Marcel Smits - Academia.edu (original) (raw)

Papers by Marcel Smits

Journal of Pineal Research, 2009

Psychopharmacology, 2011

To establish whether long-term use of melatonin influences pubertal development, sleep quality an... more To establish whether long-term use of melatonin influences pubertal development, sleep quality and mental health development in children as compared with the normal Dutch population of the same age. This follow-up research study was conducted in children included in a previous melatonin dose-finding trial. Outcomes were measured using questionnaires (Strength and Difficulties Questionnaire (SDQ), Children's Sleep Habits Questionnaire (CSHQ) and Tanner Stages) adopted for Dutch children. Mean duration of therapy, persistence of effect, adverse events and (other) reasons leading to cessation of therapy were additional objectives of this study. Mean years of usage (n=51) was 3.1 years (min 1.0 year, max 4.6 years), mean dose 2.69 mg (min 0.3 mg, max 10 mg). Mean SDQ score, mean CSHQ score and Tanner Stages standard deviation scores did not differ in a statistically significant way from published scores of the general Dutch population of the same age and sex. This follow-up study de...

Journal of Intellectual Disability Research, 2010

Background In some of our patients with intellectual disability (ID) and sleep problems, the init... more Background In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to melatonin is yet unknown. We hypothesise that this loss of response is associated with slow melatonin metabolism. Method In this study, we determined melatonin clearance in two female (aged 61 and 6 years) and one male (aged 3 years) patients who had chronic insomnia, late melatonin onset and mild ID, and whose sleep quality worsened a few weeks after initial good response to melatonin treatment, suggesting melatonin tolerance. After a 3-week washout period, patients received melatonin 1.0, 0.5 or 0.1 mg, respectively. Salivary melatonin level was measured just before melatonin administration, and

To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-w... more To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-wake rhythm in patients with delayed sleep phase disorder. Design: Meta analysis of papers indexed for PubMed, Embase, and the abstracts of sleep and chronobiologic societies (1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009). Patients: Individuals with delayed sleep phase disorder. Interventions: Administration of melatonin. Measurements and Results: A meta-analysis of data of randomized controlled trials involving individuals with delayed sleep phase disorder that were published in English, compared melatonin with placebo, and reported 1 or more of the following: endogenous melatonin onset, clock hour of sleep onset, wake-up time, sleep-onset latency, and total sleep time. The 5 trials including 91 adults and 4 trials including 226 children showed that melatonin treatment advanced mean endogenous melatonin onset by 1.18 hours (95% confidence interval [CI]: 0.89-1.48 h) and clock hour of sleep onset by 0.67 hours (95% CI: 0.45-0.89 h). Melatonin decreased sleep-onset latency by 23.27 minutes (95% CI: 4.83 -41.72 min). The wake-up time and total sleep time did not change significantly. Conclusions: Melatonin is effective in advancing sleep-wake rhythm and endogenous melatonin rhythm in delayed sleep phase disorder. Keywords: Melatonin, delayed sleep phase disorder, meta-analysis Citation: van Geijlswijk IM; Korzilius HPLM; Smits MG. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. SLEEP

Psychopharmacology, 2010

Rationale Pharmacokinetics of melatonin in children might differ from that in adults. Objectives ... more 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 (r s =−0.33, p=0.022) and SO (r s =−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.

Psychopharmacologia, Jul 29, 2010

Rationale Pharmacokinetics of melatonin in children might differ from that in adults. Objectives ... more 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 (r s =−0.33, p=0.022) and SO (r s =−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.

Backgroud and objective: To evaluate onset and stability of melatonin treatment effect

Sleep

To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-w... more To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-wake rhythm in patients with delayed sleep phase disorder. Meta analysis of papers indexed for PubMed, Embase, and the abstracts of sleep and chronobiologic societies (1990-2009). Individuals with delayed sleep phase disorder. Administration of melatonin. A meta-analysis of data of randomized controlled trials involving individuals with delayed sleep phase disorder that were published in English, compared melatonin with placebo, and reported 1 or more of the following: endogenous melatonin onset, clock hour of sleep onset, wake-up time, sleep-onset latency, and total sleep time. The 5 trials including 91 adults and 4 trials including 226 children showed that melatonin treatment advanced mean endogenous melatonin onset by 1.18 hours (95% confidence interval [CI]: 0.89-1.48 h) and clock hour of sleep onset by 0.67 hours (95% CI: 0.45-0.89 h). Melatonin decreased sleep-onset latency by 23.27...

