Dynamics of cortisol in depression and anxiety disorders PDF
Preview Dynamics of cortisol in depression and anxiety disorders
Dynamics of cortisol in depression and anxiety disorders Gerthe Veen Gerthe Veen Dynamics of cortisol in depression and anxiety disorders Cover design: Maria Heesen Print: Ponsen en Looijen, Ede, The Netherlands © 2009 G. Veen, Amsterdam, The Netherlands Dynamics of cortisol in depression and anxiety disorders Proefschrift ter verkrijging van de graad van Doctor aan de Universiteit Leiden op gezag van Rector Magnificus Prof. Mr. P.F. van der Heijden, volgens besluit van College voor Promoties ter verdediging op donderdag 29 april 2010 klokke 16.15 uur door Gertje Veen geboren te Nootdorp in 1971 Promotiecommissie: Promotor: Prof. Dr. F.G. Zitman Copromotoren: Dr. I.M. van Vliet Dr. R.H. de Rijk Overige leden: Prof. Dr. E.R. de Kloet Prof. Dr. B.W.J.H. Penninx (Vrije Universiteit Amsterdam) Prof. Dr. A.J.W. van der Does Contents Chapter 1 Introduction and thesis outline...............................................................................................7 Chapter 2 Need for alternative ways of phenotyping of mood, anxiety, and somatoform disorders in biological resear.................................................................................................31 Chapter 3 The influence of psychiatric comorbidity on the dexamethasone/CRH test in major depression.................................................................................................................................37 Chapter 4 Basal cortisol levels in relation to dimensions and DSM-IV categories of depression and anxiety................................................................................................................................53 Chapter 5 Salivary cortisol, serum lipids and adiposity in patients with depressive and anxiety disorders....................................................................................................................................73 Chapter 6 C-reactive protein polymorphisms are associated with plasma C-reactive protein levels and the cortisol awakening response in basal conditions.......................................89 Chapter 7 Summary and discussion......................................................................................................105 Samenvatting (Dutch summary).........................................................................................133 Dankwoord (Acknowledgements)......................................................................................141 Curriculum Vitae...................................................................................................................145 List of publications................................................................................................................149 Chapter 1 Introduction and thesis outline Introduction and thesis outline Introduction All organisms must maintain a complex and dynamic equilibrium, or homeostasis, which is constantly challenged by internal and external forces termed stressors. Stress occurs when homeostasis is threatened or perceived to be so; homeostasis is reestablished by various physiological and behavioral adaptive responses. During evolution the organism has developed a stress-system to deal with factors which may disturb homeostasis, of which the Hypothalamus-Pituitary-Adrenal (HPA) axis is an important part. Neuroendocrine hormones, such as cortisol, play a major role in the maintenance of basal homeostasis as responses to threat, and are involved in the pathogenesis of diseases characterized by dyshomeostasis.1;2 The stress-system needs to have a far-reaching power over the metabolism of the body, because in times of crisis the body should be able to acutely redirect metabolism to enable a fight, flight or freeze reaction. Especially in humans, along with the development of the stress system, psychological stress factors became more important, such as fear anticipation. It is generally assumed that the organism did not develop a new stress system to cope with these psychological stressors, but used the already working stress-system, again with the HPA axis as an important part. If the stress-system plays an important role in psychological stress, it is to be expected that depression and anxiety disorders are accompanied by dysfunctions of this system.3-5 This hypothesis has been tested, mainly in research using cortisol concentrations in blood or saliva as marker for the function of the hypothalamus- pituitary-adrenal (HPA) axis. Thus far, the results were inconsistent: hypercortisolism, hypocortisolism and normal cortisol levels were found.6-14 Before one can conclude that thus the HPA axis and the stress-system are not involved in depression and anxiety disorders, several other explanations should be considered. Cortisol may not be the right marker for the stress-system in general or the HPA axis in particular. As cortisol has such a central place in the stress-system this is not very probable. Besides, the problem is not that abnormal cortisol levels are absent in patients with depressive and anxiety disorders: Abnormalities have been found repeatedly. The problem is that the abnormalities were inconsistent. Therefore, another possibility should be considered, i.e., that the phenotype or clinical picture is described insufficiently. This is less improbable than it may seem: the validity of the most used diagnostic classification system, the DSM-IV, has been questioned frequently. To