Share：
Share this content in WeChat
X
[Chinese] [PDF] 36 1
• Clinical Article •
Changes in gray matter volume in children with ADHD comorbid ASD and its relationship with serum vitamin D levels: A voxel-based morphometry study
WEI Bingyao  WANG Yubing  FENG Zhanqi  LI Mengyuan  ZHAO Zhengyang  LI Xinqi  WANG Changhao  CAO Yimeng  ZHAO Baohan  ZHAO Xin 

Cite this article as: WEI B Y, WANG Y B, FENG Z Q, et al. Changes in gray matter volume in children with ADHD comorbid ASD and its relationship with serum vitamin D levels: A voxel-based morphometry study[J]. Chin J Magn Reson Imaging, 2026, 17(10): 1-10, 20. DOI:10.12015/issn.1674-8034.2026.10.001.


[Abstract] Objective Using voxel-based morphometry (VBM), this study investigates the characteristics of whole-brain grey matter volume (GMV) changes in children with attention deficit hyperactivity disorder (ADHD) who also have autism spectrum disorder (ASD), to analyse the correlation between grey matter volume in regions of difference and serum vitamin D levels, and to construct a combined diagnostic model to assess its diagnostic value for ADHD co-occurring with ASD.Materials and Methods The study included 52 children with ADHD and co-occurring ASD (ADHD+ASD group), 59 children with ADHD (ADHD group), 54 children with ASD (ASD group) and 49 typically developing children [healthy control (HC) group]. High-resolution 3D-T1WI structural images were acquired, and VBM analysis was performed using the CAT12 toolkit in SPM12. Differences in whole-brain GMV across the four groups were compared, with age, sex and total intracranial volume (TIV) as covariates. GMV values from the regions of interest were extracted, and a partial correlation analysis was conducted to investigate their relationship with serum vitamin D levels and clinical scale scores. After standardising all continuous independent variables using Z-scores, Firth-penalised logistic regression was employed to identify independent predictors, and receiver operating characteristic (ROC) curves were constructed to assess diagnostic performance.Results Compared with the ADHD group, the ADHD + ASD group showed significantly increased GMV in the right cerebellar CrusⅠ, right fusiform gyrus/right lingual gyrus, right inferior parietal lobule and right precuneus/middle cingulate gyrus (Uncorrected at the voxel level: P < 0.001; cluster-level GRF-FWE correction: P < 0.05); the regions of increased GMV in the ADHD + ASD versus ADHD comparison largely overlapped with those in the ASD versus ADHD comparison, suggesting that the brain structural pattern of the comorbid group more closely resembles ASD. No significant differences in GMV were found between the ADHD + ASD group and the ASD group. Partial correlation analysis revealed that GMV values in the right inferior parietal lobule of the ADHD + ASD group were negatively correlated with serum vitamin D levels (r = -0.648, P_FDR = 0.004); GMV values in multiple regions of difference in the ADHD group were positively correlated with vitamin D levels, whilst GMV values in multiple brain regions of the ASD group were negatively correlated with vitamin D levels. Firth-penalised logistic regression analysis revealed that serum vitamin D levels (OR = 1.523, 95% CI: 1.302 to 1.868, P < 0.001) and right inferior parietal lobule GMV values (OR = 18.532, 95% CI: 6.332 to 77.069, P < 0.001) were independent predictors of ADHD + ASD (OR values represent the change in risk per one standard deviation increase). The area under the ROC curve (AUC) for the combined model was 0.921 (95% CI: 0.870 to 0.971), with a sensitivity of 90.4% and a specificity of 83.1%, significantly superior to those of the individual indicators.Conclusions No significant differences were found in the patterns of grey matter volume enlargement between children with ADHD and ASD compared to those with ASD alone, suggesting that the structural changes in the brains of children with comorbid conditions are more similar to those seen in ASD than in ADHD. The combination of GMV values in the right inferior parietal lobule and serum vitamin D levels has some auxiliary screening value in distinguishing whether children with a confirmed diagnosis of ADHD also have ASD; it may also provide some reference value for research into the brain development and neuropathological mechanisms of children with comorbid conditions, as well as for early clinical identification.
[Keywords] attention deficit hyperactivity disorder；autism spectrum disorder；comorbidity；magnetic resonance imaging；voxel-based morphometry；gray matter volume；vitamin D；children

WEI Bingyao1, 2, 3   WANG Yubing1, 2, 3   FENG Zhanqi1, 2, 3   LI Mengyuan4   ZHAO Zhengyang1, 2, 3   LI Xinqi1, 2, 3   WANG Changhao5   CAO Yimeng1, 2, 3   ZHAO Baohan1, 2, 3   ZHAO Xin1, 2, 3*  

1 Department of Medical Imaging, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

2 Henan International Joint Laboratory of Neuromedical Imaging, Zhengzhou 450052, China

3 Henan Provincial Key Laboratory of Pediatric Neuroimaging Medicine, Zhengzhou 450052, China

4 Department of Reproductive Medicine, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

5 Department of Radiology, the First Bethune Hospital of Jilin University, Changchun 130021, China

Corresponding author: ZHAO X, E-mail: zdsfyzx@zzu.edu.cn

Conflicts of interest   None.