Developmental Medicine & Child Neurology, 2009

Journal of Child Neurology, 2007

sheerenloo.nl.

European Journal of Neurology, 2006

The effect of melatonin, a chronobiotic drug, was explored in 29 patients with chronic fatigue sy... more The effect of melatonin, a chronobiotic drug, was explored in 29 patients with chronic fatigue syndrome (CFS) and Dim Light Melatonin onset (DLMO) later than 21.30 hours, reflective of delayed circadian rhythmicity. The patients took 5 mg of melatonin orally, 5 h before DLMO during 3 months. Their responses to the checklist individual strength (CIS), a reliable questionnaire measuring the severity of personally experienced fatigue, were assessed twice with a 6-week interval immediately before the treatment and once after 3 months treatment. In the pre-treatment period the fatigue sub-score improved significantly. After treatment, the total CIS score and the subscores for fatigue, concentration, motivation and activity improved significantly. The sub-score fatigue normalized in two of the 29 patients in the pre-treatment period and in eight of 27 patients during treatment. This change was significant. In the patients with DLMO later than 22.00 hours (n ¼ 21) the total CIS score and the sub-scores for fatigue, concentration and activity improved significantly more than in the patients (n ¼ 8) with DLMO earlier than 22.00 hours. Melatonin may be an effective treatment for patients with CFS and late DLMO, especially in those with DLMO later than 22.00 hours.

Journal of Sleep Research, 2006

SUMMAR Y In the present study we investigated sleep hygiene and actigraphically evaluated sleep i... more SUMMAR Y In the present study we investigated sleep hygiene and actigraphically evaluated sleep in 74 medication-naı¨ve children, aged 6-12 years, with rigorously diagnosed attentiondeficit/hyperactivity disorder (ADHD) and chronic sleep onset insomnia (ADHD-SOI) and 23 ADHD controls without insomnia (ADHD-noSOI). Between-group differences were analysed for lights out (sleep log), actigraphically evaluated sleep onset, sleep latency, total sleep duration, actual sleep time and sleep hygiene as measured with the Children's Sleep Hygiene Scale. We found a significant difference (P < 0.001) in mean (±SD) sleep onset between the ADHD-SOI group (21:49 ± 0:56 h) and ADHD-noSOI groups (20:41 ± 0:45 h). Sleep latency was significantly (P < 0.001) longer in ADHD-SOI (00:53 ± 0:25 h) compared to ADHD-noSOI (00:26 ± 0:25 h). The difference in total sleep duration between ADHD-SOI (9:42 ± 0:44 h) and ADHD-noSOI (10:09 ± 0:43 h) was not significantly different (P ¼ 0.18). The group difference in actual sleep time was also not significant (8:43 ± 0:52 h in ADHD-SOI versus 9:13 ± 1:16 h; P ¼ 0.40). There was no significant difference (P ¼ 0.17) in mean (±SD) total sleep hygiene score between the ADHD-SOI (56.4 ± 10.5) and ADHD-noSOI groups (53.0 ± 10.6). We conclude that there were differences in sleep onset and sleep latency in ADHD children with chronic SOI and those without insomnia; however, sleep hygiene practices were similar and did not relate to sleep characteristics.

Psychopharmacologia, Jul 29, 2010

Rationale Pharmacokinetics of melatonin in children might differ from that in adults. Objectives ... more 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 (r s =−0.33, p=0.022) and SO (r s =−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.

Behavioral Sleep Medicine, 2015

Internal and external validity of attention-deficit hyperactivity disorder in a population-based ... more Internal and external validity of attention-deficit hyperactivity disorder in a population-based sample of adults. Psychol.Med., 35, 817-827.

