Background: Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric condition that may be related to an imbalance of neural transmitters. The gut microbiota is the largest ecosystem in the human body, and the brain-gut axis theory proposes that the gut microbiome can affect brain function in multiple ways. The purpose of this study was to explore the gut microbiota in children with ADHD and assess the possible role of the gut microbiota in disease pathogenesis to open new avenues for ADHD treatment.Methods: A case-control design was used. We enrolled 17 children aged 6-12 years with ADHD who were treated in the Pediatric Outpatient Department of the First Medical Center of the Chinese PLA General Hospital from January to June, 2019. Seventeen children aged 6-12 years were selected as the healthy control (HC) group. Fecal samples of cases and controls were analyzed by shotgun metagenomics sequencing. Alpha diversity and the differences in the relative abundances of bacteria were compared between the two groups. Functional annotations were performed for the microbiota genes and metabolic pathways were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results:There was no significant difference in the alpha diversity of gut microbiota between the ADHD and HC groups. Compared with HCs, Faecalibacterium and Veillonellaceae were significantly reduced in children with ADHD (P < 0.05), Odoribacter and Enterococcus were significantly increased [linear discriminant analysis (LDA) > 2]. At the species level, Faecalibacterium prausnitzii, Lachnospiraceae bacterium, and Ruminococcus gnavus were significantly reduced in the ADHD group (P < 0.05), while Bacteroides caccae, Odoribacter splanchnicus, Paraprevotella xylaniphila, and Veillonella parvula were increased (P < 0.05). Metabolic pathway analysis revealed significant between-group differences in the metabolic pathways of neurotransmitters (e.g., serotonin and dopamine) (P < 0.05). Frontiers in Neuroscience | www.frontiersin.org 1 February 2020 | Volume 14 | Article 127 Wan et al. Gut Microbiota Role in ADHDConclusion: Composition differences of gut microbiota in subjects with ADHD may contribute to brain-gut axis alterations and affect neurotransmitter levels, which could contribute to ADHD symptoms.

Background: Infantile spasm (IS) is one of the most common catastrophic epilepsy syndromes in infancy characterized by epileptic spasm. While adrenocorticotropic hormone (ACTH) is the first-line treatment for IS, it is evident that the seizures associated with IS exhibit a clear circadian rhythm; however, the precise mechanisms underlying such seizures remain unclear. Melatonin is an important amine hormone and is regulated by circadian rhythm. Circadian proteins, especially Aryl Hydrocarbon Receptor Nuclear Trasnslocator-like Protein (ARNTL or BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), and their target proteins Period Circadian Regulator 1 (PER1), Period Circadian Regulator 2 (PER2), Cryptochrome 1 (CRY1), and Cryptochrome 2 (CRY2), play key roles in circadian rhythm. This study explored the relationships between melatonin, genes associated with circadian rhythm, and epileptic spasm. Materials and Methods: Eighteen female rats were mated with nine male rats and 16 became pregnant. Twelve pregnant rats were subjected to prenatal stress by forced swimming in cold water from the day of conception. Rat pups produced by stressed mothers received an intraperitoneal injection of N-methyl-D-aspartate (NMDA) on the 13th day after birth and were divided into four groups: NMDA (15 mg/kg), NMDA+ACTH (20 IU/kg), NMDA+melatonin (55 mg/kg), and NMDA+ACTH+melatonin (n = 36/group). Offspring from four dams that were not subjected to prenatal stress were used as controls. We then recorded latency and the frequency of flexion seizures. All offspring were sacrificed on the 14th day after birth and CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 expression was analyzed by western blotting, immunohistochemistry, and immunofluorescence. Results: NMDA induced spasm-like symptoms in rats. ACTH and melatonin significantly increased seizure latency and significantly reduced the frequency of seizures (P < 0.05). CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 expression was significantly lower in the NMDA group than the controls (P < 0.05). ACTH significantly increased the expression of CLOCK, BAML1, PER1, and CRY1 (P < 0.05) and melatonin significantly increased the expression of CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 (P < 0.05) compared with those of the NMDA group. There were no significant differences in the expression of BMAL1, CRY2, PER1, and PER2 when compared between the NMDA+ACTH+melatonin and control groups (P > 0.05). Wan et al. Circadian and Infantile Spasm Conclusion: ACTH and melatonin significantly increased the expression of circadian genes and improved NMDA-induced seizures. The anticonvulsant effects of ACTH and melatonin are likely to involve regulation of the expression of these genes.

Cutaneous vertebral medullary angiomatosis, also known as Cobb syndrome, is a rare segmental neurocutaneous syndrome. This syndrome is considered to be a non-hereditary congenital disease that is usually associated with arteriovenous malformations in the skin and spine. The clinical manifestations are complex because the lesions can involve the spine, spinal cord, skin, and even the viscera. Here, we present the case of a 10-year-old girl who was admitted to hospital due to headache with two episodes of convulsions. Previous examination at another hospital found no evidence of any abnormalities on either cranial or intracranial vascular magnetic resonance imaging (MRI). However, the patient had a history of subcutaneous hemangioma. Following exhaustive tests at our hospital, she was diagnosed with Cobb syndrome. She received surgery, treatment for decreasing intracranial pressure, and hormonal and nutritional support. She subsequently remained stable, with no recurrence of convulsions over a 9-year follow-up period. Here, we expand upon the clinical manifestations of Cobb syndrome and propose mechanisms for the underlying pathogenesis. We hope that our experience can help avoid missed diagnoses and misdiagnosis and provide more clinical evidence for early diagnosis.