Vitamin-D Deficiency As a Potential Environmental Risk Factor in Multiple Sclerosis, Schizophrenia, and Autism

Kočovská, Eva; Gaughran, Fiona; Krivoy, Amir; Meier, Ute‐Christiane

doi:10.3389/fpsyt.2017.00047

Cited by 73 publications

(67 citation statements)

References 125 publications

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“…These findings are supported by previous studies. First, schizophrenia and ASD share some environmental risk factors, such as paternal age, gestational weight gain, and vitamin D deficiency [Bilder et al, ; Kocovska et al, ; Mackay, Dalman, Karlsson, & Gardner, ; McGrath, Burne, Feron, Mackay‐Sim, & Eyles, ; McGrath et al, ; Wu et al, ]. Second, neuroimaging evidence has shown similar apparent between schizophrenia and ASD [Cauda et al, ; Cheung et al, ].…”

Section: Discussionmentioning

confidence: 99%

“…Schizophrenia and ASD are reported to share some similar apparent [Cauda et al, ; Kocovska, Gaughran, Krivoy, & Meier, ; Lionel et al, ]. There is genetic, environmental, imaging, neurochemical, and inflammation evidence for a connection between schizophrenia and ASD [Cauda et al, ; Fiksinski et al, ; Kocovska et al, ; Pavăl, ; Prata, Santos, Almeida, Coelho, & Barbosa, ]. Recently, some scientists have focused on the association between schizophrenia and ASD [Abdallah et al, ; Bakken et al, ; Bradley, Summers, Wood, & Bryson, ; Fiksinski et al, ].…”

Section: Introductionmentioning

confidence: 99%

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Association between schizophrenia and autism spectrum disorder: A systematic review and meta‐analysis

2018

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Schizophrenia and autism spectrum disorder (ASD) are significant public health problems. Scientists have recently explored the association between schizophrenia and ASD, but the findings are inconsistent. Thus, we conducted a systematic review and meta-analysis of epidemiological studies to examine the association between schizophrenia and ASD. PubMed, Embase, and the Cochrane Library were used for literature searches to identify eligible studies published in English before October 2, 2017. Relevant studies estimating the association between schizophrenia and ASD were included. The meta-analysis of the prevalence of schizophrenia in individuals with ASD encompassed 1,950,113 participants and 14,945 individuals with ASD. A random-effects model was chosen to synthesize the effect sizes of individual studies. The prevalence of schizophrenia was significantly higher in individuals with ASD than in controls (odds ratio = 3.55, 95% confidence interval: 2.08-6.05, P < .001). Both sensitivity analysis and publication bias testing revealed that the findings were robust. The systematic review of the prevalence of ASD in individuals with schizophrenia encompassed 930 participants. The prevalence of ASD in individuals with schizophrenia ranged from 3.4 to 52%. The systematic review and meta-analysis showed a significant association between schizophrenia and ASD.Lay Summary: This systematic review and meta-analysis explored the association between schizophrenia and ASD. We found that the prevalence of schizophrenia was significantly higher in individuals with ASD than in controls and the prevalence of ASD in individuals with schizophrenia ranged from 3.4 to 52%. A comprehensive estimation of schizophrenia and ASD has important implications for the diagnosis, treatment, prognosis, and development of a fundamental understanding of these disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association between schizophrenia and autism spectrum disorder: A systematic review and meta‐analysis

2018

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“…There is evidence that changes in calcium signaling may be associated with ASD [43][44][45]. Similarly, multiple studies support a link of immune dysfunction and inflammation to ASD [46][47][48], while strong evidence exists for a link with synaptic structures [49][50][51][52]. Upregulation of immune genes and downregulation of synaptic genes was observed in the postmortem brains of idiopathic ASD patients [53,54].…”

Section: Discussionmentioning

confidence: 96%

Machine learning analysis of exome trios to contrast the genomic architecture of autism and schizophrenia

Sardaar

Dionne‐Laporte

et al. 2020

BMC Psychiatry

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Background: Machine learning (ML) algorithms and methods offer great tools to analyze large complex genomic datasets. Our goal was to compare the genomic architecture of schizophrenia (SCZ) and autism spectrum disorder (ASD) using ML. Methods: In this paper, we used regularized gradient boosted machines to analyze whole-exome sequencing (WES) data from individuals SCZ and ASD in order to identify important distinguishing genetic features. We further demonstrated a method of gene clustering to highlight which subsets of genes identified by the ML algorithm are mutated concurrently in affected individuals and are central to each disease (i.e., ASD vs. SCZ "hub" genes).Results: In summary, after correcting for population structure, we found that SCZ and ASD cases could be successfully separated based on genetic information, with 86-88% accuracy on the testing dataset. Through bioinformatic analysis, we explored if combinations of genes concurrently mutated in patients with the same condition ("hub" genes) belong to specific pathways. Several themes were found to be associated with ASD, including calcium ion transmembrane transport, immune system/inflammation, synapse organization, and retinoid metabolic process. Moreover, ion transmembrane transport, neurotransmitter transport, and microtubule/ cytoskeleton processes were highlighted for SCZ. Conclusions: Our manuscript introduces a novel comparative approach for studying the genetic architecture of genetically related diseases with complex inheritance and highlights genetic similarities and differences between ASD and SCZ.

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“…69,70 Deficiency of vitamin D which exerts its effects through VDR (vitamin D receptor) has been observed in schizophrenia patients. 71 Interplay between the vitamin D system and the dopaminergic system, which plays a key role in schizophrenia etiology, has also been noted. 72 VDR is highly expressed in regions of the brain associated with schizophrenia, viz.…”

Section: Discussionmentioning

confidence: 99%

Potentially repurposable drugs for schizophrenia identified from its interactome

Karunakaran

Chaparala

Ganapathiraju

2018

Preprint

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From the schizophrenia drug-target interactome, 1 we studied the drugs that targeted multiple proteins in the interactome, or those that target proteins with many targets, or those that target novel (computationally predicted) interactors of schizophrenia associated proteins. In schizophrenia, gene expression has been described as a measurable aspect of the disease reflecting the action of risk genes. We studied each of the selected drugs using the NextBio software suite, and shortlisted those that had a negative correlation with gene expression of schizophrenia. This analysis resulted in 12 drugs whose differential gene expression (drug versus normal) had an anti-correlation with differential expression for schizophrenia (disorder versus normal). Some of these drugs were already being tested for their clinical activity in schizophrenia and other neuropsychiatric disorders. Several proteins in the protein interactome of the targets of several of these drugs were associated with various neuropsychiatric disorders. The network of genes which were differentially expressed on drug treatment, and had an anti-correlation with gene expression in schizophrenia, were significantly enriched in pathways relevant to schizophrenia etiology and GWAS genes associated with traits or diseases that had pathophysiological overlap with schizophrenia. Drugs that are structurally similar to the shortlisted drugs, or targeted the same genes as these drugs, have also demonstrated clinical activity in schizophrenia and other related disorders. This integrated computational analysis may help translate insights from the schizophrenia drug-protein interactome to clinical research -an important step, especially in the field of psychiatric drug development, facing a high failure rate.

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Vitamin-D Deficiency As a Potential Environmental Risk Factor in Multiple Sclerosis, Schizophrenia, and Autism

Cited by 73 publications

References 125 publications

Association between schizophrenia and autism spectrum disorder: A systematic review and meta‐analysis

Association between schizophrenia and autism spectrum disorder: A systematic review and meta‐analysis

Machine learning analysis of exome trios to contrast the genomic architecture of autism and schizophrenia

Potentially repurposable drugs for schizophrenia identified from its interactome

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