Neurobehavioral Moderators of Post-traumatic Disease Trajectories

New York University School Of Medicine, New York NY

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Abstract

DESCRIPTION (provided by applicant): To cogently uncover the neurobiology of emerging post-traumatic stress disorder (PTSD), we propose a conveniently powered, fMRI-based, 14 months long, longitudinal study of PTSD symptom trajectories and concurrent structural and functional brain alterations in recent trauma survivors. PTSD is a severe and often chronic psychiatric disorder that has profound public health impact by virtue of its high prevalence, persistence, accompanying functional impairment and high comorbidity with other mental, and physical disorders. Longitudinal studies of recent trauma survivors describe typical symptom trajectories including non-remission, rapid remission, and delayed, incomplete, remission. These trajectories provide an observable dimension of how PTSD develops, or remits, but a better understanding of underlying neurobiology of both PTSD and resilience can only result from linking emerging symptoms with pertinent dynamics in relevant brain circuits To date, however, the neurobehavioral correlates of evolving PTSD have not been documented in large imaging- based studies, leaving a major knowledge gap. Using the investigators combined experience in successful prospective studies of early PTSD, advanced functional neuroimaging and PTSD neurobiology we will prospectively evaluate trauma-emerging symptoms and co-occurring dynamics in brain circuitry during the year that follows trauma exposure. We will use fMRI captured response to functional probes of brain circuits involved in threat detection/reactivity and emotional regulation, one-, four- and fourteen months after a traumatic event in 240 survivors at high risk for PTSD recruited from a general hospital emergency room. We will simultaneously evaluate PTSD, depression, anxiety symptoms and memory functions previously linked with PTSD, along with brain's activation patterns to the above-mentioned functional probes, functional and structural connectivity and structural (volumetric) characteristics. We thereby aim to (1) uncover latent trajectories of PTSD symptoms progression using advanced statistical modeling methods (2) identify neural mechanisms that underlay these trajectories, and (3) identify structural brain alterations associated with PTSD symptom trajectories using high resolution structural MRI and Diffusion Tensor Imaging. Knowledge gained in this work will fill a critical gap in understanding of the pathogenesis of PTSD and its time-sequenced evolvement. It will also identify potentially modifiable neuro-cognitive mediators of symptom trajectories, towards conceiving and designing processes-targeted, stage-specific interventions, and provide critically needed information on early recovery from traumatic stress. The large scope of this work will yield enough power for detecting brain/behavior correlates.