) provided an essential link INNO-406 purchase between depressive mood and the timing and amount of sleep. Indeed, it was clear that total or partial sleep deprivation was a characteristic of spontaneous switches out. of depression.28 Patients were more likely to switch from depression into mania or hypomania during the daytime hours and from mania/hypomania into depression during sleep.29 A number of studies thus investigated the relationship between DV and clinical response. Sleep deprivation rcsponders manifested DV more often than nonrcsponders, with a pattern of improved mood in the evening.30,31 Patients with marked DV responded better to sleep deprivation than those with little. Later, the question

was asked whether Inhibitors,research,lifescience,medical the propensity Inhibitors,research,lifescience,medical to produce DV or the actual mood course on the day before sleep deprivation determined clinical response.32 For each patient six sleep deprivation nights were scheduled: two after days with a positive mood course, two after a negative mood course, and two after days without a diurnal change of mood. This strategy allowed within-patient comparison of responses. It was found that patients vary largely

in the occurrence Inhibitors,research,lifescience,medical of diurnal variations of mood. The propensity to produce DV either in terms of frequency or amplitude was positively correlated with the response to sleep deprivation. With-in patients no differences were found in responses to sleep deprivation applied after days with (positive or negative) or without. DV. Further investigations revealed that, mood variability measures rather than average daily mood improvement, correlated with the response to sleep deprivation.3 The findings with sleep Inhibitors,research,lifescience,medical deprivation suggested that DV could be a potential predictor for a patient’s likelihood to respond to different therapies eg, antidepressants.33 Indeed, a recent study has Inhibitors,research,lifescience,medical gone into some detail: patients with reversed DV had a poorer response to a serotonergic antidepressant, were less likely to have bipolar II disorder, had a higher tryptophan: large neutral amino acid ratio and had different, allele frequencies of the polymorphisms

in the promoter region of the serotonin transporter.34 These findings raise the possibility of serotonergic influence on DV, and that the symptom of evening mood worsening is of relevance to antidepressant prescribing. In healthy controls, old sleep deprivation usually has little effect on mood, rather simply increasing sleepiness and irritability. Separating subjects according to chronotype shows some differences, however, in response to sleep deprivation.35 Early chronotypes increased, and late chronotypes decreased their depressive mood score. Diurnal variations in physiology and biochemistry Many variables considered of interest for the etiology of major depression have been investigated over the 24-hour day.