The Synaptic and Circuit Functions of Vitamin D in Neurodevelopment Disorders

Ye, Xiaoshan; Zhou, Qionglin; Ren, Pengcheng; Xiang, Wei; Xiao, Le

doi:10.2147/ndt.s407731

Cited by 12 publications

(5 citation statements)

References 185 publications

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“…Vitamin D deficiency has been linked to various NDDs and psychiatric disorders, including ADHD, ASD, and schizophrenia [ 65 – 67 ]. Individuals with ADHD and ASD frequently exhibit lower levels of 25-hydroxyvitamin D (25(OH)D) in their serum compared to their healthy counterparts [ 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

Complex interplay of neurodevelopmental disorders (NDDs), fractures, and osteoporosis: a mendelian randomization study

Li,

Wu,

et al. 2024

BMC Psychiatry

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Background Neurodevelopmental disorders (NDDs), such as Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Tourette Syndrome (TS), have been extensively studied for their multifaceted impacts on social and emotional well-being. Recently, there has been growing interest in their potential relationship with fracture risks in adulthood. This study aims to explore the associations between these disorders and fracture rates, in order to facilitate better prevention and treatment. Methods Employing a novel approach, this study utilized Mendelian randomization (MR) analysis to investigate the complex interplay between ADHD, ASD, TS, and fractures. The MR framework, leveraging extensive genomic datasets, facilitated a systematic examination of potential causal relationships and genetic predispositions. Results The findings unveil intriguing bidirectional causal links between ADHD, ASD, and specific types of fractures. Notably, ADHD is identified as a risk factor for fractures, with pronounced associations in various anatomical regions, including the skull, trunk, and lower limbs. Conversely, individuals with specific fractures, notably those affecting the femur and lumbar spine, exhibit an increased genetic predisposition to ADHD and ASD. In this research, no correlation was found between TS and fractures, or osteoporosis.These results provide a genetic perspective on the complex relationships between NDDs and fractures, emphasizing the importance of early diagnosis, intervention, and a holistic approach to healthcare. Conclusion This research sheds new light on the intricate connections between NDDs and fractures, offering valuable insights into potential risk factors and causal links. The bidirectional causal relationships between ADHD, ASD, and specific fractures highlight the need for comprehensive clinical approaches that consider both NDDs and physical well-being.

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Section: Discussionmentioning

confidence: 99%

Complex interplay of neurodevelopmental disorders (NDDs), fractures, and osteoporosis: a mendelian randomization study

Li,

Wu,

et al. 2024

BMC Psychiatry

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“…In addition, there is uncertainty around the definition of vitamin D insufficiency or deficiency, 74 particularly for neurodevelopment, 14 as well as lack of clearly defined underlying mechanisms through which vitamin D influences neurodevelopment. [12][13][14][15][16][17][18][19][20][21][22] Even the most recent Cochrane review of vitamin D in pregnancy identified 30 trials in over 7000 women (without reporting child neurodevelopment) and found the quality of evidence to be moderate to very low. 75 Future studies should focus on sufficiently large (powered) samples of vitamin D-deficient populations to verify that low vitamin D in pregnancy does not pose a threat to child neurodevelopment.…”

Section: Discussionmentioning

confidence: 99%

“…11 Some evidence from observational animal and human studies suggests a role of vitamin D for neurodevelopment and functioning, although findings are inconclusive and specific underlying mechanisms driving the association are not well established. [12][13][14][15][16][17][18][19][20][21][22] A number of cohort and case-control studies have reported associations between low vitamin D in pregnancy and/or childhood and increased risk of behaviour problems such as Autism Spectrum Disorder and Attention Deficit Hyperactivity. [23][24][25][26][27] Two reviews of trials of vitamin D supplementation for children with attention-deficit/hyperactivity disorder also found a small decrease in symptoms, although authors noted the quality of evidence was low.…”

mentioning

confidence: 99%

Association of cord blood vitamin D with child neurodevelopment at 7 years of age

Gould,

Cuthbert,

Yelland

et al. 2024

J Paediatrics Child Health

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AimThe role of fetal vitamin D [25‐hydroxyvitamin D (25(OH)D)], one of the nuclear steroid transcription regulators, and brain development is unclear. We previously found a weak but persistent association between cord blood 25(OH)D and child language abilities at 18 months and 4 years of age, but no association with cognition or behaviour. The aim of this study was to investigate the association between cord blood 25(OH)D and a range of neurodevelopmental outcomes in these same children at 7 years of age.MethodsCord blood samples from 250 Australian mother–child pairs were analysed for 25(OH)D by mass spectroscopy. Children underwent tests of cognition, language, academic abilities and executive functions with a trained assessor at 7 years of age. Caregivers completed questionnaires to rate their child's behaviour and executive functioning in the home environment. Associations between standardised 25(OH)D and outcomes were assessed using regression models, taking into account possible social and demographic confounders.ResultsStandardised 25(OH)D in cord blood was not associated with any test or parent‐rated scores. Nor was there any association with the risk of having a poor test or parent‐rated score. Likewise, cord blood 25(OH)D categorised as <25, 25–50 and >50 nmol/L was not associated with test scores or parent‐rated scores.ConclusionsThere was no evidence that cord blood vitamin D concentration or deficiency was associated with cognition, language, academic abilities, executive functioning or behaviour at 7 years of age.

