Complexity of Body Movements during Sleep in Children with Autism Spectrum Disorder

Recently, measuring the complexity of body movements during sleep has been proven as an objective biomarker of various psychiatric disorders. Although sleep problems are common in children with autism spectrum disorder (ASD) and might exacerbate ASD symptoms, their objectivity as a biomarker remains to be established. Therefore, details of body movement complexity during sleep as estimated by actigraphy were investigated in typically developing (TD) children and in children with ASD. Several complexity analyses were applied to raw and thresholded data of actigraphy from 17 TD children and 17 children with ASD. Determinism, irregularity and unpredictability, and long-range temporal correlation were examined respectively using the false nearest neighbor (FNN) algorithm, information-theoretic analyses, and detrended fluctuation analysis (DFA). Although the FNN algorithm did not reveal determinism in body movements, surrogate analyses identified the influence of nonlinear processes on the irregularity and long-range temporal correlation of body movements. Additionally, the irregularity and unpredictability of body movements measured by expanded sample entropy were significantly lower in ASD than in TD children up to two hours after sleep onset and at approximately six hours after sleep onset. This difference was found especially for the high-irregularity period. Through this study, we characterized details of the complexity of body movements during sleep and demonstrated the group difference of body movement complexity across TD children and children with ASD. Complexity analyses of body movements during sleep have provided valuable insights into sleep profiles. Body movement complexity might be useful as a biomarker for ASD.     

Multi-Scale Permutation Entropy: A Potential Measure for the Impact of Sleep Medication on Brain Dynamics of Patients with Insomnia

Insomnia is a common sleep disorder that is closely associated with the occurrence and deterioration of cardiovascular disease, depression and other diseases. The evaluation of pharmacological treatments for insomnia brings significant clinical implications. In this study, a total of 20 patients with mild insomnia and 75 healthy subjects as controls (HC) were included to explore alterations of electroencephalogram (EEG) complexity associated with insomnia and its pharmacological treatment by using multi-scale permutation entropy (MPE). All participants were recorded for two nights of polysomnography (PSG). The patients with mild insomnia received a placebo on the first night (Placebo) and temazepam on the second night (Temazepam), while the HCs had no sleep-related medication intake for either night. EEG recordings from each night were extracted and analyzed using MPE. The results showed that MPE decreased significantly from pre-lights-off to the period during sleep transition and then to the period after sleep onset, and also during the deepening of sleep stage in the HC group. Furthermore, results from the insomnia subjects showed that MPE values were significantly lower for the Temazepam night compared to MPE values for the Placebo night. Moreover, MPE values for the Temazepam night showed no correlation with age or gender. Our results indicated that EEG complexity, measured by MPE, may be utilized as an alternative approach to measure the impact of sleep medication on brain dynamics.     

Simultaneous determination of multiple active components in rat plasma using ultra‐fast liquid chromatography with tandem mass spectrometry and application to a comparative pharmacokinetic study after oral administration of Suan‐Zao‐Ren decoction and Suan‐Zao‐Ren granule

Suan‐Zao‐Ren decoction has been used to treat insomnia for many years. In this work, a rapid and sensitive ultra‐fast liquid chromatography with tandem mass spectrometry method was first developed and fully validated for the simultaneous quantification of seven main active components, spinosin, mangiferin, neomangiferin, ferulic acid, liquiritin, isoliquiritin, and liquiritin apioside in rat plasma. The method was also successfully applied to compare the pharmacokinetics of these active ingredients after oral administration of Suan‐Zao‐Ren decoction and Suan‐Zao‐Ren granule. The separation was achieved on a Venusil MP C₁₈ column and the detection was conducted by the multiple reaction monitoring mode using negative ion mode. Each calibration curve had good linearity over a wide concentration range. The precision of intra‐ and interday were all within 15%, and the extraction recoveries at different analyte concentrations were all above 82.0%. The established method was successfully applied to compare the pharmacokinetic profiles of the analytes between Suan‐Zao‐Ren decoction and Suan‐Zao‐Ren granule groups. The results indicated that all the analytes had similar mean concentration‐time curves trend between two groups. No significant differences were observed in pharmacokinetic parameters of mangiferin, while the others had significant differences.     

