Antidepressant Response in Older Adults With Comorbid PTSD and MDD
Antidepressant Response in Older Adults With Comorbid PTSD and MDD
In the Investigator's ongoing studies of Posttraumatic Stress Disorder (PTSD) in older
 adults, it has been found that older adults with PTSD frequently meet the criteria for
 comorbid Major Depressive Disorder (MDD). Moreover, relative to trauma-exposed healthy
 controls (TEHCs), elders with PTSD manifest executive function deficits, fatigability, and
 mobility and physical function deficits that are consistent with what the investigator has
 observed in depressed older adults. Yet, the investigator has found that very few older
 adults with combined PTSD/MDD have received appropriate antidepressant treatment for their
 condition. These findings give rise to the questions of (1) how effective is antidepressant
 treatment for depressive symptoms in the context of PTSD/MDD and (2) are cognitive and
 physical function deficits in PTSD/MDD patients reversible with effective antidepressant
 treatment?
Chronic PTSD in older adults leads to increased risk of mortality from cardiovascular
 disease, metabolic syndrome, diabetes mellitus, and ulcerative gastrointestinal disease. PTSD
 appears to promote aging-associated syndromes such as frailty, and older patients with PTSD
 exhibit faster cognitive decline and have twice the risk of dementia compared to individuals
 without PTSD. In addition, laboratory studies report accelerated biological signatures of
 aging in PTSD patients, including shortened leukocyte telomere length, increases in
 pro-inflammatory cytokines, and increased oxidative stress. PTSD is associated with similar
 anatomical brain changes to those occurring with cognitive aging, including bilateral
 hippocampal volume reductions, specifically affecting the dentate gyrus (DG) and CA3
 subregion, and increased microvascular lesions (white matter hyperintensities [WMH]). These
 observations suggest that the adverse health and functional outcomes associated with chronic
 PTSD in older patients may be explained by a deleterious interaction between pathophysiologic
 changes underlying PTSD and the biology of aging, the end result of which is to accelerate
 senescence throughout the body and particularly in the brain. However, no prior study has
 explicitly tested this hypothesis by examining indices of aging in older adults with and
 without PTSD. In our ongoing IRB #7489, The investigator hypothesize that chronic PTSD, over
 and above other contributing factors, accelerates biological aging in the brain and body,
 leading to adverse behavioral consequences such as frailty and cognitive decline. To test
 these hypotheses, 150 individuals are being recruited who are aged≥50and diagnosed with PTSD.
 A control group of 150 age-, sex-, and trauma exposure-matched subjects without PTSD are
 being recruited and assessed. Included subjects undergo comprehensive neuropsychological
 assessment and cerebral blood volume functional magnetic resonance imaging (CBV-fMRI) to
 assess regional hippocampal metabolic activity and function. Structural MRI is performed to
 quantify WMH, regional brain volume, and cortical thickness while resting-state fMRI measures
 functional connectivity within hippocampal networks. PTSD subjects and controls are compared
 on measures of aging within the following domains: neural (DG CBV, WMH, morphology),
 cognitive (processing speed, memory, executive function, pattern separation), somatic
 (peripheral inflammatory markers, leukocyte telomere length, and measures of oxidative
 stress), and behavioral (grip strength, gait speed, fatigue levels). By elucidating the
 interaction of chronic PTSD with aging processes, data from this project may contribute to
 the development of rationally designed, personalized, and age-appropriate novel treatments.

 Interim analyses of PTSD subjects in this study demonstrate a high degree of comorbidity with
 MDD. Among participants with PTSD enrolled to date, 67.1% meet the criteria for MDD and the
 mean Hamilton Rating Scale for Depression (HRSD) is 18.1. The most prominent cognitive
 differences observed to date in our study between PTSD and TEHC subjects is executive
 dysfunction, which is common in late-life depression.

 PTSD subjects have dramatically increased fatigability and prevalence of frailty criteria
 compared to TEHCs, abnormalities which are also frequently seen in our older MDD samples.
 Yet, the investigator has found that less than 25% of these individuals are currently
 receiving an adequate dose and duration of first-line pharmacotherapy for MDD, while only
 one-third report any past medication treatment. These data raise the question of whether
 patients with combined PTSD/MDD could benefit from adequate antidepressant medication
 treatment and to what degree their cognitive and physical function deficits would be
 reversible with this therapy.
Inclusion Criteria:

 1. Individual has completed IRB 7489

 2. Diagnosed with DSM 5 MDD

 3. HRSD >=18

 4. Willing to and capable of providing informed consent and complying with study
 procedures.

 Exclusion Criteria:

 1. History of allergic or adverse reaction to

 2. Non-response to adequate trial of escitalopram (at least 4 weeks at dose of 20mg) and
 duloxetine (at least 4 weeks at dose of 60mg)during the current episode.

 3. Current treatment with psychotherapy, antidepressants, or other psychotropic
 medications.