date, the DSM has focused solely on face or clinical validity, the assertion that the diagnoses correspond to clinicians’ subjective views of a disorder. This is a weak form of validity only requiring consensus among clinical experts. One common form of validity is expressed by sensitivity and specificity, which are both low for DSM-IV diagnoses due to the extensive comorbidity, the high within-category 8 Chapter 1 heterogeneity, and the overlap of DSM-IV diagnoses by sharing criteria. Ideally, the validity of a diagnosis is determined by the correlation between the diagnosis and another criterion of the disease, for instance a biological parameter, which is considered as ‘gold standard’. As discussed above, such a gold standard has not been found. In this thesis we explore whether a dimensional approach to describe the clinical picture is a better way to disentangle the relationship between phenotype and HPA axis functioning than the DSM-IV categories. In addition to and as a consequence of that starting point, not the clinical picture (diagnosis or dimension) was central in our studies, but cortisol levels. In other words, we investigated per dimension to what extent differences in scores on that dimension correlated with cortisol levels and not which cortisol levels were found in major depression and which in anxiety disorders. In depression and anxiety also abnormalities in metabolic and immune parameters have been found, but again the results were inconsistent. To date, none of the metabolic and immune markers were sufficiently specific to contribute to the diagnosis of major depression.15 Therefore, we also investigated the relation of the cortisol levels with those biological markers, hoping to find a more consistent picture. In conclusion, we moved from an approach that puts psychiatric diagnosis in the center to an approach that puts the HPA axis in the center (see figure 1). In the following part of this introducing chapter, background information and an outline of this thesis are presented. Phenotype: HPA-axis: ▪ comorbidity ▪ cortisol ▪ dimensions Phenotype: HPA-axis: ▪ DSM-IV ▪ cortisol Metabolic system: Metabolic system: Immune system: Immune system: ▪ lipid metabolism ▪ lipid metabolism ▪ C-reactive protein ▪ C-reactive protein ▪ adiposity ▪ adiposity Figure 1. Structure of thesis Associations between HPA axis function, phenotypic characteristics, metabolic and immune factors in depression and anxiety disorders. Associations might be bidirectional and may also exist between ‘nodes’, but are left out in the picture for the purpose of clarity. 9 Introduction and thesis outline Major depressive disorder and anxiety disorders Depression and anxiety disorders are invalidating affective disorders accompanied by diminished functioning or well-being and increased mortality. Major depressive disorder (MDD) is characterized by a depressed mood and/or the loss of interest and pleasure in nearly all activities. In addition to these essential features, alterations in appetite, sleep disturbances, psychomotor changes, fatigue and decreased energy, feelings of worthlessness, cognitive problems (e.g. inability to make decisions), and thoughts of death are considered to be characteristics symptoms. For a diagnosis according to DSM-IV (APA, 1994), one of the essential features together with at least four additional symptoms have to be present most of the day, nearly every day, for at least two weeks. MDD is a common psychiatric disorder, with a 12 month prevalence of 5.8% in the Netherlands.16 Anxiety disorders are characterized by an excessive feeling of overwhelming anxiety, irrational fear and avoidance behaviour. The anxiety is often accompanied by physical symptoms such as sweating, cardiac disturbances, diarrhea or dizziness. Anxiety disorders include panic disorder, social anxiety disorder, post-traumatic stress disorder (PTSS), obsessive-compulsive disorder, generalized anxiety disorder, and specific phobia. Each anxiety disorder has specific symptoms, but all the symptoms cluster around excessive, irrational fear and threat. The 12 month prevalence of all anxiety disorders is 12.4% in the Netherlands.16 Depressive and anxiety disorders are considered as stress-related disorders, marked by a dysfunction of the HPA axis.5 Stress Stress and stress vulnerability are assumed to play major etiological roles in depression and anxiety disorders. The acute stress response is reflected in the rapid activation of the sympathetic nervous system, which leads to the release of epinephrine and norepinephrine. The sympathic pathways (epinephrine) elevate heart rate, blood pressure, respiration, glucose synthesis and cognitive arousal/attention. Simultaneously, the parasympathic pathways (e.g., norepinephrine and other catecholamines) are activated leading to a decrease in food intake, sleep and sexual drive. As part of the stress response, the hypothalamus releases corticotrophin- releasing hormone (CRH) inducing the release of adrenocorticotropic hormone (ACTH) from the pituitary gland, which stimulates the adrenal cortex to produce and secrete corticosteroids. This leads to elevated circulating levels of corticosteroids, in man mainly cortisol (figure 2). The acute stress response is adaptive to homeostasis. In the long term, chronic or repeating stress may impair physiological functions, such as growth, reproduction, metabolism, and immunocompetence, and imposes an increased risk for depression and anxiety disorders.17-19 10
Description:The list of books you might like
