Newsletter SignupSearch

Publication

From genetics to systems biology of stress-related mental disorders

Citation:
Neurobiology of Stress 2021; 15: https://doi.org/10.1016/j.ynstr.2021.100393
Authored By:
Shareefa Dalvie, Chris Chatzinakos, Obada Al Zoubi, Foivos Georgiadis, PGC-PTSD Systems Biology workgroup, Lee Lancashire, Nikolaos P. Daskalakis
Abstract:
Mild traumatic brain injury (mTBI) is among the most common injuries sustained by post-9/11 veterans; however, these injuries often occur within the context of psychological trauma. Blast exposure, even in the absence of a diagnosable TBI, leads to changes in neural connectivity and congitive functioning. Therefore, considering clinical comorbidities and injury characteristics is critical to understanding the long-term effects of mTBI. Research is moving towards identifying diagnostic and prognostic blood-based biomarkers for TBI; however, few studies include other prevalent clinical and medical comorbidities related to deployment. Here, we present the initial cross-sectional relationships between plasma biomarkers, clinical, and medical comorbidities in a well-characterized longitudinal sample of 550 post-9/11 veteran men and women. We examined biomarkers associated with inflammation (interleukin 6 and 10, tumor necrosis factor α, and eotaxin) and neurodegeneration (neurofilament light, glial fibrillary acidic protein (GFAP), tau, brain derived neurotrophic factor, amyloid ß 40 and 42, phosphorylated neurofilament heavy chain, and neuron specific enolase). Univariate analyses of covariance (ANCOVA) were conducted to determine mean level differences between close blast (blasts that occur within 0–10 meters) and mTBI groups. Our primary findings were twofold: (1) Inflammatory markers were consistently higher in participants exposed to close blasts and were strongly related to deployment-related psychopathology. (2) GFAP was consistently lower in participants exposed to blast and mTBI and lower GFAP was associated with more severe psychological symptoms. More research is clearly needed; however, our findings indicate that chronic increased inflammation and decreased GFAP may be related to close blast exposure. Many individuals will be exposed to some form of traumatic stress in their lifetime which, in turn, increases the likelihood of developing stress-related disorders such as post-traumatic stress disorder (PTSD), major depressive disorder (MDD) and anxiety disorders (ANX). The development of these disorders is also influenced by genetics and have heritability estimates ranging between ∼30 and 70%. In this review, we provide an overview of the findings of genome-wide association studies for PTSD, depression and ANX, and we observe a clear genetic overlap between these three diagnostic categories. We go on to highlight the results from transcriptomic and epigenomic studies, and, given the multifactorial nature of stress-related disorders, we provide an overview of the gene-environment studies that have been conducted to date. Finally, we discuss systems biology approaches that are now seeing wider utility in determining a more holistic view of these complex disorders.
Published in:
Neurobiology of Stress

More Publications

September 9, 2022

Sensors

Deep Learning for Daily Monitoring of Parkinson’s Disease Outside the Clinic Using Wearable Sensors

June 1, 2022

JAMA Network Open

Association of Posttraumatic Stress Disorder With Accelerated Cognitive Decline in Middle-aged Women

March 23, 2022

Journal of Neurotrauma

A Framework to Advance Biomarker Development in the Diagnosis, Outcome Prediction, and Treatment of Traumatic Brain Injury

February 26, 2022

Translational Psychiatry

Plasma biomarkers associated with deployment trauma and its consequences in post-9/11 era veterans: initial findings from the TRACTS longitudinal cohort

January 31, 2022

Biological Psychiatry

Noncoding RNAs: Stress, Glucocorticoids, and Posttraumatic Stress Disorder

December 1, 2021

Neurotrauma Reports

Neurotrauma Reports Special Collection: Null Hypothesis Initiative

Cohen Veterans Bioscience - Advancing Brain Health

Get the latest updates in TBI and PTSD research

Sign up for our newsletter to learn how we’re advancing solutions for brain trauma.

This field is for validation purposes and should be left unchanged.