If you want to read the PDF, try requesting it from the authors.

Abstract

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.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... . Vitamin D has an important role in brain homeostasis, neurodevelopment, ageing, and signifi cantly, in gene regulation. Also, it has been shown to bind to more than 2700 genes and to regulate the expression of more than 200 of them [2,[4][5][6]. Many studies suggested that vitamin D has an important role as a neuroactive steroid, which can affect neuronal differentiation, axonal connectivity and brain structure and function. ...
... Vitamin D has an important role in brain homeostasis, neurodevelopment, ageing, and signifi cantly, in gene regulation. Also, it has been shown to bind to more than 2700 genes and to regulate the expression of more than 200 of them [2,[4][5][6]. Many studies suggested that vitamin D has an important role as a neuroactive steroid, which can affect neuronal differentiation, axonal connectivity and brain structure and function. ...
... 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). The ASD children generally tolerated well the supplementation with vitamin D. The autism symptoms of the children improved signifi cantly, following 4 months of vitamin D3 therapy [4]. Vitamin D has an important role in the regulation of both innate and adaptive immune responses. ...
Article
Full-text available
... . Vitamin D has an important role in brain homeostasis, neurodevelopment, ageing, and signifi cantly, in gene regulation. Also, it has been shown to bind to more than 2700 genes and to regulate the expression of more than 200 of them [2,[4][5][6]. Many studies suggested that vitamin D has an important role as a neuroactive steroid, which can affect neuronal differentiation, axonal connectivity and brain structure and function. ...
... Vitamin D has an important role in brain homeostasis, neurodevelopment, ageing, and signifi cantly, in gene regulation. Also, it has been shown to bind to more than 2700 genes and to regulate the expression of more than 200 of them [2,[4][5][6]. Many studies suggested that vitamin D has an important role as a neuroactive steroid, which can affect neuronal differentiation, axonal connectivity and brain structure and function. ...
... 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). The ASD children generally tolerated well the supplementation with vitamin D. The autism symptoms of the children improved signifi cantly, following 4 months of vitamin D3 therapy [4]. Vitamin D has an important role in the regulation of both innate and adaptive immune responses. ...
Article
Full-text available
... The exact definition of being healthy or having only a mild illness is not clear. Authors had included study by Saad et al. [7], which was performed on children with autism spectrum disorder (ASD), a complex neurodevelopmental syndrome. The association between the risk of ASD and VitD insufficiency has been reported. ...
... However, whether ASD will influence VitD metabolism and the effect of ASD on VitD metabolism has not been demonstrated [8]. So, the study by Saad et al. [7] was not excluded. Furthermore, conditions or drug therapy might affect VitD metabolism including malabsorption, anticonvulsants, steroids, and antifungal medications. ...
... In addition, study by Saad et al. [7] was retracted and this may cause flaw and bias, other studies were included in the MENA region since only two. ...
... In order to summarize the actual knowledge on the subject, we identified nine studies investigating the effect of vitamin D supplementation on ASD core symptoms ( Table 3): four double-blind randomized placebo-controlled trials [101][102][103][104], one randomized controlled trial [105], four open-label intervention trials [31,[106][107][108]. The characteristics of these studies notably differ from one another in terms of sample size (from 19 to 109 children), age range (from 0 to 18 years), treatment duration (3 months to 3 years), way of administration (intramuscular or oral) and dosage of vitamin D supplementation (ranging from 300 IU/kg daily to 150.000 IU monthly) regardless serum 25 (OH)D levels. ...
... Conflicting results were reported about the potential benefits of vitamin D supplementation on core symptoms in autistic patients [99][100][101][102][103][104][105][106][107][108][109]. In fact, while some of the studies showed positive effects of vitamin D on ASD core symptoms [31,97,103,106], others failed to confirm such effects [104,108]. ...
... Conflicting results were reported about the potential benefits of vitamin D supplementation on core symptoms in autistic patients [99][100][101][102][103][104][105][106][107][108][109]. In fact, while some of the studies showed positive effects of vitamin D on ASD core symptoms [31,97,103,106], others failed to confirm such effects [104,108]. An interesting finding from the open-label trial of Saad and colleagues [31] was the correlation between ASD-related symptoms and serum 25(OH)D levels: when exceeded 100 nmol/L (40 ng/mL), the behavioral problems improved, reappearing when vitamin D therapy was discontinued and serum 25(OH)D levels dropped below 75 nmol/L (30 ng/mL). ...
Article
Vitamin D is a neurosteroid hormone crucially involved in neurodevelopment. Neural cell proliferation, neurotransmission, oxidative stress and immune function represent the main mechanisms mediated by vitamin D in the Central Nervous System. Therefore, its deficiency during pregnancy and early childhood may significantly impact on a developing brain, leading to possible adverse neuropsychological outcomes including Autism Spectrum Disorder (ASD). Significant vitamin D deficiency is described within children affected by ASD and in pregnant mothers whose offspring will later develop ASD, suggesting a possible role of the hormone as a contributing risk factor in the etiopathogenesis of ASD. We reviewed the actual literature on the potential contributing role of prenatal and early postnatal vitamin D deficiency in ASD etiopathogenesis, at both genetic and environmental levels, and the possible effect of vitamin D supplementation in autistic children. Conflicting but promising results emerged on the topic. Further Randomized Controlled Trials studies carried out during pregnancy and early infancy are necessary for better understanding the possible contribution of vitamin D deficiency in the etiopathogenesis of autism and the potential efficacy of the hormone supplementation in the improvement of ASD core symptoms.
... Nutritional or supplemental approaches may be helpful in modulating immune function in people with ASD. Several studies have found children with ASD to be deficient in serum levels of vitamin D (25-hydroxycholecalciferol), and serum levels were found to be negatively associated with language and behavioral scores on the ABC and the Childhood Autism Rating Scale (CARS) (Desoky et al., 2017;Saad et al., 2018), (Feng et al., 2017). Serum vitamin D levels also negatively correlated with the presence of anti-myelin-associated glycoprotein autoantibodies (Mostafa and Al-Ayadhi, 2012a). ...
... This fat-soluble vitamin has important immunomodulatory and neuroprotective functions (Aranow, 2011;Wrzosek et al., 2013), and deficiency may be contributing to immune and behavioral abnormalities in people with ASD. Daily supplementation with Vitamin D, not to exceed 5,000 IU/day, was found to significantly improve behavioral outcomes and lowered elevation of CD5 expression in children with ASD, supporting a role for Vitamin D in modulating the immune system (Desoky et al., 2017;Feng et al., 2017;Saad et al., 2018). As previously discussed, children with ASD have altered T cell profiles, perhaps due to altered transcriptional activity (Ahmad et al., 2017b). ...
Article
Full-text available
Autism spectrum disorders (ASD) are a group of heterogeneous neurological disorders that are highly variable and are clinically characterized by deficits in social interactions, communication, and stereotypical behaviors. Prevalence has risen from 1 in 10,000 in 1972 to 1 in 59 children in the United States in 2014. This rise in prevalence could be due in part to better diagnoses and awareness, however, these together cannot solely account for such a significant rise. While causative connections have not been proven in the majority of cases, many current studies focus on the combined effects of genetics and environment. Strikingly, a distinct picture of immune dysfunction has emerged and been supported by many independent studies over the past decade. Many players in the immune-ASD puzzle may be mechanistically contributing to pathogenesis of these disorders, including skewed cytokine responses, differences in total numbers and frequencies of immune cells and their subsets, neuroinflammation, and adaptive and innate immune dysfunction, as well as altered levels of immunoglobulin and the presence of autoantibodies which have been found in a substantial number of individuals with ASD. This review summarizes the latest research linking ASD, autoimmunity and immune dysfunction, and discusses evidence of a potential autoimmune component of ASD.
... However, the included children with autism had serum vitamin D levels < 30 ng/ml, which was inconsistent with the inclusion criteria of the present study; therefore, it was excluded. After full text screening, four RCT articles met the inclusion criteria; however, among them, the article of Saad et al. [49] was retracted because the validity of the research results was not demonstrated [50,51]. Ultimately, three RCTs were included in the analysis. ...
... In an year-long study, Infante et al. [66] suggested that a combination of omega-3 and vitamin D supplementation could effectively improve the core symptoms in children with autism. Saad et al. [49] found a significant symptom improvement after appropriate vitamin D supplementation in children with autism. However, Kerley et al. [67] found that when children with autism and those with asthma received the same dose of vitamin D simultaneously, the increase in serum 25(OH)D levels in children with autism remained significantly smaller than that in children with asthma in the control group even after being supplemented for a longer duration. ...
Article
Objective: We conducted a meta-analysis of randomized controlled trials to explore whether vitamin D supplementation is beneficial for symptom improvement in children with autism spectrum disorder. Methods: We systematically searched the PubMed database, EMBASE, Cochrane Library, Web of Science, Sino-Med, Wanfang Data, and China National Knowledge Infrastructure mainly up to September 2019. Using a fixed effects model, we calculated the standard mean difference with 95% confidence interval. Furthermore, we analyzed baseline serum 25-hydroxyvitamin D levels and outcome scores including the Social Responsiveness Scale and Child Autism Rating Scale scores after vitamin D supplementation. Results: There was no significant difference in baseline serum 25-hydroxyvitamin D levels among 203 children included from three studies in the meta-analysis. After vitamin D supplementation, the outcome scores in the experimental group were dramatically elevated compared with those in the control group (p = 0.03). Conclusion: Vitamin D supplementation improves the typical symptoms of autism spectrum disorder, as indicated by reduced Social Responsiveness Scale and Child Autism Rating Scale scores; thus, it is beneficial for children with autism spectrum disorder.
... 30 There is a strong association between maternal infection and an increased incidence of ASD in Oral vitamin D supplementation improves signs and symptoms of ASD. 34 In studies with children with ASD, it was found that children with a history of ASD had significantly lower vitamin D levels than healthy children and a significant association between autism severity and serum vitamin D levels. 35 In a study conducted by Saad et al., on 122 children with ASD, 57% had deficiency D and 30% have vitamin D insufficiency. ...
... 35 In a study conducted by Saad et al., on 122 children with ASD, 57% had deficiency D and 30% have vitamin D insufficiency. 34 Another study also found the same conclusion where vitamin D levels were lower in ASD children compared to controls. 36 ...
Article
Full-text available
The tendency for autism spectrum disorders or also known as Autism Spectrum Disorder (ASD) is increasing globally, even becoming 1 per 54 in 2016. Until now, the cause of autism is not known for certain, ASD is considered to be a combination of genetic and environmental factors. One of the environmental factors in this case is related to nutrition, one of which is vitamin D. Vitamin D deficiency is often found among children with ASD. Several studies have shown that vitamin D is involved in various brain bioprocesses including neuromodulation and nerve transmission and brain function while also influencing inflammatory processes, autoimmune disorders, oxidative stress and also neurotransmitters that are widely associated with the possibility of ASD. This review aims to describe vitamin D deficiency may contribute to ASD disorders. Based on this, in the future, it is necessary to consider when treating patients with ASD to consider the need to check the patient's vitamin D levels and if there is a deficiency it can be advised to sunbathe and or be given additional vitamin D intake.
... Vitamin D is a potent fat-soluble neurosteroid which is involved in many physiological mechanisms including calcium and phosphorus level regulation in the body and brain. In animal studies, it has been reported that vitamin D deficiency was associated with abnormalities in brain development and structural alterations such as enlarged brain at birth, enlarged ventricles, and neurotransmission changes [69,70]. Early brain enlargement is due to increased gray matter and volume of ventricles and the Page | 317 striatum, a brain region involved in motor programming and responsible for the stereotypic behavior observed in children with ASD and animal models. ...
