Handling missing data in rest-activity time series measured by actimetry.

A handling procedure of off-wrist episodes in actimetry time series of motor activity is presented using two records (regular vs. irregular sleep-wake cycle and daytime activity) of 14 consecutive days sampled in 1-minute epochs. We generated single missing value (NA) intervals of 1 h, 2 h, 4 h, 6 h, 12 h, and 24 h as well as random NA episodes following probabilistic rules to simulate real-life off-wrist episodes. Then, we replaced these episodes with "zeroes" (i.e., the default of immobility records), mean or median of the remaining 13 days corresponding to the missing bins. Single missing episodes of up to 12 h resulted in less than 5% variation from the original values. The irregular series showed higher variability in acrophase, MESOR, L5, M10 and RA compared to the regular series. Random missing allocation simulating real-life off-wrist episodes resulted in significant changes in most parameters, and the imputation of zeroes significantly increased the variance; however, replacing NA with mean or median resulted in patterns similar to those of NA. We recommend replacing 'zeroes' with NA whenever possible, given the risk of inflating invariance using zeroes. If the parameters cannot be computed in the presence of NA, we recommend using the weekly mean of corresponding timepoints.

6-Sulfatoxymelatonin predicts treatment response to fluoxetine in major depressive disorder.

BACKGROUND: To date, no biomarker has been able to predict antidepressant response at an early blockade of norepinephrine or serotonin uptake. The transient nocturnal increase in plasma melatonin levels is upregulated by blocking these uptakes. The aim of this study was to test whether fluoxetine increase in urinary 6-sulfatoxymelatonin (aMT6s) is an indicator of serotonin uptake blockade. METHODS: A total of 20 women (35-45 years of age) recruited from the community had a diagnosis of major depressive disorder confirmed by the Structured Clinical Interview for DSM-IV. Depressive symptoms were evaluated by the Beck Depression Inventory (BDI). Participants were instructed to take 20 mg of fluoxetine every morning. Every 4 weeks, the dose could be increased by 20 mg until symptom remission. The concentration of aMT6s was evaluated in overnight urine samples collected 1 day before and 1 day after the first fluoxetine dose. RESULTS: An increase in aMT6s correlated to a decrease in BDI score evaluated on day 45 (ρ = -0.67, p = 0.024) was observed. CONCLUSIONS: Nocturnal increase in urinary aMT6s after the first day of medication use links the early mechanism of action of fluoxetine to its clinical output 45 days later. Thus, the relationship between urinary aMT6s excretion 1 day before/1 day after is a biomarker for predicting clinical output earlier, reducing illness burden and health care costs.