Moreover, the 5-HT2c receptor subtype is considered to be relevant to the therapeutic properties of SSRIs, and―to link this to chronobiology―5-HT2c receptor agonists, which mimic the effects of light in rat CNS.79 Sleep shifts and zeitgebers as therapy The

above concepts point toward a multimodal approach to using chronobiological therapies in major depression. “Wake therapy” (increasing the level of process S) induces rapid clinical improvement in all diagnostic subgroups; phase advance (changing the timing of sleep) maintains the response, as does light, drugs acting Inhibitors,research,lifescience,medical on the serotonergic system, or rTMS (which Inhibitors,research,lifescience,medical acts on the SCN80). Increasing Veliparib PARP zeitgeber strength improves the consistency of entrainment and circadian amplitude: this may be one mechanism underlying the therapeutic efficacy of bright light and the melatonin agonist. There is inhibitor Paclitaxel evidence that depressed patients, including those with SAD, have greater day-today and within-day mood variability than controls.81,82 In SAD patients, it has been shown that increasing

zeitgeber strength Inhibitors,research,lifescience,medical with light therapy reduced or eliminated both group differences in mean level and variability of mood.82 Other zeitgebers (social cues, activity, and food) are important for improving behavioral feedback from peripheral clocks to overall cntrainment stability. This is extremely important in bipolar patients.37 The combination needed by the clinician for the sought-after rapid and long-lasting antidepressant, might well be an eclectic mix of these nonpharmacological Inhibitors,research,lifescience,medical modalities with antidepressant drugs. Conclusion We live in a 24-h society that is no longer strongly synchronized to the change in daylength or temperature across the seasons.

A permanent “summer day” is the result of artificial lighting, yet it is of insufficient intensity for Inhibitors,research,lifescience,medical stable entrainment. Too little is known of the sequelae of irregular patterns of light exposure on a vulnerable AV-951 circadian system, and how light could trigger or alleviate a depressive phase. Could part of the increase in prevalence of depression in modern society be related to such factors? Genetic predisposition, hormonal fluctuations, environmental stress, and altered light-dark cycles could all induce rhythm disturbances. Conversely, altered sleep patterns, hyperarousal, eating behavior, and mood state could feed back onto the circadian system via hormones and effects on peripheral oscillators. These new insights provide us with useful strategies and a variety of methods to improve robustness of the circadian pacemaker and better synchronize its timing with respect to the day-night cycle.