Chapter
Full-text available
Autism spectrum disorder (ASD) and schizophrenia are two major neurodevelopmental disorders that differ in their age of onset and clinical profile. ASD and schizophrenia are characterized by varying degrees of brain dysfunction associated with behavioral abnormalities and differences in clinical outcomes. The causes of both disorders are unknown, but it is well recognized that their etiopathogenetic mechanisms involve an interaction between a strong genetic vulnerability and environmental factors. This combination then leads to epigenetic changes of gene expression and subsequent neuronal alterations responsible for synaptic plasticity and additional synapse formation. Additional pathogenetic mechanisms involve dysregulation of the immune system and brain-gut axis dysfunctions. Brain function analysis showed that individuals with ASD and schizophrenia have alterations in GABAergic and glutamatergic transmission. GammaAminobutyric acid (GABA) and glutamate represent the major inhibitory and excitatory neurotransmitters in the brain, respectively. Preclinical and clinical studies have been investigating how an imbalance between the inhibitory (GABA) and excitatory (glutamate) neurotransmissions during early phases of neurodevelopment may be useful in discovering novel molecular targets for potential drug therapy. Current treatments for both ASD and schizophrenia include antipsychotic medications such as risperidone, olanzapine, clozapine, and aripiprazole, which target specific neurotransmitter receptors of the dopamine and serotonin systems. Despite the genetic vulnerability associated with ASD and schizophrenia, and the response (full or partial) to antipsychotic medications, treatments are still needed that can address the molecular mechanisms of the disorders in order to improve long-term overall health and quality of life. Recently, an emphasis has been put on environmental modifiable risk factors, including nutrition status and dietary patterns, which can play a role in disease prevention, treatment, and managing symptoms. Prenatal nutrition quality has been considered a candidate risk factor for both ASD and schizophrenia. For example, the inhibitory neurotransmitter GABA is derived from the decarboxylation of glutamate, which utilizes pyridoxal phosphate, the active form of vitamin B6,as a cofactor. Vitamin deficiencies, such as low vitamin D, during early phases of life have been reported to be associated with both ASD and schizophrenia. In addition, alterations in vitamin D levels are associated with immune system dysregulations and systemic inflammation. This includes neuroinflammation, which has recently been considered one of the major pathogenetic mechanisms underlying both ASD and schizophrenia. Additionally, omega-3 polyunsaturated fatty acids such as α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docasahexaenoic acid (DHA) showed anti-inflammatory effects by regulating cytokine production and lowering pro-inflammatory activity of leukocytes. The anti-inflammatory effects of omega-3 fatty acids have recently been acknowledged as a mechanism for reducing psychosis severity amongst highrisk populations. In fact, the chronic low-grade systemic inflammation characterized by the hyperproduction and activity of cytokines is involved in the development of mental illnesses including ASD and schizophrenia. Moreover, evidence showed that in subjects with schizophrenia, a diet rich in carotenoids found in fruit and vegetables caused an increase in the serum levels of brainderived neurotrophic factor (BDNF), which is associated with brain plasticity and learning and memory mechanisms. Thus, we can speculate that adopting a functional, anti-inflammatory dietary pattern, rich in functional foods will help to support normal brain function and to ameliorate disease manifestation and progression in this specific population.
... Treatment of an ASD rat model with high-dose vitamin D revealed significant protective effects [161]. In contrast to supplementation in animal trials, the first randomized controlled clinical study analyzing the daily supplementation of 300 IU vitamin D3/kg for 4 months on 109 children with ASD, resulting in significant improvement of autism symptoms, was retracted 1 month ago [162]. This lets us conclude that vitamin D 3 can be suggested as possible preventive treatment for the prevention of ASD, but more studies supplementing pregnant women and their children with adequate levels of vitamin D 3 have to be performed. ...
Chapter
Full-text available
Approximately 90% of the elderly population in the western countries has at least a mild to moderate vitamin D hypovitaminosis. Besides the well-known function of vitamin D in calcium homeostasis, it has been recently found that several enzymes and receptors involved in its homeostasis are expressed in the nervous system and brain suggesting also an important role in the brain homeostasis. Interestingly, epidemiological and clinical studies found reduced vitamin D level associated with an increased risk of several neurodegenerative disorders. In this chapter, we focus on a potential link between vitamin D and Alzheimer's disease, Parkinson's disease, multiple sclerosis, prion disease, and motor neuron disease. Epidemiological studies were summarized, an overview of the known potential underlying pathomolecular mechanisms are given, and results from clinical studies dealing with vitamin D supplementation were presented. As an outlook, recent literature suggesting an impact of vitamin D on autism spectrum disease, depression , and schizophrenia are briefly discussed. In conclusion, the identification of an abundant vitamin D metabolism in the brain and the tight link between the increasing number of several neurological and mental disorders emphasize the need of further research making a clear recommendation of the intake and supplementation of vitamin D in a growing elderly population.
... Un ensayo clínico aleatorizado mostró que la administración de 300 ui vitamina D3/ kg/día sin exceder 5000 ui/día mejora el puntaje en la escala cars hasta por cuatro meses. 51 En casos de esclerosis tuberosa asociada a autismo ha tenido buenas aceptaciones. 52 Estimulación transcraneal con corriente directa: es un procedimiento poco invasivo que ayuda en la función social y en el manejo de emociones. ...
Article
p>El trastorno del espectro autista (tea) es un desorden del desarrollo complejo caracterizado principalmente por carencias en la comunicación y en la interacción social, así como por patrones de comportamiento, intereses o actividades repetidas y restrictivas. La prevalencia es mayor en niños. Se desconocen las causas exactas de las anomalías o irregularidades en las conexiones neuronales subyacentes a la enfermedad, pero etiológicamente el tea se considera un padecimiento multifactorial. Se han propuesto diferentes mecanismos fisiopatológicos para explicar las manifestaciones del trastorno, entre los que destaca una alteración en el balance de señales excitadoras e inhibidoras mediadas por el glutamato y el ácido gamma amino-butírico (gaba), respectivamente, en circuitos que controlan funciones cognitivas como la memoria y aprendizaje. El tratamiento del tea consiste en apoyo psicopedagógico y farmacológicos, cada caso debe ser individualizado. Esta revisión aborda aspectos relevantes de los mecanismos fisiopatológicos, características clínicas y terapéutica de este trastorno.</p
... 7 A randomized clinical trial completed in 2016 involving 109 children with autism disorder treated with high dose of vitamin D showed significant improvement of symptoms without frequent adverse outcomes. 8 While these data suggest that there is a potential for high-dose vitamin D as a symptomatic or preventive treatment, additional large-scale clinical trials are needed to determine whether this is truly effective and safe. ...
Article
Full-text available
Children with autism spectrum disorder have been found to have lower levels of vitamin D than their peers. Our case report supports the hypothesis that vitamin D may be an effective treatment for developmental delay in autism. In addition, we review the literature surrounding vitamin D deficiency as a potential cause of autism spectrum disorder and the role that vitamin D may play in treatment.
... Vitamin D is either absorbed by food or produced in the skin by sunlight (Baggerly et al. 2015). The main sources rich in vitamin D include dairy products, seafood, egg yolk, enriched and legumes (Saad et al. 2018;Schmid and Walther 2013). Moreover, vitamin D deficiency has been reported in many countries, including developed and developing countries, such as Iran (Tabrizi et al. 2018). ...
Article
Iron and vitamin D deficiency are the common problems in Iranian adolescents. This study aimed to examine whether the theory of planned behaviour (TPB) implemented in the educational intervention were effectiveness to improve behavioural intention to intake iron and vitamin D supplements among adolescent girls. Quasi-experimental study was used to enrol 175 adolescent girls aged 12–14 years attending community-based practices in the Gonabad, Iran. We evaluated the effects of a behavioural intervention for adolescents compared to usual care controls, on the TPB constructs and adolescent’s behavioural intentions to intake vitamin D and iron supplements, assessed at baseline and post-intervention. Bivariate analysis was used to assess whether the health provider training improved outcomes. Mean scores of knowledge, attitude, subjective norm, perceived behavioural control (PBC) and behavio\ural intention before intervention were, respectively, 20.65, 25.88, 25.82, 20.12 and 11.22, and after the intervention, were, respectively, 23.74, 25.48, 18.27, 11.33 and 11.82. All the constructs except the attitude in the intervention group were significantly higher (p < 0.001) than the control group, indicating that adolescent’s behavioural intention to intake iron and vitamin D supplements significantly improved in intervention group compared control group. Therefore, constructs of the TPB could be a significant determinate to change multiple behavioural intention in different populations. Given the importance of the use of supplements by female adolescents, it is necessary to pay more attention to the issue of training in this field and to remove the existing obstacles. Abbreviations: TPB: Theory of planned behavior; PBC: perceived behavioral control; IDA: iron deficiency anemia
... Thus, the Authors hypothesised a link between VD and ASD, suggesting a potential role for VD as a risk factor for ASD. However, it should be noted that few interventional studies have been carried out on VD supplementation in ASD patients [113]. As regards biological mechanisms linking VD to ASD, some Authors suggested that vitamin D low levels could lead to brain development disorders [112,114,115] due to its crucial role in brain development. ...
Article
Objective: to summarise the activities that Vitamin D (VD) carries out in the brain and to clarify the potential role of VD in neurological diseases. Methods: a literature research has been performed in Pubmed using the following keywords: ‘Vitamin D’, ‘nervous system’, ‘brain’. Results: the studies reviewed show that VD contributes to cerebral activity in both embryonic and adult brain, helping the connectivity of neural circuits responsible for locomotor, emotional and reward-dependent behavior. Low VD serum levels have been found in patients affected by Alzheimer Disease, Parkinson Disease, Multiple Sclerosis, Autism Spectrum Disorders, Sleep Disorders and Schizophrenia. Discussion: findings are controversial and should be interpreted with caution, since most of the studies performed have observational study set and few interventional studies are available, producing conflicting results. Overall, it can be stated that the potential role of Vitamin D in neurological diseases is mostly unclear and further randomised controlled trials are needed to understand better whether Vitamin D supplementation treatment can be useful in brain disorders.
... In context of ASD, the plausible mechanisms of action of vitamin D are anti-inflammatory effects on the brain and regulation of serotonin. In a randomized clinical trial done by Saad et al. (2018), improvement in behavioral measures (Autism Evaluation Checklist, CARS, SRS) was observed 4 months after supplementation of vitamin D in children with ASD [49]. Sunlight is the best source of vitamin D, however, cheese, egg yolk; fatty fish such as tuna, salmon also provide the vitamin. ...
Article
Full-text available
Autism spectrum disorder (ASD) is a complex, heterogenous group of neurodevelopmental disorders that result due to interaction of genes and environmental factors. ASD is associated with behavioural alterations and deficits in social communication. Current research on pathophysiology has proposed a link between severity of symptoms of ASD and gastrointestinal disturbances. Intestinal inflammation, dysregulation of gut microbiome may affect intestinal permeability, mucosal immune function and subsequently cause GI symptoms. Studies have also proposed the role of metabolic activity of the gut microbiome and dietary components (food allergens/toxins) to be associated with behavioral alterations in neurodevelopmental conditions including ASD. The present review aims to highlight the potential role of nutrients and dietary changes on gastrointestinal pathology and symptoms of ASD.
... Moreover, Egyptian and Qatari children with ASD were also found to have significantly lower vitamin D levels compared to controls (Bener et al. 2014;Meguid et al. 2010). Clinical trials have shown that dietary supplementation of vitamin D alleviated ASD symptoms and improved the overall quality of life (Saad et al. 2016;Saad et al. 2018). ...
Article
Full-text available
This study assesses the correlation between vitamin-D deficiency and autism spectrum disorder (ASD) in Jordan. We performed a case–controlled cross-sectional analysis to assess vitamin D levels in 83 children with ASD aged less than 8 years old compared to 106 healthy controls. In addition, the association between vitamin D deficiencies and gastrointestinal (GI) complains and electroencephalogram (EEG) abnormalities commonly found in children with ASD was investigated. Vitamin D levels in ASD patients were significantly lower. Also, Vitamin D levels in ASD patients had significant correlation with GI complains, but no correlation between vitamin D levels and Ca²⁺or EEG abnormalities was detected. These data suggest a possible role for vitamin D deficiency in the pathophysiology of ASD.
