[Neurotrophic theories of stress and neurobiology of antidepressants: applications in psycho-oncology].

For some years, the concept of stress has been accepted as a reference framework for the study of disturbances of psychological adjustment to cancer. Stress is defined as a state of physiological and psychological << tension >> resulting from the interaction between an individual and her environment. Damaging consequences of chronic stress include functional and structural alterations of the central nervous system, which have to be understood in order to propose effective treatment strategies for frequently encountered psychopathological responses to cancer. The clinical manifestations of stress include anxious and depressive symptoms which can reach pathological intensity under the form of major depression and post-traumatic stress disorder. Depression also represents a type of post-traumatic stress syndrome. These clinical entities commonly require the use of antidepressant treatments. Because of some obstacles, however, studies assessing the use and efficacy of antidepressants in oncology remain extremely scanty. Furthermore, clinical conditions characterized by drug treatment resistance are still uneasily managed due to partial understanding of the fine-tuned mechanisms of action of antidepressants. A thorough discussion of these mechanisms is therefore needed in order to precisely delineate (1) the neurobiological bases of the physiopathology of stress and (2) how to extend this knowledge to the care of depression in oncology. Maybe more important in this respect is the fact that recent scientific data provide a growing support for the potential role of psychological variables in the evolution and prognosis of cancer. In this paper, we travel back to the origins of antidepressant action theories, with the monoaminergic hypothesis, that revealed the role of serotonin and norepinephrine in the physiopathology of depression. We will focus on signal transduction cascades leading to the expression of genes coding for transcription and growth factors (CREB and BDNF). The importance of neuronal atrophy in the physiopathology of chronic stress and of neurogenesis in the action of antidepressants will also be emphasized. Finally, we present the information processing hypothesis, which provides strong support to the use of combined treatment strategies, associating psychotherapy and pharmacological approaches in the care of severe depression in patients with cancer.