Previous research by the applicant has found characteristic alterations in several major hormonal systems in combat-related PTSD, including norepinephrine, cortisol, and especially an unusual thyroid hormone profile characterized by marked elevations of both free and total triiodothyronine (T3). In this competing continuation proposal, the applicant will attempt to extend these findings to diverse samples of men and women with PTSD. Thirty women subjects with PTSD related to sexual trauma will be recruited from the Women's Trauma Program of the Yale Psychiatric Institute. A smaller pilot series of women with PTSD related to physical trauma will also be recruited from this source. Eighty-four female psychiatric outpatients with PTSD related to childhood sexual abuse will be recruited from the National Center for PTSD Division in White River Junction, Vermont. Thirty women veterans with PTSD related to a military trauma history, mostly nurses, will be recruited from the National Center for PTSD Division in Menlo Park, California. Thirty women with PTSD related to sexual trauma will be recruited from the Crime Victims Study Program at the University of South Carolina in Charleston. Thirty male PTSD patients will also be recruited from the Crime Victim Study Unit. An additional group of Korean conflict veterans with PTSD will be recruited from the applicant's own site, i.e., the National Center for PTSD Division at the West Haven, CT VA Medical Center. Reference is made to control groups of at least 30 normal subjects of each sex, although the source of the control subjects and other details regarding them are not provided. The study will employ a group comparison design with six dependent measures: total T3, free T3, total T4, free T4, thyrotropin (TSH), and thyroxine-binding globulin (TBG). Each dependent measure will be analyzed by one way ANOVA with post-hoc tests used to identify which group means differ significantly. A multivariate statistical approach, using stepwise discriminant analyses and multidimensional scaling, will also be used to determine whether profiles of three or more hormonal measures can discriminate group differences on a level of accuracy above any single hormonal measure. The applicant will also use recently available SCID data on 160 West Haven VA veterans with PTSD to assess the status of comorbid diagnoses, including Panic Disorder, Major Depressive Disorder, and several categories of Substance Abuse, as potential confounding variables, in regression analyses with total T3, free T3, and TBG. In collaboration with Dr. Michael Johnson of the University of South Carolina, the same dependent measures will be studied in a population of both women and men with Panic Disorder, with and without a history of traumatic stress. Another component of this project, in collaboration with Dr. Steven Woodward of the Menlo Park National Center for PTSD, will assess the relationship between total and free T3 measures and measures of sleep disturbance, including percent time awake during the night, number of eye movements per minute of REM, and number of anterior tibialis EMG bursts per minute of REM. In another component, in collaboration with Dr. Steven Southwick of the West Haven VAMC, hormonal measures will be obtained prior to, after five weeks of, and after ten weeks of treatment with propranolol in 30 PTSD veteran subjects, and in 30 PTSD placebo-treated controls. The data will be analyzed to determine whether high pre-treatment total T3 predicts better clinical improvement with propranolol, and whether change scores for total T3 correlate with change scores for PTSD symptomatology as measured by the Clinician-Administered PTSD (CAPS).
