The development of chronomedicine: the study of biological rhythms and sleep applied to depression
Keywords:
Chronobiology, Circadian Rhythms, Mental Health, Psychiatry, Mood Disorders, Actimetry, Actigraphy, Time SeriesAbstract
http://hdl.handle.net/10183/223192
The increasing morbidity and mortality of depression justifies the search for improvement of its diagnosis and of subtypes of the disorder that present peculiarities in terms of clinical treatment. A better understanding of the multiple biological and psychological facets of depression is essential for the development of more effective therapies. In this context, research on biological rhythms, including sleep, representes a recent and promising line of investigation of the etiology, improvement of the prognosis and treatment approach in the clinical course of depression. The rhythmicity of biological functions in mammals is maintained by complex molecular machinery, and the main environmental stimulus that synchronizes biological clocks is the light-dark cycle. However, social routines also interfere with this mechanism, as they determine exposure to light and feeding times, as well as resting activity patterns. Clinical evidence describes that dysfunctions of this timing system is present in a variety of morbid clinical conditions, such as obesity, diabetes, hypercholesterolemia, cardiovascular disease and cancer. Mood alterations have also been widely studied in models of circadian "misalignment" or “disruption”. For example, depressed patients have a distinct pattern of physical movement, motor reaction time and psychomotor activity. In addition, up to 90% of depressed patients report changes in sleep, such as difficulty falling asleep, staying asleep and waking up in the morning earlier than desired. This thesis explores the associations of these parameters of motor activity and sleep measured subjectively (by quantitative questionnaires) and objectively (by actimetry) with depression. Initially, two methodological studies are described that aim to validate a quantitative instrument on sleep hygiene, and to study the impacts of off-wrist periods of actimeters in the calculations of motor activity parameters. The following are the studies developed that associate the subjective and objective assessment of sleep, activity rhythms and exposure to light with depressive symptoms and major depressive disorder. This thesis documents methodological advances and proofs of concept that enable the creation of new hypotheses in studies of the association between biological rhythms and depression. In addition, the studies described provide evidence that depression (and other psychiatric disorders) should be examined from the perspective of Chronomedicine, the study of the impacts of "time" on physiology, endocrinology, metabolism and behavior at different organizational levels.
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