Stress spectrum disorders in oncology.

PURPOSE OF REVIEW: In this study, we will review the clinical, biological and research challenges resulting from the application of the traumatic stress framework to the psychological experience of cancer. Theoretical controversy over that conceptual shift and tentative neurobiological correlations are discussed. We will attempt to extract significant advances from the general literature and describe new directions for therapeutic strategies. RECENT FINDINGS: The traumatic nature of cancer experience is supported by epidemiology, but criticized by many authors, highlighting methodological caveats and conceptual contradictions. However, neuroimaging studies provide common findings in cancer patients with posttraumatic stress disorder, as it has been described in posttraumatic stress disorder patients. The carcinogenic effects of catecholamines and glucocorticoids could open the way for a deeper understanding of correlations between psychological factors and cancer prognosis. SUMMARY: Cancer is a unique psychological experience. Its relapsing course and life-threatening nature constitute a potential source of severe and chronic stress, resulting in long-term psychological distress, poor quality of life and psychopathology. Biological consequences of cumulative stress include catecholamine hyperactivity and glucocorticoid dysregulation, and also affect the immune system. The understanding of those physiopathologic pathways needs further investigation, as the development of adequate screening tools does. In order to integrate all those challenges, multidisciplinary approaches are warranted.

Psychosocial factors, biological mediators, and cancer prognosis: a new look at an old story.

PURPOSE OF REVIEW: The present article briefly reviews the prognostic role of psychosocial factors in cancer and concentrates on biological markers that may mediate such relationships. We focus on specific markers that show promising mediating roles. RECENT FINDINGS: The article reviews the prognostic role of psychosocial factors as shown in longitudinal studies and in previous reviews. We present the general stress response and its relevance to cancer progression. The main focus of the article is on the prognostic roles of specific biomarkers that had to meet three criteria for being accepted as biomarkers - being related to a psychosocial factor at the level of the brain, the circulation, and the tissue/cellular level. We review studies supporting the mediating roles of neurohormones and neurotransmitters (e.g., cortisol, norepinephrine), the vagal nerve and inflammation, interleukin-1, DNA damage, and the hormone oxytocin. SUMMARY: These biomarkers may mediate the relationships between certain psychosocial factors (e.g., hopelessness, social support) and cancer progression. Future studies should test the effects of altering such biomarkers on the prognosis of patients scoring high/low on their associated psychosocial factors. Clinical implications that need to be tested are provided.

The relationship between heart rate variability and time-course of carcinoembryonic antigen in colorectal cancer.

BACKGROUND: Identifying new prognostic factors is important for guiding treatments and preventing metastasis in cancer. Vagal nerve activity may predict prognosis in cancer due to its roles in modulating inflammation, sympathetic activity and oxidative stress. This study tested the relationship between heart rate variability (HRV), a vagal nerve index, and the colon cancer (CC) marker carcinoembryonic antigen (CEA), in an 'historical prospective' design. METHODS: We examined data of 72 CC patients, without inflammatory or cardiac diseases, of whom 38 had baseline electrocardiograms (ECG) and 12 month CEA levels. We measured HRV (SDNN, RMSSD) from brief archived ECG. Multiple confounders were considered. RESULTS: Controlling for effects of tumor stage and treatment-orientation, baseline HRV predicted CEA levels at 12 months (r=-.43, p=.006). Patients with SDNN<20 ms had significantly higher CEA at 12months than those with SDNN>20 ms. CONCLUSION: These preliminary results showed that higher HRV predicts lower levels of a tumor marker, one year later, independent of confounders. This supports the hypothesized role of vagal activity in tumor modulation. Replication in larger samples is needed.

[Neurotrophic theories of stress and neurobiology of antidepressants: applications in psycho-oncology]. / Théories neurotrophiques du stress et neurobiologie des antidépresseurs: applications en psycho-oncologie.

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.

[Stress and allostatic load: perspectives in psycho-oncology]. / Stress et charge allostatique : perspectives en psycho-oncologie.