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“…As mentioned earlier, gut microbiota also plays a role in gut GABA production and maintenance of normal gut GABA levels. Nutritional support of the GABAergic system with GABA or GABA receptor ligands, food, and vitamins has been suggested as treatment options for neurodevelopmental and aging-related disorders associated with GABAergic dysfunction [32][33][34]. Vitamin D deficiency is known to induce an E/I imbalance and supplementation has been reported to recover impairments of the GABAergic system [33,35].…”

Section: Introductionmentioning

confidence: 99%

“…Nutritional support of the GABAergic system with GABA or GABA receptor ligands, food, and vitamins has been suggested as treatment options for neurodevelopmental and aging-related disorders associated with GABAergic dysfunction [32][33][34]. Vitamin D deficiency is known to induce an E/I imbalance and supplementation has been reported to recover impairments of the GABAergic system [33,35]. These findings highlight the importance of diet in maintaining healthy brain function and the opportunity for nutritional support to correct the E/I imbalance.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Oral GABA on the Nervous System: Potential for Therapeutic Intervention

Almutairi,

Sivadas,

Kwakowsky

2024

Nutraceuticals

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Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS), plays a pivotal role in maintaining the delicate balance between inhibitory and excitatory neurotransmission. Dysregulation of the excitatory/inhibitory balance is implicated in various neurological and psychiatric disorders, emphasizing the critical role of GABA in disease-free brain function. The review examines the intricate interplay between the gut–brain axis and CNS function. The potential impact of dietary GABA on the brain, either by traversing the blood–brain barrier (BBB) or indirectly through the gut–brain axis, is explored. While traditional beliefs questioned GABA’s ability to cross the BBB, recent research challenges this notion, proposing specific transporter systems facilitating GABA passage. Animal studies provide some evidence that small amounts of GABA can cross the BBB but there is a lack of human data to support the role of transporter-mediated GABA entry into the brain. This review also explores GABA-containing food supplements, investigating their impact on brain activity and functions. The potential benefits of GABA supplementation on pain management and sleep quality are highlighted, supported by alterations in electroencephalography (EEG) brain responses following oral GABA intake. The comprehensive overview encompasses GABA’s sources in the diet, including brown rice, soy, adzuki beans, and fermented foods. GABA’s presence in various foods and supplements, its association with gut microbiota, and its potential as a therapeutic strategy for neurological disorders are thoroughly examined. The articles were retrieved through a systematic review of the databases: OVID, SCOPUS, and PubMed (keywords “GABA”, “oral GABA“, “sleep”, “cognition”, “neurodegenerative”, “blood-brain barrier”, “gut microbiota”, “supplements” and “therapeutic”, and by searching reference sections from identified studies and review articles). This review presents the relevant literature available on the topic and discusses the mechanisms, effects, and hypotheses that suggest oral GABA benefits range from neuroprotection to blood pressure control. The literature suggests that oral intake of GABA affects the brain illustrated by changes in EEG scans and cognitive performance, with evidence showing that GABA can have beneficial effects for multiple age groups and conditions. The potential clinical and research implications of utilizing GABA supplementation are vast, spanning a spectrum of diseases ranging from neurodegeneration to blood pressure regulation. Importantly, recommendations for the use of oral GABA should consider the dosage, formulation, and duration of treatment as well as potential side effects. Effects of GABA need to be more thoroughly investigated in robust clinical trials to validate efficacy to progress the development of alternative treatments for a variety of disorders.

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The Synaptic and Circuit Functions of Vitamin D in Neurodevelopment Disorders

Cited by 12 publications

References 185 publications

Complex interplay of neurodevelopmental disorders (NDDs), fractures, and osteoporosis: a mendelian randomization study

Complex interplay of neurodevelopmental disorders (NDDs), fractures, and osteoporosis: a mendelian randomization study

Association of cord blood vitamin D with child neurodevelopment at 7 years of age

The Effect of Oral GABA on the Nervous System: Potential for Therapeutic Intervention

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