1 Given that Romidepsin molecular weight antidepressants act on neurotransmitter mechanisms also involved in circadian rhythm generation and entrainment, only untreated patients may reveal an “endogenous”
rhythm disturbance, if present. The second question regards conceptual clarity. What do we mean by a clock disturbance in depression? What one sees clinically may have its origins at a variety of different levels―not necessarily the hypothalamic biological clock itself, but epiphenomena related to altered rhythmic behavior, disturbed sleep, or abnormal environmental input. The third question is whether the studies purporting to document circadian rhythm disturbances in Inhibitors,research,lifescience,medical depression have been adequately carried
out. Alas, methodological issues characterize most investigations―not in terms of scientific caliber or intent, but because it was previously not sufficiently recognized how strongly “masking” (behavioral or environmental factors that modify the variable measured) obscures the underlying endogenous rhythms. This Inhibitors,research,lifescience,medical is a particular problem with measuring the core body temperature rhythm, since temperature is easily Inhibitors,research,lifescience,medical and rapidly masked by motor activity, postural change, meals, etc. Cortisol increases with stress, particularly at the evening nadir; thus, this circadian marker is also often masked by psychophysiological response. Melatonin, the pineal hormone considered to provide the best estimate of circadian rhythm phase, is suppressed by light, particularly in the evening: it is sensitive to masking by light as Inhibitors,research,lifescience,medical low as ca 100 lux.10 Thus, even indoor room light may delay the apparent
onset of nocturnal secretion. Only in the last decade have controlled protocols using state-oft-he-art chronobiological techniques provided unequivocal circadian markers. The fourth question concerns which models Inhibitors,research,lifescience,medical are useful. Concepts of an underlying genetic and stress-related vulnerability for depression can be discussed in terms of both neurotransmitter and circadian rhythm dysregulation. Here, I will draw on the two-process model of sleep-wake regulation11 as a way these of understanding some aspects of depressive symptomatology. Trie final question is whether we can find out about putative circadian mechanisms underlying affective disorder through understanding clinically successful chronobiological treatments. Circadian rhythm or sleep manipulations do improve depression and provide some fascinating clues. Clinical observations Periodicity in affective disorders (from seasonal recurrence to 48-h rapid cycling) is the clinical observation; diurnal variation of mood, early morning awakening, and sleep disturbances are the classical symptoms that have linked depression with circadian rhythm function.