psychotherapy
8. Current unstable or untreated medical illness
9. Any condition that would exclude clinical MRI exam (e.g. pacemaker, paramagnetic metallic prosthesis, surgical clips, shrapnel, necessity for constant medicinal patch, some tattoos, severe obesity, claustrophobia)
10. History of untoward reaction to pramipexole