Since its origins as a scientific field back in the late seventies, psycho-oncology has remained notably descriptive. Few conceptual advances have been achieved in the study of psychodynamics and biological underpinnings of psychological adjustment to the experience of cancer. Moreover, the specific aspects of psychopathological responses to cancer, as well as their optimal pharmacological management remain poorly understood. On the other hand, recent years have been characterized by significant progress in the delineation of biological mechanisms of stress and its consequences for the brain, body, and general health. In this paper, we examine the applicability of the concept of allostatic load to the study of stress and psychopathology related to the cancer experience. While homeostasis refers to maintaining specific biological parameters constant, allostasis can be defined as the process of maintaining stability through change. In this context, excessive or dysregulated activity of allostatic (adaptive) systems leads to deleterious effects for the brain (reduced neurogenesis, altered cell death processes, and dendritic branching) and body (increased cardiovascular risk). These damaging effects of cumulated stress have been refered to as the allostatic load, or the cost inflicted to the organism in order to maintain stability. We hypothesize that the concept of allostatic load is particularly relevant to the multiple, repeated and chronic stressors associated with the experience of cancer. In the light of this model, we propose a new classification of psychopathological conditions in psycho-oncology: the cancer-specific stress syndrome, with its three clinical subtypes (depressive, post-traumatic, and dysallostatic). Suggestions are formulated for some biological correlates of psychodynamic processes and for the study of innovative pharmacological approaches in the treatment of stress-related disorders in oncology (anticonvulsants, CRH antagonists, 5HT-1A receptor agonists...).

[Psychological stress in oncology: the role of glucocorticoids]. / Stress psychologique en oncologie: le rôle des glucocorticoïdes.

During the last years, the correlations between biological processes, psychological adjustment and stress disorders have received increasing attention and a growing body of research results has been published in the general literature. In the realm of psycho-oncology, however, conceptual models on this topic and studies aimed at their validation have remained relatively scanty. On the basis of our observations and available literature in the field of post-traumatic and depressive stress disorders in oncology, we have proposed to apply the concept of allostatic load to the study and understanding of the psychological experience of cancer. This strategy has led us to the formulation of a novel classification of adjustment disorders in oncology and the creation of the clinical entity named "cancer-specific stress syndrome". Depending on clinical presentation of the syndrome, one distinguishes three subtypes, namely the depressive, post-traumatic and "dysallostatic" (mixed) forms. In the present paper, we examine the role of glucocorticoids and their relationships with one of the basic components of allostatic load--a failure to counter-regulate the immune system by the hypothalamic-pituitary-adrenal axis--in the physiopathology of stress disorders in oncology. Conflicting theories are presented--glucocorticoid cascade versus insufficient glucocorticoid signal transmission--and studies measuring potential correlations between stress and cortisol in oncology are critically reviewed. The results of this process provide substantial support for the application of the allostatic load model and post-traumatic phenomenology, but important advances have yet to be achieved before definitive conclusions can be established in this field. Such advances could lead to profound changes in the way we understand and treat psychological distress in patients with cancer, both pharmacologically and psychotherapeutically.

Psychiatric disorders in oncology: recent therapeutic advances and new conceptual frameworks.

PURPOSE OF REVIEW: Major advances achieved in anticancer treatment have resulted in significant increases in cancer patients' survival periods. At the same time, growing awareness of the psychologic impact of the diagnosis and treatment of cancer on quality of life has created the need for deeper insights into the adjustment process, its disorders, and effective strategies for the treatment of psychiatric morbidity. The wider availability of brain imaging techniques and other neurobiologic tools is creating major opportunities for a scientific understanding of psychodynamic processes. RECENT FINDINGS: Several elements indicate a stress-system activation in response to cancer. The existence of traumatic stress-like syndromes has received increasing support. Structural brain imagery has revealed volumetric alterations of the amygdala, a major participant in emotional and fear responses. Hypotheses about functional modifications at the hypothalamic-pituitary-adrenal axis level may have significant implications for the identification, treatment, and even prevention of psychopathology. Finally, longitudinal studies assessing psychologic adjustment confirm the need for psychosocial and pharmacologic interventions. SUMMARY: Our understanding of the cancer experience at the emotional and cognitive levels remains insufficient, leading to weakly positive results of psychosocial intervention models. The use of antidepressant medication has received substantial empiric and scientific support, but a risk of antidepressant-induced carcinogenesis has not been excluded, which should keep clinicians from overprescribing attitudes. Finally, improving the quality of doctor-patient communication and the psychologic impact of carrying a genetic marker of cancer risk should be the focus of further attention.

Psychosocial rehabilitation of cancer patients after curative therapy.

The concept of rehabilitation of cancer patients is based on the relatively recent awareness of the strong interrelations existing between physical, psychological and social aspects of human life. Cancer potentially disrupts all of these primary components of quality of life. The aim of rehabilitation is to promote global physical and psychosocial adjustment by acting at all modifiable levels, namely strengthening individual coping resources through psychotherapy, improving quantity and quality of familial and social support, and restoring optimal physical functioning.