Comprehensive assessment of sleep duration, insomnia, and brain structure within the UK Biobank cohort.

STUDY OBJECTIVES: To assess for associations between sleeping more than or less than recommended by the National Sleep Foundation (NSF), and self-reported insomnia, with brain structure. METHODS: Data from the UK Biobank cohort were analyzed (N between 9K and 32K, dependent on availability, aged 44 to 82 years). Sleep measures included self-reported adherence to NSF guidelines on sleep duration (sleeping between 7 and 9 hours per night), and self-reported difficulty falling or staying asleep (insomnia). Brain structural measures included global and regional cortical or subcortical morphometry (thickness, surface area, volume), global and tract-related white matter microstructure, brain age gap (difference between chronological age and age estimated from brain scan), and total volume of white matter lesions. RESULTS: Longer-than-recommended sleep duration was associated with lower overall grey and white matter volumes, lower global and regional cortical thickness and volume measures, higher brain age gap, higher volume of white matter lesions, higher mean diffusivity globally and in thalamic and association fibers, and lower volume of the hippocampus. Shorter-than-recommended sleep duration was related to higher global and cerebellar white matter volumes, lower global and regional cortical surface areas, and lower fractional anisotropy in projection fibers. Self-reported insomnia was associated with higher global gray and white matter volumes, and with higher volumes of the amygdala, hippocampus, and putamen. CONCLUSIONS: Sleeping longer than recommended by the NSF is associated with a wide range of differences in brain structure, potentially indicative of poorer brain health. Sleeping less than recommended is distinctly associated with lower cortical surface areas. Future studies should assess the potential mechanisms of these differences and investigate long sleep duration as a putative marker of brain health.

Associations between treatment with melatonin and suicidal behavior: a nationwide cohort study.

STUDY OBJECTIVES: Melatonin is often prescribed to patients with sleep disorders who are known to have elevated suicide risks, yet melatonin's association with suicidal behavior remains to be examined. We investigated whether individuals prescribed melatonin had higher rates of suicide and suicide attempts when compared to individuals who were not prescribed this drug, including both those with and without known mental disorders. METHODS: A cohort design was applied to longitudinal, register data on all persons aged ≥ 10 years in Denmark during 2007-2016. Based on data from the National Prescription Registry, periods of being in treatment with melatonin were defined using information on the number of tablets and the daily defined dose. We calculated incidence rate ratios for suicide and suicide attempts, as identified in register records, comparing those in treatment with melatonin to those not in treatment. RESULTS: Among 5,798,923 individuals, 10,577 (0.2%) were treated with melatonin (mean treatment length, 50 days) during the study period. Of those, 22 died by suicide and 134 had at least 1 suicide attempt. People in treatment with melatonin had a 4-fold higher rate of suicide (incidence rate ratio, 4.8; 95% CI, 3.0-7.5) and a 5-fold higher rate of suicide attempt (incidence rate ratio, 5.9; 95% CI, 4.4-8.0) than those not in treatment and when adjusting for sex and age group. CONCLUSIONS: Treatment with melatonin was associated with suicide and suicide attempt. Although there are several possible explanations, attention to suicide risk is particularly warranted for people with mental comorbidity who are in treatment with melatonin. CITATION: Høier NK, Madsen T, Spira AP, et al. Associations between treatment with melatonin and suicidal behavior: a nationwide cohort study. J Clin Sleep Med. 2022;18(10):2451-2458.