This study will evaluate which parts of the brain are affected by treatment with behavioral therapy versus medication therapy in people with post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is an anxiety disorder that can develop after exposure to a traumatic event. PTSD symptoms may include emotional numbness, loss of interest in activities that were once enjoyable, irritability, and sleep problems. Medication therapy, behavioral therapy, and a combination of both therapies are among the available treatment options for people with PTSD. Cognitive behavioral therapy (CBT), a type of talking therapy that has been shown to be effective in treating PTSD, teaches patients how to alter their thinking to, in turn, improve how they feel. A selective serotonin reuptake inhibitor (SSRI) is a type of medication that has also been effective in treating PTSD. Information about the comparative physiological effects of each of these treatments on people with PTSD is needed. This study will evaluate which parts of the brain are affected by CBT treatment versus SSRI treatment in people with PTSD.

Participants with and without PTSD will be enrolled in this 12-week, open label study. Following a screening visit to determine eligibility, participants with PTSD will be offered a choice of either CBT or SSRI treatment. Those participants who choose CBT will attend 16 therapy sessions. The first phase of therapy will focus on the development of emotional and interpersonal regulation skills. The second phase will use a modified form of prolonged exposure therapy, which has been effective in reducing symptoms of PTSD. Participants who elect to receive medication will take sertraline, an SSRI that has been safe and effective in treating PTSD. These participants will attend 12 treatment sessions. Pre- and post-treatment fear response will be assessed in all participants using fMRI scans to measure brain responses and using saliva samples to test cortisol levels. All participants will also self-administer saliva samples at various points during the 3 days prior to fMRI scanning. Other outcomes will be assessed throughout the study using questionnaires.

Inclusion Criteria:

For people with PTSD:

• Meets DSM-IV criteria for PTSD
• Medically healthy
• Right handed
• Learned English prior to age 5
• Agrees to use an effective form of contraception throughout the study

For healthy controls:

• Medically healthy
• Right handed
• Has experienced a qualifying traumatic event
• Does not meet DSM-IV criteria for present or past PTSD
• Learned English prior to age 5
• Agrees to use an effective form of contraception throughout the study

Exclusion Criteria:

For people with PTSD:

• Meets DSM-IV criteria for panic disorder within 6 months prior to study entry
• Current suicide risk
• History of DSM-IV diagnosis of any the following conditions: schizophrenia, bipolar mood disorder, obsessive compulsive disorder (including trichotillomania), or eating disorder
• Meets DSM-IV criteria for substance use or dependence within the 6 months prior to study entry
• Any substance abuse within 2 weeks prior to study entry
• Score of greater than 22 on the 17-item Hamilton Rating Scale for Depression (HAM-D) with depressive symptoms secondary to PTSD
• Current participation in cognitive behavioral psychotherapy that is specifically designed to treat PTSD
• Concomitant psychoactive medications
• History of cerebrovascular accident (CVA) or any disorder that causes chronic neurological problems
• Medical illness with central nervous system (CNS) involvement or currently taking medication that affects the CNS
• Unstable general medical illness requiring intervention (e.g., HIV infection)
• Pregnant, breastfeeding, or plans to become pregnant
• Presence of internal metallic objects, such as heart pacemaker, shrapnel, bullets, surgical prostheses, surgical clips, or pins
• History of gastric bypass surgery

For healthy controls:

• Any history of generalized anxiety disorder or panic disorder
• Any history of psychotic disorder, bipolar disorder, or cyclothymia
• Any history of substance abuse or dependence within the 6 months prior to study entry
• Any substance use within 2 weeks prior to study entry
• Any other Axis I disorder within the year prior to study entry, including obsessive-compulsive disorder and trichotillomania
• Unstable general medical illness requiring intervention (e.g., HIV infection)
• Presence of internal metallic objects, such as heart pacemaker, shrapnel, bullets, surgical prostheses, surgical clips, or pins
• Concomitant psychoactive medications
• Patients with a history of cerebrovascular accident (CVA) or any disorder that causes chronic neurological problems
• Medical illness with central nervous system (CNS) involvement or currently taking medication that affects the CNS
• Cognitive impairment or severe Axis II disorder that will likely affect participation in the study
• Pregnant, breastfeeding, or plans to become pregnant