Received  2026-07-28
Accepted  2026-09-15
DOI: 10.12015/issn.1674-8034.2026.10.001
Cite this article as: WEI B Y, WANG Y B, FENG Z Q, et al. Changes in gray matter volume in children with ADHD comorbid ASD and its relationship with serum vitamin D levels: A voxel-based morphometry study[J]. Chin J Magn Reson Imaging, 2026, 17(10): 1-10, 20. DOI:10.12015/issn.1674-8034.2026.10.001.

[1]
FARAONE S, BANASCHEWSKI T, COGHILL D, et al. The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder[J]. Neurosci Biobehav Rev, 2021, 128: 789-818. DOI: 10.1016/j.neubiorev.2021.01.022.
[2]
PRASAD M, KUMMINIMANA R. Attention-deficit/hyperactivity disorder: insights, advances and challenges in research and practice[J]. Postep Psychiatr Neurol, 2025, 34(3): 196-206. DOI: 10.5114/ppn.2025.153717.
[3]
MAENNER M, WARREN Z, WILLIAMS A, et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020[J]. MMWR Surv Summ, 2023, 72(2): 1-14. DOI: 10.15585/mmwr.ss7202a1.
[4]
LORD C, BRUGHA T S, CHARMAN T, et al. Autism spectrum disorder[J/OL]. Nat Rev Dis Primers, 2020, 6(1): 5 [2026-07-28]. https://doi.org/10.1038/s41572-019-0138-4. DOI: 10.1038/s41572-019-0138-4.
[5]
HOURS C, RECASENS C, BALEYTE J. ASD and ADHD Comorbidity: What Are We Talking About?[J/OL]. Front Psychiatry, 2022, 13: 6 [2026-07-28]. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.837424/full. DOI: 10.3389/fpsyt.2022.837424.
[6]
CRAIG F, LAMANNA A, MARGARI F, et al. Overlap Between Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder: Searching for Distinctive/Common Clinical Features[J]. Autism Res, 2015, 8(3): 328-337. DOI: 10.1002/aur.1449.
[7]
ZHANG J W, HU T, ZHAO B B, et al. Changes in cerebral gray matter volume in patients with tremor-dominant Parkinson's disease: A voxel-based morphometry study[J]. Chin J Magn Reson Imaging, 2025, 16(6): 42-47. DOI: 10.12015/issn.1674-8034.2025.06.006.
[8]
LIU H, LI T, QIN R, et al. Altered gray matter networks in the co-occurrence of autism spectrum disorder and attention deficit hyperactivity disorder[J/OL]. Behav Brain Res, 2025, 495: 9 [2026-07-28]. https://www.sciencedirect.com/science/article/abs/pii/S0166432825003742. DOI: 10.1016/j.bbr.2025.115787.
[9]
WANG H, ZHAO X, LIU R, et al. Vitamin D Plays a Crucial Role in Regulating Dopamine Nervous System in Brain[J]. Prog Biochem Biophys, 2024, 51(7): 1530-1539. DOI: 10.16476/j.pibb.2023.0422.
[10]
PERTILE R, BRIGDEN R, RAMAN V, et al. Vitamin D: A potent regulator of dopaminergic neuron differentiation and function[J]. J Neurochem, 2023, 166(5): 779-789. DOI: 10.1111/jnc.15829.
[11]
CUI X Y, PERTILE R, RAMAN V, et al. Vitamin D differentiates dopamine neurons in vitro, increasing neurite architecture, dopamine release and expression of relevant synaptic proteins[J/OL]. J Steroid Biochem Mol Biol, 2025, 247: 6 [2026-07-28]. https://www.sciencedirect.com/science/article/abs/pii/S0960076025000093. DOI: 10.1016/j.jsbmb.2025.106681.
[12]
WANG Z Q, DING R, WANG J. The Association between Vitamin D Status and Autism Spectrum Disorder (ASD): A Systematic Review and Meta-Analysis[J/OL]. Nutrients, 2021, 13(1): 14 [2026-07-28]. https://www.mdpi.com/2072-6643/13/1/86. DOI: 10.3390/nu13010086.
[13]
ISMAIL Y A, EL-BAYAA N M, FOUAD M M, et al. The association between serum vitamin D concentration and Attention Deficit/Hyperactivity Disorder: a systematic review and meta-analysis of observational and interventional studies[J/OL]. Middle East Curr Psychiatry-MECPsych, 2025, 32(1): 14 [2026-07-28]. https://link.springer.com/article/10.1186/s43045-025-00586-y. DOI: 10.1186/s43045-025-00586-y.
[14]
