Biomarkers for combat-related PTSD: focus on molecular networks from high-dimensional data

Abstract

Posttraumatic stress disorder (PTSD) and other deployment-related outcomes originate from a complex interplay between constellations of changes in DNA, environmental traumatic exposures, and other biological risk factors. These factors affect not only individual genes or bio-molecules but also the entire biological networks that in turn increase or decrease the risk of illness or affect illness severity. This review focuses on recent developments in the field of systems biology which use multidimensional data to discover biological networks affected by combat exposure and post-deployment disease states. By integrating large-scale, high-dimensional molecular, physiological, clinical, and behavioral data, the molecular networks that directly respond to perturbations that can lead to PTSD can be identified and causally associated with PTSD, providing a path to identify key drivers. Reprogrammed neural progenitor cells from fibroblasts from PTSD patients could be established as an in vitro assay for high throughput screening of approved drugs to determine which drugs reverse the abnormal expression of the pathogenic biomarkers or neuronal properties.

Diagnostic Biomarkers for Posttraumatic Stress Disorder: Promising Horizons from Translational Neuroscience Research

“…Indeed, the likelihood of characterizing one biological marker associated with the suggested 636,120 different ways in which an individual can present with PTSD (6) is vanishingly small. Rather, it is more prudent that future studies develop a cross-dimensional, comprehensive biological and psychological phenotypic profile in individuals with PTSD to: (1) characterize biomarkers for specific clusters of symptoms and/or (2) uncover divergent biological profiles of PTSD using more complex statistical techniques (142). In order to be compatible with the RDoC approach, biomarkers should be dimensional as well as transdiagnostic—in effect, not biomarkers specific to PTSD as a DSM disorder, but biomarkers of features associated with PTSD.…”

A decennial review of psychotraumatology: what did we learn and where are we going?

“…Collaborative efforts from the PGC have led to progress on finding epigenome-wide significant sites related to risk for PTSD (Smith et al, 2019). Systems biology advances, in large part driven by complex data-driven agnostic analytic approaches to multidimensional data (Neylan, Schadt, & Yehuda, 2014), are developing and hold promise and will be needed to co-analyse data on multiple omics platforms simultaneously. With regard to a detailed functional understanding of molecular mechanisms, studies conducted in the past decade have elucidated how functional genetic variants interact with environmental events (e.g.…”

Circulating miRNA associated with posttraumatic stress disorder in a cohort of military combat veterans

“…However, our ability to prevent the onset of PTSD and to treat it once symptoms present is limited, based in large part on our minimal understanding of the biological mechanisms related to the onset and maintenance of this disorder. Due to the complex biological nature of PTSD, investigating the molecular networks involved may provide valuable information on the pathogenesis of the disorder and therapeutic targets (Neylan, Schadt, & Yehuda, 2014). Although promising biomarkers have been proposed, due to the multifaceted and heterogeneous nature of the disorder, a variety of biomarkers likely reflect separate aspects of mechanisms associated with PTSD (Jergovic et al, 2015; Michopoulos, Norrholm, & Jovanovic, 2015).…”