Second, the mechanisms by which childhood traumatic events decrease the AAO in BD remain unclear. It is likely that this is mediated through the induction of a cascade of neurobiological and neuroendocrine events. Previous studies have suggested that childhood trauma can have long-lasting effects on the catecholamine response to psychological stress3536 and induce hyper reactivity of the corticoid-releasing factor system373839, as well as altering the structure and function of the medial prefrontal cortex and hippocampus40. Although the effects of such trauma are probably not specific to BD, our data suggests that a history of childhood trauma in BD produces long-term disturbances of neurobiological mechanisms that are required to regulate stress and stress-resilience41, with this then interacting with alterations in genetic regulation of the serotonergic system. Such physiological changes may lower the threshold for the onset of BD, including via sensitization to other environmental triggering factors.
