Share：
Share this content in WeChat
X
[Chinese][PDF]2811
• Review •
Neuroimaging characteristics and genetic mechanisms of autism spectrum disorder: The current status and prospects of multimodal data integration
LUO Dan  ZHAO Chunfeng  LIU Heng 

Cite this article as: LUO D, ZHAO C F, LIU H. Neuroimaging characteristics and genetic mechanisms of autism spectrum disorder: The current status and prospects of multimodal data integration[J]. Chin J Magn Reson Imaging, 2024, 15(12): 160-164, 170. DOI:10.12015/issn.1674-8034.2024.12.024.


[Abstract] Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, the pathological mechanism of which involves the interaction between neuroimaging abnormalities and genetic factors. This paper reviews the neuroimaging characteristics of ASD and the specific effects of genetic variations on brain structure and function, exploring the important role of integrating neuroimaging and genetic data in deciphering the pathological mechanisms of ASD. It also points out the limitations of existing research and proposes future prospects, aiming to provide new directions for the precise diagnosis and personalized intervention of ASD.
[Keywords] autism spectrum disorders；neuroimaging；magnetic resonance imaging；multimodal imaging；genetics

LUO Dan   ZHAO Chunfeng   LIU Heng*  

Department of Radiology, Affiliated Hospital of Zunyi Medical University, Engineering Research Center of Intelligent Medical Imaging in Guizhou Higher Education Institutions, Medical Imaging Center of Guizhou Province, Zunyi563000, China

Corresponding author: LIU H, E-mail: zmcliuh@163.com

Conflicts of interest   None.

Received  2024-08-26
Accepted  2024-12-10
DOI: 10.12015/issn.1674-8034.2024.12.024
Cite this article as: LUO D, ZHAO C F, LIU H. Neuroimaging characteristics and genetic mechanisms of autism spectrum disorder: The current status and prospects of multimodal data integration[J]. Chin J Magn Reson Imaging, 2024, 15(12): 160-164, 170. DOI:10.12015/issn.1674-8034.2024.12.024.

