Serum Galanin in Children with Autism Spectrum Disorder.

Recent studies have attempted to measure several biomarkers to understand the complex interactions of the anatomic systems that may be involved in autism spectrum disorder (ASD). In CNS, galanin takes part in a variety of pathological and physiological processes. Prior research has indicated it is involved in several neuropsychiatric disorders and has a role in inhibiting the neuronal firing and release of serotonin, norepinephrine, and acetylcholine. To date, serum galanin levels have not been investigated in the context of ASD. This study aimed, therefore, to compare the serum galanin levels of children with ASD and healthy controls and to reveal any association between galanin level and the severity of ASD, as well as other psychological and demographic parameters. Serum galanin levels were measured by radioimmunoassay in 116 children with ASD and 98 healthy children. We observed significantly increased serum concentrations of galanin in children with ASD relative to healthy children. Moreover, children with severe ASD had significantly higher galanin levels than those with less severe disease. We also confirmed significant positive correlations between galanin and psychiatric parameters in children with ASD. For the first time, we suggest a possible correlation between serum galanin and the degree of ASD severity. Increased galanin levels may play a role in the pathogenesis of ASD.

Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a frequent developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and nonverbal communication, and stereotyped patterns of interests and activities. It has been previously reported that there is vitamin D deficiency in autistic children; however, there is a lack of randomized controlled trials of vitamin D supplementation in ASD children. METHODS: This study is a double-blinded, randomized clinical trial (RCT) that was conducted on 109 children with ASD (85 boys and 24 girls; aged 3-10 years). The aim of this study was to assess the effects of vitamin D supplementation on the core symptoms of autism in children. ASD patients were randomized to receive vitamin D3 or placebo for 4 months. The serum levels of 25-hydroxycholecalciferol (25 (OH)D) were measured at the beginning and at the end of the study. The autism severity and social maturity of the children were assessed by the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and the Autism Treatment Evaluation Checklist (ATEC). TRIAL REGISTRATION NUMBER: UMIN-CTR Study Design: trial number: UMIN000020281. RESULTS: Supplementation of vitamin D was well tolerated by the ASD children. The daily doses used in the therapy group was 300 IU vitamin D3/kg/day, not to exceed 5,000 IU/day. The autism symptoms of the children improved significantly, following 4-month vitamin D3 supplementation, but not in the placebo group. This study demonstrates the efficacy and tolerability of high doses of vitamin D3 in children with ASD. CONCLUSIONS: This study is the first double-blinded RCT proving the efficacy of vitamin D3 in ASD patients. Depending on the parameters measured in the study, oral vitamin D supplementation may safely improve signs and symptoms of ASD and could be recommended for children with ASD. At this stage, this study is a single RCT with a small number of patients, and a great deal of additional wide-scale studies are needed to critically validate the efficacy of vitamin D in ASD.

A review of the bidirectional relationship between psychiatric disorders and diabetes mellitus.

The prevalence of type 2 diabetes is rising worldwide, including Saudi Arabia. Among patients with diabetes, 30% suffer from mental disorders, such as depression, schizophrenia, delirium, and substance misuse (for example, tobacco smoking). Moreover, these disorders appear to share a bidirectional relationship with diabetes. For example, the incidence of diabetes has been shown to be 2-4 times greater in patients with schizophrenia than in normal individuals; also, there is a known association between depression and diabetes. In this review, we focus specifically on the bidirectional relationship between diabetes and psychiatric disorders, including the effects of antipsychotic drugs.

Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children.

OBJECTIVES: Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and non-verbal communication, and stereotyped patterns of interests and activities. Vitamin-D deficiency was previously reported in autistic children. However, the data on the relationship between vitamin D deficiency and the severity of autism are limited. METHODS: We performed a case-controlled cross-sectional analysis conducted on 122 ASD children, to assess their vitamin D status compared to controls and the relationship between vitamin D deficiency and the severity of autism. We also conducted an open trial of vitamin D supplementation in ASD children. RESULTS: Fifty-seven percent of the patients in the present study had vitamin D deficiency, and 30% had vitamin D insufficiency. The mean 25-OHD levels in patients with severe autism were significantly lower than those in patients with mild/moderate autism. Serum 25-OHD levels had significant negative correlations with Childhood Autism Rating Scale (CARS) scores. Of the ASD group, 106 patients with low-serum 25-OHD levels (<30 ng/ml) participated in the open label trial. They received vitamin D3 (300 IU/kg/day not to exceed 5000 IU/day) for 3 months. Eighty-three subjects completed 3 months of daily vitamin D treatment. Collectively, 80.72% (67/83) of subjects who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the CARS and aberrant behavior checklist subscales that measure behavior, stereotypy, eye contact, and attention span. CONCLUSION: Vitamin D is inexpensive, readily available and safe. It may have beneficial effects in ASD subjects, especially when the final serum level is more than 40 ng/ml. TRIAL REGISTRATION NUMBER: UMIN-CTR Study Design: trial Number: R000016846.

