Peripheral Iron Levels in Autism Spectrum Disorders vs. Other Neurodevelopmental Disorders: Preliminary Data

Giacomo, Andrea De; Medicamento, Silvia; Pedaci, Chiara; Giambersio, Donatella; Giannico, Orazio Valerio; Petruzzelli, Maria Giuseppina; Simone, Marta; Corsalini, Massimo; Marzulli, Lucia; Matera, Emilia

doi:10.3390/ijerph19074006

Cited by 12 publications

(7 citation statements)

References 27 publications

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“…In the DEG analysis, erythrocyte differentiation, erythrocyterelated disorders, and heme metabolism were enriched in children with ASD, and our clinical data from routine blood tests validated the significant changes in erythrocyte-related parameters (RBC, HCT, MCH, RDW-CV, and MCHC) in ASD patients. Erythrocyte parameters can reflect iron status (61), and thus the results presented above imply that abnormalities in iron metabolism affect the course of ASD, as reported in previous studies (62,63). ALAS2 (64, 65), SLC4A1 (66), AHSP (67), EPB42 (68), and GMPR (69) were identified as ASD hub genes, and these are associated with erythrocytes, especially with regard to changes in hemoglobin, which are closely related to iron metabolism.…”

Section: Discussionsupporting

confidence: 66%

Novel insights into the immune cell landscape and gene signatures in autism spectrum disorder by bioinformatics and clinical analysis

et al. 2023

Front. Immunol.

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The pathogenesis of autism spectrum disorder (ASD) is not well understood, especially in terms of immunity and inflammation, and there are currently no early diagnostic or treatment methods. In this study, we obtained six existing Gene Expression Omnibus transcriptome datasets from the blood of ASD patients. We performed functional enrichment analysis, PPI analysis, CIBERSORT algorithm, and Spearman correlation analysis, with a focus on expression profiling in hub genes and immune cells. We validated that monocytes and nonclassical monocytes were upregulated in the ASD group using peripheral blood (30 children with ASD and 30 age and sex-matched typically developing children) using flow cytometry. The receiver operating characteristic curves (PSMC4 and ALAS2) and analysis stratified by ASD severity (LIlRB1 and CD69) showed that they had predictive value using the “training” and verification groups. Three immune cell types – monocytes, M2 macrophages, and activated dendritic cells – had different degrees of correlation with 15 identified hub genes. In addition, we analyzed the miRNA-mRNA network and agents-gene interactions using miRNA databases (starBase and miRDB) and the DSigDB database. Two miRNAs (miR-342-3p and miR-1321) and 23 agents were linked with ASD. These findings suggest that dysregulation of the immune system may contribute to ASD development, especially dysregulation of monocytes and monocyte-derived cells. ASD-related hub genes may serve as potential predictors for ASD, and the potential ASD-related miRNAs and agents identified here may open up new strategies for the prevention and treatment of ASD.

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Section: Discussionsupporting

confidence: 66%

Novel insights into the immune cell landscape and gene signatures in autism spectrum disorder by bioinformatics and clinical analysis

et al. 2023

Front. Immunol.

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“…A former clinical study indicated that 93 children with ASD had lower ferritin and higher mean corpuscular volume (MCV value) compared to 74 children with no neurodevelopmental disorders other than ASD [ 66 ]. The ASD gruop showed significantly higher MCV values due to a deficiency of vitamin B12 and folic acid.…”

Section: Iron Signaling and Asdmentioning

confidence: 99%

“…The ASD gruop showed significantly higher MCV values due to a deficiency of vitamin B12 and folic acid. Folic acid is essential for the correct synthesis of red blood cells [ 66 ]. Vitamin B12 is an essential component for DNA synthesis, and vitamin B12 deficiency causes neurologic and psychiatric symptoms, such as motor dysfunction, sensory and memory deficits, and cognitive impairment.…”

Section: Iron Signaling and Asdmentioning

confidence: 99%

“…Vitamin B12 is an essential component for DNA synthesis, and vitamin B12 deficiency causes neurologic and psychiatric symptoms, such as motor dysfunction, sensory and memory deficits, and cognitive impairment. Collectively, ASD patients were more likely to have hypoferritinemia based on deficient vitamin B12 as well as folic acid, inducing ASD-related neurological symptoms [ 66 ]. Additionally, a deficiency of iron and vitamin D, as well as iron-deficient anemia, were more common in ASD subjects as compared to control children [ 67 ].…”

