Posttraumatic Stress Disorder (PTSD) is the product of traumatic stress operating on individual diatheses that span the spectrum of human variation in vulnerability to psychopathology. This interaction yields extensive phenotypic heterogeneity in samples of individuals with PTSD, one manifestation of which is a severe and diverse pattern of diagnostic comorbidity with commonly co-occurring disorders ranging from those of the """"""""internalizing"""""""" spectrum (i.e., the unipolar mood and anxiety disorders) to the externalizing spectrum (i.e., antisocial behavior, the addictions, and disorders of impulse control). Dr. Miller's research program is focused on understanding the influence of enduring, temperament-based propensities towards internalizing and externalizing behavior on the form and expression of posttraumatic psychopathology. Through a series of studies, he and his colleagues have found evidence of internalizing and externalizing subtypes of PTSD across genders and trauma types. He has recently extended this work using confirmatory factor analysis and biometric twin modeling to implicate a genetic basis for the internalizing and externalizing dimensions underlying these subtypes. One limitation of work thus far has been a reliance on cross- sectional datasets and the resulting inability to evaluate the stability of the typology over time or the transactional relationships that likely exist between class membership and life stress. Therefore, the proposed study will conduct four- (Time 2) and six-year (Time 3) follow-up assessments of veterans who recently completed extensive assessments for Dr. Miller's prior Merit Review-funded study """"""""The Structure of PTSD Comorbidity"""""""". The study will also include assessment of new onset life stressors occurring between Time 2 and 3 to examine the stress- generative effects of internalizing and externalizing psychopathology as well as the symptom exacerbating effects of such stressors. This intensively-assessed sample of veterans offers a unique opportunity for longitudinal examination of a broad array of psychiatric symptoms and modeling influences on their trajectories.

Public Health Relevance

Posttraumatic Stress Disorder (PTSD) is associated with a severe and diverse pattern of diagnostic comorbidity. The proposed study will longitudinally examine a broad array of psychiatric symptoms in veterans with chronic PTSD symptomatology and model influences on their trajectories of change over time. We propose to conduct four- and six-year follow-up assessments of PTSD and comorbid disorders in veterans who participated in the first phase of the PI's study """"""""The Structure of PTSD Comorbidity"""""""". The study will feature an assessment of new onset life stressors occurring between Time 2 and 3 to examine the stress-generative effects of psychopathology as well as the symptom exacerbating effects of such stressors.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
1I01CX000431-01A1
Application #
8140929
Study Section
Mental Health and Behavioral Science A (MHBA)
Project Start
2011-07-01
Project End
2015-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
1
Fiscal Year
2011
Total Cost
Indirect Cost
Name
VA Boston Health Care System
Department
Type
DUNS #
034432265
City
Boston
State
MA
Country
United States
Zip Code
02130
Ratanatharathorn, Andrew; Boks, Marco P; Maihofer, Adam X et al. (2017) Epigenome-wide association of PTSD from heterogeneous cohorts with a common multi-site analysis pipeline. Am J Med Genet B Neuropsychiatr Genet 174:619-630
Duncan, L E; Ratanatharathorn, A; Aiello, A E et al. (2017) Largest GWAS of PTSD (N=20?070) yields genetic overlap with schizophrenia and sex differences in heritability. Mol Psychiatry :
Wolf, Erika J; Logue, Mark W; Stoop, Tawni B et al. (2017) Accelerated DNA Methylation Age: Associations with PTSD and Mortality. Psychosom Med :
Sadeh, Naomi; Wolf, Erika J; Logue, Mark W et al. (2016) Polygenic Risk for Externalizing Psychopathology and Executive Dysfunction in Trauma-Exposed Veterans. Clin Psychol Sci 4:545-558
Sadeh, Naomi; Wolf, Erika J; Logue, Mark W et al. (2016) EPIGENETIC VARIATION AT SKA2 PREDICTS SUICIDE PHENOTYPES AND INTERNALIZING PSYCHOPATHOLOGY. Depress Anxiety 33:308-15
Wisco, Blair E; Miller, Mark W; Wolf, Erika J et al. (2016) The impact of proposed changes to ICD-11 on estimates of PTSD prevalence and comorbidity. Psychiatry Res 240:226-233
Wolf, Erika J; Miller, Mark W; Kilpatrick, Dean et al. (2015) ICD-11 Complex PTSD in US National and Veteran Samples: Prevalence and Structural Associations with PTSD. Clin Psychol Sci 3:215-229
Sadeh, Naomi; Miller, Mark W; Wolf, Erika J et al. (2015) Negative emotionality and disconstraint influence PTSD symptom course via exposure to new major adverse life events. J Anxiety Disord 31:20-7
Logue, Mark W; Smith, Alicia K; Baldwin, Clinton et al. (2015) An analysis of gene expression in PTSD implicates genes involved in the glucocorticoid receptor pathway and neural responses to stress. Psychoneuroendocrinology 57:1-13
Reardon, Annemarie F; Hein, Christina L; Wolf, Erika J et al. (2014) Intermittent explosive disorder: associations with PTSD and other Axis I disorders in a US military veteran sample. J Anxiety Disord 28:488-94

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