The chronotherapeutic treatment of bipolar disorders: A systematic review and practice recommendations from the ISBD task force on chronotherapy and chronobiology

Circadian clocks coordinate physiology and behavior with the 24h solar day to provide temporal homeostasis with the external environment. The molecular clocks that drive these intrinsic rhythmic changes are based on interlocked transcription/translation feedback loops that integrate with diverse environmental and metabolic stimuli to generate internal 24h timing. In this review we highlight recent advances in our understanding of the core molecular clock and how it utilizes diverse transcriptional and post-transcriptional mechanisms to impart temporal control onto mammalian physiology. Understanding the way in which biological rhythms are generated throughout the body may provide avenues for temporally directed therapeutics to improve health and prevent disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Circadian rhythms are approximately 24-h oscillations in behavior and physiology, which are internally generated and function to anticipate the environmental changes associated with the solar day. A conserved transcriptional-translational autoregulatory loop generates molecular oscillations of 'clock genes' at the cellular level. In mammals, the circadian system is organized in a hierarchical manner, in which a master pacemaker in the suprachiasmatic nucleus (SCN) regulates downstream oscillators in peripheral tissues. Recent findings have revealed that the clock is cell-autonomous and self-sustained not only in a central pacemaker, the SCN, but also in peripheral tissues and in dissociated cultured cells. It is becoming evident that specific contribution of each clock component and interactions among the components vary in a tissue-specific manner. Here, we review the general mechanisms of the circadian clockwork, describe recent findings that elucidate tissue-specific expression patterns of the clock genes and address the importance of circadian regulation in peripheral tissues for an organism's overall well-being.

Recognition that psychological and behavioral factors play an important role in insomnia has led to increased interest in therapies targeting these factors. A review paper published in 1999 summarized the evidence regarding the efficacy of psychological and behavioral treatments for persistent insomnia. The present review provides an update of the evidence published since the original paper. As with the original paper, this review was conducted by a task force commissioned by the American Academy of Sleep Medicine in order to update its practice parameters on psychological and behavioral therapies for insomnia. A systematic review was conducted on 37 treatment studies (N = 2246 subjects/patients) published between 1998 and 2004 inclusively and identified through Psyclnfo and Medline searches. Each study was systematically reviewed with a standard coding sheet and the following information was extracted: Study design, sample (number of participants, age, gender), diagnosis, type of treatments and controls, primary and secondary outcome measures, and main findings. Criteria for inclusion of a study were as follows: (a) the main sleep diagnosis was insomnia (primary or comorbid), (b) at least 1 treatment condition was psychological or behavioral in content, (c) the study design was a randomized controlled trial, a nonrandomized group design, a clinical case series or a single subject experimental design with a minimum of 10 subjects, and (d) the study included at least 1 of the following as dependent variables: sleep onset latency, number and/or duration of awakenings, total sleep time, sleep efficiency, or sleep quality. Psychological and behavioral therapies produced reliable changes in several sleep parameters of individuals with either primary insomnia or insomnia associated with medical and psychiatric disorders. Nine studies documented the benefits of insomnia treatment in older adults or for facilitating discontinuation of medication among chronic hypnotic users. Sleep improvements achieved with treatment were well sustained over time; however, with the exception of reduced psychological symptoms/ distress, there was limited evidence that improved sleep led to clinically meaningful changes in other indices of morbidity (e.g., daytime fatigue). Five treatments met criteria for empirically-supported psychological treatments for insomnia: Stimulus control therapy, relaxation, paradoxical intention, sleep restriction, and cognitive-behavior therapy. These updated findings provide additional evidence in support of the original review's conclusions as to the efficacy and generalizability of psychological and behavioral therapies for persistent insomnia. Nonetheless, further research is needed to develop therapies that would optimize outcomes and reduce morbidity, as would studies of treatment mechanisms, mediators, and moderators of outcomes. Effectiveness studies are also needed to validate those therapies when implemented in clinical settings (primary care), by non-sleep specialists. There is also a need to disseminate more effectively the available evidence in support of psychological and behavioral interventions to health-care practitioners working on the front line.