Post-diagnostic research on rare genetic developmental disorders presents new opportunities (and a few challenges) for discovery neuroscience and translation. In this talk, Kate will describe and discuss neurodevelopmental phenotypes arising from rare, high penetrance genomic variants which directly influence pre-synaptic vesicle cycling (SVC disorders). She will focus on Synaptotagmin-1 Associated Neurodevelopmental Disorder (also known as Baker Gordon Syndrome), first described in 2015 and now diagnosed in more than 50 children and young people worldwide. She will then present work-in-progress by her group on the neurodevelopmental spectrum of SVC disorders more broadly, and discuss opportunities for collaborative neuroscience which can bridge the gaps between genetic cause and complex neurological, cognitive and mental health outcomes.

Chronic exercise is a powerful intervention that lowers the incidence of most age-related diseases while promoting healthy metabolism in humans. However, illness, injury or age prevent many humans from consistently exercising. Thus, identification of molecular targets that can mimic the benefits of exercise would be a valuable tool to improve health outcomes of humans with neurodegenerative or mitochondrial diseases, or those with enforced sedentary lifestyles. Using a novel exercise platform for Drosophila, we have identified octopaminergic neurons as a key subset of neurons that are critical for the exercise response, and shown that periodic daily stimulation of these neurons can induce a systemic exercise response in sedentary flies. Octopamine is released into circulation where it signals through various octopamine receptors in target tissues and induces gene expression changes similar to exercise. In particular, we have identified several key molecules that respond to octopamine in skeletal muscle, including the mTOR modulator Sestrin, the PGC-1α homolog Spargel, and the FNDC5/Irisin homolog Iditarod. We are currently testing these molecules as potential therapies for multiple diseases that reduce mobility, including the PolyQ disease SCA2 and the mitochondrial disease Barth syndrome.

Research evidence indicates that psychosocial stressors such as work-life stress serves as a negative occupational exposure relating to poor health behaviors including smoking, poor food choices, low levels of exercise, and even decreased sleep time, as well as a number of chronic health outcomes. The association between work-life stress and adverse health behaviors and chronic health suggests that Occupational Health Psychology (OHP) interventions such as leadership support trainings may be helpful in mitigating effects of work-life stress and improving health, consistent with the Total Worker Health approach. This presentation will review workplace psychosocial stressors and leadership training approaches to reduces stress and improve health, highlighting a randomized controlled trial, the Military Employee Sleep and Health study.

Black Americans experience diverse racism-related stressors throughout the lifespan. Disproportionately high trauma exposure, economic disadvantage, explicit racism and inequitable treatment are stressors faced by many Black Americans. These experiences have a cumulative negative impact on psychological and physical health. However, little is understood about how experiences of racism, such as discrimination, can mediate health outcomes via their effects on neurobiology. I will present clinical, behavioral, physiological and neurobiological data from Black American participants in the Grady Trauma Project, a longstanding study of trauma conducted in inner-city Atlanta. These data will be discussed in the context of both risk and resilience/adaptation perspectives. Finally, recommendations for future clinical neuroscience research and targets for intervention in marginalized populations will be discussed.