Association of Ala72Ser polymorphism with COMT enzyme activity and the risk of schizophrenia in Koreans

Catechol-O-methyltransferase (COMT) inactivates circulating catechol hormones, catechol neurotransmitters, and xenobiotic catecholamines by methylating their catechol moieties. The COMT gene has been suggested as a candidate gene for schizophrenia through linkage analyses and molecular studies of velo-cardio-facial syndrome. A coding polymorphism of the COMT gene at codon 108/158 (soluble/membrane-bound form) causing a valine to methionine substitution has been shown to influence enzyme activity, but its association with schizophrenia is inconclusive. We have screened 17 known polymorphisms of the COMT gene in 320 Korean schizophrenic patients and 379 controls to determine whether there is a positive association with a nonsynonymous single-nucleotide polymorphism (rs6267) at codon 22/72 (soluble/membrane-bound form) causing an alanine-to-serine (Ala/Ser) substitution. With the Ala/Ala genotype as a reference group, the combined genotype (Ala/Ser and Ser/Ser)-specific adjusted odds ratio was 1.82 (95% CI=1.19–2.76; P=0.005), suggesting the Ser allele as a risk allele for schizophrenia. However, the Val/Met polymorphism was not associated with an increased risk of schizophrenia in Koreans (OR=0.88, 95% CI=0.64–1.21; P=0.43). The Ala72Ser substitution was correlated with reduced COMT enzyme activity. Our results support previous reports that the COMT haplotype implicated in schizophrenia is associated with low COMT expression.     

The effects of the new guidance ‘take your sleeping pills 7 h before your wake-up time’: a pilot study

The aim of this study is to investigate the effectiveness and practicality of the newly proposed guidance to take hypnotics 7 h before one’s usual wake-up time, compared to the conventional guidance to do so 30 min before bedtime. Subjects with primary insomnia who were not satisfied with their hypnotics were included between November 2014 and October 2015. Participants were instructed to take their own sleeping pills 7 h before their usual wake-up times, and sleep-related time variables and symptom questionnaires were assessed at baseline and after 2 weeks. Among 32 subjects, 23 patients were successfully followed up. Adhering to the said 7-h instruction, 73.9 % (n = 17) were satisfied with their sleeping pills. Mean hypnotics administration time was significantly delayed from 9:32 p.m. ± 0:58 to 10:55 p.m. ± 0:46 (p < 0.001), duration from pills to wake-up time (PTW) was shortened from 9.0 ± 1.1 to 7.1 ± 0.8 h (p < 0.001), and sleep latency (p = 0.023) was significantly shortened. Scores of ISI and PSQI significantly improved (p < 0.001), and the improvements of ISI and PSQI were positively correlated with the shortened sleep latency (r = 0.49, p < 0.05) and PTW (r = 0.54, p < 0.05), respectively. Advising patients to take hypnotics about 7 h before their usual wake-up time could increase the level of satisfaction with their original medication as is. In incorporating concepts of cognitive-behavioral therapy, this recommendation may serve as a simple but considerably useful guidance on the proper timing for taking prescribed sleeping pills.

     

Neurochemical Changes Associated with Stress-Induced Sleep Disturbance in Rats: In Vivo and In Vitro Measurements

The goal of this study was to quantitatively assess the changes in the cerebral neurochemical profile and to identify those factors that contribute to the alteration of endogenous biomolecules when rats are subjected to stress-induced sleep disturbance. We exposed Sprague-Dawley rats (controls: n = 9; stress-induced sleep perturbation rats: n = 11) to a psychological stressor (cage exchange method) to achieve stress-induced sleep perturbation. In vivo magnetic resonance imaging assessments were carried out using a high-resolution 9.4 T system. For in vivo neurochemical analysis, a single voxel was localized in the right dorsal hippocampal region, and in vivo spectra were quantified for 17 cerebral neurochemical signals. Rats were sacrificed upon completion of the magnetic resonance spectroscopy protocol, and whole-brain tissue was harvested from twenty subjects. The dopamine and serotonin signals were obtained by performing in vitro liquid chromatography-tandem mass spectrometry on the harvested tissue. In the right dorsal hippocampal region, the gamma-aminobutyric-acid (GABA) and glutamine (Gln) concentrations were significantly higher in the sleep-perturbed rats than in the sham controls. The ratios of Gln/Glu (glutamate), Gln/tCr (total-creatine), and GABA/Glu were also significantly higher in the sleep-perturbed group, while serotonin concentrations were significantly lower in the sleep-perturbed rats. Pearson correlation results among individual rat data indicate that concentrations of dopamine (DA) and serotonin (5-HT) were significantly higher in SSP rats. A larger correlation coefficient was also observed for the SSP rats. Analysis of the correlation between the in vivo and in vitro signals indicated that the concentrations of Gln, 5-HT, and DA exhibited a significant negative correlation in the SSP rat data but not in that of control rats. The authors propose that the altered and correlated GABA, Gln, 5-HT, and DA concentrations/ratios could be considered key markers of neurological function in animal models of stress-induced sleep perturbation.     

Effect of sleep environment of preschool children on children’s sleep problems and mothers’ mental health

Sleep and Biological Rhythms - We evaluated the sleep environment factors that influence children’s sleep, and the relationship between co-sleeping and parenting stress and parents’...