Role of neuroinflammation mediated potential alterations in adult neurogenesis as a factor for neuropsychiatric symptoms in Post-Acute COVID-19 syndrome-A narrative review.

Persistence of symptoms beyond the initial 3 to 4 weeks after infection is defined as post-acute COVID-19 syndrome (PACS). A wide range of neuropsychiatric symptoms like anxiety, depression, post-traumatic stress disorder, sleep disorders and cognitive disturbances have been observed in PACS. The review was conducted based on PRISMA-S guidelines for literature search strategy for systematic reviews. A cytokine storm in COVID-19 may cause a breach in the blood brain barrier leading to cytokine and SARS-CoV-2 entry into the brain. This triggers an immune response in the brain by activating microglia, astrocytes, and other immune cells leading to neuroinflammation. Various inflammatory biomarkers like inflammatory cytokines, chemokines, acute phase proteins and adhesion molecules have been implicated in psychiatric disorders and play a major role in the precipitation of neuropsychiatric symptoms. Impaired adult neurogenesis has been linked with a variety of disorders like depression, anxiety, cognitive decline, and dementia. Persistence of neuroinflammation was observed in COVID-19 survivors 3 months after recovery. Chronic neuroinflammation alters adult neurogenesis with pro-inflammatory cytokines supressing anti-inflammatory cytokines and chemokines favouring adult neurogenesis. Based on the prevalence of neuropsychiatric symptoms/disorders in PACS, there is more possibility for a potential impairment in adult neurogenesis in COVID-19 survivors. This narrative review aims to discuss the various neuroinflammatory processes during PACS and its effect on adult neurogenesis.

Improved attitudes of interns versus undergraduate medical students towards patients with mental illness in Saudi Arabia.

BACKGROUND: The attitudes of medical students towards mental illness are important since these students will be providing care to this group in the future. AIMS: To assess the beliefs and attitudes of undergraduate medical students regarding mental illness and to compare students at different levels. METHODS: This descriptive, cross-sectional study was conducted among undergraduate medical students in the College of Medicine, Majmaah University, Saudi Arabia, during the 2018-2019 academic years. Male students were included from Years 3-5 (25 from each year) and 25 male interns using the proportionate stratified random sampling method. The participants responded to the Beliefs about Mental Illness (BMI) Scale and the Attitudes towards Mental Illness Questionnaire (AMIQ). RESULTS: Bonferroni post hoc tests were used to conduct between-group comparisons of the year 3 group, who were at the beginning of their psychiatric training, with the other groups with more training. This revealed significant differences in scores for 11 of 21 items on the BMI Scale (P < 0.05). All questions regarding the 4 vignettes of the AMIQ (substance abuse, depression, psychosis, and obsessive compulsive disorders) showed a significant difference between students in year 3 and those in the other groups who had more psychiatric training (P < 0.05). CONCLUSIONS: The current medical psychiatric training positively improved the beliefs and attitudes of medical students towards patients with mental illnesses.

Polymorphism of interleukin-1ß and interleukin-1 receptor antagonist genes in children with autism spectrum disorders.

In this study, we first investigated interleukin-1 beta (IL-1ß) and IL-1 receptor antagonist (IL-1RA) levels in a cohort of Egyptian children with autism spectrum disorder (ASD) and in healthy controls. Second, we examined the single-nucleotide polymorphisms (SNPs) at positions -31 and - 511 of the IL-1ß gene promoter and IL1RA and assessed the association between IL1B and IL1RA polymorphisms with ASD. We examined IL1ß promoter polymorphism at -511 (IL-1ß-511) and - 31 (IL-1ß-31) and IL1RA gene polymorphism in 80 children with ASD and 60 healthy children. The children with ASD had significantly higher levels of IL-1ß and IL-1RA than the controls. The children with ASD also had significantly higher frequencies of homozygous (CC) and heterozygous (TC) genotype variants of IL-1ß-511, and IL-1RA than the controls. Moreover, the frequency of the IL-1ß-511 allele (C) was higher in the ASD group than in the controls (p = .001). The homozygous and heterozygous variants of IL-1RA allele II were also significantly higher in the ASD group than in the control group. There was no significant association between the IL-1ß-31 genotype and autism classes. However, there were significant differences in the distribution of the IL-1RA heterogeneous genotype and allele II among children with severe autism. The inflammatory role of cytokines has been implicated in a variety of neuropsychiatric pathologies, including autism. Our data show alterations in the IL-1ß system, with abnormally increased serum levels of IL-1ß and IL-1RA in the children with ASD. Further, polymorphisms in the IL-1ß-511 and IL-1RA genotype variants correlated positively with autism severity and behavioral abnormalities. IL-1ß-511 and IL-1RA gene polymorphisms could impact ASD risk and may be used as potential biomarkers of ASD. Variations in the IL-1ß and IL-1RA systems may have a role in the pathophysiology of ASD.