[1]
HIROTA T, KING B H. Autism spectrum disorder: A review[J]. JAMA, 2023, 329(2): 157-168. DOI: 10.1001/jama.2022.23661.
[2]
PRETZSCH C M, ECKER C. Structural neuroimaging phenotypes and associated molecular and genomic underpinnings in autism: a review[J/OL]. Front Neurosci, 2023, 17: 1172779 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/37457001/. DOI: 10.3389/fnins.2023.1172779.
[3]
FREWER V, GILCHRIST C P, COLLINS S E, et al. A systematic review of brain MRI findings in monogenic disorders strongly associated with autism spectrum disorder[J]. J Child Psychol Psychiatry, 2021, 62(11): 1339-1352. DOI: 10.1111/jcpp.13510.
[4]
ILIOSKA I, OLDEHINKEL M, LLERA A, et al. Connectome-wide mega-analysis reveals robust patterns of atypical functional connectivity in autism[J]. Biol Psychiatry, 2023, 94(1): 29-39. DOI: 10.1016/j.biopsych.2022.12.018.
[5]
AGGARWAL P, GUPTA A. Multivariate graph learning for detecting aberrant connectivity of dynamic brain networks in autism[J]. Med Image Anal, 2019, 56: 11-25. DOI: 10.1016/j.media.2019.05.007.
[6]
SATTERSTROM F K, KOSMICKI J A, WANG J, et al. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism[J]. Cell, 2020, 180(3): 568-584.e23. DOI: 10.1016/j.cell.2019.12.036.
[7]
CHIEN Y L, CHEN Y C, GAU S S. Altered cingulate structures and the associations with social awareness deficits and CNTNAP2 gene in autism spectrum disorder[J/OL]. Neuroimage Clin, 2021, 31: 102729 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/34271514/. DOI: 10.1016/j.nicl.2021.102729.
[8]
LEE J K, ANDREWS D S, OZONOFF S, et al. Longitudinal evaluation of cerebral growth across childhood in boys and girls with autism spectrum disorder[J]. Biol Psychiatry, 2021, 90(5): 286-294. DOI: 10.1016/j.biopsych.2020.10.014.
[9]
SMITH S S, BENANNI S, JONES Q, et al. Manipulation of alpha4betadelta GABA(A) receptors alters synaptic pruning in layer 3 prelimbic prefrontal cortex and impairs temporal order recognition: Implications for schizophrenia and autism[J/OL]. Brain Res, 2024, 1835: 148929 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/38599510/. DOI: 10.1016/j.brainres.2024.148929.
[10]
LU M H, HSUEH Y P. Protein synthesis as a modifiable target for autism-related dendritic spine pathophysiologies[J]. FEBS J, 2022, 289(8): 2282-2300. DOI: 10.1111/febs.15733.
[11]
HAZLETT H C, GU H, MUNSELL B C, et al. Early brain development in infants at high risk for autism spectrum disorder[J]. Nature, 2017, 542(7641): 348-351. DOI: 10.1038/nature21369.
[12]
YANG D Y, BEAM D, PELPHREY K A, et al. Cortical morphological markers in children with autism: a structural magnetic resonance imaging study of thickness, area, volume, and gyrification[J/OL]. Mol Autism, 2016, 7: 11 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/26816612/. DOI: 10.1186/s13229-016-0076-x.
[13]
LIBERO L E, SCHAER M, LI D D, et al. A longitudinal study of local gyrification index in young boys with autism spectrum disorder[J]. Cereb Cortex, 2019, 29(6): 2575-2587. DOI: 10.1093/cercor/bhy126.
[14]
DURET P, SAMSON F, PINSARD B, et al. Gyrification changes are related to cognitive strengths in autism[J]. Neuroimage Clin, 2018, 20: 415-423. DOI: 10.1016/j.nicl.2018.04.036.
[15]
YASUNO F, MAKINODAN M, TAKAHASHI M, et al. Microstructural anomalies evaluated by neurite orientation dispersion and density imaging are related to deficits in facial emotional recognition via perceptual-binding difficulties in autism spectrum disorder[J]. Autism Res, 2020, 13(5): 729-740. DOI: 10.1002/aur.2280.
[16]
SURGENT O, RIAZ A, AUSDERAU K K, et al. Brainstem white matter microstructure is associated with hyporesponsiveness and overall sensory features in autistic children[J/OL]. Mol Autism, 2022, 13(1): 48 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/36536467/. DOI: 10.1186/s13229-022-00524-3.
[17]
ZHAO Y, YANG L, GONG G, et al. Identify aberrant white matter microstructure in ASD, ADHD and other neurodevelopmental disorders: A meta-analysis of diffusion tensor imaging studies[J/OL]. Prog Neuropsychopharmacol Biol Psychiatry, 2022, 113: 110477 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/34798202/. DOI: 10.1016/j.pnpbp.2021.110477.
[18]
LI M, WANG Y, TACHIBANA M, et al. Atypical structural connectivity of language networks in autism spectrum disorder: A meta-analysis of diffusion tensor imaging studies[J]. Autism Res, 2022, 15(9): 1585-1602. DOI: 10.1002/aur.2789.
[19]
ZHANG M, HU X, JIAO J, et al. Brain white matter microstructure abnormalities in children with optimal outcome from autism: a four-year follow-up study[J/OL]. Sci Rep, 2022, 12(1): 20151 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/36418886/. DOI: 10.1038/s41598-022-21085-8.
[20]
QIN B, WANG L, ZHANG Y, et al. Enhanced topological network efficiency in preschool autism spectrum disorder: A diffusion tensor imaging study[J/OL]. Front Psychiatry, 2018, 9: 278 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/29997534/. DOI: 10.3389/fpsyt.2018.00278.
