Most disorders follow the Diathesis-Stress Model where the trajectory begins with a predisposition vulnerability (early-onset bipolar) or no predisposition (late-onset bipolar). However, the symptoms begin to precipitate once a major stressor is experienced with or without a predisposition and the effects of chronic stress, in particular, perpetuate the symptoms. As we explore in this paper, chronic stress makes the hippocampus vulnerable to damage and the reason why the hippocampus is so susceptible is that it has the most receptor sites for glucocorticoids e.g., cortisol. The hippocampal damage e.g., the changes in volume further perpetuate the symptoms of a disorder. Moreover, cortisol levels can serve as a biomarker to predict the development of various disorders. For example, we have seen lower cortisol levels upon awakening were a distinctive feature of active suicidal ideation.
Malik, Hinza Batool, "The Effect of Long-term Stress on Hippocampus and the Involvement in the Pathophysiology of Psychological Disorders, Suicide, and Alcohol Use Disorder" (2020). Undergraduate Research Awards. 55.