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Background: Light Therapy (LT) when combined with standard antidepressant treatment for unipolar depression hastens recovery. We studied the influence of LT timing on the antidepressant efficacy of LT and the influence of the season of treatment and recurrence on the response to treatment., Methods: We studied 70 inpatients affected by Unipolar Depression, treated for three weeks with combined LT and venlafaxine. Two-third of the patients received LT following a predictive algorithm based on MEQ scores; the others received LT at 11:00 a.m. Severity of depression was rated on the Hamilton Depression Rating Scale (HDRS). A subgroup of patients wore activity monitors., Results: HDRS scores significantly decreased during treatment (Friedman's ANOVA: χ2=186.82, p<0.00001). LT administered in the early morning showed a better relative efficacy than late morning (F=4.576; p=0.012) with the clinical improvement correlating with an advance in rest-activity rhythm acrophase (r=-0.336; p=0.017). Season of hospitalization interacted with LT timing and time in influencing response to treatment (F=3.101; p=0.049) and season of episode recurrence significantly interacted with LT timing, season of hospitalization and time (F=5.925; p=0.0035)., Limitations: The major limitation of the study is the small sample size when considering simultaneously LT schedules, season of treatment and recurrence. Moreover, even if none of the patients fulfilled DSM-IV criteria for seasonal pattern of recurrence, they were not administered any questionnaire about seasonality., Conclusions: We confirmed the usefulness of LT as a non-pharmacological antidepressant therapy for non-seasonal depression. Season and timing of administration and timing of the rest-activity cycle affected response to treatment., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Catechol-O-methyltransferase (COMT) inactivates norepinephrine and dopamine via methyl conjugation, and a G-A transition in the COMT gene (rs4680) influences the enzyme activity. It is a current area of debate whether rs4680 can influence antidepressant response in major depressive disorder, and whether this influence extends to bipolar depression. Chronotherapeutic interventions, such as sleep deprivation and light therapy, are multi-target in nature and are effective in bipolar depression. Here we studied the effect of rs4680 on response to sleep deprivation combined with light therapy (36 h awake followed by a night of undisturbed sleep, with 10,000 lx light administered for 30 min during the night awake and upon awakening) in 87 bipolar depressed inpatients. Patients who were homozygotic for the Val/Val variant showed a significantly less efficient antidepressant effect after the night awake than those who were heterozygotic and homozygotic for the Met variant. This effect of rs4680 is similar to its observed influence on response to serotonergic and noradrenergic drug treatments in major depressive disorder. This is the first study reporting an influence of rs4680 on antidepressant response in bipolar depression. This finding supports the hypothesis of a major role for catecholamines in the mechanism of action of chronotherapeutics, and for rs4680 in modulating this effect., (2009 Elsevier B.V. All rights reserved.)