Posttraumatic stress disorder (PTSD) is prevalent among combat Veterans and is a substantial public health burden. Several psychotherapies, including cognitive processing therapy (CPT) and prolonged exposure therapy, have been recommended as efficacious for the treatment of PTSD and are being disseminated nationally in the VA Healthcare System. Yet many individuals show limited benefit from such treatments. Accumulating evidence indicates that episodic memory deficits may be one factor limiting psychotherapy treatment efficacy in PTSD. The proposed study will determine whether verbal memory is a specific predictor of CPT outcomes in PTSD, including both symptom reductions and functional outcomes. The study will also determine the pathways by which memory functioning affects treatment outcomes by examining relationships between memory functioning, treatment engagement, recall of treatment content, and illness course. More specifically, analyses will examine whether memory for treatment content affects the relationship between memory functioning and treatment outcomes.

Accumulating evidence indicates that memory dysfunction: 1) is prominent in PTSD; and 2) adversely affects psychotherapy outcomes. Identifying mechanisms underlying the relationship between memory dysfunction and poor treatment outcomes is crucial to provide empirical guidance regarding appropriate rehabilitation targets to reduce the impact of cognitive dysfunction on therapy outcomes.

In this study, the investigators aim to examine the specific effects of verbal memory on both PTSD symptoms and functional outcomes during CPT (Aim 1); identify the pathways by which cognitive dysfunction affects psychotherapy treatment response, with a focus on memory for treatment content and treatment adherence (Aim 2).

To achieve these aims, the investigators will enroll 105 Veterans with PTSD, who will complete a standard course of cognitive processing therapy (CPT) and complete longitudinal assessments of PTSD symptoms, functional status, treatment adherence, and memory for treatment content. This study does not randomize participants to treatment since all participants will be initiating CPT.

Recruitment. Participants will primarily be drawn from clinical referrals for PTSD therapy at the Corporal Michael J. Crescenz VA Medical Center (CMC VAMC) or its Community Based Outpatient Clinics (CBOCs).

Procedures. Participants will provide written informed consent and undergo intake screening. Major assessments will be conducted with participants at study entry (baseline), after session 6, and after session 12 (critical endpoint assessment) of CPT.

Baseline Visit (180-240 mins). Baseline procedures (before starting CPT) include diagnostic interviews, questionnaires assessing mood and functioning, a neurocognitive assessment, and additional memory measures. Participants will complete structured interview assessments for psychiatric conditions including PTSD, stressful life events, sociodemographics and medical history, and traumatic brain injury. Self-report assessments of mood, functional status (e.g., social adjustment), combat exposure, and behavioral functioning will also be administered. The neurocognitive assessment will include conventional neuropsychological tests and tests drawn from the Penn Computerized Neurocognitive Battery to assess multiple cognitive domains including memory, attention, speed of information processing, executive functioning, social cognition, and an IQ estimate. Additional experimental measures of memory processes from cognitive science will also be administered.

Psychotherapy. After the baseline visit, participants will begin a standard course of CPT (12 sessions) following standardized protocols (Resick et al, 2008) with the investigators' study therapists, who will all have extensive, formalized training in CPT and be supervised by an expert in CPT. Therapists will be blinded to scores on cognitive measures. After the initial CPT session, participants will complete questionnaires of treatment expectancy and self-efficacy (10 mins). At every following CPT visit, patients will complete brief questionnaires of adherence and application of treatment, depression symptoms, and suicide risk.

Mid-Treatment Assessments (20-30 mins). At CPT sessions 4, 6, 8, and 12 (end), participants will complete measures of memory for treatment content, treatment expectancy, and brief re-assessments of PTSD, mood, and functioning.

End of Treatment Assessment (120-180 mins). At the end of treatment, a final visit will consist of questionnaires and interviews to assess symptoms of PTSD, mood, functioning, cognitive functioning and memory for treatment content.

Although not a clinical trial, the investigators will examine individual change in symptoms at treatment end. Participants who drop out and are not able to be re-engaged will be contacted by study staff and asked to participate in a final assessment. After this visit is complete (or if the participant refuses), Veterans will be offered additional treatment at CMC VAMC as appropriate, with a warm handoff from study staff to the clinical team. Treatment non-responders, defined as participants displaying less than a 10-point reduction in CAPS Scores at follow-up, will also be referred for further treatment.

Inclusion Criteria:

• DSM-5 criteria for PTSD via the Clinician Administered PTSD Scale (CAPS-5)
• Willing to initiate CPT

Exclusion Criteria:

• Substance use disorder (moderate or above) not in remission for >1 mo
• Severe psychiatric illness (e.g., psychosis)
• Significant current suicidal or homicidal intent, including a specific plan
• Dementia, neurological disorder, or severe traumatic brain injury (TBI; i.e., loss of consciousness > 24h)
• Inability to speak or read English

Veterans

Final datasets will be shared upon written request. The PI and his team will create de-identified, study-specific dataset, replacing identifying information with study-specific codes. Investigators requesting access to a dataset will be asked to sign a Letter of Agreement or Data Use Agreement that will need to be approved by the local VA Information Security Officers and Privacy Officer. The investigators will follow specific VA Office of Research & Development Guidance.

Datasets meeting VA standards for disclosure to the public will be made available within one year of publication of primary results.

20 weeks