... Overall, the most substantial improvements observed were on the CARS assessments, which was conducted by a professional evaluator and is less susceptible to placebo-effect 20 . CARS is a stable and consistent diagnostic tool with high predictive validity 21 and has been used to evaluate participants before and after therapeutic interventions in multiple studies 20,22,23 . For the follow up CARS, the evaluator collected current information based on each question's unique criteria. ...
Article
Full-text available
Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.
... Eight trials [56][57][58][59][60][61][62][63] had been performed in Europe, five [64][65][66][67][68] in North America, three [69][70][71] in Middle East and Africa, one [72] in Australia, and three [73][74][75] in Asia. The number of participants was 880 and 2958 in the control and intervention groups, respectively. ...
Article
Full-text available
Background/objectives: Optimal doses of vitamin D (VitD) supplement in different populations are unclear. We aim to evaluate the relationship between VitD supplementation and post-intervention serum 25-hydroxyvitamin D [25(OH)D] concentration, to provide a recommended dosage of VitD for achieving an optimal 25(OH)D concentration for different populations. Subjects/methods: Literature search was conducted in Embase, etc. Randomized controlled trials about VitD supplemental intakes and their effect on 25(OH)D concentration were enrolled. The effect on 25(OH)D concentration between different supplementation doses in each population group was compared by meta-analysis. Multivariate meta-regression model is utilized to establish reference intake dosage of VitD. Results: A total of 136 articles were included about children (3-17 years), adults (18-64 years), postmenopausal women, the elderly ( >64 years), pregnant, or lactating women. Overall, intervention groups obtained higher 25(OH)D concentration than controls and there was obvious dose-response effect between intake dose and 25(OH)D concentration. Baseline 25(OH)D concentration and age were significant indicators for 25(OH)D concentration. To reach sufficient 25(OH)D concentration (75 nmol/L), the recommended VitD supplemental intakes was 1340 and 2250 IU/day for children and pregnant women, 2519 and 797 IU/day for European adults aged 18-64 and 65-85 years, 729, 2026, and 1229 IU/day for adults in North America, Asia and Middle East and Africa, respectively. Conclusions: Regional- and age-specific recommended dosages of VitD supplements for population to achieve optimal 25(OH)D concentrations have been suggested.
... Interestingly, vitamin D deficiency was assessed as a risk factor for ASD [52]. A recent clinical study reported that oral vitamin D supplementation in children for ASD improved Childhood Autism Rating Scale scores compared with the placebo group [53]. Moreover, vitamin D acts as an inhibitor of the mTOR signaling pathway. ...
Article
Full-text available
The mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cell metabolism, growth, and proliferation. The overactivation of mTOR has been implicated in the pathogenesis of syndromic autism spectrum disorder (ASD), such as tuberous sclerosis complex (TSC). Treatment with the mTOR inhibitor rapamycin improved social interaction deficits in mouse models of TSC. Prenatal exposure to valproic acid (VPA) increases the incidence of ASD. Rodent pups that are exposed to VPA in utero have been used as an animal model of ASD. Activation of the mTOR signaling pathway was recently observed in rodents that were exposed to VPA in utero, and rapamycin ameliorated social interaction deficits. The present study investigated the effect of rapamycin on social interaction deficits in both adolescence and adulthood, and gene expressions in mice that were exposed to VPA in utero. We subcutaneously injected 600 mg/kg VPA in pregnant mice on gestational day 12.5 and used the pups as a model of ASD. The pups were intraperitoneally injected with rapamycin or an equal volume of vehicle once daily for 2 consecutive days. The social interaction test was conducted in the offspring after the last rapamycin administration at 5–6 weeks of ages (adolescence) or 10–11 weeks of age (adulthood). Whole brains were collected after the social interaction test in the adulthood, and microarray and Western blot analyses were performed. Mice that were exposed to VPA and treated with vehicle exhibited a decrease in social interaction compared with control mice that were treated with vehicle. Rapamycin treatment in VPA-exposed mice improved social deficits. Mice that were exposed to VPA and treated with vehicle exhibited the aberrant expression of genes in the mTOR signaling pathway, and rapamycin treatment recovered changes in the expression of some genes, including Fyb and A330094K24Rik. Rapamycin treatment suppressed S6 phosphorylation in VPA-exposed mice. Aberrant gene expression was associated with social interaction deficits in VPA-exposed mice. Rapamycin may be an effective treatment for non-syndromic ASD in adolescent and adult patients who present impairments in the mTOR signaling pathway. Electronic supplementary material The online version of this article (10.1186/s13041-018-0423-2) contains supplementary material, which is available to authorized users.
... Calcium supplementation via consumption of enriched cows' milk together with weight-bearing exercise was found to have a synergistic and positive effect on bone mineral density accrual (91). One recent double-blinded randomised controlled trial of oral vitamin D supplementation in children with ASD revealed significant effects on the core manifestations of ASD and 300 IU vitamin D3/kg/day was reported to be generally well tolerated (92). ...
Article
Full-text available
Many children with Autism Spectrum Disorders (ASDs) have been reported to suffer from conditions (i.e. gastrointestinal distress, abnormal sensory processing, etc.) that may interfere with their nourishment. To compensate for possible deficiencies stemming from food selectivity and idiosyncratic eating habits and to alleviate some of the symptoms of A S D, a number of dietary strategies have been implemented by caregivers. Such strategies may include supplementation of diets with probiotics, omega-3 fatty acids, antioxidants, vitamins and minerals. Exclusion of certain nutrients from the diet (such as gluten, casein, carbohydrates, etc.) has also been resorted to. There are a vast number of studies conducted on dietary interventions in children with A S D, however, the results of these studies are confusing and inconclusive.Thispaper aims to critically review scientific studies on dietary strate¬ gies as applied to children with A S D and deduce practical implications from existing researches.
... In research with individuals with ASD, the general trend has remained single supplementation. For example, Saad and colleagues [99] studied 109 children with ASD on vitamin D supplementation for 4 months, and found positive effects on both vitamin D serum and clinical rating results of core ASD symptoms. Another study of 38 children with ASD conducted by Kerley and colleagues [100] utilizing a lower dosage of vitamin D3 for a longer period (20 weeks) found improvements in only one domain of self-care (such as feeding, clothing, and personal hygiene). ...
Article
Purpose of Review There is an increased use of dietary and nutritional treatments among families of children with attention-deficit/hyperactivity disorder, autism spectrum disorder, and other neurodevelopmental disorders. With unclear and sometimes contradictory information regarding the effectiveness and safety of such treatments, this review critically reviews available research. Recent Findings This review identified treatments with promising and increasing levels of evidence including the few foods diet, PUFAs, probiotic treatments, and broad spectrum micronutrients; treatments with inconclusive or inconsistent findings such as gluten-free or additive-free diets, and those treatments with little evidence for effectiveness such as a sugar-free diet. Summary There is reasonably robust evidence for the use of some dietary and nutritional approaches such as reduction of food dyes and supplementing with essential fatty acids and broad spectrum micronutrients. Additionally, the literature reviewed provided theoretical mechanisms for these treatments. Many methodological challenges (such as sample size, length of intervention, and difficulties with researcher blinding) were reviewed, demonstrating the need for a well-designed, well-controlled replications studies to provide further guidance and reassurance to families and health professionals.
... Then, a 3-month cross-sectional study conducted on 122 ASD children found that cholecalciferol supplementation at the dose of 300 IU/kg/day (not to exceed 5.000 IU/day) significantly improved CARS scores when the target of serum 25(OH)D ≥75 nmol/L was achieved 47 . Similar findings have been recently replicated in a double-blinded randomized clinical trial conducted on 109 ASD children, where cholecalciferol administration at a dose of 300 IU/kg/day for 4 months led to a significant improvement in autism symptoms 81 . An open-label study conducted on thirtyseven children with ASD and vitamin D deficiency showed that cholecalciferol administration at large bolus doses (150.000 ...
Article
Full-text available
Introduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by abnormal development of cognitive, social, and communicative skills. Although ASD aetiology and pathophysiology are still unclear, various nutritional factors have been investigated as potential risk factors for ASD development, including omega-3 polyunsaturated fatty acids (PUFAs) and vitamin D deficiency. In fact, both omega-3 PUFAs and vitamin D are important for brain development and function. Case report: Herein, we report the case of a 23-year-old young adult male with autism who was referred to our Unit due to a 12-month history of cyclic episodes of restlessness, agitation, irritability, oppositional and self-injurious behaviours. Laboratory tests documented a markedly altered omega-6/omega-3 balance, along with a vitamin D deficiency, as assessed by serum levels of 25-hydroxyvitamin D. Omega-3 and vitamin D co-supplementation was therefore started, with remarkable improvements in ASD symptoms throughout a 24-month follow-up period. A brief review of the literature for interventional studies evaluating the efficacy of omega-3 or vitamin D supplementation for the treatment of ASD-related symptoms is also provided. Conclusion: To our knowledge, this is the first case reporting remarkable beneficial effects on ASD symptoms deriving from omega-3 and vitamin D combination therapy. This case report suggests omega-3 and vitamin D co-supplementation as a potential safe-effective therapeutic strategy to treat core symptoms of ASD. However, larger studies are needed to evaluate the real efficacy of such therapeutic approach in a broader sample of ASD patients.
... Several studies have been reported based on the role of the supplementation of minerals and multi-vitamins in improving the symptoms of ASD [95][96][97]. However, additional studies are required [98] to develop minerals and vitamins-based supplementation for the betterment of the symptoms of ASD. ...
Article
Full-text available
Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder characterized by the impairment of the cognitive function of a child. Studies suggested that the intestinal microbiota has a critical role in the function and regulation of the central nervous system, neuroimmune system and neuroendocrine system. Any adverse changes in the gut-brain axis may cause serious disease. Food preferences and dietary patterns are considered as key in influencing the factors of ASD development. Several recent reviews narrated the importance of dietary composition on controlling or reducing the ASD symptoms. It has been known that the consumption of probiotics confers several health benefits by positive amendment of gut microbiota. The influence of probiotic intervention in children with ASD has also been reported and it has been considered as an alternative and complementary therapeutic supplement for ASD. The present manuscript discusses the role of microbiota and diet in the development of ASD. It also summarizes the recent updates on the influence of dietary supplements and the beneficial effect of probiotics on ASD symptoms. An in-depth literature survey suggested that the maternal diet and lifestyle are greatly associated with the development of ASD and other neurodevelopmental disorders. Mounting evidences have confirmed the alteration in the gut microbial composition in children suffering from ASD. However, the unique profile of microbiome has not yet been fully characterized due to the heterogeneity of patients. The supplementation of probiotics amended the symptoms associated with ASD but the results are inconclusive. The current study recommends further detailed research considering the role of microbiome, diet and probiotics in the development and control of ASD.
... Only few studies have evaluated the role of VD supplementation for ASD treatment. Moreover, two of those that have reported positive results (83,84) have been largely debated for the methods used to collect data and to evaluate results (85,86). Furthermore, the most recent research has been retracted because a re-analysis of the data collected with the study discovered previously unidentified problems with missing data and recording irregularities that led the Editors to have no longer confidence in the findings reported (87). ...
Article
Full-text available
Autism spectrum disorder is a neurodevelopmental disorder characterized by reduced social interactions, impaired communications, and stereotypic and repetitive behavior with different degrees of severity. The etiology of autism spectrum disorder is unknown, although the interaction of genetic and environmental factors is believed to play a fundamental role in the process. The main aim of this narrative review is to discuss the current knowledge about the interrelationships between vitamin D deficiency during pregnancy and autism spectrum disorder development. Literature analysis showed that vitamin D supplementation during pregnancy plays a role in conditioning the development and function of the nervous system. Studies carried out in vitro and in experimental animals have shown that vitamin D deficiency can be associated with structural and functional abnormalities of the nervous system that can be observed in autism spectrum disorder patients. Moreover, it has been reported that vitamin D deficiency during pregnancy could be a risk factor for autism spectrum disorder development in the offspring, that children with autism spectrum disorder have significantly lower serum levels of vitamin D than normal children and that supplementation of vitamin D in autism spectrum disorder children is associated with a reduction in psychiatric manifestations. However, the data currently available do not adequately support the hypothesis that vitamin D may be a factor which contribute to the etiology of autism spectrum disorder. The effects of vitamin D supplementation during pregnancy should be better studied to establish whether and when fetal vulnerability is highest and if vitamin D supplementation is able to reduce the risk of structural and functional alterations of the nervous system and autism spectrum disorder development. The role of vitamin D after birth must be better defined to evaluate if vitamin D administration is potentially effective in reducing autism spectrum disorder manifestations.
