Because the timing of sleep appears relevant for determining mood state, genetic factors may provide a chronobiological vulnerability for depression and affect dysregulation, in that wrong or poor alignment of internal phase with the side world increases susceptibility to depressive as well as dysphoric mood swings. New findings on desynchronization in clock gene expression may illustrate the chronobiological vulnerability for

depression and affect dysregulation. The clock genes in the SCN gradually adapt to a phase shift of the lightdark cycle (as found in shift work, transmeridian flight), whereas clock genes in the muscle, Inhibitors,research,lifescience,medical liver, and lung resynchronize at their own rates.44 This results in a “double desynchronization”—“internal desynchronization” Inhibitors,research,lifescience,medical between different clocks in the body and brain, and “external desynchronization” between the timing of body rhythms with respect to the light-dark cycle. As Wirz-Justice has pointed out in a review paper, the temporal orchestra can get quickly out of tune and this misalignment has profound effects

on mood, sleep, and health.19 Genetic vulnerabilty and stress influence circadian rhythms and sleep patterns, leading to symptoms characteristic Inhibitors,research,lifescience,medical of affective disorders.45 Specifically, genetic vulnerability may influence circadian rhythms and sleep patterns by a decreased cellular resilience associated with lower resistance to stressful events, thus leading to affective disturbances.45-48 Circadian regulation interacts with, and is determined by, neurotransmitter Inhibitors,research,lifescience,medical function; for example, the highest concentrations of central nervous system (CNS) serotonin are in the SCN.49 CNS serotonin turnover undergoes marked circadian

and seasonal rhythmicity50 and is rapidly stimulated by light exposure.51 This links the important role of light as zeitgeber or synchronizer of the circadian system, to the role of serotonin in mood disorders, indirectly supported by combination therapies of light and selective serotonin reuptake inhibitors Inhibitors,research,lifescience,medical (SSRIs).52,53 Stable internal and external phase relationships appear to be crucial for a stable and euthymic mood state. Any misalignment brings with it the propensity for mood fluctuation, Florfenicol particularly in vulnerable individuals. Chronobiological concepts emphasize the important role of zeitgebers to stabilize phase, with light and melatonin being the most important. But other zeitgebers, such as dark (and rest) periods, regularity of social schedules and meal times also play a role. Regular dark phases themselves appear to regulate the mood swings of rapid cyclers,54 and, in a selleck chemicals preliminary trial, “dark therapy” diminished manic symptoms as rapidly as the conventional antipsychotics generally used.55 Psychomotor activity and sleep-wake cycle disturbances are core symptoms of mood disorders, often heralding later emerging affective changes.