[Circadian rhythms and depression]. / Störung zirkadianer Rhythmen im Kontext depressiver Erkrankungen.

Depressive disorders are associated with various neurobiological alterations like hyperactivity of the hypothalamic-pituitary-adrenal axis, altered neuroplasticity and altered circadian rhythms. Relating to the circadian symptoms, a process is adopted in which individual genetic factors together with social, psychological and physical stressors may lead to a decompensation of the circadian system. The causal connections between depressive disorders and disturbed circadian rhythms have not been completely clarified. Chronobiological therapy is based on these disturbed processes. For the treatment of the circadian symptoms, various scientifically tested chronotherapeutics are available with however different effectiveness and evidence like light therapy or sleep deprivation. The successful treatment of depression also frequently leads to a improvement in altered circadian rhythm.

Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein kinase activity in hypothalamus correlating with circadian rhythms alterations.

Patients with liver cirrhosis show disturbances in sleep and in its circadian rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The mechanisms of these disturbances are poorly understood. Rats with porta-caval shunt (PCS), a model of MHE, show sleep disturbances reproducing those of cirrhotic patients. The aims of this work were to characterize the alterations in circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous and rewarding activity and of temperature, (b) timing of the onset of activity following turning-off the light, (c) synchronization to light after a phase advance and (d) the molecular mechanisms contributing to these alterations in circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and rewarding activities (wheel running). PCS rats show more rest bouts during the active phase, more errors in the onset of motor activity and need less time to re-synchronize after a phase advance than control rats. Circadian rhythm of body temperature is also slightly altered in PCS rats. The internal period length (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show increased content of cGMP in hypothalamus while the activity of cGMP-dependent protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG pathway in hypothalamus would contribute to altered circadian rhythms and synchronization to light.

The times they're a-changing: effects of circadian desynchronization on physiology and disease.

Circadian rhythms are endogenous and need to be continuously entrained (synchronized) with the environment. Entrainment includes both coupling internal oscillators to external periodic changes as well as synchrony between the central clock and peripheral oscillators, which have been shown to exhibit different phases and resynchronization speed. Temporal desynchronization induces diverse physiological alterations that ultimately decrease quality of life and induces pathological situations. Indeed, there is a considerable amount of evidence regarding the deleterious effect of circadian dysfunction on overall health or on disease onset and progression, both in human studies and in animal models. In this review we discuss the general features of circadian entrainment and introduce diverse experimental models of desynchronization. In addition, we focus on metabolic, immune and cognitive alterations under situations of acute or chronic circadian desynchronization, as exemplified by jet-lag and shiftwork schedules. Moreover, such situations might lead to an enhanced susceptibility to diverse cancer types. Possible interventions (including light exposure, scheduled timing for meals and use of chronobiotics) are also discussed.

Chronotherapeutics and psychiatry: setting the clock to relieve the symptoms.

Circadian rhythms are near 24-h cycles in a number of physiological and behavioural parameters and the underpinning circadian timing systems is one of the key homeostatic regulatory systems in mammalian physiology. Many common psychiatric conditions are associated with disrupted sleep, including a common occurrence of delayed or advanced phase sleep syndromes, which in themselves may be indicative of dysregulated circadian timing in these disorders. In this article we discuss the evidence for abnormal circadian rhythms in seasonal affective disorder, bipolar disorder and attention deficit/hyperactivity disorder. Much of this evidence suggest that these conditions are associated with either phase delays or phase advances of core phase markers of the circadian clock such as melatonin or core body temperature, suggesting the presence of circadian desynchrony in these conditions. We also highlight findings that pharmacological and/or behavioural interventions that ameliorate circadian misalignments are efficacious in producing symptomatic relief, suggesting an intrinsic link between the circadian and affective systems that can be manipulated for clinical benefit.

[Social environment and social rhythms]. / Environnement social et rythmes sociaux.

The social environment lies at the aetiopathogenic heart of many diseases including bipolar disorders. It has been established that disturbances of social rhythms as a result of more or less severe events predispose to relapse of a mood disorder. Treatments are offered to regulate social rhythms. These may be incorporated into psychoeducational programmes or form a specific programme themselves (IPSRT), incorporating interpersonal therapies.

[Psychological stress in oncology: the role of glucocorticoids]. / Stress psychologique en oncologie: le rôle des glucocorticoïdes.

During the last years, the correlations between biological processes, psychological adjustment and stress disorders have received increasing attention and a growing body of research results has been published in the general literature. In the realm of psycho-oncology, however, conceptual models on this topic and studies aimed at their validation have remained relatively scanty. On the basis of our observations and available literature in the field of post-traumatic and depressive stress disorders in oncology, we have proposed to apply the concept of allostatic load to the study and understanding of the psychological experience of cancer. This strategy has led us to the formulation of a novel classification of adjustment disorders in oncology and the creation of the clinical entity named "cancer-specific stress syndrome". Depending on clinical presentation of the syndrome, one distinguishes three subtypes, namely the depressive, post-traumatic and "dysallostatic" (mixed) forms. In the present paper, we examine the role of glucocorticoids and their relationships with one of the basic components of allostatic load--a failure to counter-regulate the immune system by the hypothalamic-pituitary-adrenal axis--in the physiopathology of stress disorders in oncology. Conflicting theories are presented--glucocorticoid cascade versus insufficient glucocorticoid signal transmission--and studies measuring potential correlations between stress and cortisol in oncology are critically reviewed. The results of this process provide substantial support for the application of the allostatic load model and post-traumatic phenomenology, but important advances have yet to be achieved before definitive conclusions can be established in this field. Such advances could lead to profound changes in the way we understand and treat psychological distress in patients with cancer, both pharmacologically and psychotherapeutically.

Mood regulation in seasonal affective disorder patients and healthy controls studied in forced desynchrony.

In healthy subjects, both the duration of wakefulness and the circadian pacemaker have been demonstrated to be involved in the regulation of mood. Some features of affective disorders suggest that these two factors also play a role in the dysregulation of mood. In particular, disturbances of the circadian pacemaker have been proposed to be a pathogenetic factor in Seasonal Affective Disorder, winter type (SAD). This report presents a test of this proposition. To this end seven SAD patients and matched controls were subjected to a 120-h forced desynchrony protocol, in which they were exposed to six 20-h days. This protocol enables us to discriminate the extent to which the course of mood is determined by the imposed 20-h sleep-wake cycle from the influence of the circadian pacemaker on that course. Patients participated during a depressive episode, after recovery upon light therapy and in summer. Controls were studied in winter and in summer. Between SAD patients and controls no significant differences were observed in the period length nor in the timing of the endogenous circadian temperature minimum. In both groups, sleep-wake cycle- and pacemaker-related components were observed in the variations of mood, which were not significantly different between conditions.