... Several studies have been reported based on the role of the supplementation of minerals and multi-vitamins in improving the symptoms of ASD [95][96][97]. However, additional studies are required [98] to develop minerals and vitamins-based supplementation for the betterment of the symptoms of ASD. ...
... Some researchers were of the opinion that oral vitamin D supplementation can improve signs and symptoms of ASD [20] . A study done on 100 autistic children showed dramatic improvements in 25% of children who were treated with high doses of vitamin D [21] . ...
Article
Full-text available
Objectives: To study the role of vitamin D deficient diet in development of autism spectrum disorders in Saudi children aged 3-10 years in Northern region (Arar) and Eastern region (Dammam) in the Kingdom of Saudi Arabia Design: Case-control study Setting: Al Amal Mental health complex, Arar; Shumua Al Amal Centre for Special Education and Rehabilitation, Shamah Autism Centre and Prince Sultan Rehabilitation Complex, Dammam, Saudi Arabia Subjects: Data on 100 Saudi autistic children aged 3-10 years and 100 normal children were collected via a questionnaire. The questionnaire inquired about sociodemographic characteristics, family history, ante-natal history and developmental history of the children. Intervention: Non-interventional Main outcome measure: To find out the association between vitamin D rich diet and development of autism in children Results: There was a significant association between vitamin D deficient diet and autism. Increased maternal age was observed in autistic children when compared to normal children. Conclusion: Children were found to have a deficiency in consumption of food rich in vitamin D. The vitamin D deficient diet of the child along with increased maternal age during pregnancy may contribute to development and severity of autism.
... Vitamin D exerts an immunomodulatory effect through helper T-cells and CD4 + CD25 + regulatory T-cells, and regulatory T-cells prevent autoimmunity by inhibiting Th17 cells (Chambers and Hawrylowicz, 2011). Some scholars have found that vitamin D supplementation can increase the proportion of regulatory T-cells in the body, upregulate the production of dendritic cells, and upregulate interleukin (IL)-10, thereby reducing the intensity of autoimmune attacks, inhibiting damage to tissues by immune cells, and reducing the severity of autoimmune diseases (Saad et al., 2018). Mostafa et al. found that 70% of children with ASD had higher anti-myelin-associated glycoprotein (anti-MAG) levels, and research suggests that serum 25-(OH)D) levels are significantly negatively correlated with anti-MAG levels (Mostafa and Al-Ayadhi, 2012). ...
Article
Full-text available
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can lead to severe social behavioral difficulties, which mainly manifests as social communication and interaction disorders; narrow interests; and repetitive, stereotyped behaviors. In recent years, the prevalence of ASD has increased annually, and it has evolved from a rare disease to one with a high incidence among childhood developmental disorders. The pathogenesis of ASD is considered to be the interaction of genetic and environmental factors. There is increasing evidence that vitamin D deficiency in pregnancy and early childhood can lead to the occurrence of ASD. Studies have demonstrated that vitamin D intervention can significantly improve the symptoms of ASD, but the underlying mechanism is still unclear. Therefore, exploring the neuroprotective mechanism of vitamin D against ASD is a huge challenge currently being worked on by current basic and clinical researchers, a task which is of great significance for the clinical promotion and optimization of vitamin D in the treatment of ASD. To further clarify the relationship between vitamin D and ASD, this review summarizes the correlation between vitamin D level and ASD, the effects of vitamin D supplementation on ASD, the possible mechanism of vitamin D involved in ASD, and insights from ASD animal models.
... Furthermore, there are negative correlations between the vitamin D levels and core symptoms of ASD (12). Moreover, vitamin D supplementation might improve the core symptoms of ASD (5,11,13). Skin under sun irradiation is a major source of vitamin D in vivo. Other factors (14) also affect the vitamin D concentrations, including genetic polymorphisms, age, geographical location and latitude, lifestyle (exposure behavior and culture), UVB dose, clothing and body surface area (BSA) exposure. ...
Article
Full-text available
Objective: This study aimed to investigate the possible association among vitamin D, screen time and other factors that might affect the concentration of vitamin D in children with autism spectrum disorder (ASD). Methods: In total, 306 children with ASD were recruited, and data, including their age, sex, height, weight, screen time, time of outdoor activity, ASD symptoms [including Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS) and Autism Diagnostic Observation Schedule–Second Edition (ADOS-2)] and vitamin D concentrations, were collected. A multiple linear regression model was used to analyze the factors related to the vitamin D concentration. Results: A multiple linear regression analysis showed that screen time (β = −0.122, P = 0.032), age (β = −0.233, P < 0.001), and blood collection month (reflecting sunshine duration) (β = 0.177, P = 0.004) were statistically significant. The vitamin D concentration in the children with ASD was negatively correlated with screen time and age and positively correlated with sunshine duration. Conclusion: The vitamin D levels in children with ASD are related to electronic screen time, age and sunshine duration. Since age and season are uncontrollable, identifying the length of screen time in children with ASD could provide a basis for the clinical management of their vitamin D nutritional status.
... Limitations of the study include the small number of patients and the lack of placebo. However, this study is certainly worthy of a randomized controlled follow-up study and emphasizes the importance of correcting vitamin D deficiencies in patients with epilepsy (including autistic patients with seizures) [21]. ...
Article
The disorder of the automatic spectrum is a neurodolevating disorder characterized by a decrease in social interactions, communication and stereotypical disorders and repeated behaviors with various degrees of gravity. A number of systematic reviews and meta- analyses have described prenatal and perinatal factors, as well as factors related to maternal nutrition and lifestyle. There is evidence to support the importance of vitamin D in the normal structure and function of the nervous system. The effects of VD administration during pregnancy on the mother and conception before and after birth have been repeatedly investigated. It has been found that preventing VD can reduce the risk of autism.
... hyperactivity). Though positive results of antioxidants [328], minerals, and vitamins [329,330] in autistic patients have been reported, they are not convincing, thus, further studies are needed. ...
Article
Full-text available
Emerging evidence indicates that the gut microbiota play a crucial role in the bidirectional communication between the gut and the brain suggesting that gut microbes may shape neural development, modulate neurotransmission and affect behavior, and thereby contribute to the pathogenesis and/or progression of many neurodevelopmental, neuropsychiatric, and neurological conditions. This review summarizes recent data on the role of microbiota–gut–brain axis in the pathophysiology of neuropsychiatric and neurological disorders including depression, anxiety, schizophrenia, autism spectrum disorders, Parkinson’s disease, migraine, and epilepsy. Also, the involvement of microbiota in gut disorders co-existing with neuropsychiatric conditions is highlighted. We discuss data from both in vivo preclinical experiments and clinical reports including: (1) studies in germ-free animals, (2) studies exploring the gut microbiota composition in animal models of diseases or in humans, (3) studies evaluating the effects of probiotics, prebiotics or antibiotics treatment as well as (4) the effects of fecal microbiota transplantation.
... Supplementation of Vitamin D and omega-3-fatty acids is correlated with improving the irritability symptoms of children with ASD. Vitamin D has also been shown to improve hyperactivity symptoms in children [18,19]. Insufficient Vitamin D is common in autistic children and may also be associated as a risk factor for developing ASD [20]. ...
... As vitamin and mineral deficiencies are common in ASD patients [55,[136][137][138][139], vitamin-mineral supplements are frequently investigated [140,141]. Improvements in several ASD symptoms due to vitamin and mineral supplementations were reported [60,[142][143][144][145]. On the other hand, Stewart et al. [146] suggested that dietary supplementation, including vitamin and mineral supplements, should be done carefully, as they may not provide sufficient amounts of the deficient nutrient or may cause excessive intake. ...
Article
Full-text available
Autism spectrum disorder (ASD) is a neurodevelopmental disorder, where social and communication deficits and repetitive behaviors are present. Plant-derived bioactives have shown promising results in the treatment of autism. In this sense, this review is aimed at providing a careful view on the use of plant-derived bioactive molecules for the treatment of autism. Among the plethora of bioactives, curcumin, luteolin, and resveratrol have revealed excellent neuroprotective effects and can be effectively used in the treatment of neuropsychological disorders. However, the number of clinical trials is limited, and none of them have been approved for the treatment of autism or autism-related disorder. Further clinical studies are needed to effectively assess the real potential of such bioactive molecules.
... During the past decade, the search for causes of autism has been expanded to include the possible influences from maternal infections or other inflammatory processes during pregnancy, inborn disturbances of metabolism, and altered intestinal microbiome during infancy and early childhood. (Finegold et al. 2010;Hallmayer et al. 2011;Gondalia et al. 2012;Boccuto et al. 2013;De Angelis et al. 2013;West et al. 2014;Son et al. 2015;Wang et al. 2016;Saad et al. 2018;Sandin et al. 2017;Bai et al. 2019;Kang et al. 2019). Wolf and Goldberg (1986) reported the long term (mean 17 years, range 8-24 years) outcome of 64 individuals with autism based on DSM-III. ...
Article
Full-text available
The course of 187 individuals ages 3–21 years with Autistic Disorder was traced through a period of 20 years (enrollment: 1995–1998, follow up: 2014–2019). Specific genetic and environmental causes were identified in only a minority. Intellectual disability coexisted in 84%. Few became independent with 99% living at home with relatives, in disability group homes or in residential facilities. Seven individuals (3.7%) attained postsecondary education, two receiving baccalaureate degrees, two receiving associate degrees, and three receiving certificates from college disability programs. It may be anticipated that the long term outcome for individuals currently diagnosed with Autism Spectrum Disorder (ASD) will be substantially better than for individuals with Autistic Disorder in this cohort.