BABAEI P, DAMIRCHI A, HOSEINI Z, et al. Co-treatment of vitamin D supplementation and aerobic training improves memory deficit in ovariectomized rat[J]. Int J Neurosci, 2020, 130(6): 595-600. DOI: 10.1080/00207454.2019.1699082.
[15]
MUNNS C, SHAW N, KIELY M, et al. Global Consensus Recommendations on Prevention and Management of Nutritional Rickets[J]. Horm Res Paediatr, 2016, 85(2): 83-106. DOI: 10.1159/000443136.
[16]
GUELL X, SCHMAHMANN J. Cerebellar Functional Anatomy: a Didactic Summary Based on Human fMRI Evidence[J]. Cerebellum, 2020, 19(1): 1-5. DOI: 10.1007/s12311-019-01083-9.
[17]
KONG Y, ROSER M, BEGUE I, et al. Cerebellum and social abilities: A structural and functional connectivity study in a transdiagnostic sample[J/OL]. Hum Brain Mapp, 2024, 45(10): 13 [2026-07-28]. https://onlinelibrary.wiley.com/doi/10.1002/hbm.26749. DOI: 10.1002/hbm.26749.
[18]
CHEN J R, WEI Z, XU C Y, et al. Social visual preference mediates the effect of cortical thickness on symptom severity in children with autism spectrum disorder[J/OL]. Front Psychiatry, 2023, 14: 11 [2026-07-28]. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1132284/full. DOI: 10.3389/fpsyt.2023.1132284.
[19]
JIANG Y, TAO Q Y, WEI Y, et al. Meta-analysis of aberrant white matter microstructure and gray matter volume in autism spectrum disorder[J/OL]. Psychiatry Res Neuroimaging, 2026, 356: 9 [2026-07-28]. https://www.sciencedirect.com/science/article/abs/pii/S0925492725001659. DOI: 10.1016/j.pscychresns.2025.112110.
[20]
XU M X, JU X D. Abnormal Brain Structure Is Associated with Social and Communication Deficits in Children with Autism Spectrum Disorder: A Voxel-Based Morphometry Analysis[J/OL]. Brain Sci, 2023, 13(5): 12 [2026-07-28]. https://www.mdpi.com/2076-3425/13/5/779. DOI: 10.3390/brainsci13050779.
[21]
IMAMIZU H, KONDO T. Key role of the default mode network in transfer of motor learning from previous experience[J]. PLoS Biol, 2025, 23(8): 3 [2026-07-28]. https://doi.org/10.1371/journal.pbio.3003310. DOI: 10.1371/journal.pbio.3003310.
[22]
LI C, ZHANG R, ZHOU Y, et al. Gray matter asymmetry alterations in children and adolescents with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder[J]. Eur Child Adolesc Psych, 2024, 33(8): 2593-2604. DOI: 10.1007/s00787-023-02323-4.
[23]
LI Y, ZHOU C, JI F. Research Progress on Abnormal Gray Matter Structures in Children and Adolescents with Attention Deficit Hyperactivity Disorder[J]. Psychology Monthly, 2024, 19(4): 226-228, 231. DOI: 10.19738/j.cnki.psy.2024.04.068.
[24]
CHEN C, SUN S L, CHEN R Y, et al. A multimodal neuroimaging meta-analysis of functional and structural brain abnormalities in attention-deficit/hyperactivity disorder[J/OL]. Prog Neuro-Psychopharmacol Biol Psychiatry, 2025, 136: 9 [2026-07-28]. https://www.sciencedirect.com/science/article/abs/pii/S0278584624002677. DOI: 10.1016/j.pnpbp.2024.111199.
[25]
YU M M, GAO X Y, NIU X Y, et al. Meta-analysis of structural and functional alterations of brain in patients with attention-deficit/hyperactivity disorder[J/OL]. Front Psychiatry, 2023, 13: 22 [2026-07-28]. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.1070142/full. DOI: 10.3389/fpsyt.2022.1070142.
[26]
ANWAR M J, ALENEZI S K, ALHOWAIL A H. Molecular insights into the pathogenic impact of vitamin D deficiency in neurological disorders[J/OL]. Biomed Pharmacother, 2023, 162 [2026-07-28]. https://www.sciencedirect.com/science/article/pii/S0753332223005061. DOI: 10.1016/j.biopha.2023.114718.
[27]
