Impact of Stress Exposure on Mental and Physical Health across the Life Span: Molecular mechanisms, Neurobiological abnormalities, and Novel Pathways for Intervention

Abstract

Stress exposures across the lifespan are known to have potent and long-lasting negative effects on mental health, and on the vulnerability to develop several metabolic dysfunctions. Importantly, the outcomes depend on the timing of the exposure as stress experienced at different neurodevelopmental windows (early in life, adolescence, adulthood, and old age) can lead to different negative outcomes via the involvement of distinct molecular and neurobiological mechanisms. Therefore, this symposium will integrate behavioural, immunological, and molecular findings from preclinical studies and clinical cohorts to dissect biological pathways that are involved in the effect of stress exposure at different stages and that can explain the onset of different negative outcomes. Moreover, we will also discuss promising new targets for preventing the negative effects of stress on brain function, cognition, affective behaviours, and physical health. Dr. Christoph Anacker will present data on how the serotonin system modulates neuroinflammatory responses to early life adversity in the mouse hippocampus across the lifespan, including adolescence, adulthood, and old age. He will show that rescuing impairments in serotonin signalling that result from early life adversity reduces neuroinflammation in the hippocampus, as well as associated deficits in neural signalling. Dr. Cattaneo will show data on inflammation related pathways as main biological systems affected by exposure to stress early in life both in animal models as well as in humans across lifespan and she will also discuss how this can also drive comorbidities between mental and physical diseases. She will also show how stress occurring at a different life period, at adulthood, enhance the risk for psychopathology by activating a different set of inflammatory pattern drive by specific and distinct epigenetic signatures. Dr. Nikolaos Daskalakis will show data on effects due to exposure to adversities at different ages (early in life and adolescence) and their additive effect on stress responses and vulnerability based on genetic background. He will show how animals exposed to early in life stress, upon exposure to adolescence-onset social isolation, exhibit sensorimotor gating deficits linked to hippocampus gene expression signature. He will also show human hippocampal post-mortem data of childhood trauma survivors with and without genetic susceptibility for stress.