Estimating trace deposition time with circadian biomarkers: a prospective and versatile tool for crime scene reconstruction

Linking biological samples found at a crime scene with the actual crime event represents the most important aspect of forensic investigation, together with the identification of the sample donor. While DNA profiling is well established for donor identification, no reliable methods exist for timing forensic samples. Here, we provide for the first time a biochemical approach for determining deposition time of human traces. Using commercial enzyme-linked immunosorbent assays we showed that the characteristic 24-h profiles of two circadian hormones, melatonin (concentration peak at late night) and cortisol (peak in the morning) can be reproduced from small samples of whole blood and saliva. We further demonstrated by analyzing small stains dried and stored up to 4 weeks the in vitro stability of melatonin, whereas for cortisol a statistically significant decay with storage time was observed, although the hormone was still reliably detectable in 4-week-old samples. Finally, we showed that the total protein concentration, also assessed using a commercial assay, can be used for normalization of hormone signals in blood, but less so in saliva. Our data thus demonstrate that estimating normalized concentrations of melatonin and cortisol represents a prospective approach for determining deposition time of biological trace samples, at least from blood, with promising expectations for forensic applications. In the broader context, our study opens up a new field of circadian biomarkers for deposition timing of forensic traces; future studies using other circadian biomarkers may reveal if the time range offered by the two hormones studied here can be specified more exactly

Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT

Contains fulltext : 86695.pdf (publisher's version ) (Open Access)Rationale Pharmacokinetics of melatonin in children might differ from that in adults. Objectives This study aims to establish a dose–response relationship for melatonin in advancing dim light melatonin onset (DLMO), sleep onset (SO), and reducing sleep onset latency (SOL) in children between 6 and 12 years with chronic sleep onset insomnia (CSOI). Methods The method used for this study is the randomized, placebo-controlled double-blind trial. Children with CSOI (n=72) received either melatonin 0.05, 0.1, and 0.15 mg/kg or placebo during 1 week. Sleep was assessed with log and actigraphy during this week and the week before. Outcomes were the shifts in DLMO, SO, and SOL. Results Treatment with melatonin significantly advanced SO and DLMO by approximately 1 h and decreased SOL by 35 min. Within the three melatonin groups, effect size was not different, but the circadian time of administration (TOA) correlated significantly with treatment effect on DLMO (rs=-0.33, p=0.022) and SO (rs=-0.38, p=0.004), whereas clock TOA was correlated with SO shift (r=-0.35, p=0.006) and not with DLMO shift. Conclusions No dose–response relationship of melatonin with SO, SOL, and DLMO is found within a dosage range of 0.05–0.15 mg/kg. The effect of exogenous melatonin on SO, SOL, and DLMO increases with an earlier circadian TOA. The soporific effects of melatonin enhance the SO shift. This study demonstrates that melatonin for treatment of CSOI in children is effective in a dosage of 0.05 mg/kg given at least 1 to 2 h before DLMO and before desired bedtime.13 p