Physicians' Knowledge and Attitude towards Mental Health in Saudi Arabia.

BACKGROUND: Physicians working in Saudi Arabia belong to different countries and may have differences in knowledge and attitude towards psychiatry. We evaluated non-psychiatric physician's knowledge and attitude towards psychiatric disorders, such as anxiety and depression, in the Kingdom of Saudi Arabia. METHODS: A descriptive cross-sectional study design was used. The current knowledge and attitude towards anxiety and depression of physicians were determined by using a questionnaire. We distributed 180 study questionnaires at various hospitals to be answered by physicians in the Riyadh Province of Saudi Arabia. One hundred and forty-two completed questionnaires were included in the study. The participants were divided into three groups: (1) 63(44.4%) general practitioners (GPs), (2) 55 (38.7%) specialists and (3) 24 (16.9%) family practitioners. Data were analysed using the chi-square, ANOVA and independent sample t-test. RESULTS: GPs and specialists showed a negative attitude towards psychiatric patients, but family practitioners showed a positive attitude. There were statistically significant differences (p<0.05) in the knowledge regarding anxiety and depression among the groups. The relationship between specialty and knowledge was statistically significant (p<0.05) and the effect of first language is insignificant (p>0.05). CONCLUSION: Expansive enlightenment programmes, continued medical education and inclusion of psychiatric posting in rotating residential internship programme during undergraduate courses are required for physicians not only to fill the gap in knowledge and attitude but also to improve their cognitive, communication and interpersonal skills.

Frequency of Dendritic Cells and Their Expression of Costimulatory Molecules in Children with Autism Spectrum Disorders.

The aim of our study was to evaluate the frequencies of myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) in children with ASD. Subjects were 32 children with ASD and 30 healthy children as controls. The numbers of mDCs and pDCs and the expression of CD86 and CD80 on the entire DCs were detected by flow cytometry. ASD children had significantly higher percentages of mDCs and pDCs when compared to controls. We found significant inverse relationships between serum 25-hydroxyvitamin D levels and the frequencies of mDCs and pDCs in autistic children. Our data suggested that DCs could play a role in the clinical course of ASD. The relationship of DCs to immune disorders in ASD remains to be determined.

A randomized, double-blind, placebo-controlled clinical trial of the efficacy of treatment with zinc in children with intractable epilepsy.

This study was conducted to assess the efficacy of oral zinc supplementation in children with intractable epilepsy. Forty-five children aged between three and 12 years and diagnosed with idiopathic intractable epilepsy at Assiut University Hospital, Assiut, Egypt were recruited. The patients were randomly allocated to two groups: the intervention group received oral zinc supplementation (1 mg/kg/day) while the placebo group received placebo, each for six months. The parents of each child filled in a detailed questionnaire that covered demographic characteristics, type of seizures, frequency, duration of seizures, previous hospital admissions, postictal phenomena and the occurrence of status epilepticus. The primary outcome (frequency of seizures) was compared between the two groups. Zinc supplementation resulted in a significant reduction of seizure frequency in 31% of the treated children. Zinc is an important trace element. Our results suggest that it has mildly beneficial effects in children with intractable epilepsy. We recommend further investigation of oral zinc supplementation as an adjunctive therapy for managing intractable epilepsy in children. Zinc therapy may be an option in treatment protocols for intractable epilepsy in the near future.

A Randomized, Placebo-controlled Trial of Digestive Enzymes in Children with Autism Spectrum Disorders.

OBJECTIVE: There is growing evidence for a gut-brain connection associated with autism spectrum disorders (ASDs). This suggests a potential benefit from introduced digestive enzymes for children with ASD. METHODS: We performed a double-blind, randomized clinical trial on 101 children with ASD (82 boys and 19 girls) aged from 3 to 9 years. ASD patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition, text revision (DSM-IV-TR) diagnostic criteria. Structured interviews of at least one hour each both with the parents and the child were performed. Later on, another two hours-session was conducted applying the Childhood Autism Rating Scale (CARS). ASD patients were randomized to receive digestive enzymes or placebo. RESULTS: The ASD group receiving digestive enzyme therapy for 3 months had significant improvement in emotional response, general impression autistic score, general behavior and gastrointestinal symptoms. Our study demonstrated the usefulness of digestive enzyme in our population of ASD patients. CONCLUSION: Digestive enzymes are inexpensive, readily available, have an excellent safety profile, and have mildly beneficial effects in ASD patients. Depending on the parameter measured in our study, we propose digestive enzymes for managing symptoms of ASD. Digestive enzyme therapy may be a possible option in treatment protocols for ASD in the future.