SOMELAR-DURACZ K, JURGENSON M, VIIL J, et al. Unpredictable chronic mild stress does not exacerbate memory impairment or altered neuronal and glial plasticity in the hippocampus of middle-aged vitamin D deficient mice[J/OL]. Eur J Neurosci, 2024, 59(7): 1696-1722. DOI: 10.1111/ejn.16256.
[28]
ALI A, SHAH S A, ZAMAN N, et al. Vitamin D exerts neuroprotection via SIRT1/nrf-2/ NF-kB signaling pathways against D-galactose-induced memory impairment in adult mice[J/OL]. Neurochem Int, 2021, 142 [2026-07-28]. https://www.sciencedirect.com/science/article/abs/pii/S0197018620302849. DOI: 10.1016/j.neuint.2020.104893.
[29]
PAOLICELLI R C, BOLASCO G, PAGANI F, et al. Synaptic Pruning by Microglia Is Necessary for Normal Brain Development[J]. Science, 2011, 333(6048): 1456-1458. DOI: 10.1126/science.1202529.
[30]
MENG J, ZHANG Y. Progress in microglia-mediated neuroinflammation and synaptic pruning in autism spectrum disorder[J]. Journal of Xiamen University (Natural Science), 2024, 63(5): 841-849. DOI: 10.6043/j.issn.0438-0479.202403035.
[31]
CUI X, PERTILE R, LIU P, et al. Vitamin d regulates tyrosine hydroxylase expression: n-cadherin may be a possible mediator[J]. Neuroscience, 2015, 304: 90-100. DOI: 10.1016/j.neuroscience.2015.07.048.
[32]
FARAONE S, WARD C, BOUCHER M, et al. Role of serotonin in the neurobiology of attention-deficit/hyperactivity disorder: a systematic literature review[J]. Expert Opin Ther Targets, 2025, 29(9): 637-654. DOI: 10.1080/14728222.2025.2552324.
[33]
OYA M, MATSUOKA K, KUBOTA M, et al. Effects of Extended-Release Methylphenidate on Dopamine and Norepinephrine Transporters in Adults With Attention-Deficit/Hyperactivity Disorder: A Longitudinal Dual-Tracer PET Study[J]. Psychiatry Clin Neurosci, 2026, 80(1): 48-54. DOI: 10.1111/pcn.13911.
[34]
MACDONALD H, KLEPPE R, SZIGETVARI P, et al. The dopamine hypothesis for ADHD: An evaluation of evidence accumulated from human studies and animal models[J/OL]. Front Psychiatry, 2024, 15: 19 [2026-07-28]. https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1492126/full. DOI: 10.3389/fpsyt.2024.1492126.
[35]
FOLEGO-TEMOTEO I, LIMA Y, GREVET E, et al. A comprehensive overview of the biological foundations of ADHD[J/OL]. Biosci Rep, 2026, 46(6): 47 [2026-07-28]. https://doi.org/10.1042/bsr20254061. DOI: 10.1042/bsr20254061.
[36]
MÁCOVÁ L, KANCHEVA R, BICÍKOVÁ M. Molecular Regulation of the CNS by Vitamin D[J/OL]. Physiol Res, 2023, 72: S339-S356 [2026-07-28]. https://doi.org/10.33549/physiolres.935248. DOI: 10.33549/physiolres.935248.
[37]
KADHIM R A, BABAN R S, OMRANI A, et al. Serum Levels of 25-OH Vitamin D3 and Vitamin D Receptor among Iraqi Children with Autism Spectrum Disorder[J]. Adv Life Sci, 2024, 11(1): 233-236.
[38]
SAAD K, ABDEL-RAHMAN A A, ELSEROGY Y M, et al. Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children[J]. Nutr Neurosci, 2016, 19(8): 346-351. DOI: 10.1179/1476830515y.0000000019.
[39]
JIA F, SHAN L, WANG B, et al. Bench to bedside review: Possible role of vitamin D in autism spectrum disorder[J]. Psychiatry Res, 2018, 260: 360-365. DOI: 10.1016/j.psychres.2017.12.005.
[40]
COSKUN S, SIMSEK S, CAMKURT M A, et al. Association of polymorphisms in the vitamin D receptor gene and serum 25-hydroxyvitamin D levels in children with autism spectrum disorder[J]. Gene, 2016, 588(2): 109-114. DOI: 10.1016/j.gene.2016.05.004.

PREV Clinical application progress of imaging-based body composition analysis
NEXT Identification of brain structural alterations and key molecular pathways in Alzheimer<sup><sup>,</sup></sup>s disease using voxel-based morphometry and the Allen Human Brain Atlas
  


LINK


Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn