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Mental health is increasingly being recognized as both a leading cause of disability worldwide and an important area of opportunity for biological breakthroughs. A major limitation in the current diagnosis and management of severe psychiatric conditions is the exclusive reliance on subjective clinical information in the absence of available laboratory tests. A lack of objective biomarkers that reliably identify mental health disorders, and which could serve as targets for diagnosis, treatment response monitoring, and the development of novel therapeutics, remains a fundamental challenge of psychiatry today. Although clinical tests are well established in other areas of medicine, their development in psychiatry has been relatively slow. So far, no biomarkers or other risk markers are available to create profiles to enhance prediction and therapeutic selection in psychiatry. As novel 'omics-based technologies – such as genomics, proteomics, and metabolomics – and advanced imaging modalities enable researchers to probe the molecular to systemic underpinnings of various disorders, opportunities arise to explore the biological basis for mental health and disease. It is anticipated that specific alterations in blood-based molecular biomarkers, such as DNA, RNA, protein, and metabolite levels, will lead to standardized tests to facilitate diagnosis as they reflect the underlying etiology and mechanisms of disease. They may also pave the way for earlier and more effective treatment and monitoring of patients. Ultimately, the coordinated effort of relevant civilian and military stakeholders – including researchers, physicians and funders – together with standardization initiatives, will be vital to overcoming existing challenges to advance personalized mental health care using sensitive and specific biomarkers.

High‐intensity interval training (HIIT) has become a popular fitness training approach under both civilian and military settings. Consisting of brief and intense exercise intervals, HIIT requires less time commitment yet is able to produce the consistent targeted physical adaptations as conventional endurance training. To effectively characterize and monitor HIIT‐induced cellular and molecular responses, a highly accessible yet comprehensive biomarker discovery source is desirable. Both gene differential expression (DE) and gene set (GS) analyses were conducted using hair follicle transcriptome established from pre and postexercise subjects upon a 10‐day HIIT program by RNA‐Seq, Comparing between pre and posttraining groups, differentially expressed protein coding genes were identified. To interpret the functional significance of the DE results, a comprehensive GS analysis approach featuring multiple algorithms was used to enrich gene ontology (GO) terms and KEGG pathways. The GS analysis revealed enriched themes such as energy metabolism, cell proliferation/growth/survival, muscle adaptations, and cytokine–cytokine interaction, all of which have been previously proposed as HIIT responses. Moreover, related cell signaling pathways were also measured. Specifically, G‐protein‐mediated signal transduction, phosphatidylinositide 3‐kinases (PI3K) – protein kinase B (PKB) and Janus kinase (JAK) – Signal Transducer and Activator of Transcription (STAT) signaling cascades were over‐represented. Additionally, the RNA‐Seq analysis also identified several HIIT‐responsive microRNAs (miRNAs) that were involved in regulating hair follicle‐specific processes, such as miR‐99a. For the first time, this study demonstrated that both existing and new biomarkers like miRNA can be explored for HIIT using the transcriptomic responses exhibited by the hair follicle.

BACKGROUND: A convenient biosensor for real‐time measurement of biomarkers for in‐field psychophysiological stress research and military operations is desirable. We evaluated a hand‐held device for measuring salivary amylase as a stress marker in medical technicians undergoing combat casualty care training using two different modalities in operating room and field settings. METHODS: Salivary amylase activity was measured by two biosensor methods: directly sampling saliva with a test strip placed under the tongue or pipetting a fixed volume of precollected saliva onto the test strip, followed by analyzing the sample on the strip using a biosensor. The two methods were compared for their accuracy and sensitivity to detect the stress response using an enzyme assay method as a standard. RESULTS: The measurements from the under‐the‐tongue method were not as consistent with those from the standard assay method as the values obtained from the pipetting method. The under‐the‐tongue method did not detect any significant increase in the amylase activity due to stress in the operating room (P > 0.1), in contrast to the significant increases observed using the pipetting method and assay method with a significance level less than 0.05 and 0.1, respectively. Furthermore, the under‐the‐tongue method showed no increased amylase activity in the field testing, while both the pipetting method and assay method showed increased amylase activity in the same group (P < 0.1). CONCLUSION: The accuracy and consistency of the biosensors need to be improved when used to directly measure salivary amylase activity under the tongue for stress assessment in military medical training.

LAY SUMMARY Moral injury (MI) refers to the distress experienced when people do, or do not, do something that goes against their morals or values. It can also occur when people perceive that their values have been betrayed. MI is associated with several mental health conditions, including posttraumatic stress disorder (PTSD), depression, and anxiety. A potential risk factor for MI may include difficulties with emotion regulation (ER). Difficulties with ER refers to the ability to manage emotions. It is associated with the same mental health conditions linked to MI, including PTSD. The purpose of this study was to examine whether difficulties with ER were associated with MI in a Canadian military personnel and Veteran sample. Participants completed several questionnaires assessing for MI, difficulties with ER, and other mental health symptoms, such as PTSD, while they were inpatients at a psychiatric hospital. It was found that MI and perceived betrayals were associated with symptoms of PTSD. Symptoms of PTSD, depression, and anxiety were also associated with one another. Difficulties with ER were also associated with symptoms of PTSD, depression, and anxiety but were not related to MI. The findings serve as a first step in examining potential risk factors of MI.

Purpose: Blood biomarkers are a useful tool to study concussion. However, their interpretation is complicated by a number of potential biological confounds, including exercise. This is particularly relevant in military and athletic settings where injury commonly occurs during physical exertion. The impact of high-intensity interval training (HIIT) on putative brain injury biomarkers remains under-examined. The purpose of this study was to observe the effects of HIIT on a panel of blood biomarkers associated with brain injury.

LAY SUMMARY There has been increasing interest in understanding the impact of blast exposure on health and performance in military members and Veterans. This phenomenon has proven difficult to study because personnel diagnosed with blast-induced mild traumatic brain injury (mTBI) typically also exhibit emotional difficulties such as posttraumatic stress disorder (PTSD), likely because the events that led to mTBI in theatre were also emotionally traumatic. In turn, this comorbidity makes it difficult to tease apart symptoms uniquely due to blast-induced mTBI or PTSD. Researchers have therefore explored surrogate settings wherein the effects of blast exposure can be assessed in an operationally realistic, yet scientifically more controlled manner, such as breacher and sniper training. To that aim, researchers administered a measure of post-concussive symptomatology and two mental health scales to breachers and snipers, as well as sex- and age-matched military controls. The breachers and snipers reported greater levels of post-concussive symptoms, but not poorer mental health outcomes. Therefore, post-concussive symptoms and mental health outcomes might be dissociable when the impact of repetitive exposure to low-level blast is assessed in the context of training and operations, rather than following warzone deployment involving primarily high-level blast exposure.

Post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are highly prevalent and closely related disorders. Affected individuals often exhibit substantially overlapping symptomatology – a major challenge for differential diagnosis in both military and civilian contexts. According to our symptom assessment, the PTSD group exhibited comparable levels of concussion symptoms and severity to the mTBI group. An objective and reliable system to uncover the key neural signatures differentiating these disorders would be an important step towards translational and applied clinical use. Here we explore use of MEG (magnetoencephalography)-multivariate statistical learning analysis in identifying the neural features for differential PTSD/mTBI characterisation. Resting state MEG-derived regional neural activity and coherence (or functional connectivity) across seven canonical neural oscillation frequencies (delta to high gamma) were used. The selected features were consistent and largely confirmatory with previously established neurophysiological markers for the two disorders. For regional power from theta, alpha and high gamma bands, the amygdala, hippocampus and temporal areas were identified. In line with regional activity, additional connections within the occipital, parietal and temporal regions were selected across a number of frequency bands. This study is the first to employ MEG-derived neural features to reliably and differentially stratify the two disorders in a multi-group context. The features from alpha and beta bands exhibited the best classification performance, even in cases where distinction by concussion symptom profiles alone were extremely difficult. We demonstrate the potential of using 'invisible' neural indices of brain functioning to understand and differentiate these debilitating conditions.

Currently, there is strong interest within the military to better understand the effects of long-term occupational exposure to repeated low-level blast on health and performance. To gain traction on the chronic sequelae of blast, we focused on breaching—a tactical technique for gaining entry into closed/blocked spaces by placing explosives and maintaining a calculated safe distance from the detonation. Using a cross-sectional design, we compared the neuropsychological and neurocognitive profiles of breaching instructors and range staff to sex- and age-matched Canadian Armed Forces (CAF) controls. Univariate tests demonstrated that breaching was associated with greater post-concussive symptoms (Rivermead Post Concussion Symptoms Questionnaire) and lower levels of energy (RAND SF-36). In addition, breaching instructors and range staff were slower on a test that requires moving and thinking simultaneously (i.e., cognitive-motor integration). Next, using a multivariate approach, we explored the impact of other possible sources of injury, including concussion and prior war-zone deployment on the same outcomes. Concussion history was associated with higher post-concussive scores and musculoskeletal problems, whereas deployment was associated with higher post-concussive scores, but lower energy and greater PTSD symptomatology (using PCL-5). Our results indicate that although breaching, concussion, and deployment were similarly correlated with greater post-concussive symptoms, concussion history appears to be uniquely associated with altered musculoskeletal function, whereas deployment history appears to be uniquely associated with lower energy and risk of PTSD. We argue that the broader injury context must, therefore, be considered when studying the impact of repetitive low-level explosives on health and performance in military members.

Military Breachers and Range Staff (MBRS) are subjected to repeated sub-concussive blasts, and they often report symptoms that are consistent with a mild traumatic brain injury (mTBI). Biomarkers of blast injury would potentially aid blast injury diagnosis, surveillance and avoidance. Our objective was to identify plasma metabolite biomarkers in military personnel that were exposed to repeated low-level or sub-concussive blast overpressure. A total of 37 military members were enrolled (18 MBRS and 19 controls), with MBRS having participated in 8–20 breaching courses per year, with a maximum exposure of 6 blasts per day. The two cohorts were similar except that the number of blast exposures were significantly higher in the MBRS, and the MBRS cohort suffered significantly more post-concussive symptoms and poorer health on assessment. Metabolomics profiling demonstrated significant differences between groups with 74% MBRS classification accuracy (CA). Feature reduction identified 6 metabolites that resulted in a MBRS CA of 98%, and included acetic acid (23.7%), formate (22.6%), creatine (14.8%), acetone (14.2%), methanol (12,7%), and glutamic acid (12.0%). All 6 metabolites were examined with individual receiver operating characteristic (ROC) curve analyses and demonstrated areas-under-the-curve (AUCs) of 0.82–0.91 (P ≤ 0.001) for MBRS status. Several parsimonious combinations of three metabolites increased accuracy of ROC curve analyses to AUCs of 1.00 (P < 0.001), while a combination of volatile organic compounds (VOCs; acetic acid, acetone and methanol) yielded an AUC of 0.98 (P < 0.001). Candidate biomarkers for chronic blast exposure were identified, and if validated in a larger cohort, may aid surveillance and care of military personnel. Future point-of-care screening could be developed that measures VOCs from breath, with definitive diagnoses confirmed with plasma metabolomics profiling.