Article
Background Vitamin D is a secosteroid hormone that is important for its role in calcium homeostasis to maintain skeletal health. Linear growth faltering and stunting remain pervasive indicators of poor nutrition status among infants and children under five years of age around the world, and low vitamin D status has been linked to poor growth. However, existing evidence on the effects of vitamin D supplementation on linear growth and other health outcomes among infants and children under five years of age has not been systematically reviewed. Objectives To assess effects of oral vitamin D supplementation on linear growth and other health outcomes among infants and children under five years of age. Search methods In December 2019, we searched CENTRAL, PubMed, Embase, 14 other electronic databases, and two trials registries. We also searched the reference lists of relevant publications for any relevant trials, and we contacted key organisations and authors to obtain information on relevant ongoing and unpublished trials. Selection criteria We included randomised controlled trials (RCTs) and quasi‐RCTs assessing the effects of oral vitamin D supplementation, with or without other micronutrients, compared to no intervention, placebo, a lower dose of vitamin D, or the same micronutrients alone (and not vitamin D) in infants and children under five years of age who lived in any country. Data collection and analysis We used standard Cochrane methodological procedures. Main results Out of 75 studies (187 reports; 12,122 participants) included in the qualitative analysis, 64 studies (169 reports; 10,854 participants) contributed data on our outcomes of interest for meta‐analysis. A majority of included studies were conducted in India, USA, and Canada. Two studies reported for‐profit funding, two were categorised as receiving mixed funding (non‐profit and for‐profit), five reported that they received no funding, 26 did not disclose funding sources, and the remaining studies were funded by non‐profit funding. Certainty of evidence varied between high and very low across outcomes (all measured at endpoint) for each comparison. Vitamin D supplementation versus placebo or no intervention (31 studies) Compared to placebo or no intervention, vitamin D supplementation (at doses 200 to 2000 IU daily; or up to 300,000 IU bolus at enrolment) may make little to no difference in linear growth (measured length/height in cm) among children under five years of age (mean difference (MD) 0.66, 95% confidence interval (CI) ‐0.37 to 1.68; 3 studies, 240 participants; low‐certainty evidence); probably improves length/height‐for‐age z‐score (L/HAZ) (MD 0.11, 95% CI 0.001 to 0.22; 1 study, 1258 participants; moderate‐certainty evidence); and probably makes little to no difference in stunting (risk ratio (RR) 0.90, 95% CI 0.80 to 1.01; 1 study, 1247 participants; moderate‐certainty evidence). In terms of adverse events, vitamin D supplementation results in little to no difference in developing hypercalciuria compared to placebo (RR 2.03, 95% CI 0.28 to 14.67; 2 studies, 68 participants; high‐certainty evidence). It is uncertain whether vitamin D supplementation impacts the development of hypercalcaemia as the certainty of evidence was very low (RR 0.82, 95% CI 0.35 to 1.90; 2 studies, 367 participants). Vitamin D supplementation (higher dose) versus vitamin D (lower dose) (34 studies) Compared to a lower dose of vitamin D (100 to 1000 IU daily; or up to 300,000 IU bolus at enrolment), higher‐dose vitamin D supplementation (200 to 6000 IU daily; or up to 600,000 IU bolus at enrolment) may have little to no effect on linear growth, but we are uncertain about this result (MD 1.00, 95% CI ‐2.22 to 0.21; 5 studies, 283 participants), and it may make little to no difference in L/HAZ (MD 0.40, 95% CI ‐0.06 to 0.86; 2 studies, 105 participants; low‐certainty evidence). No studies evaluated stunting. As regards adverse events, higher‐dose vitamin D supplementation may make little to no difference in developing hypercalciuria (RR 1.16, 95% CI 1.00 to 1.35; 6 studies, 554 participants; low‐certainty evidence) or in hypercalcaemia (RR 1.39, 95% CI 0.89 to 2.18; 5 studies, 986 participants; low‐certainty evidence) compared to lower‐dose vitamin D supplementation. Vitamin D supplementation (higher dose) + micronutrient(s) versus vitamin D (lower dose) + micronutrient(s) (9 studies) Supplementation with a higher dose of vitamin D (400 to 2000 IU daily, or up to 300,000 IU bolus at enrolment) plus micronutrients, compared to a lower dose (200 to 2000 IU daily, or up to 90,000 IU bolus at enrolment) of vitamin D with the same micronutrients, probably makes little to no difference in linear growth (MD 0.60, 95% CI −3.33 to 4.53; 1 study, 25 participants; moderate‐certainty evidence). No studies evaluated L/HAZ or stunting. In terms of adverse events, higher‐dose vitamin D supplementation with micronutrients, compared to lower‐dose vitamin D with the same micronutrients, may make little to no difference in developing hypercalciuria (RR 1.00, 95% CI 0.06 to 15.48; 1 study, 86 participants; low‐certainty evidence) and probably makes little to no difference in developing hypercalcaemia (RR 1.00, 95% CI 0.90, 1.11; 2 studies, 126 participants; moderate‐certainty evidence). Four studies measured hyperphosphataemia and three studies measured kidney stones, but they reported no occurrences and therefore were not included in the comparison for these outcomes. Authors' conclusions Evidence suggests that oral vitamin D supplementation may result in little to no difference in linear growth, stunting, hypercalciuria, or hypercalcaemia, compared to placebo or no intervention, but may result in a slight increase in length/height‐for‐age z‐score (L/HAZ). Additionally, evidence suggests that compared to lower doses of vitamin D, with or without micronutrients, vitamin D supplementation may result in little to no difference in linear growth, L/HAZ, stunting, hypercalciuria, or hypercalcaemia. Small sample sizes, substantial heterogeneity in terms of population and intervention parameters, and high risk of bias across many of the included studies limit our ability to confirm with any certainty the effects of vitamin D on our outcomes. Larger, well‐designed studies of long duration (several months to years) are recommended to confirm whether or not oral vitamin D supplementation may impact linear growth in children under five years of age, among both those who are healthy and those with underlying infectious or non‐communicable health conditions.
Article
Full-text available
Objectives: The aim of this study was to examine the combined effects of perceptual-motor exercises and vitamin D3 supplementation on the reduction of stereotypical behavior in children with autism disorder (ASD). Methods: In this study, 100 eligible children with age ranging from 6 to 9 years were randomly selected and divided into four groups: Group A—perceptual-motor exercises (n = 25); Group B—25-hydroxycholecalciferol (25 (OH) D) (n = 25); Group C—perceptual-motor exercises and 25 (OH) D (n = 25); and Group D—control (n = 25). Results: The stereotypes decreased from elementary level, 17% in Group A, 13% in Group B and 28% in Group C among the participants. There was no change in the stereotypical in the control group during the interventions. Also, the stereotypes in Group C showed the highest decrease, compared to the other three groups. Conclusions: We concluded that combination of perceptual-motor exercises and vitamin D3 supplementation in children with ASD leads to significant reduction in their stereotypic behaviors.
Article
Full-text available
Vitamin or mineral supplementation is considered to be the most commonly used medical treatment for autism spectrum disorder (ASD), in addition to other interventions such as neurological and psychological interventions. There is not much evidence of therapeutic efficacy between vitamin and mineral supplementation and improvements in ASD. However, several researchers have noted that patients with ASD have various metabolic and nutritional abnormalities including issues with sulfation, methylation, glutathione redox imbalances, oxidative stress, and mitochondrial dysfunction. There is some evidence that vitamin and mineral supplementation may support these basic physiologic processes. Recently, the nutritional status of ASD patients has been gaining focus in this particular area. Pointing out the nutritional status as a potential etiological factor for attention/communication disorders, more importance has been given to this particular point. Moreover, autistic specific considerations like the feature and behavior of ASD might be increased or at least fall in the higher risk due to the sub-optimal nutritional status.
Article
Full-text available
Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that may cause lifelong disability. The aetiology of ASD involves gene-environmental interaction. Vitamin D plays an important role in brain development and maturation. Objective: This study was aimed to compare serum vitamin D in children with autism spectrum disorder with that of the healthy control. Methods: This case-control study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. Blood sample from 50 diagnosed children with ASD and 50 apparently healthy children among 3 to 10 years age group, were tested for serum 25(OH) D. To assess the association independent t test and chi square test were done by using SPSS. Results: The mean serum vitamin D levels of both the groups were lower than the normal reference value. Again, the mean serum vitamin D was lower in ASD compared to that of control, but the difference was statistically non-significant. Among ASD children, 38.0% had deficient, 42.0% had insufficient and 20.0% had sufficient serum vitamin D. Among healthy children, 36.0% had deficient, 30.0% had insufficient and 34.0% had sufficient serum vitamin D level. However, vitamin D deficiency and insufficiency was not associated with ASD. Conclusion: It may be concluded that, vitamin D deficiency is prevalent in Bangladesh among both ASD children and apparently healthy control and the mean serum vitamin D was lower in ASD children compared to that of healthy control, but the difference was statistically non-significant. Therefore, for proper growth and development more outdoor activity and adequate dietary intake of vitamin D rich food are recommended to overcome the situation. Bangladesh Med Res Counc Bull 2021; 47(1): 29-33
Article
Full-text available
Autism spectrum disorder (ASD) is characterized by impairments in social interaction, communication skills, and repetitive and restrictive behaviors and interests. Even though there is a biological basis for an effect of specific nutrition factors on ASD symptoms and there is scientific literature available on this relationship, whether nutrition factors could play a role in ASD treatment is unclear. The goal of the current literature review was to summarize the available scientific literature on the relation between nutrition and autism spectrum disorder (ASD) symptoms in childhood, and to formulate practical dietary guidelines. A comprehensive search strategy including terms for ASD, nutrition factors (therapeutic diets, dietary patterns, specific food products, fatty acids and micronutrients) and childhood was developed and executed in six literature databases (Cinahl, Cochrane, Ovid Embase, PsycInfo, PubMed and Web of Science). Data from meta-analyses, systematic reviews and original studies were qualitatively summarized. A total of 5 meta-analyses, 29 systematic reviews and 27 original studies were retrieved that focused on therapeutic diets, specific food products, fatty acids and micronutrients and ASD symptoms during childhood. Results of the available studies were sparse and inconclusive, and hence, no firm conclusions could be drawn. There is currently insufficient evidence for a relation between nutrition and ASD symptoms in childhood, making it impossible to provide practical nutrition guidelines; more methodological sound research is needed.
Article
Full-text available
We evaluated the efficacy of vitamin D (VID), omega-3 long chain polyunsaturated fatty acids (omega-3 LCPUFA, OM), or both (VIDOM) on core symptoms of ASD. New Zealand children with ASD (n = 73; aged 2.5–8.0 years) received daily 2000 IU vitamin D3, 722 mg docosahexaenoic acid, both, or placebo. Outcome measures were Social Responsiveness Scale (SRS) and Sensory Processing Measure (SPM). Of 42 outcome measures comparisons (interventions vs. placebo), two showed greater improvements (P = 0.03, OM and VIDOM for SRS-social awareness) and four showed trends for greater improvements (P < 0.1, VIDOM for SRS-social communicative functioning, OM for SRS-total, VIDOM for SPM-taste/smell and OM for SPM-balance/motion). Omega-3 LCPUFA with and without vitamin D may improve some core symptoms of ASD but no definitive conclusions can be made.
Article
Several lines of evidence from family history studies, immunogenetics, maternal immune activation, neuroinflammation, and systemic inflammation support an immune subtype of autism spectrum disorder (ASD). Current Food and Drug Administration (FDA) approved medications for ASD do not address the underlying pathophysiology of ASD, have not consistently been shown to address the core symptoms of ASD, and are currently only approved for treating irritability in children and adolescents. In this article, we review the immune modulatory effects of the two currently FDA-approved treatments for ASD. We then provide an overview of current data on emerging treatments for ASD from multiple fields of medicine with immune modulatory effects. Although further research is needed to more clearly establish the efficacy and safety of immune modulatory treatments, early data on repurposing medications used to treat systemic inflammation for ASD demonstrate potential benefit and further research is warranted.
Article
Full-text available
This study aims to describe the implementation and barriers of Indonesian language learning for autistic children at the SLB Mitra Ananda Colomadu. This research is a qualitative descriptive study where the subjects were two class teachers and four grade VII autistic students at SLB Mitra Ananda. Data is collected through observation, interviews, and documentation. The results showed that the implementation of Indonesian language learning at the Ananda Colomadu Partner Autism SLB used the ABA and Individual Learning Program (PPI) methods tailored to the students' abilities. The 2013 curriculum is difficult to implement because the limited Indonesian language learning materials did not meet the child's conditions. Various efforts have been made by the teacher to overcome these obstacles: using PPI, creating independent learning media, and learning the latest methods that are applicable to learn Indonesian for autistic children.[Penelitian ini bertujuan untuk mendeskripsikan pelaksanaan dan hambatan pembelajaran Bahasa Indonesia untuk anak autis di SLB Autis Mitra Ananda Colomadu. Penelitian ini merupakan penelitian deskriptif kualitatif. Subjek penelitiannya adalah dua guru kelas dan empat siswa autis kelas VII di SLB Autis Mitra Ananda. Data dikumpulkan melalui observasi, wawancara dan dokumentasi. Hasil penelitian menunjukkan bahwa pelaksanaan pembelajaran Bahasa Indonesia di SLB Autis Mitra Ananda Colomadu menggunakan metode ABA dan Program Pembelajaran Individual (PPI) yang disesuaikan dengan kemampuan siswa. Kurikulum 2013 tidak dapat diterapkan sepenuhnya karena materi pelajaran Bahasa Indonesia yang tidak sesuai dengan kondisi anak dan media pembelajaran yang terbatas. Berbagai upaya dilakukan guru untuk mengatasi hambatan terebut: misalnya menggunakan PPI, membuat media pembelajaran mandiri dan mempelajari berbagai metode terbaru yang dapat diterapkan dalam pembelajaran Bahasa Indonesia untuk anak autis.]