To investigate whether ADHD-related sleep-onset insomnia (SOI) is a circadian rhythm disorder, we... more To investigate whether ADHD-related sleep-onset insomnia (SOI) is a circadian rhythm disorder, we compared actigraphic sleep estimates, the circadian rest-activity rhythm, and dim light melatonin onset (DLMO) in ADHD children having chronic idiopathic SOI with that in ADHD children without sleep problems. Participants were 87 psychotropic-medication-naive children, aged 6 to 12 yrs, with rigorously diagnosed ADHD and SOI (ADHD-SOI) and

Annals of Nutrition and Metabolism

Migraine prevalence is associated with gastrointestinal disorders. Possible underlying mechanisms... more Migraine prevalence is associated with gastrointestinal disorders. Possible underlying mechanisms could be increased gut permeability and inflammation. Probiotics may decrease intestinal permeability as well as inflammation, and therefore may reduce the frequency and/or intensity of migraine attacks. Therefore we assessed feasibility, possible clinical efficacy, and adverse reactions of probiotic treatment in migraine patients. 29 migraine patients took 2 g/d of a probiotic food supplement (Ecologic®Barrier, 2.5×10 9 cfu/g) during 12 weeks. Participants recorded frequency and intensity of migraine in a headache diary and completed the Migraine Disability Assessment Scale (MIDAS) and Henry Ford Hospital Headache Disability Inventory (HDI) at baseline and after 12 weeks of treatment. Compliance was measured every 4 weeks by counting the remaining sachets with probiotics. The study was completed by 27/29 (93%) patients who took 95% of the supplements. Obstipation was reported by 4 patients during the first 2 weeks of treatment only. The mean±standard deviation (SD) number of migraine days/month decreased significantly from 6.7±2.4 at baseline to 5.1±2.2 (P=0.008) in week 5-8 and 5.2±2.4 in week 9-12 (P=0.001). The mean±SD intensity of migraine decreased significantly from 6.3±1.5 at baseline to 5.5±1.9 after treatment (P=0.005). The MIDAS score improved from 24.8±25.5 to 16.6±13.5 (P=0.031). However, the mean HDI did not change significantly. In conclusion, probiotics may decrease migraine supporting a possible role for the intestine in migraine management. Feasibility and lack of adverse reactions justify further placebo-controlled studies.

Journal of Pineal Research, 2009

Psychopharmacology, 2011

To establish whether long-term use of melatonin influences pubertal development, sleep quality an... more To establish whether long-term use of melatonin influences pubertal development, sleep quality and mental health development in children as compared with the normal Dutch population of the same age. This follow-up research study was conducted in children included in a previous melatonin dose-finding trial. Outcomes were measured using questionnaires (Strength and Difficulties Questionnaire (SDQ), Children's Sleep Habits Questionnaire (CSHQ) and Tanner Stages) adopted for Dutch children. Mean duration of therapy, persistence of effect, adverse events and (other) reasons leading to cessation of therapy were additional objectives of this study. Mean years of usage (n=51) was 3.1 years (min 1.0 year, max 4.6 years), mean dose 2.69 mg (min 0.3 mg, max 10 mg). Mean SDQ score, mean CSHQ score and Tanner Stages standard deviation scores did not differ in a statistically significant way from published scores of the general Dutch population of the same age and sex. This follow-up study de...

Journal of Intellectual Disability Research, 2010

Background In some of our patients with intellectual disability (ID) and sleep problems, the init... more Background In some of our patients with intellectual disability (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment, while the good response returned only after considerable dose reduction. The cause for this loss of response to melatonin is yet unknown. We hypothesise that this loss of response is associated with slow melatonin metabolism. Method In this study, we determined melatonin clearance in two female (aged 61 and 6 years) and one male (aged 3 years) patients who had chronic insomnia, late melatonin onset and mild ID, and whose sleep quality worsened a few weeks after initial good response to melatonin treatment, suggesting melatonin tolerance. After a 3-week washout period, patients received melatonin 1.0, 0.5 or 0.1 mg, respectively. Salivary melatonin level was measured just before melatonin administration, and

