Chronobiology comes of age

Handbook of clinical neurology, 2012

Psychological Medicine, 2005

Chronotherapeutics (light and wake therapy) in affective disorders* The Committee on Chronotherapeutics was recently formed by the International Society for Affective Disorders (ISAD), which has asked us to provide a consensus review of chronotherapeutics (light and wake therapy) in affective disorders. We consider these non-pharmaceutical, biologically based therapies to be potentially powerful adjuvants ready for clinical application. We also stress the need for additional studies, both in-patient and outpatient , to broaden the evidence base for indications and efficacy. The theme of adjuvant therapy is of increasing interest. Many of the lectures at the 2nd ISAD Meeting (Cancun, Mexico, March 2004) emphasized that combination treatments-such as cognitive behavioural therapy added to antidepressants (Paykel, 2004 ; Scott, 2004)-could help treat the residual symptoms that indeed portend relapse (Thase, 2004). The meeting highlighted expansion of interest in the development of new concepts for treating depressive illness (i.e. drug targets other than monoamines)-to wit : 'New antidepressants are needed and they are on their way ' (Pinder, 2004). On a pragmatic plane, the World Health Organization (WHO) has placed emphasis on the 'need to demonstrate that interventions are not only effective and sustainable, but also affordable ' (Chisholm, 2004). The meeting symposia shared the realization that the long-sought, faster-acting, relapse-preventing antidepressants are still not at hand, and that the field must continue to pursue combinations of psychological and pharmacological interventions. Missing from discussion, however, was consideration of light therapy and sleep deprivation, whose well-demonstrated efficacy-alone or in combination (Berger, 2004 ; Benedetti et al. 2004a ; Martiny et al. 2004; Terman, 2004 ; Wu, 2004)-could fulfil the WHO mandates of affordability and sustainability. The apparent blindness to these treatments by the psychiatric mainstream most likely stems from the prevailing neuropharmacological paradigm, and-if we may face realities-the commercial drawback that they cannot be patented (Studwell, 2004). In spite of many fascinating recent advances in development of new classes of antidepressant drugs (Holden, 2003), they are not yet ready for clinical use. By contrast, chronobiological interventions are already available and offer prospects no less potent than any candidate drug (Wirz-Justice et al. 2004). Chronotherapeutics-treatments based on the principles of circadian rhythm organization and sleep physiology-offers mental health practitioners a set of non-pharmaceutical, rapid and effective antidepressant modalities for monotherapy or as adjuvants to conventional medication. Here, we consider supplemental light exposure and sleep deprivation (more positively known as 'wake therapy ') as first-line treatments for major depression. Light therapy was first developed and has been established as the treatment of choice for winter seasonal affective disorder (SAD ; Partonen & Magnusson, 2001). The use of light therapy has expanded beyond SAD (Lam, 1998), with evidence for efficacy in premenstrual (Lam et al. 1999) and antepartum (Epperson et al. 2004) depression, bulimia nervosa (Blouin et al. 1996 ; Lam, 1998; Braun et al. 1999), as well as sleep-wake cycle disturbances [delayed and advanced sleep phase syndromes (Abbott, 2003; Reid et al. 2004) and Alzheimer's dementia (Skjerve et al. 2004)]. Evidence for the usefulness of these treatments for non-seasonal major depression is less clear, with both positive (Yamada et al. 1995) and lack of effects (Mackert et al. 1991) on record. Most studies have been of much shorter duration than required for testing new antidepressants, even

Psychiatric Annals, 1987

Journal of affective disorders, 2006

Use of online technology to promote recovery and self-management in psychosis (SMART)