Article
Introduction: Autism is a neurodevelopmental disorder that negatively affects a child's interaction and communication with the environment. The signals between intestine, brain, and microbiota change in autism. Altering the composition of microbiota may contribute to the development of clinical symptoms. Diet is one of the most important factors influencing intestinal microbiota. Aim: This study aimed to investigate the role of intestinal microbiota in gastrointestinal (GI) and behavioral problems seen in children with autism and discuss the potential effect of diet on intestinal microbiota in reducing these problems. Methods: The database Web of Science was searched for relevant studies. The combinations of the following terms were used for the search: ‘autism' or ‘autistic' and ‘microbiome' or ‘microbiota' or ‘gut bacteria' or ‘gut microbiota' or ‘gut microbiome.' The analysis included human studies evaluating the relationship between GI problems and/or behavioral problems and intestinal microbiota in autism in the English language with no time limitation. Results: The initial search resulted in 691 studies, with 14 studies fully meeting the inclusion criteria. In these studies, high growth rates of Clostridium histolyticum, C. perfringens, and Sutterella; high ratio of Escherichia/Shigella; and low ratio of Bacteroidetes/Firmicutes were generally related to GI problems, while relative abundance of Desulfovibrio, Clostridium spp., and Bacteroides vulgatus were associated with behavior disorders. Conclusions: Published studies on the relationship of gastrointestinal and behavioral problems with gut microbiota in autism are very limited and contradictory. The fact that the results of the studies are not consistent with each other may be explained by the differences in the age of participants, geographical region, sample size, presence of GI problems in the selected control group, and feces or biopsy samples taken from different regions of GI system. With the available information, it is not yet possible to develop a gut microbiota-based nutritional intervention to treat GI symptoms for people with autism.
Article
Full-text available
Importance Vitamin D may be important for neurodevelopment. The optimal daily dose of vitamin D for early brain development is not known. Objectives To test whether a higher (1200 IU) vs standard (400 IU) dose of vitamin D3 has beneficial effects on neurodevelopment in the first 2 years of life and whether serum 25-hydroxyvitamin D concentration is associated with neurodevelopment. Design, Setting, and Participants This double-blind, interventional randomized clinical trial involved healthy infants born full-term between January 1, 2013, and June 30, 2014, at a maternity hospital in Helsinki, Finland, at the 60th northern latitude. Two-year follow-up was conducted by May 30, 2016. Data analysis was by the intention-to-treat principle. Data were analyzed from November 1, 2020, to May 31, 2021. Interventions Randomization of 404 infants to receive 400 IU of oral vitamin D3 supplementation daily and 397 infants to receive 1200 IU of oral vitamin D3 supplementation daily from 2 weeks to 24 months of age. Main Outcomes and Measures Primary outcomes were child total developmental milestone scores at 12 and 24 months of age measured using the Ages and Stages Questionnaire (total score is calculated as a mean of the 5 subscale scores: total score range, 0-60, where 0 indicates delay in all developmental domains and 60 indicates that the child can master all age-specific skills) as well as externalizing, internalizing, and dysregulation problems and competencies scores at 24 months measured using the Infant-Toddler Social and Emotional Assessment (range 0-2, where 0 indicates no problems or no competencies and 2 indicates a high level of problems or a high level of competencies; variables were standardized to the mean [SD] of 0 [1]). Secondary outcomes were specific skills, problems, and competencies derived from these questionnaires. Results Of the 987 families recruited, 495 children were randomly assigned to receive 400 IU of vitamin D3, and 492 children were randomly assigned to receive 1200 IU of vitamin D3. A total of 801 families participated in the follow-up at 12 and/or 24 months, with 404 children (207 girls [51.2%]) in the 400-IU group and 397 children (198 girls [49.9%]) in the 1200-IU group. All children were of Northern European ethnicity. No differences were found between the 400-IU group and the 1200-IU group in the mean (SD) adjusted Ages and Stages Questionnaire total score at 12 months (45.0 [7.1] vs 46.2 [7.9]; mean difference [MD], 1.17 [95% CI, –0.06 to 2.38]) or 24 months (50.9 [5.3] vs 51.5 [5.5]; MD, 0.48 [95% CI, –0.40 to 1.36]). No differences were found between the 400-IU group and the 1200-IU group at 24 months in the mean (SD) adjusted Infant-Toddler Social and Emotional Assessment externalizing domain score (–0.07 [1.00] vs 0.07 [0.98]; MD, 0.15 [95% CI, –0.01 to 0.31]), internalizing domain score (0.04 [1.06] vs –0.02 [0.98]; MD, –0.07 [95% CI, –0.24 to 0.1.0]), dysregulation domain score (–0.00 [1.04] vs 0.02 [0.96]; MD, 0.02 [95% CI, –0.14 to 0.18]), or competencies score (–0.02 [1.02] vs 0.01 [1.02]; MD, 0.03 [95% CI, –0.13 to 0.20]). The 1200-IU group did have a higher risk in the adjusted model of scoring 1.5 SDs or more on the externalizing domain score (odds ratio, 2.33 [95% CI, 1.19-4.56]; P = .01). Levels of serum 25-hydroxyvitamin D were not associated with the primary outcomes. Conclusions and Relevance Higher-than-standard vitamin D3 doses provide no systematic benefits for child neurodevelopment up to 2 years of age. However, the potential disadvantageous effects of higher doses could not be fully excluded; even if minimal, the potential nonbeneficial effects of higher-than-standard doses warrant further studies in which both safety and benefits should be evaluated. Trial Registration ClinicalTrials.gov Identifier: NCT01723852
Article
עבודה זו עוסקת בשאלה "כיצד משפיעה התזונה על התפתחות המוח בשלבי החיים השונים, ובאיזה אופן היא משפיעה על ילדים ומתבגרים בעלי ADHD ו-ASD?" מוצג בה הקשר המדעי בין התזונה למוח ולהופעתן של הפרעות נוירולוגיות, כמו גם סקירה של מקום התזונה בשלבים הראשונים של האדם – כעובר וכתינוק. פרק אחד מוקדש לתזונת האם, המהווה את מקור תזונתו של הילד בתקופות אלה ולאחר מכן ישנה סקירה של תקופות הילדות וההתבגרות, תוך חקירת השפעתם של רכיבי מזון שונים על הופעתם של תסמיני ADHD ו-ASD. העבודה חותמת בסממנים המאותתים כי התנהגות הילד עשויה להיות קשורה בתזונה ולאחר סיכום הדברים מציעה מסקנות יישומיות להורים.
Poster
Full-text available
Childhood vitamin D deficiency and autism spectrum disorder.
Article
Full-text available
Objective: The effect of vitamin D supplementation on the risk of Autism Spectrum Disorder (ASD) is conflicting. The aim of this study was to estimate the efficacy of vitamin D supplementation on ASD in children. Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) in which vitamin D supplementation was used as a therapy in children with ASD. The PubMed, PsychINFO, Cochrane CENTRAL library, Web of Science, and Cinahl databases were searched from inception to March 20, 2019, for all publications on vitamin D and ASD with no restrictions. Studies involving individuals aged <18 years diagnosed with ASD and with all functional outcomes assessed by measurement scales for ASD were included. Mean differences were pooled, and a meta-analysis was performed using a random-effects model due to differences between the individual RCTs. Results: There were five RCTs with 349 children with ASD in the review, of which three RCTs were included in the meta-analysis. Vitamin D supplementation indicated a small but significant improvement in hyperactivity scores (pooled MD: −3.20; 95% CI: [−6.06, −0.34]) with low heterogeneity (I² = 10%, p = 0.33), but there were no other statistically significant differences in ASD symptoms between groups as measured by validated scales. Conclusion: Vitamin D supplementation appears to be beneficial for hyperactivity but not for core symptoms or other co-existing behaviors and conditions of ASD. Future RCTs with large sample sizes examining the effect of vitamin D supplementation on ASD among individuals with low serum vitamin D levels at baseline are needed.
Article
Full-text available
Yaygınlığı giderek artan otizm spektrum bozuklukları; sosyal etkileşimde belirgin farklı tutumlar, takıntılı ve tekrarlanan davranışlar, motor becerileri iyi kullanamama gibi birçok semptom ile karakterize nörolojik bir hastalıktır. Otizmde anormal beslenme alışkanlıkları, besin tüketiminde seçicilik ve gastrointestinal sistem problemleri gibi beslenme problemleri de görülmektedir. Ayrıca otizmde mikrobiyota da sağlıklı bireylere göre farklıdır. Bu nedenle görülen semptomları azaltmak için beslenme tedavilerinin uygulanması elzemdir. Vitamin ve mineral takviyeleri, probiyotik takviyesi, ketojenik diyet, glutensiz kazeinsiz diyet en çok tercih edilen ve otizmde görülen semptomları azalttığı gösterilen beslenme tedavilerindendir. Bu derlemede, otizmde görülen beslenme ile ilgili sorunlar ve güncel beslenme tedavilerinin etkisini araştıran yayınlar değerlendirilerek özetlenmiştir.
Article
Mutations in the methyl-CpG binding protein 2 (MECP2) gene cause Rett syndrome (RTT), an X-linked neurodevelopmental disorder predominantly impacting females. MECP2 is an epigenetic transcriptional regulator acting mainly to repress gene expression, though it plays multiple gene regulatory roles and has distinct molecular targets across different cell types and specific developmental stages. In this review, we summarize MECP2 loss-of-function associated transcriptome and proteome disruptions, delving deeper into the latter which have been comparatively severely understudied. These disruptions converge on multiple biochemical and cellular pathways, including those involved in synaptic function and neurodevelopment, NF-κB signaling and inflammation, and the vitamin D pathway. RTT is a complex neurological disorder characterized by myriad physiological disruptions, in both the central nervous system and peripheral systems. Thus, treating RTT will likely require a combinatorial approach, targeting multiple nodes within the interactomes of these cellular pathways. To this end, we discuss the use of dietary supplements and factors, namely, vitamin D and polyunsaturated fatty acids (PUFAs), as possible partial therapeutic agents given their demonstrated benefit in RTT and their ability to restore homeostasis to multiple disrupted cellular pathways simultaneously. Further unravelling the complex molecular alterations induced by MECP2 loss-of-function, and contextualizing them at the level of proteome homeostasis, will identify new therapeutic avenues for this complex disorder.
Chapter
Full-text available
INTRODUCTION Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that involves exhibiting unusual behaviors in the communication and interaction, using nonverbal communication in the field of social interaction, continuing, maintaining, and understanding interaction and it is grouped under a single heading with Asperger syndrome, childhood disintegrative disorder, and common developmental disorders as well as undefined disorders seen at the beginning of the developmental period, which are defined in DSM-5 (APA, 2013). Originally, autism which was introduced to the literature by Kanner (1943), and described as “excessive loneliness in children, having anxiety and tension in interaction with other people, and unnecessarily repeating words” (pp. 248-249).
Article
Full-text available
Vitamin D may play an important role in the etiology of Autism Spectrum Disorders (ASD). Vitamin D is regarded as a neuroactive steroid affecting brain development and function. It plays an essential role in myelination, which is important for connectivity in the brain. Studies have shown that decreased vitamin D levels in patients, decreased maternal vitamin D levels during pregnancy, and decreased exposure to solar UVB might increase the risk for ASD. In addition, autism symptoms and global functioning may improve after vitamin D supplementation. Here, we sought to aggregate information from previous publications on vitamin D levels and ASD, in order to achieve a higher statistical power and thereby to determine the validity of vitamin D deficiency as a risk factor for ASD. For this meta-analysis, 11 studies met the inclusion and exclusion criteria, accounting for a total of 870 ASD patients and 782 healthy controls. Levels of serum 25(OH) D in participants with ASD were significantly lower than controls, suggesting that lower vitamin D level might be a risk factor for ASD.