The internal link of serum steroid hormones levels in insomnia,depression, and Alzheimer's disease rats: Is there an effective way to distinguish among these three diseases based on potential biomarkers?

Insomnia, depression, and Alzheimer's disease are all neurodegenerative diseases and are associated with the levels of steroid hormones. To investigate the internal connection and difference of steroid hormones among these three diseases and distinguish them from the perspective of biomarkers, an easy, quick, and efficient high‐performance liquid chromatography with tandem mass spectrometry method was established and validated to determine six steroid hormones simultaneously in rat serum. The separation was accomplished on a SHIM‐PACK XR‐ODS chromatographic column with 0.1% v/v formic acid and methanol as the mobile phase and the detection was performed with electrospray ionization source in the positive ion mode. Based on the concentrations of steroid hormones, all the groups could be distinguished obviously from each other by using partial least square discriminant analysis. Meanwhile, 11‐deoxycortisol, corticosterone, and cortisol were identified as potential biomarkers and 100% of samples were classified correctly by Bayes’ discriminant function. These biomarkers were further screened by one‐way analysis of variance and cortisol was significantly different among all these groups. Bayes’ discriminant function was also built by cortisol and the classification accuracy was 87.2%. This workflow including determination of steroid hormones and discrimination among three neurological diseases would provide a basis for further clinical studies.     

Molecular Regulation of Betulinic Acid on α3β4 Nicotinic Acetylcholine Receptors

Betulinic acid (BA) is a major constituent of Zizyphus seeds that have been long used as therapeutic agents for sleep-related issues in Asia. BA is a pentacyclic triterpenoid. It also possesses various anti-cancer and anti-inflammatory effects. Current commercially available sleep aids typically use GABAergic regulation, for which many studies are being actively conducted. However, few studies have focused on acetylcholine receptors that regulate wakefulness. In this study, we utilized BA as an antagonist of α3β4 nicotinic acetylcholine receptors (α3β4 nAChRs) known to regulate rapid-eye-movement (REM) sleep and wakefulness. Effects of BA on α3β4 nAChRs were concentration-dependent, reversible, voltage-independent, and non-competitive. Site-directed mutagenesis and molecular-docking studies confirmed the binding of BA at the molecular level and showed that the α3 subunit L257 and the β4 subunit I263 residues affected BA binding. These data demonstrate that BA can bind to a binding site different from the site for the receptor’s ligand, acetylcholine (ACh). This suggests that BA may be an effective antagonist that is unaffected by large amounts of ACh released during wakefulness and REM sleep. Based on the above experimental results, BA is likely to be a therapeutically useful sleep aid and sedative.     

Chemical Composition and Potential Properties in Mental Illness (Anxiety,Depression and Insomnia) of Agarwood Essential Oil: A Review

As a valuable medicinal herb and spice, agarwood is widely used in the fields of daily chemistry, traditional medicine, religion and literary collection. It mainly contains sesquiterpenes and 2-(2-phenylethyl)chromones, which are often used to soothe the body and mind, relieve anxiety, act as an antidepressant and treat insomnia and other mental disorders, presenting a good calming effect. This paper reviews the chemical composition of the essential oils of different sources of agarwood, as well as the progress of research on the sedative and tranquilizing pharmacological activity and mechanism of action of agarwood essential oil (AEO), and then analyzes the current problems of AEO research and its application prospects in the treatment of mental diseases.     

Medicinal Plants Used for Anxiety,Depression, or Stress Treatment: An Update

Depression, anxiety, stress, and other mental disorders, which are on the rise worldwide, are indications that pharmacological therapy can have serious adverse effects, which is why many patients prefer to use herbal products to treat these symptoms. Here, we reviewed plants and products derived from them that are commonly used for the above indications, focusing on clinical data and safety profiles. While lavender, hops, maypop, lemon balm, and valerian have consistently been shown in clinical trials to relieve mild forms of neurological disorders, particularly depression, anxiety, and stress, currently available data do not fully support the use of peppermint for anxiety disorders and depression. Recent studies support the use of saffron for depression; however, its toxicological profile raises safety concerns. St. John’s wort is effective in alleviating mild to moderate depression; however, careful use is necessary particularly due to possible interactions with other drugs. In conclusion, more studies are needed to validate the mechanism of action so that these plants can be used successfully and safely to alleviate or eliminate various mental disorders.