The purpose of this study is to test the differences between four active treatment conditions for combat-related Post Traumatic Stress Disorder (PTSD): virtual reality exposure therapy (VRE) or prolonged imaginal exposure therapy (PE), both with DCS or placebo, as well as to examine predictors for PTSD and response to treatment in active duty military personnel, veterans, and civilians who served in Iraq and Afghanistan.

Post Traumatic Stress Disorder (PTSD) is an anxiety disorder that can develop following exposure to traumatic events and includes symptoms of re-experiencing the trauma, such as through nightmares and flashbacks, avoidance and numbing, and physical hyperarousal. PTSD has been estimated to affect 10-20% of returning Operation Iraqi Freedom (OIF)/Operation Enduring Freedom (OEF) veterans. The most effective intervention found for PTSD is exposure therapy, which can be delivered in different formats, e. g. via virtual reality (VR) and as imaginal exposure. The goal of this study is to test the difference between 4 study conditions: virtual reality exposure therapy (VRE) or prolonged imaginal exposure therapy (PE), both combined with an antibiotic drug, DCS (active pill vs. placebo). D-Cycloserine (DCS), a drug that has been FDA approved for over 20 years, has been hypothesized to enhance the therapeutic effects of exposure therapy.). A secondary purpose of this study is to examine predictors for PTSD and response to PTSD intervention in active duty military personnel, veterans, and civilians who served in Iraq/Afghanistan. Psychophysiological factors (e.g. heart rate, blood pressure) and/or a genetic polymorphism (BDNF Val66Met) obtained from a saliva sample will be examined.

The two primary co-aims are

1. to examine the effects of DCS versus placebo (PLA) augmentation of exposure therapy on PTSD symptoms, and
2. to examine the relative efficacy of virtual reality enhanced exposure therapy (VRE) and exposure therapy (PE) on PTSD symptoms.

Inclusion Criteria:

1. Diagnosis of OEF-OIF (Operations Enduring Freedom or Iraqi Freedom) Combat Related PTSD;
2. Female participants of childbearing potential must agree to use an effective method of birth control (i.e., oral contraceptive, Norplant, diaphragm, condom, or spermicide) during the course of the study, or to remain abstinent from sex, to ensure they do not become pregnant during the course of the study;
3. Ability to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments;
4. Participants must be literate in English;
5. Patients must be medically healthy and willing to take the study drug;
6. VRE stimuli available must be consistent with subject's trauma.

Exclusion Criteria:

1. Lifetime or current diagnosis of schizophrenia or other psychotic disorder, bipolar disorder;
2. Participation in a clinical trial during the previous 3 months;
3. Current evidence or history of significant unstable medical illness or organic brain impairment, including stroke, CNS tumor, demyelinating disease, cardiac, pulmonary, gastrointestinal, renal or hepatic impairment;
4. Patients who in the investigator's judgment pose a current suicidal or homicidal risk;
5. Alcohol, medication, or illegal substance dependence within the past 90 days;
6. Treatment with any other concomitant medication with primarily CNS activity, or treatment with any medication that the PI judges not acceptable for this study;
7. history of seizures;
8. Pregnancy or lactation.