Article
Full-text available
People with neurodevelopmental disorders and intellectual disabilities have much greater health care needs. Mainly staying indoors, such people generally have low 25-hydroxyvitamin D (25(OH)D) concentrations. The Vitamin D Task Force of the American Academy of Developmental Medicine and Dentistry (AADMD) reviewed the evidence of 25(OH)D concentrations that benefit the health of persons with developmental disabilities. Maintaining recommended optimal serum 25(OH)D concentrations year long will benefit skeletal development in infants, children, and adolescents, and benefit musculoskeletal health and neuromuscular coordination in adult patients, and decrease risk of falls. Maintaining optimal concentrations decreases risks and severities of autoimmune diseases, cardiovascular disease, many types of cancer, dementia, types 1 and 2 diabetes mellitus, and respiratory tract infections. Other benefits include improved dental and oral health and improved physical performance. The Task Force recommends that 25(OH)D concentrations for optimal health to be in the range of 75 to 125 nmol/L, which can be achieved using between 800 and 4000 IU/day vitamin D3 and sensible exposure to solar UVB radiation. The paper also discusses the potential risks of higher 25(OH)D concentrations, the evidence from and limitations of randomized controlled trials, and the recommendations by various groups and agencies.
Article
Full-text available
Background: There is growing evidence for a gut-brain connection associated with autism spectrum disorders (ASD). 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 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.
Article
Full-text available
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by a complex interaction between genetic and environmental risk factors. Among the environmental factors, vitamin D3 (cholecaliferol) seems to play a significant role in the etiology of ASD because this vitamin is important for brain development. Lower concentrations of vitamin D3 may lead to increased brain size, altered brain shape, and enlarged ventricles, which have been observed in patients with ASD. Vitamin D3 is converted into 25-hydroxyvitamin D3 in the liver. Higher serum concentrations of this steroid may reduce the risk of autism. Importantly, children with ASD are at an increased risk of vitamin D deficiency, possibly due to environmental factors. It has also been suggested that vitamin D3 deficiency may cause ASD symptoms. Here, we report on a 32-month-old boy with ASD and vitamin D3 deficiency. His core symptoms of autism improved significantly after vitamin D3 supplementation. This case suggests that vitamin D3 may play an important role in the etiology of ASD, stressing the importance of clinical assessment of vitamin D3 deficiency and the need for vitamin D3 supplementation in case of deficiency. Copyright © 2015 by the American Academy of Pediatrics.
Article
Full-text available
The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC.Molecular Psychiatry advance online publication, 29 July 2014; doi:10.1038/mp.2014.74.
Article
Full-text available
Vitamin D deficiency has been proposed as a possible risk factor for developing autism spectrum disorder (ASD). 25-Hydroxyvitamin D3 (25(OH)D3) levels were examined in a cross-sectional population-based study in the Faroe Islands. The case group consisting of a total population cohort of 40 individuals with ASD (aged 15-24 years) had significantly lower 25(OH)D3 than their 62 typically-developing siblings and their 77 parents, and also significantly lower than 40 healthy age and gender matched comparisons. There was a trend for males having lower 25(OH)D3 than females. Effects of age, month/season of birth, IQ, various subcategories of ASD and Autism Diagnostic Observation Schedule score were also investigated, however, no association was found. The very low 25(OH)D3 in the ASD group suggests some underlying pathogenic mechanism.
Article
Full-text available
A growing body of literature suggests that higher serum 25-hydroxyvitamin D [25(OH)D] concentrations, either in utero or in early life, may reduce the risk of autism. For example, an ecological study in the companion paper inversely correlated solar UV-B doses in the United States with prevalence of autism among those aged 6-17 y. That study proposed that vitamin D deficiency during pregnancy could account for this finding, although the findings are also consistent with childhood vitamin D deficiency contributing to the condition. Also, in a recent study, children with autism had lower serum 25(OH)D concentrations than did control subjects (19 vs. 33 ng/ml), despite parents of each group reporting the same amount of sun exposure. The same study found highly significant inverse correlations between 25(OH)D and autism rating scales and between 25(OH)D and levels of an antineuronal antibody. This finding indicates that higher serum 25(OH)D concentrations may reduce the symptoms of established autism. Because activated vitamin D, a secosteroid, upregulates DNA-repair genes, vitamin D deficiency during development may inhibit the repair of de novo DNA mutations in fetuses and infants and thus contribute to risk of autism. Vitamin D might also reduce the risk or severity of autism through its anti-inflammatory actions, antiautoimmune effects, increasing seizure threshold, increasing T-regulatory cells, protecting the mitochondria, and upregulating glutathione, which scavenges oxidative by-products and chelates (captures and excretes) heavy metals. Vitamin D deficiency during pregnancy and childhood is a widespread and growing epidemic.
Article
Full-text available
Evidence is mounting that vitamin D deficiency is intimately involved in autism. We report on autism prevalence by US state for those aged 6-17 y in 2010 with respect to indices of solar UV-B (UVB) doses. We calculated autism prevalence rates for white, black and Asian Americans by using total prevalence and relative populations of minors for each ethnic group by state. Analyses omit AK and HI (considered extreme cases), WY (no data), along with AZ and ND for black Americans (low numbers) and DC, ME, MT, ND and SD for Asian Americans (low numbers). For white Americans, the regression coefficient for solar UVB doses and autism prevalence ranged from -0.52 in January to -0.57 in October. For black Americans, the regression coefficient for latitude was 0.61, whereas those for solar UVB ranged from -0.55 to -0.61. For Asian Americans, the values for solar UVB ranged from -0.28 to -0.38. The inverse correlation between solar UVB and autism prevalence is similar to that for many types of cancer in the US. The journal literature indicates that adverse effects on fetal brain development during pregnancy due to vitamin D deficiency can explain these findings. However, we cannot rule out a role of vitamin D deficiency in early life. These results add to the evidence that vitamin D deficiency may be an important risk factor for autism and suggest that pregnant women and autistic individuals raise their serum 25-hydroxyvitamin D concentrations above 30 ng/ml.
Article
Full-text available
Understanding the factor structure of autistic symptomatology is critical to the discovery and interpretation of causal mechanisms in autism spectrum disorder. We applied confirmatory factor analysis and assessment of measurement invariance to a large (N = 9635) accumulated collection of reports on quantitative autistic traits using the Social Responsiveness Scale, representing a broad diversity of age, severity, and reporter type. A two-factor structure (corresponding to social communication impairment and restricted, repetitive behavior) as elaborated in the updated Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) criteria for autism spectrum disorder exhibited acceptable model fit in confirmatory factor analysis. Measurement invariance was appreciable across age, sex, and reporter (self vs other), but somewhat less apparent between clinical and nonclinical populations in this sample comprised of both familial and sporadic autism spectrum disorders. The statistical power afforded by this large sample allowed relative differentiation of three factors among items encompassing social communication impairment (emotion recognition, social avoidance, and interpersonal relatedness) and two factors among items encompassing restricted, repetitive behavior (insistence on sameness and repetitive mannerisms). Cross-trait correlations remained extremely high, that is, on the order of 0.66-0.92. These data clarify domains of statistically significant factoral separation that may relate to partially-but not completely-overlapping biological mechanisms, contributing to variation in human social competency. Given such robust intercorrelations among symptom domains, understanding their co-emergence remains a high priority in conceptualizing common neural mechanisms underlying autistic syndromes.
Article
Full-text available
The purpose of this study was to evaluate scores generated from the Autism Treatment Evaluation Checklist (ATEC), a parent-rated measure, and those derived from professionally completed Childhood Autism Rating Scale (CARS) evaluations. A cohort of 56 participants diagnosed with an autism spectrum disorder was used for the study, and each child was evaluated independently by the parent using the ATEC and a health care professional using the CARS. The Spearman's rank correlation statistic ρ was used to evaluate the correlation between ATEC and CARS scores. It was observed that there was a significant correlation between total ATEC and CARS scores (ρ = .71). Specific domains in the ATEC evaluation significantly correlated with CARS scores. Sensitivity, specificity, and receiver operating characteristic confirmed the association between CARS and ATEC domains. The results help to validate the utility of the parentally completed ATEC in comparison with an established, professional-related measure of autism.
Article
Full-text available
A role for vitamin D in the regulation of immune function was first proposed after the identification of Vitamin D receptors in lymphocytes. It has since been recognized that the active form of vitamin D, 1α,25(OH)₂D₃, has direct affects on naïve and activated helper T cells, regulatory T cells, activated B cells and dendritic cells. There is a growing body of literature linking vitamin D (serum 25(OH)D, oral intake and surrogate indicators such as latitude) to various immune-related conditions, including allergy, although the nature of this relationship is still unclear. This review explores the findings of epidemiological, clinical and laboratory research, and the potential role of vitamin D in promoting the inappropriate immune responses which underpin the rise in a broad range of immune diseases.
Article
Full-text available
Recent studies have implicated physiological and metabolic abnormalities in autism spectrum disorders (ASD) and other psychiatric disorders, particularly immune dysregulation or inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures ('four major areas'). The aim of this study was to determine trends in the literature on these topics with respect to ASD. A comprehensive literature search from 1971 to 2010 was performed in these four major areas in ASD with three objectives. First, publications were divided by several criteria, including whether or not they implicated an association between the physiological abnormality and ASD. A large percentage of publications implicated an association between ASD and immune dysregulation/inflammation (416 out of 437 publications, 95%), oxidative stress (all 115), mitochondrial dysfunction (145 of 153, 95%) and toxicant exposures (170 of 190, 89%). Second, the strength of evidence for publications in each area was computed using a validated scale. The strongest evidence was for immune dysregulation/inflammation and oxidative stress, followed by toxicant exposures and mitochondrial dysfunction. In all areas, at least 45% of the publications were rated as providing strong evidence for an association between the physiological abnormalities and ASD. Third, the time trends in the four major areas were compared with trends in neuroimaging, neuropathology, theory of mind and genetics ('four comparison areas'). The number of publications per 5-year block in all eight areas was calculated in order to identify significant changes in trends. Prior to 1986, only 12 publications were identified in the four major areas and 51 in the four comparison areas (42 for genetics). For each 5-year period, the total number of publications in the eight combined areas increased progressively. Most publications (552 of 895, 62%) in the four major areas were published in the last 5 years (2006-2010). Evaluation of trends between the four major areas and the four comparison areas demonstrated that the largest relative growth was in immune dysregulation/inflammation, oxidative stress, toxicant exposures, genetics and neuroimaging. Research on mitochondrial dysfunction started growing in the last 5 years. Theory of mind and neuropathology research has declined in recent years. Although most publications implicated an association between the four major areas and ASD, publication bias may have led to an overestimation of this association. Further research into these physiological areas may provide insight into general or subset-specific processes that could contribute to the development of ASD and other psychiatric disorders.
Article
Full-text available
Autism is a neurodevelopmental disorder characterized by impairments in communication and reciprocal social interaction, coupled with repetitive behavior, which typically manifests by 3 years of age. Multiple genes and early exposure to environmental factors are the etiological determinants of the disorder that contribute to variable expression of autism-related traits. Increasing evidence indicates that altered fatty acid metabolic pathways may affect proper function of the nervous system and contribute to autism spectrum disorders. This review provides an overview of the reported abnormalities associated with the synthesis of membrane fatty acids in individuals with autism as a result of insufficient dietary supplementation or genetic defects. Moreover, we discuss deficits associated with the release of arachidonic acid from the membrane phospholipids and its subsequent metabolism to bioactive prostaglandins via phospholipase A(2)-cyclooxygenase biosynthetic pathway in autism spectrum disorders. The existing evidence for the involvement of lipid neurobiology in the pathology of neurodevelopmental disorders such as autism is compelling and opens up an interesting possibility for further investigation of this metabolic pathway.
Article
Full-text available
This study examines whether maternal vitamin D deficiency is a risk factor for infantile autism disease (IAD). We used epidemiologic data seasonal variation of birth rates and prevalence of IAD for cohorts born before 1985. For seven studies reporting spring-to-summer excess birth rates for IAD, the season progressed from broad near 30 degrees N latitude, spring/summer in midlatitudes, to winter at the highest latitude. Also, using data from 10 studies, we found a strong effective latitudinal (related to wintertime solar ultraviolet B radiation) increase in IAD prevalence. These findings are consistent with maternal vitamin D deficiency's being a risk factor for IAD, possibly by affecting fetal brain development as well as possibly by affecting maternal immune system status during pregnancy. Further investigation of this hypothesis is warranted.