Section: Iron Signaling and Asdmentioning

confidence: 99%

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Lipid-Based Molecules on Signaling Pathways in Autism Spectrum Disorder

Yui

Imataka

Yoshihara

2022

IJMS

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The signaling pathways associated with lipid metabolism contribute to the pathophysiology of autism spectrum disorder (ASD) and provide insights for devising new therapeutic strategies. Prostaglandin E2 is a membrane-derived lipid molecule that contributes to developing ASD associated with canonical Wnt signaling. Cyclooxygenase-2 plays a key role in neuroinflammation and is implicated in the pathogenesis of neurodevelopmental diseases, such as ASD. The endocannabinoid system maintains a balance between inflammatory and redox status and synaptic plasticity and is a potential target for ASD pathophysiology. Redox signaling refers to specific and usually reversible oxidation–reduction reactions, some of which are also involved in pathways accounting for the abnormal behavior observed in ASD. Redox signaling and redox status-sensitive transcription factors contribute to the pathophysiology of ASD. Cannabinoids regulate the redox balance by altering the levels and activity of antioxidant molecules via ROS-producing NADPH oxidase (NOX) and ROS-scavenging superoxide dismutase enzymes. These signaling cascades integrate a broad range of neurodevelopmental processes that may be involved in the pathophysiology of ASD. Based on these pathways, we highlight putative targets that may be used for devising novel therapeutic interventions for ASD.

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“…According to existing research, brain iron is closely related to neurological diseases ( 49 , 51 , 52 ). In ADHD and RLS, the same is true.…”

Section: Discussionmentioning

confidence: 99%

Association among attention-deficit hyperactivity disorder, restless legs syndrome, and peripheral iron status: a two-sample Mendelian randomization study

Xiao,

Shi,

Lan

et al. 2024

Front. Psychiatry

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BackgroundEpidemiological evidence indicates a high correlation and comorbidity between Attention Deficit Hyperactivity Disorder (ADHD) and Restless Legs Syndrome (RLS).ObjectiveWe aimed to investigate the causal relationship and shared genetic architecture between ADHD and RLS, as well as explore potential causal associations between both disorders and peripheral iron status.MethodsWe performed two-sample Mendelian randomization (MR) analyses using summary statistics from genome-wide meta-analyses of ADHD, RLS, and peripheral iron status (serum iron, ferritin, transferrin saturation, and total iron binding capacity). Additionally, we employed linkage disequilibrium score regression (LDSC) to assess genetic correlations between ADHD and RLS using genetic data.ResultsOur MR results supports a causal effect from ADHD (as exposure) to RLS (as outcome) (inverse variance weighted OR = 1.20, 95% CI: 1.08-1.34, p = 0.001). Conversely, we found no a causal association from RLS to ADHD (inverse variance weighted OR = 1.04, 95% CI: 0.99-1.09, p = 0.11). LDSC analysis did not detect a significant genetic correlation between RLS and ADHD (Rg = 0.3, SE = 0.16, p = 0.068). Furthermore, no evidence supported a causal relationship between peripheral iron deficiency and the RLS or ADHD onset. However, RLS may have been associated with a genetic predisposition to reduced serum ferritin levels (OR = 1.20, 95% CI: 1.00-1.04, p = 0.047).ConclusionThis study suggests that ADHD is an independent risk factor for RLS, while RLS may confer a genetic predisposition to reduced serum ferritin levels.LimitationsThe GWAS summary data utilized originated from populations of European ancestry, limiting the generalizability of conclusions to other populations.Clinical implicationsThe potential co-occurrence of RLS in individuals with ADHD should be considered during diagnosis and treatment. Moreover, iron supplementation may be beneficial for alleviating RLS symptoms.

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Peripheral Iron Levels in Autism Spectrum Disorders vs. Other Neurodevelopmental Disorders: Preliminary Data

Cited by 12 publications

References 27 publications

Novel insights into the immune cell landscape and gene signatures in autism spectrum disorder by bioinformatics and clinical analysis

Novel insights into the immune cell landscape and gene signatures in autism spectrum disorder by bioinformatics and clinical analysis

Lipid-Based Molecules on Signaling Pathways in Autism Spectrum Disorder

Association among attention-deficit hyperactivity disorder, restless legs syndrome, and peripheral iron status: a two-sample Mendelian randomization study

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