Abstract

Bodily reactions to acute stressors are by design adaptive enabling individuals to operate within defined homeostatic limits. However, more protracted forms of stress, including uncontrollable stress encountered during early stages of life, result in a myriad of adverse outcomes, not least stress-related disorders such as depression and anxiety. When faced with such stress, humans and other animals elicit a variety of coping strategies to offset stress intensity and harm, but for some, stress ‘gets under the skin’ and leaves lasting impacts. This talk considers the brain science and psychology of stress and focuses on so-called top-down cognitive control processes that collectively suppress stress circuits centred on the amygdala, striatum and periaqueductal grey (PAG). A new theory will be introduced that links mitochondrial function in the prefrontal cortex with top-down cognitive control, which it will be argued may account for both the beneficial (i.e., stress resilience) and maladaptive consequences of repeated exposure to uncontrollable stressors. Empirical support for this theory will be introduced and discussed using data derived from in-vivo respirometry, high-resolution magnetic resonance imaging, and computer-automated touchscreen-based tasks in rodents. Finally, the implications of this research for developing new interventions for depression and anxiety-related conditions will be considered, including a novel scientific justification for psilocybin and other hallucinogenic drugs in treatment-refractory depression.

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