The impact of early-life stress in the development and course of bipolar disorder: Mechanisms and implications

Traumatic events experienced throughout the different stages of childhood and adolescence are frequent circumstances with a detrimental impact on the physical and psychological health of the individual. A growing body of evidence shows the trauma-related effects on the hypothalamic-pituitary-adrenal axis, the sympathetic nervous system, the serotonin system, the immune system, on brain development, structure, and connectivity. Interestingly, a relation was found between early life stress and Bipolar Disorder: the patients who were exposed to childhood trauma showed a worsened course of the disorder with poor clinical and psychopathological factors. According to the kindling hypothesis, early environmental stressors interact with the genetic susceptibility through epigenetic mechanisms, making the subject more vulnerable to milder stressors, and lowering the threshold for the occurrence of subsequent mood episodes. Understanding these processes is crucial to the discovery of new targets of treatment to reduce or, possibly, revert the effect of early life stress on bipolar disorder.