Distinguishing and phenotype monitoring of traumatic brain injury and post-concussion syndrome including chronic migraine in serum of Iraq and Afghanistan war veterans

• Published in: PloS one 2019-04, Vol.14 (4), p.e0215762
• Main Authors: Hanas, Jay S, Hocker, James R S, Lerner, Megan R, Couch, James R
• Format: Article
• Language: English
• Subjects: Adult; Afghan Campaign 2001; Amyloidosis; Autoimmune diseases; Autoimmunity; Autophagy; Biochemistry; Biology and Life Sciences; Biomarkers; Biomolecules; Biotechnology; Blood; Blood-brain barrier; Brain; Brain injuries; Brain Injuries, Traumatic - complications; Chronic Disease; Civilians; Computer and Information Sciences; Concussion; Cytokines; Dementia disorders; Depression (Mood disorder); Depression - blood; Depression - diagnosis; Depression - etiology; Diagnosis; Diagnosis, Differential; Female; Genetic aspects; Head injuries; Headache; Headaches; Health aspects; Humans; Immune response; Iraq War, 2003-2011; Male; Medicine; Medicine and Health Sciences; Mental depression; Mental disorders; Middle Aged; Migraine; Migraine Disorders - blood; Migraine Disorders - diagnosis; Migraine Disorders - etiology; Military personnel; Neurons; Novels; Parathyroid hormone; Parathyroid hormones; Patient monitoring equipment; Phagocytosis; Phenotypes; Physiological aspects; Physiological responses; Physiology; Plasma; Post traumatic stress disorder; Post-concussion syndrome; Post-Concussion Syndrome - blood; Post-Concussion Syndrome - diagnosis; Post-Concussion Syndrome - etiology; Posttraumatic stress disorder; Proteins; Retrospective Studies; Social Sciences; Stress Disorders, Post-Traumatic - blood; Stress Disorders, Post-Traumatic - diagnosis; Stress Disorders, Post-Traumatic - etiology; Studies; Traumatic brain injury; United States; Veterans; War-Related Injuries - complications
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0215762

Traumatic Brain Injury (TBI) and persistent post-concussion syndrome (PCS) including chronic migraine (CM) are major health issues for civilians and the military. It is important to understand underlying biochemical mechanisms of these conditions, and be able to monitor them in an accurate and minimally invasive manner. This study describes the initial use of a novel serum analytical platform to help distinguish TBI patients, including those with post-traumatic headache (PTH), and to help identify phenotypes at play in these disorders. The hypothesis is that physiological responses to disease states like TBI and PTH and related bodily stresses are reflected in biomolecules in the blood in disease-specific manner. Leave one out (serum sample) cross validations (LOOCV) and sample randomizations were utilized to distinguished serum samples from the following TBI patient groups: TBI +PTSD + CM + severe depression (TBI "most affected" group) vs healthy controls, TBI "most affected" vs TBI, TBI vs controls, TBI + CM vs controls, and TBI + CM vs TBI. Inter-group discriminatory p values were ≤ 10-10, and sample group randomizations resulted in p non-significant values. Peptide/protein identifications of discriminatory mass peaks from the TBI "most affected" vs controls and from the TBI plus vs TBI minus CM groups yielded information of the cellular/molecular effects of these disorders (immune responses, amyloidosis/Alzheimer's disease/dementia, neuronal development). More specific biochemical disease effects appear to involve blood brain barrier, depression, migraine headache, autoimmunity, and autophagy pathways. This study demonstrated the ability for the first time of a novel, accurate, biomarker platform to monitor these conditions in serum, and help identify biochemical relationships leading to better understanding of these disorders and to potential therapeutic approaches.