To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-w... more To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-wake rhythm in patients with delayed sleep phase disorder. Design: Meta analysis of papers indexed for PubMed, Embase, and the abstracts of sleep and chronobiologic societies (1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009). Patients: Individuals with delayed sleep phase disorder. Interventions: Administration of melatonin. Measurements and Results: A meta-analysis of data of randomized controlled trials involving individuals with delayed sleep phase disorder that were published in English, compared melatonin with placebo, and reported 1 or more of the following: endogenous melatonin onset, clock hour of sleep onset, wake-up time, sleep-onset latency, and total sleep time. The 5 trials including 91 adults and 4 trials including 226 children showed that melatonin treatment advanced mean endogenous melatonin onset by 1.18 hours (95% confidence interval [CI]: 0.89-1.48 h) and clock hour of sleep onset by 0.67 hours (95% CI: 0.45-0.89 h). Melatonin decreased sleep-onset latency by 23.27 minutes (95% CI: 4.83 -41.72 min). The wake-up time and total sleep time did not change significantly. Conclusions: Melatonin is effective in advancing sleep-wake rhythm and endogenous melatonin rhythm in delayed sleep phase disorder. Keywords: Melatonin, delayed sleep phase disorder, meta-analysis Citation: van Geijlswijk IM; Korzilius HPLM; Smits MG. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. SLEEP

Psychopharmacology, 2010

Rationale Pharmacokinetics of melatonin in children might differ from that in adults. Objectives ... more 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 (r s =−0.33, p=0.022) and SO (r s =−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.

Psychopharmacologia, Jul 29, 2010

Rationale Pharmacokinetics of melatonin in children might differ from that in adults. Objectives ... more 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 (r s =−0.33, p=0.022) and SO (r s =−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.

Backgroud and objective: To evaluate onset and stability of melatonin treatment effect

Sleep

To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-w... more To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-wake rhythm in patients with delayed sleep phase disorder. Meta analysis of papers indexed for PubMed, Embase, and the abstracts of sleep and chronobiologic societies (1990-2009). Individuals with delayed sleep phase disorder. Administration of melatonin. A meta-analysis of data of randomized controlled trials involving individuals with delayed sleep phase disorder that were published in English, compared melatonin with placebo, and reported 1 or more of the following: endogenous melatonin onset, clock hour of sleep onset, wake-up time, sleep-onset latency, and total sleep time. The 5 trials including 91 adults and 4 trials including 226 children showed that melatonin treatment advanced mean endogenous melatonin onset by 1.18 hours (95% confidence interval [CI]: 0.89-1.48 h) and clock hour of sleep onset by 0.67 hours (95% CI: 0.45-0.89 h). Melatonin decreased sleep-onset latency by 23.27...

Developmental Medicine & Child Neurology, 2009

Journal of Child Neurology, 2007

sheerenloo.nl.

European Journal of Neurology, 2006

The effect of melatonin, a chronobiotic drug, was explored in 29 patients with chronic fatigue sy... more The effect of melatonin, a chronobiotic drug, was explored in 29 patients with chronic fatigue syndrome (CFS) and Dim Light Melatonin onset (DLMO) later than 21.30 hours, reflective of delayed circadian rhythmicity. The patients took 5 mg of melatonin orally, 5 h before DLMO during 3 months. Their responses to the checklist individual strength (CIS), a reliable questionnaire measuring the severity of personally experienced fatigue, were assessed twice with a 6-week interval immediately before the treatment and once after 3 months treatment. In the pre-treatment period the fatigue sub-score improved significantly. After treatment, the total CIS score and the subscores for fatigue, concentration, motivation and activity improved significantly. The sub-score fatigue normalized in two of the 29 patients in the pre-treatment period and in eight of 27 patients during treatment. This change was significant. In the patients with DLMO later than 22.00 hours (n ¼ 21) the total CIS score and the sub-scores for fatigue, concentration and activity improved significantly more than in the patients (n ¼ 8) with DLMO earlier than 22.00 hours. Melatonin may be an effective treatment for patients with CFS and late DLMO, especially in those with DLMO later than 22.00 hours.

