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Title Sleepdisturbances and fatigue in the NESDA cohort. Participants Hoogendijk, Penninx, Van Dyck, Smit, Zitman, Nolen… Background Sleep disturbances and fatigue are prevalent and disabling symptoms of both depression and anxiety disorders, especialy rumination in e.g. generalized anxiety disorder. Many psychiatric decompensations start with sleepdisturbances. In is unknown, however, whether such a sleepdisturbance is just the first symptom of the disorder, or the event that challenges the disorder. In other words: is a sleepdisturbance the cause or the consequence of e.g. depression? Do ruminating subjects have problems falling asleep due to the content of their thoughts or do they ruminate to fill up the time, that they can not sleep? Sleepdisturbances are usualy treated with benzodiazapines, that frequently result in other sleepdisturbances, drowsyness and dependence. These siteeffects and subsequent fatigue are an importand cause of decreased labour productivity. Therefore, the prevention and adequate treament of these disorders is of paramount importance. Study aim and objectives - The aim of the NESDA-sleep project is to study the long term prognosis of sleep disturbances in anxiety and depression in order to contribute to improved quality of care and prevention of chronicity. Within the overall study, three study objectives are distinguished: (1) Describing the long term prognosis of sleep disturbances in anxiety and depression in terms of course (chronicity, development of co-morbidity, suicidal behaviour) and public health consequences (disability, mortality, costs). (‘descriptive psychiatric epidemiology’) (2) Examining demographic, behavioral, physical, biological, genetic and psychosocial determinants of the long-term prognosis of sleep disturbances in anxiety and depression. (‘explanatory psychiatric epidemiology’) (3) Examining whether gene expression profiles and fMRI indicators of brain systems functioning predict the long-term prognosis of sleep disturbances in anxiety and depression. (‘biological psychiatric research’) Background - Sleep disturbances and fatigue are prevalent and invalidating symptoms of both depression and anxiety disorders, especialy rumination in e.g. generalized anxiety disorder. Many psychiatric decompensations start with sleepdisturbances. In is unknown, however, whether such a sleepdisturbance is just the first symptom of the disorder, or the event that challenges the disorder. In other words: is a sleepdisturbance the cause or the consequence of e.g. depression? Do ruminating subjects have problems falling asleep due to the content of their thoughts or do they ruminate to fill up the time, that they can not sleep? Sleepdisturbances are usualy treated with benzodiazapines, that frequently result in other sleepdisturbances, drowsyness and dependence. These siteeffects and subsequent fatigue are an importand cause of decreased labour productivity. Therefore, the public health relevance of sleep disturbances in anxiety and depression is undisputed. Aetiological research has yielded few risk factors that are open to primary preventative intervention at a large scale. Given an extremely variable natural history, the most viable route for prevention is to influence the course in those with an unfavourable prognosis. A second route would be to influence public health- and economic consequences, the development of co-morbidity and the development of suicidal behaviour. For this, data on the long term course and consequences of sleep disturbances in anxiety and depression (objective 1), and data on factors predicting the prognosis (objective 2) are necessary. These data are practically unavailable, especially for anxiety disorders. Available data suggest that demographic and psychosocial factors predict only a small portion of the variance in outcome. Clinical factors and underlying biological factors are probably more important. As in aetiological work, the prognosis is probably determined by interaction of demographic, psychosocial, genetic, biological and clinical factors. No study has been able to integrate all five domains. Recently, the technology necessary to integrate biological and genetic measures in epidemiological studies has become available, allowing the integration of biological and psychosocial research paradigms within an epidemiological framework. Gene expression profiles and functional imaging of brain structures have recently received attention since they were found to be important for depression. However, data on their importance in terms of predicting the course of depression and in relationship to anxiety are lacking. Therefore, we will examine the role these two play in the prognosis of anxiety and depression (objective 3). With regard to treatment, very little is known about the long-term care trajectories and the factors determining the long term provision of care in those with sleep disturbances in anxiety and depression. Study design – The design of the NESDA study is an 8-year longitudinal cohort study that will include 2850 persons aged 18 through 65 years and conduct assessments at baseline and after 1, 4 and 8 years of follow-up. NESDA is designed to be representative of those with depression and anxiety in different health care settings and in different stages of the developmental history of the disorders. Therefore, the sample is stratified for setting (community, primary care and specialised mental health) and will include different phases of illness (normals, high familial risk, first episodes and recurrent episodes of depression (Major Depressive Disorder, minor depression and dysthymia) and anxiety (Social Phobia, Generalized Anxiety Disorder and Panic Disorder). Because of the well-known close relationship between anxiety and depression, both will be studied in concert. NESDA will include both dimensional and categorical measurements of anxiety and depression as well as a range of other medical, psychosocial and biological (incl. genetical) variables. Objective 3 will be assessed in a subsample of 300 NESDA subjects. Sleep and fatigue symptoms and the use of benzodiazepines and antidepressants will be assessed at baseline and during follow-up. In the 15-item screening instrument (N=40500?) one question is on fatigue, one on nervousness and one on medication for anxiety, depression, stress or tension. During the baseline (and follow-up) interview, the BENDEP questionnair for benzodiazapine dependence will be used. This will be in addition to a regular 9-item medication questionnair. Moreover, the 6-item self-report Insomnia Rating Scale will be used. Anxiety and depression diagnosis will be made using the CIDI interview and disorder severity will be assessed using the Inventory of Depressive Symptoms (IDS), the Beck anxiety index and the fear questionnair. Especialy the IDS contains a number of items concerning sleep and fatigue. All subjects will fil out the MDQ for bipolar symptoms. In case unipolar depressed subjects turn out to be bipolar during the NESDA followup period, we will test them with special emphasis on sleep disturbances. Feasibility - The NESDA consortium consists of academic and non-academic research groups with established expertise in conducting longitudinal studies on anxiety and depression in different health care settings. Feasibility is enhanced by the formal consortium, intensifying existing co-operation among participating centres, and by the opportunity to build on (i) existing research cohorts (NEMESIS and ARIADNE), (ii) GP practices already involved in academic research, (iii) regional mental health centers, which all participate in the consortium and (iv) the opportunity to test procedures in an ongoing pilot study in Amsterdam (AMSTAD). The program is designed and budgeted for ten years. The official start date of the program is November 1, 2003.