Medical Hypotheses, 2011

Severe affective and behavioral dysregulation, labeled as severe mood dysregulation (SMD), is a widely spread phenomenon among adolescent psychiatric patients. This phenotype constitutes severe impairment across multiple settings, including various symptoms, such as non-episodic anger, mood instability, and hyperarousal. Moreover, SMD patients often show depression and reduced need for sleep. Despite a lifetime prevalence of 3.3%, systematic research is still scarce, and treatments that have been established do not account for the range of symptoms present in SMD. Considering the circadian dysfunctions, two hormones, melatonin and cortisol, are essential. When these hormones are dysregulated, the circadian rhythm gets out of synchrony. Since evidence is emerging showing that the worse the sleep-wake cycle is entrained, the worse the psychiatric symptoms are depicted, the importance of proper circadian functioning becomes clear. Chronotherapy as the controlled exposure to environmental stimuli (e.g. light) acting on biological rhythms has shown therapeutic effects. In both seasonal and major depression chronotherapy has been implemented, decreasing depressive symptoms and stabilizing circadian rhythms. Preliminary evidence from SMD related disorders, namely attention-deficit/hyperactivity disorder and pediatric bipolar depression, indicates that morning light therapy elicits positive influences on other symptoms as well. Hence, light therapy might not only be effective for depressive symptoms and circadian rhythms, but might also be beneficial for symptoms including inattention and irritability. We hypothesize that light therapy might be a helpful adjunctive treatment enhancing affective and circadian functioning, and eliciting positive influences on behavior. Physiologically, changes of both cortisol levels and melatonin production are expected.

theories associating sleep and circadian rhythm disturbances with depression have been proposed. Current evidence supports the existence of associations between these, but the direction of causality remains elusive. Given the existence of chronobiological disturbances in depression and evidence regarding their treatment in improving depression, a chrono-biological approach, including timely use of light and mela-tonin agonists, could complement the treatment of MDD. Keywords Chronobiology · Circadian rhythm · Major depressive disorder · Mood disorder · Light environment · Melatonin

Bioscience Journal, 2015

Affective disorders have been linked to abnormal biological rhythms. Depression- and anxiety-related behaviors can be altered following changes of daily periods of environmental light. The aim of this study was to investigate the effect of daily light cycle on both anxiety- and depressive-like behaviors of rats. Wistar male rats were exposed to constant dark or constant light during one week and compared to control animals exposed to 12/12h light/dark cycle regarding to anxiety-like behaviors and general activity on open field test and depressive-like behaviors on the forced swimming test. Data showed that rats exposed to one week of constant light exhibited increased number of quadrants crossed in the open field. No change on anxiety-like behaviors (time and quadrants crossed in the center of apparatus) was observed in the open field test. One week of constant dark increased the time of immobility behavior in the forced swimming test relative to control 12/12h light/dark treatment....

Organisms use circadian and circannual rhythms in cells or cell complexes for time measurements, thus the term biological clocks. Properties and models of biological clocks are discussed. In mammals, the biological clock system perceives light signals via the retina. Signals are then led to the suprachiasmatic nucleus (SCN) of the brain, functioning as the central clock region. Via pathways – involving the pineal organ and its production of the 'sleep' hormone melatonin – the rhythmic signals from the SCN affect body cells, hormone balances etc. Light strongly affects the circadian rhythms and also circannual and seasonal phenomena. Light can trigger the SCN and cause phase shifts of the circadian rhythms. The rhythms can be used by organisms to measure day/night length and control processes that should start at specific times of the year (photoperiodic control). Health effects might be expected when the clock system has deficiencies. Clinical effects of malfunctioning circadian light perception and of defect functions of the circadian system are discussed. Rhythm disturbances can result, for example, in sleep disorders and in depressive syndromes, and are connected with forms of cancer etc. Therapeutic effects of light treatment are reported. So-called Seasonal Affective Disorders (SAD) are reported to be light dependent and light treatment successful in several cases. Light induced rhythm disturbances also occur due to shift-work or jet travels over time zones.

Indian Journal of Medical Research 2014; 140: 574- 575.

2013

be truly designated “dialogues, ” I will raise specific and critical questions about the putative circadian rhythm disturbances in depression, provide a model within which to understand them, and summarize the present status and application of chronobiological therapies. This short overview will not go into detail of the clinical and experimental findings related to biological rhythms in depression, which have been extensively reviewed elsewhere. 1-9 I Chronobiologists predicate their work on a primary axiom, that temporal order is essential for health. Psychological, behavioral, physiological, and hormonal rhythms are specifically and functionally timed (entrained or synchronized) with respect to sleep and the day-night cycle. The converse premise implies that temporal disorder