Journal of Sleep Research, 2006

SUMMAR Y In the present study we investigated sleep hygiene and actigraphically evaluated sleep i... more SUMMAR Y In the present study we investigated sleep hygiene and actigraphically evaluated sleep in 74 medication-naı¨ve children, aged 6-12 years, with rigorously diagnosed attentiondeficit/hyperactivity disorder (ADHD) and chronic sleep onset insomnia (ADHD-SOI) and 23 ADHD controls without insomnia (ADHD-noSOI). Between-group differences were analysed for lights out (sleep log), actigraphically evaluated sleep onset, sleep latency, total sleep duration, actual sleep time and sleep hygiene as measured with the Children's Sleep Hygiene Scale. We found a significant difference (P < 0.001) in mean (±SD) sleep onset between the ADHD-SOI group (21:49 ± 0:56 h) and ADHD-noSOI groups (20:41 ± 0:45 h). Sleep latency was significantly (P < 0.001) longer in ADHD-SOI (00:53 ± 0:25 h) compared to ADHD-noSOI (00:26 ± 0:25 h). The difference in total sleep duration between ADHD-SOI (9:42 ± 0:44 h) and ADHD-noSOI (10:09 ± 0:43 h) was not significantly different (P ¼ 0.18). The group difference in actual sleep time was also not significant (8:43 ± 0:52 h in ADHD-SOI versus 9:13 ± 1:16 h; P ¼ 0.40). There was no significant difference (P ¼ 0.17) in mean (±SD) total sleep hygiene score between the ADHD-SOI (56.4 ± 10.5) and ADHD-noSOI groups (53.0 ± 10.6). We conclude that there were differences in sleep onset and sleep latency in ADHD children with chronic SOI and those without insomnia; however, sleep hygiene practices were similar and did not relate to sleep characteristics.

Psychopharmacologia, Jul 29, 2010

Rationale Pharmacokinetics of melatonin in children might differ from that in adults. Objectives ... more 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 (r s =−0.33, p=0.022) and SO (r s =−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.

Behavioral Sleep Medicine, 2015

Internal and external validity of attention-deficit hyperactivity disorder in a population-based ... more Internal and external validity of attention-deficit hyperactivity disorder in a population-based sample of adults. Psychol.Med., 35, 817-827.

To investigate whether ADHD-related sleep-onset insomnia (SOI) is a circadian rhythm disorder, we... more To investigate whether ADHD-related sleep-onset insomnia (SOI) is a circadian rhythm disorder, we compared actigraphic sleep estimates, the circadian rest-activity rhythm, and dim light melatonin onset (DLMO) in ADHD children having chronic idiopathic SOI with that in ADHD children without sleep problems. Participants were 87 psychotropic-medication-naive children, aged 6 to 12 yrs, with rigorously diagnosed ADHD and SOI (ADHD-SOI) and

Annals of Nutrition and Metabolism

Migraine prevalence is associated with gastrointestinal disorders. Possible underlying mechanisms... more Migraine prevalence is associated with gastrointestinal disorders. Possible underlying mechanisms could be increased gut permeability and inflammation. Probiotics may decrease intestinal permeability as well as inflammation, and therefore may reduce the frequency and/or intensity of migraine attacks. Therefore we assessed feasibility, possible clinical efficacy, and adverse reactions of probiotic treatment in migraine patients. 29 migraine patients took 2 g/d of a probiotic food supplement (Ecologic®Barrier, 2.5×10 9 cfu/g) during 12 weeks. Participants recorded frequency and intensity of migraine in a headache diary and completed the Migraine Disability Assessment Scale (MIDAS) and Henry Ford Hospital Headache Disability Inventory (HDI) at baseline and after 12 weeks of treatment. Compliance was measured every 4 weeks by counting the remaining sachets with probiotics. The study was completed by 27/29 (93%) patients who took 95% of the supplements. Obstipation was reported by 4 patients during the first 2 weeks of treatment only. The mean±standard deviation (SD) number of migraine days/month decreased significantly from 6.7±2.4 at baseline to 5.1±2.2 (P=0.008) in week 5-8 and 5.2±2.4 in week 9-12 (P=0.001). The mean±SD intensity of migraine decreased significantly from 6.3±1.5 at baseline to 5.5±1.9 after treatment (P=0.005). The MIDAS score improved from 24.8±25.5 to 16.6±13.5 (P=0.031). However, the mean HDI did not change significantly. In conclusion, probiotics may decrease migraine supporting a possible role for the intestine in migraine management. Feasibility and lack of adverse reactions justify further placebo-controlled studies.