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Chronobiology and Psychiatry ARTICLE IN PRESS Sleep Medicine Reviews (2007) 11, 423–427 www.elsevier.com/locate/smrv GUEST EDITORIAL Chronobiology and psychiatry We can begin with the ancient Greeks, meander experience. It was as if there was suddenly a through Latin footnote-sprinkled chapters in the scientific language in which to express the clinical 1621 Anatomy of Melancholy, and dive into the observations, a framework for formulating experi- writings of late nineteenth century German psy- ments. Tom Wehr and I called it Pittendrighian chiatrists. All describe daily and seasonal cycles in psychiatry, attempting to understand underlying many aspects of mental illness. Depression in rules by which, for example, manic-depressive particular is linked to characteristic rhythm ab- patients shifted circadian phase earlier and later normalities: diurnal mood variation and early according to clinical state.8 According to our morning awakening, longer-term periodicities such theory, if we simply phase advanced the sleep– as regular manic-depressive cycles or seasonally wake cycle of a bipolar depressed patient, we linked episodes.1 But it was very difficult to could improve depression. Indeed, the effect of connect these clinical observations over the cen- this circadian manipulation was remarkable.9 The turies in any heuristic manner to an underlying patient’s diurnal rhythm of mood shifted day by biological timing system, lacking grounding in day across the window of waking, a kind of jet-lag circadian biology, a field which only began its with positive clinical response—but depre- modern development in the 1960s.2 One could ssion returned as she slowly re-entrained. We observe altered rhythms, but there was no theore- rephrased the Pittendrighian ‘‘internal coincidence tical construct to explain them. It was primarily the model’’ to apply to these ‘‘depressogenic’’ phase pioneering work of Ju¨rgen Aschoff and Colin relationships.10 Pittendrigh that gave us a rigorous framework for Later, the concepts of adequate zeitgebers, understanding temporal behaviour. Today, not phase response curves to light, and dawn and dusk only has the existence of a central circadian oscillators responding to daylength (photoperiod) pacemaker (localised in the suprachiasmatic were crucial in the development of light therapy nuclei) been established, but also peripheral clocks to treat seasonal affective disorder (reviewed in are found in every organ and every cell.3 Zeitgebers Ref. 11). It is remarkable how fruitful has been this (synchronising agents) are required to reset and hypothesis-driven therapy based on neurobiological stabilise these central and peripheral clocks—the concepts, inspiring elegant studies of mechanism. light–dark cycle is the major zeitgeber, but social Clinical trials by many researchers have tested the cues, mealtimes, exercise, etc. play a complemen- antidepressant response to different paradigms: tary role. Growing understanding of the complex extension of the photoperiod to simulate a summer feedback loops in clock gene expression that day, early morning light to phase advance the create ‘‘the day within’’ reveal how a mutation or circadian pacemaker, and dose-intensity-duration polymorphism at the molecular level can be (and recently, spectrum) of light exposure. Yet, pathological: mice with a CLOCK mutation mani- since these are not typically the classical clinical fest behaviour that is strikingly similar to human trials of ‘‘placebo’’ light vs. ‘‘active’’ light, they do mania4; two family pedigrees of advanced not fulfil criteria for inclusion in conventional sleep phase syndrome have a hPer25 or CK1d meta-analyses—in spite of the fact that the quality mutation y.6 of clinical research is as high as one could wish In 1976, Pittendrigh and Daan wrote five papers (see Terman’ s review in this issue12). that expounded the formal properties of circadian In 1982, Borbe´ly developed a two-process model rhythms.7 Reading these was an extraordinary of sleep regulation.13 For the first time, the 1087-0792/$ - see front matter & 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.smrv.2007.08.003 ARTICLE IN PRESS 424 GUEST EDITORIAL circadian system was integrated into sleep re- Table 1 Circadian rhythms and psychiatry: what search, and considered important as determining is important? timing and architecture of sleep by virtue of its interaction with homeostatic drive. For someone Stable internal and external phase relationships working in psychiatry, this was a fascinating Appropriate entrainment to the light–dark and concept, in particular because Basel was one of sleep–wake cycle the first clinics in the early 1970s to investigate the Enough light, enough darkness Adequate retinal function remarkable and counterintuitive antidepressant Sufficient social zeitgebers effect of a single night’s sleep deprivation in 14 Reconsider the zeitgeber function of timed patients with major depression. This paradoxical activity and meals intervention improved depression within hours, but how or why was a mystery. We tried to apply the two-process model to understand how sleep depri- vation could be antidepressant.15 circadian rhythms and sleep, with results that are These models were an amazing stimulus to basic immediately clinically relevant. research, and they remain so. However, they Till Roenneberg et al.21 have taken the original remain less recognised in clinical psychiatry. If the concept of morningness and eveningness prefer- literature on circadian rhythms in depression is ences and further developed it into a questionnaire reviewed,1 the evidence points to a variety of that asks how and when people actually sleep on changes—disturbances of phase (early or late), work and free days. Importantly, the analyses reduced rhythm amplitude, and increased day-to- recognise the interactions of chronotype with day variability, rather than any single or specific external zeitgebers, correcting for sleep deficit phase disturbance as predicted by our original during the week and rebounds over the weekend to hypotheses. Individuals vulnerable to depression better estimate an individual’s sleep duration. As a are vulnerable to changes in sleep duration and web-based tool now available in many languages, timing. the questionnaire has the advantage of large We still do not know how sleep deprivation numbers permitting epidemiological-type ana- works, though in rodents it can diminish amplitude lyses.22 Chronotype is genetically based, but of the circadian pacemaker in the suprachiasmatic modified by age and sex. It is well known that nuclei,16 as well as many downstream circadian teenagers sleep late, but with this questionnaire neurotransmitter rhythms.17 A lower amplitude the delay shift could be quantified—drifting later rhythm can be more easily shifted and reentrained. 15 min/year from age 12–20 and thereafter slowly After a 20-year hiatus (sleep deprivation does not advancing back in old age. The pattern was fit the current psychopharmacological zeitgeist), a observed in rural as well as urban areas, suggesting new generation of clinician researchers has begun a biological rather than social phenomenon—more using sleep deprivation again, combining the evidence supporting political (and health) demands advantages of its rapidity of onset (that no drug that teenagers’ school times should be later! It is can yet approach) with medication and/or light to the extreme late chronotypes who have the great- maintain the usually short-term response (see est problems (as detailed in Ref. 23 in this issue), Benedetti et al.’s review in this issue18). We still for which Roenneberg and co-workers have coined do not know how light works, but our models the colourful and immediately comprehensible predict the importance of a strong zeitgeber for term ‘‘social jetlag’’.24 appropriate synchronisation of central and periph- Our Basel lab has been fortunate in having had eral clocks. Strong entrainment appears to be the close connections with one of the fathers of key to good behavioural, cognitive and emotional circadian biology, Ju¨rgen Aschoff, during his last well-being—not only in depression (Table 1). We years in Freiburg. He was particularly supportive of have shown that even in healthy subjects, a small and interested in the constant routine thermo- misalignment of sleep with respect to the circadian regulatory studies developed by Kurt Kra¨uchi. system (internal phase angle difference a little Kra¨uchi’s review in this issue25 pays hommage to more than an hour), can increase sleepiness and Aschoff’s pioneering concepts and experiments, diminish mood.19 providing a concise introduction to how the This special issue of Sleep Medicine Reviews, circadian system regulates temperature rhythms, ‘‘Chronobiology and Psychiatry’’ covers a broad as well as a convincing argument against direct domain of sleep medicine impinging on and involvement of temperature in sleep homeostasis. becoming an integral part of psychiatry.20 The first Many experiments tease out the crucial role of three reviews address basic aspects of human distal skin temperature (hands and feet) as being ARTICLE IN PRESS GUEST EDITORIAL 425 the ‘‘physiological gate’’ to sleep onset. Warm feet be slowed down—a very important clinical trial. promote a rapid sleep onset, cold feet prevent it. The findings emphasise the necessity of long-term Individuals with vasospastic syndrome have a regular chronotherapeutics. Their concepts are circadian sleep disorder, caused by going to bed applicable to many psychiatric and other sleep–
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