No abstract

Prenatal stress is known to epigenetically program offspring physiology and behaviour, and may become a risk factor for adult complex diseases. To gain insight into the underlying environment-gene interactions, we used proton nuclear magnetic resonance spectroscopy to analyze urinary metabolomes of male and female adolescents who were in utero during the 1998 Quebec Ice Storm. Metabolomic profiles in adolescent groups were found to be significantly different. Higher prenatal stress exposure generated alterations in metabolic pathways involved in energy metabolism and protein biosynthesis, such as branched-chain amino acid synthesis, alanine metabolism, and ketone body metabolism. Dysregulation of energy and protein metabolism suggests an increased risk of metabolic diseases like insulin resistance, diabetes, and obesity. These findings are consistent with prior observations of physiological phenotypes from this cohort. Understanding the impact of natural disasters on health risks will provide new and improved therapeutic strategies to mitigate stress-associated adverse health outcomes. Using metabolomic biomarkers may also assist in the prediction and prevention of these adverse outcomes.

A 61-year-old man sustained a mild traumatic brain injury (mTBI) following a pedestrian versus vehicle traffic accident. Post injury, he began to experience symptoms including light-headedness, spatial disorientation, nausea, fatigue and prominent dizziness brought on by postural change, physical activity or eye movements. Symptoms of dizziness persisted for over 5 years, despite numerous extensive and rigorous vestibular and vision therapy regimens. All investigations suggested normal peripheral and central vestibular functioning. The patient underwent 10 sessions of repetitive transcranial magnetic stimulation (rTMS) treatment, with stimulation of the left dorsolateral prefrontal cortex at 70% of resting motor threshold and a frequency of 10 Hz. Dizziness symptom severity and frequency were reduced by greater than 50% at 3 months post treatment, with a clinically significant reduction of dizziness disability from 40 to 21 points on the Dizziness Handicap Inventory. We propose rTMS as a safe, effective and cost-effective treatment option for patients who experience persistent post-traumatic dizziness secondary to mTBI.

Determinants of lifetime health are complex and emphasize the need for robust predictors of disease risk. Allostatic load (AL) has become a clinical framework to estimate the cumulative biological burden associated with chronic stress. To assist knowledge translation in the developmental origins of health and disease field, clinically valid methods for reliable AL assessment in experimental models are urgently needed. Here, we introduce the rat cumulative allostatic load measure (rCALM), as a new preclinical knowledge translation tool to assess the burden of chronic stress. First, we identified an array of stress-associated physiological markers that are particularly sensitive to hypothalamic–pituitary–adrenal axis dysregulation by ancestral prenatal stress. Second, we determined which of these markers are susceptible to an intervention by environmental enrichment (EE) to mitigate AL. The markers most responsive to stress and EE therapy were assembled to become operationalized in the rCALM. Third, the new rCALM was validated for the ability to indicate future disease risks. The results show that the rCALM estimates the burden of chronic stress and serves as a proxy to estimate stress resilience and vulnerability to disease. Using the rCALM we showed that enrichment therapy can offset the adverse health outcomes linked to a high AL. Thus, the rCALM provides a model for the development of new test strategies that facilitate knowledge translation in preclinical animal models.