Serotonin, cortisol, and stress-related psychopathology : from bench to bed

Stress has been implicated in the etiology of many psychiatric disorders, the most common stress-related disorder being major depressive disorder. However, stressful events do not automatically lead to psychopathology, important is the interaction between the stressor and someone’s vulnerability to stress and psychiatric disorders. This vulnerability is individual and likely to be determined by genetic, psychosocial, and biological factors. Two biological systems that have been related to the development of stress-related psychiatric disorders are the hypothalamus-pituitary-adrenal(HPA)-axis and the serotonergic system. In the present thesis, the interaction of these systems on coping with stress in rats and vulnerability to psychopathology in humans was investigated. The results indicate that changes in serotonergic activity and HPA-axis activity as a consequence of a disease process, treatment condition or other environmental factors may have behavioral consequences in both animals and humans. For example, low serotonergic activity may increase susceptibility to stress and HPA-axis activity, which in combination with individual genetic make-up may result in psychiatric symptoms. Impaired HPA-axis function is associated with more severe symptoms of major depressive disorder. We plead for the inclusion of a separate “serotonergic” symptom profile list in psychiatric questionnaires, and future incarnations of the DSM.

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