Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arylalkylamine N-acetyltransferase (AANAT; serotonin N-acetyltransferase, EC 2.3.1.87) plays a unique transduction role in vertebrate physiology as the key interface between melatonin production and regulatory mechanisms. Circulating melatonin is elevated at night in all vertebrates, because AANAT activity increases in the pineal gland in response to signals from the circadian clock. Circadian regulation of melatonin synthesis is implicated in a variety of human problems, including jet lag, shift work, insomnia, and abnormal activity rhythms in blind persons. In this report AANAT was studied in the rhesus macaque to better understand human melatonin regulation. AANAT mRNA is abundant in the pineal gland and retina, but not elsewhere; AANAT mRNA is uniformly distributed in the pineal gland, but is limited primarily to the photoreceptor outer segments in the retina. Day and night levels of pineal and retinal AANAT mRNA are similar. In contrast, AANAT activity and protein increase more than 4-fold at night in both tissues. The activity of hydroxyindole-O-methyltransferase, the last enzyme in melatonin synthesis, is tonically high in the pineal gland, but is nearly undetectable in the retina; hydroxyindole O-methyltransferase mRNA levels exhibited a similar pattern. This supports the view that the source of circulating melatonin in primates is the pineal gland. The discovery in this study that rhesus pineal AANAT mRNA is high at all times is of special importance because it shows that posttranscriptional control of this enzyme plays a dominant role in regulating melatonin synthesis.
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PMID:Melatonin synthesis enzymes in Macaca mulatta: focus on arylalkylamine N-acetyltransferase (EC 2.3.1.87). 1236 61

Insomnia is the predominant sleep concern in children with autistic spectrum disorder (ASD), and its nature is most likely multifactorial, with neurochemical (abnormalities in serotonergic transmission or melatonin levels), psychiatric (anxiety), and behavioral (poor sleep habits) etiological factors involved. Children with ASD experience sleep problems similar to those of typically developing children, although the prevalence is markedly higher, occurring in 44-83% of school-aged children with ASD. Caregivers usually report that insomnia is the most frequent sleep disorder, described as disorders of initiating and maintaining sleep, restless sleep, bedtime resistance, co-sleeping, alterations of sleep hygiene, and early awakenings in the morning. Many actigraphic studies have added information on sleep disorders, confirming the questionnaire findings in the majority of cases. There are relatively few polysomnographic data for ASD, compared with questionnaire studies, and most of these studies reported a reduction in total sleep time and more undifferentiated sleep in the youngest patients. These findings were associated with several sleep microstructure alterations during rapid eye movement (REM) sleep, and with non-REM (NREM) sleep microstructure changes that appeared to be related to cognitive impairment rather than to the autistic core. Moreover, few data about other less frequent sleep disorders, such as periodic limb movements disorder and obstructive sleep apnea syndrome, bruxism, and the influence of epilepsy and EEG abnormalities, are available. Both pharmacologic and behavioral interventions have been suggested for the treatment of sleep problems in autistic children. The most common types of behavioral interventions are complete extinction (removing reinforcement to reduce a behavior) and various forms of graduated extinction. Melatonin has shown promising results in the treatment of insomnia in children with ASD. Although controlled studies are limited, there are more data demonstrating the safety and effectiveness of melatonin in ASD than for other sedative/hypnotic drugs. Finally, a dual treatment for insomnia in ASDs with melatonin and behavioral techniques has been suggested. A recent study using a combination of genetic and functional experimental techniques reported evidence that low melatonin concentration caused by a primary deficit in acetylserotonin methyltransferase activity is a risk factor for ASD. Sleep problems usually start at the same age as developmental regression, suggesting a higher vulnerability at this period of life. Further studies, beginning at younger ages, are necessary to better investigate these aspects and the role of melatonin in insomnia in children with ASD.
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PMID:Epidemiology and management of insomnia in children with autistic spectrum disorders. 2021 44