Article
Full-text available
The development of a scale to assess drug and other treatment effects on severely mentally retarded individuals was described. In the first stage of the project, an initial scale encompassing a large number of behavior problems was used to rate 418 residents. The scale was then reduced to an intermediate version, and in the second stage, 509 moderately to profoundly retarded individuals were rated. Separate factor analyses of the data from the two samples resulted in a five-factor scale comprising 58 items. The factors of the Aberrant Behavior Checklist have been labeled as follows: (I) Irritability, Agitation, Crying; (II) Lethargy, Social Withdrawal; (III) Stereotypic Behavior; (IV) Hyperactivity, Noncompliance; and (V) Inappropriate Speech. Average subscale scores were presented for the instrument, and the results were compared with empirically derived rating scales of childhood psychopathology and with factor analytic work in the field of mental retardation.
Article
Full-text available
Accumulating data have provided evidence that 1 alpha,25 dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] is involved in brain function. Thus, the nuclear receptor for 1,25-(OH)(2)D(3) has been localized in neurons and glial cells. Genes encoding the enzymes involved in the metabolism of this hormone are also expressed in brain cells. The reported biological effects of 1,25-(OH)(2)D(3) in the nervous system include the biosynthesis of neurotrophic factors and at least one enzyme involved in neurotransmitter synthesis. 1,25-(OH)(2)D(3) can also inhibit the synthesis of inducible nitric oxide synthase and increase glutathione levels, suggesting a role for the hormone in brain detoxification pathways. Neuroprotective and immunomodulatory effects of this hormone have been described in several experimental models, indicating the potential value of 1,25-(OH)(2)D(3) pharmacological analogs in neurodegenerative and neuroimmune diseases. In addition, 1,25-(OH)(2)D(3) induces glioma cell death, making the hormone of potential interest in the management of brain tumors. These results reveal previously unsuspected roles for 1,25-(OH)(2)D(3) in brain function and suggest possible areas of future research.
Article
Full-text available
Serotonin (5-HT) has long been implicated in social behavior and impulsivity, but the mechanisms through which it modulates self-control remain unclear. We observed the effects of manipulating 5-HT function on behavior in the ultimatum game, where players must decide whether to accept or reject fair or unfair monetary offers from another player. Participants with depleted 5-HT levels rejected a greater proportion of unfair offers, but not fair offers, without showing changes in mood, fairness judgment, basic reward processing, or response inhibition. Our results suggest that 5-HT plays a critical role in regulating emotion during social decision-making.
Article
Objective: High prevalence of vitamin D deficiency was previously reported in children with Autism Spectrum Disorder (ASD), but little is known about the efficacy of vitamin D3 treatment in ASD, although data from pilot studies seem promising. We hypothesized that serum vitamin D levels are reduced in ASD and correlate with the severity of disease. Also, we hypothesized that vitamin D3 treatment may be beneficial for a considerable portion of children with ASD. Methods: In total, 215 children with ASD and 285 healthy control children were recruited in our study. Thirty seven of 215 ASD children received vitamin D3 treatment. The Autism Behaviour Checklist (ABC) and the Childhood Autism Rating Scale (CARS) were used to assess autism symptoms. High-performance liquid chromatography was used to assess the serum 25-hydroxyvitamin D [25(OH) D] level. Evaluations of ABC, CARS, and serum 25(OH) D levels were performed before and after 3 months of treatment. Results: Serum levels of 25(OH) D were significantly lower in ASD children than typically developing children. Levels of serum 25(OH) D were negatively correlated with ABC total scores and language subscale scores. After vitamin D3 supplementation, symptom scores were significantly reduced on the CARS and ABC. In addition, the data also suggest that treatment effects were more pronounced in younger children with ASD. Conclusion: Vitamin D deficiency might contribute to the aetiology of ASD. Supplementation of vitamin D3, which is a safe and cost-effective form of treatment, may significantly improve the outcome of some children with ASD, especially younger children (identifier ChiCTR-CCC-13004498). Clinical trial registration: The trial 'Association of Polymorphisms of Vitamin D Metabolism-Related Genes With Autism and the Treatment of Autism with Vitamin D' has been registered at www.chictr.org/cn/proj/show.aspx? proj=6135 (identifier ChiCTR-CCC-13004498).
Article
The developmental disabilities questions in the 2014 National Health Interview Survey (NHIS) were changed from previous years, including question reordering and a new approach to asking about autism spectrum disorder (ASD). This report examines survey-based estimates of the lifetime prevalence of ASD, intellectual disability (ID), and any other developmental delay (other DD) following the inclusion of a standalone ASD question, the inclusion of specific diagnoses in the ASD question, and the ASD question preceding the other DD question, and compares them with estimates from previous years.
Article
Objectives: Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and nonverbal 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 is limited. Methods: We performed a case-controlled cross sectional analysis conducted on a 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 % of the patients in the present study had vitamin D deficiency, and thirty % 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 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 5,000 IU/day) for three months. Eighty-three subjects completed three 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 ABC 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.
Article
Background There is increasing interest in oxytocin as a therapeutic to treat social deficits in autism spectrum disorders (ASD). The aim of this study was to investigate the efficacy of a course of oxytocin nasal spray to improve social behavior in youth with ASD.Methods In a double-blind, placebo-controlled trial across two Australian university sites between February 2009 and January 2012, 50 male participants aged between 12 and 18 years, with Autistic or Asperger's Disorder, were randomized to receive either oxytocin (n = 26) or placebo (n = 24) nasal sprays (either 18 or 24 International Units), administered twice-daily for 8 weeks. Participants were assessed at baseline, after 4- and 8-weeks of treatment, and at 3-month follow-up. Primary outcomes were change in total scores on the caregiver-completed Social Responsiveness Scale and clinician-ratings on the Clinical Global Impressions-Improvement scale. Secondary assessments included caregiver reports of repetitive and other developmental behaviors and social cognition. Clinical trial registration: Australian New Zealand Clinical Trials Registry www.anzctr.org.au ACTRN12609000513213.ResultsParticipants who received oxytocin showed no benefit following treatment on primary or secondary outcomes. However, caregivers who believed their children received oxytocin reported greater improvements compared to caregivers who believed their child received placebo. Nasal sprays were well tolerated and there was no evidence of increased side effects resulting from oxytocin administration.Conclusions This is the first evaluation of the efficacy for a course of oxytocin treatment for youth with ASD. Although results did not suggest clinical efficacy, further research is needed to explore alternative delivery methods, earlier age of intervention, and the influence of caregiver expectation on treatment response.
Article
Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established. Here, we present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE. The proposed mechanism explains 4 major characteristics associated with autism: the low concentrations of serotonin in the brain and its elevated concentrations in tissues outside the blood-brain barrier; the low concentrations of the vitamin D hormone precursor 25-hydroxyvitamin D [25(OH)D3]; the high male prevalence of autism; and the presence of maternal antibodies against fetal brain tissue. Two peptide hormones, oxytocin and vasopressin, are also associated with autism and genes encoding the oxytocin-neurophysin I preproprotein, the oxytocin receptor, and the arginine vasopressin receptor contain VDREs for activation. Supplementation with vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder.-Patrick, R. P., Ames, B. N. Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.
Article
Unlabelled: Autism spectrum disorder (ASD) is a common and severe neuro-developmental disorder in early childhood which is defined by social and communication deficits and repetitive and stereotypic behaviours. The aetiology of ASD remains poorly understood. Susceptibility to development of ASD has significant environmental components, in addition to the profound genetic heritability. Few genes have been associated to the risk for ASD development. There is substantial evidence implicating chronic neurological inflammation and immune dysregulation leading to upregulation of inflammatory cytokines in the ASD brain, probably due to altered blood-brain barrier function. The immune system is characterized by excessive and skewed cytokine responses, modulated T cell reactivity, decreased regulation and production of immunosuppressive cytokines, modified NK function and increased autoantibody production. Conclusion: The perinatal environment generates vulnerability to chronic neuro-inflammation in the brain associated with profound modulation and dysregulation in the immune system leading to the rapid development of ASD in genetically susceptible children.
Article
We tested whether maternal vitamin D insufficiency during pregnancy is related to the autism phenotype. Serum 25(OH)-vitamin D concentrations of 929 women were measured at 18 weeks' pregnancy. The mothers of the three children with a clinical diagnosis of autism spectrum disorder had 25(OH)-vitamin D concentrations above the population mean. The offspring of 406 women completed the Autism-Spectrum Quotient in early adulthood. Maternal 25(OH)-vitamin D concentrations were unrelated to offspring scores on the majority of scales. However, offspring of mothers with low 25(OH)-vitamin D concentrations (<49 nmol/L) were at increased risk for 'high' scores (≥2SD above mean) on the Attention Switching subscale (odds ratio: 5.46, 95 % confidence interval: 1.29, 23.05). The involvement of maternal vitamin D during pregnancy in autism requires continued investigation.
Article
Vitamin D is a member of the superfamily of nuclear steroid transcription regulators and as such, exerts transcriptional control over a large number of genes. Several other steroids, such as thyroid hormones, vitamin A, androgens and the glucocorticoids, are known as 'neurosteroids' and their role in brain development and function is well defined. It has only been in the last decade or so that vitamin D has been thought to function as a neurosteroid. In this review we have collated a diverse array of data describing the presence of vitamin D metabolites and the receptor in the brain, the evidence that vitamin D may be an important modulator of brain development, and the potential role of vitamin D in neurological and neuropsychiatric disorders.
Article
Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. A potential role for immune dysfunction has been suggested in ASD. To test this hypothesis, we investigated evidence of differential cytokine release in plasma samples obtained from 2 to 5 year-old children with ASD compared with age-matched typically developing (TD) children and children with developmental disabilities other than autism (DD). Participants were recruited as part of the population based case-control CHARGE (Childhood Autism Risks from Genetics and Environment) study and included: 97 participants with a confirmed diagnosis of ASD using standard assessments (DSM IV criteria and ADOS, ADI-R), 87 confirmed TD controls, and 39 confirmed DD controls. Plasma was isolated and cytokine production was assessed by multiplex Luminex™ analysis. Observations indicate significant increases in plasma levels of a number of cytokines, including IL-1β, IL-6, IL-8 and IL-12p40 in the ASD group compared with TD controls (p<0.04). Moreover, when the ASD group was separated based on the onset of symptoms, it was noted that the increased cytokine levels were predominantly in children who had a regressive form of ASD. In addition, increasing cytokine levels were associated with more impaired communication and aberrant behaviors. In conclusion, using larger number of participants than previous studies, we report significantly shifted cytokine profiles in ASD. These findings suggest that ongoing inflammatory responses may be linked to disturbances in behavior and require confirmation in larger replication studies. The characterization of immunological parameters in ASD has important implications for diagnosis, and should be considered when designing therapeutic strategies to treat core symptoms and behavioral impairments of ASD.
Article
To investigate empirically the possibility of an environmental trigger for autism among genetically vulnerable children that is positively associated with precipitation. We used regression analysis to investigate autism prevalence rates and counts first in relation to mean annual county-level precipitation and then to the amount of precipitation a birth cohort was exposed to when younger than 3 years, controlling for time trend, population size, per capita income, and demographic characteristics. In some models, we included county fixed-effects rather than a full set of covariates. Counties in California, Oregon, and Washington. Children born in California, Oregon, and Washington between 1987 and 1999. Main Exposure County-level precipitation. County-level autism prevalence rates and counts. County-level autism prevalence rates and counts among school-aged children were positively associated with a county's mean annual precipitation. Also, the amount of precipitation a birth cohort was exposed to when younger than 3 years was positively associated with subsequent autism prevalence rates and counts in Oregon counties and California counties with a regional developmental services center. These results are consistent with the existence of an environmental trigger for autism among genetically vulnerable children that is positively associated with precipitation. Further studies focused on establishing whether such a trigger exists and identifying the specific trigger are warranted.
  • L R Harms
  • T H Burne
  • D W Eyles
  • Mcgrath
Harms, L.R., Burne, T.H., Eyles, D.W., & McGrath, J.J. (2011).
Autism treatment evaluation checklist
  • B Rimland
  • M Edelson
Rimland, B., & Edelson, M. (1999). Autism treatment evaluation checklist. San Diego: Autism Research I