Proposed research will examine time-of-day effects on trauma-related fear extinction using Prolonged Exposure Therapy (PE) telemedicine for Posttraumatic Stress Disorder (PTSD) in the National Center for PTSD (NCPTSD). The primary mechanistic outcome measure will be change in psychophysiological reactivity to script-driven imagery (SDI-PR) measured, in person, at pre-treatment, after 5 PE sessions (mid-treatment), and after all 10 PE sessions (post-treatment). A secondary mechanistic outcome will be session-to-session reduction in peak subjective units of distress (SUDS) ratings to imaginal exposures. The primary clinical outcome will be change in Clinican Administered PTSD Scale (CAPS-5) severity score; a secondary clinical outcome will be session-to-session reduction in self-reported PTSD symptoms using the PTSD checklist (PCL-5). Participants meeting inclusion criteria (described below) will be randomized to either PE sessions that begin from 07:00 to a time no later than 2 hours past a participant's customary rise time, or to the last treatment session of the day beginning at 16:00 or later (26 per arm). Participants will complete daily at-home imaginal-exposure homework within the same time frame as their PE sessions are scheduled, i.e., within 2 hours of awakening for morning (AM) group and between 16:00 and 2 hours before bedtime for late afternoon (PM) group.

Proposed research will examine time-of-day effects on trauma-related fear extinction using PE therapy for PTSD in the National Center for PTSD (NCPTSD). The primary mechanistic outcome measure will be change in SDI-PR; a secondary mechanistic outcome will be session-to-session reduction in peak SUDS ratings to imaginal exposures. The primary clinical outcome will be change in CAPS-5 severity score; a secondary clinical outcome will be session-to-session reduction in self-reported PTSD symptoms (PCL-5). Participants meeting inclusion criteria (described below) will be randomized to either PE sessions that begin from 07:00 to a time no later than 2 hours past a participant's customary rise time, or to the last treatment session of the day beginning at 16:00 or later. Participants will complete daily at-home imaginal-exposure homework within the same time frame as their PE sessions are scheduled (i.e., within 2 hours of awakening for morning group and between 16:00 and 2 hours before bedtime for late afternoon group). The assessment schedule will be identical for all participants. Participants who meet study inclusion criteria at screening will first begin a 7-day, pre-study sleep-monitoring period with wrist actigraphy, sleep diaries and completion of a diurnal profile of salivary cortisol levels. Trauma-related fear will be assessed using the standard SDI procedures detailed below at pre-treatment, after 5 PE sessions (mid-treatment), and after all 10 PE sessions (post-treatment). The CAPS-5 will be administered at these same times. PCL-5 measurements will be obtained at each treatment session and SUDs will be obtained during all treatment sessions that include imaginal exposure (sessions 3-8). All SDI sessions will be carried out at a standardized time of day in the late-afternoon (15:00-17:00). PE treatment will be administered at a targeted rate of once per week. At each PE and assessment session, pre-session saliva samples will be obtained for cortisol measurement and normalized using the diurnal profile of cortisol obtained during the sleep-assessment week. Participants will wear the wrist actigraph and complete sleep diaries throughout PE. The diurnal cortisol profile will be repeated at the post-treatment assessment.

Inclusion Criteria:

1. a diagnosis of PTSD as defined by DSM-5, with a minimum CAPS severity score of 26, a minimum PCL-5 score of 31, or a score of 2 or above on CAPS-5 Item B2 (concerning distressing dreams)
2. interest in starting a course of PE
3. availability for appointments at that will either begin from 07:00 to a time no longer than 2 hours past their customary rise time, or to the last treatment session of the day beginning at 16:00 or later
4. Age range of 18-70
5. A Morningness-Eveningness Questionnaire (MEQ) score above 25.
6. Non-exclusionary psychotropic medications must have been stable for 3 weeks prior to Screening/Assessment with intention to remain stable throughout participation.

Exclusion Criteria:

1. current or past history of bipolar I disorder, schizophrenic or other psychotic disorders,
2. current organic brain disorder including moderate to severe traumatic brain injury
3. factitious disorder or malingering
4. pregnant or planning to become pregnant in the next four months at time of screening [if a participant does become pregnant during study procedures, the situation will be reviewed on a case-by-case basis and the participant's wishes will be considered in deciding whether the participant will continue with the study or withdraw.]
5. current moderate or severe substance use disorder with symptoms present within the past three months
6. diagnosed moderate to severe sleep apnea, narcolepsy, periodic limb movement, or restless legs syndrome that result in daytime sleepiness indicated by Epworth Sleepiness Scale (ESS) above 10
7. active risk of harm to self or others
8. evidence of clinically significant hepatic or renal disease or any other acute or unstable medical condition that might interfere with safe conduct of the study
9. current participation in trauma-focused cognitive-behavioral therapy (e.g., Cognitive Processing Therapy, Written Exposure Therapy, Eye Movement Desensitization and Reprocessing Therapy)
10. prior treatment with an adequate dose of PE (i.e., 8 or more sessions) to the traumatic event that would be the index trauma for treatment in the study
11. having no memory of their traumatic event
12. daily use of benzodiazepines
13. methadone or suboxone maintenance therapy for past opioid addiction
14. diagnosis of Cushing's disease, Addison's disease or use of medications that target cortisol directly such as those used to treat Cushing's disease [ketoconazole, mitotane (Lysodren), metyrapone (Metopirone), and Mifepristone (Korlym, Mifeprex)], those used to treat Addison's disease [Hydrocortisone (Cortef), prednisone or methylprednisolone], as well as cortisone or dexamethasone.
15. persons who would habitually awaken so early that more than 2 h would elapse before a morning PE session could occur; or those who engage in habitual shiftwork or transmeridian travel

We will share data every January 15 and July 15 with the NIMH Data Archives (NDA) under a NIMH Data Repositories Data Submission Agreement between NIMH and VA Boston Health System (VABHS). Data sharing is required for all NIMH-funded research projects. The NDA DSA will be approved by the VABHS IRB. Each participant will be assigned Global Unique ID (GUID) and data shared will contain no identifiable information. Shared data will include scored psychophysiological, self-report instruments, cortisol, actigraphy, and fully de-identified demographic data.

Study data will become available following the end of the study and the publication of results.

Investigators can apply to the NIMH Data Archive (NDA) for permission to use these data.

Therapists will be unaware of study hypotheses. therapy supervisor and assessors will be unaware of hypothesis and participants' treatment arms