[21]
YI T, JI C, WEI W, et al. Cortical-cerebellar circuits changes in preschool ASD children by multimodal MRI[J/OL]. Cereb Cortex, 2024, 34(4): bhae090 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/38615243/. DOI: 10.1093/cercor/bhae090.
[22]
KIM J I, BANG S, YANG J J, et al. Classification of preschoolers with low-functioning autism spectrum disorder using multimodal MRI data[J]. J Autism Dev Disord, 2023, 53(1): 25-37. DOI: 10.1007/s10803-021-05368-z.
[23]
QING P, ZHANG X, LIU Q, et al. Structure-function coupling in white matter uncovers the hypoconnectivity in autism spectrum disorder[J/OL]. Mol Autism, 2024, 15(1): 43 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/39367506/. DOI: 10.1186/s13229-024-00620-6.
[24]
XU G, GENG G, WANG A, et al. Three autism subtypes based on single-subject gray matter network revealed by semi-supervised machine learning[J]. Autism Res, 2024, 17(10): 1962-1973. DOI: 10.1002/aur.3183.
[25]
GUO X, WANG X, ZHOU R, et al. Altered temporospatial variability of dynamic amplitude of low-frequency fluctuation in children with autism spectrum disorder[J/OL]. J Autism Dev Disord, 2024 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/39663323/. DOI: 10.1007/s10803-024-06661-3.
[26]
XIE J, ZHANG W, SHEN Y, et al. Abnormal spontaneous brain activity in females with autism spectrum disorders[J/OL]. Front Neurosci, 2023, 17: 1189087 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/37521682/. DOI: 10.3389/fnins.2023.1189087.
[27]
LINKE A C, CHEN B, OLSON L, et al. Altered development of the hurst exponent in the medial prefrontal cortex in preschoolers with autism[J/OL]. Biol Psychiatry Cogn Neurosci Neuroimaging, 2024 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/39293740/. DOI: 10.1016/j.bpsc.2024.09.003.
[28]
GOODWILL A M, LOW L T, FOX P T, et al. Meta-analytic connectivity modelling of functional magnetic resonance imaging studies in autism spectrum disorders[J]. Brain Imaging Behav, 2023, 17(2): 257-269. DOI: 10.1007/s11682-022-00754-2.
[29]
KIEMES A, DAVIES C, KEMPTON M J, et al. GABA, glutamate and neural activity: A systematic review with meta-analysis of multimodal (1)H-MRS-fMRI studies[J/OL]. Front Psychiatry, 2021, 12: 644315 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/33762983/. DOI: 10.3389/fpsyt.2021.644315.
[30]
TAVARES V, FERNANDES L A, ANTUNES M, et al. Sex differences in functional connectivity between resting state brain networks in autism spectrum disorder[J]. J Autism Dev Disord, 2022, 52(7): 3088-3101. DOI: 10.1007/s10803-021-05191-6.
[31]
LEPPING R J, MCKINNEY W S, MAGNON G C, et al. Visuomotor brain network activation and functional connectivity among individuals with autism spectrum disorder[J]. Hum Brain Mapp, 2022, 43(2): 844-859. DOI: 10.1002/hbm.25692.
[32]
WANG J, WANG X, WANG R, et al. Atypical resting-state functional connectivity of intra/inter-sensory networks is related to symptom severity in young boys with autism spectrum disorder[J/OL]. Front Physiol, 2021, 12: 626338 [2024-08-19]. https://pubmed.ncbi.nlm.nih.gov/33868000/. DOI: 10.3389/fphys.2021.626338.
[33]
MARTINEZ K, MARTINEZ-GARCIA M, MARCOS-VIDAL L, et al. Sensory-to-cognitive systems integration is associated with clinical severity in autism spectrum disorder[J]. J Am Acad Child Adolesc Psychiatry, 2020, 59(3): 422-433. DOI: 10.1016/j.jaac.2019.05.033.
[34]
BEDNARZ H M, KANA R K. Patterns of cerebellar connectivity with intrinsic connectivity networks in autism spectrum disorders[J]. J Autism Dev Disord, 2019, 49(11): 4498-4514. DOI: 10.1007/s10803-019-04168-w.
[35]
CHEN B, LINKE A, OLSON L, et al. Greater functional connectivity between sensory networks is related to symptom severity in toddlers with autism spectrum disorder[J]. J Child Psychol Psychiatry, 2021, 62(2): 160-170. DOI: 10.1111/jcpp.13268.
[36]
SILBEREIS J C, POCHAREDDY S, ZHU Y, et al. The cellular and molecular landscapes of the developing human central nervous system[J]. Neuron, 2016, 89(2): 248-268. DOI: 10.1016/j.neuron.2015.12.008.
[37]
MONTEIRO P, FENG G. SHANK proteins: roles at the synapse and in autism spectrum disorder[J]. Nat Rev Neurosci, 2017, 18(3): 147-157. DOI: 10.1038/nrn.2016.183.
[38]
BACON C, RAPPOLD G A. The distinct and overlapping phenotypic spectra of FOXP1 and FOXP2 in cognitive disorders[J]. Hum Genet, 2012, 131(11): 1687-1698. DOI: 10.1007/s00439-012-1193-z.
[39]
YEUNG K S, TSO W W Y, IP J J K, et al. Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism[J/OL]. Mol Autism, 2017, 8: 66 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/29296277/. DOI: .
[40]
BERTO S, TREACHER A H, CAGLAYAN E, et al. Association between resting-state functional brain connectivity and gene expression is altered in autism spectrum disorder[J/OL]. Nat Commun, 2022, 13(1): 3328 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/35680911/. DOI: .
[41]
BOSE R, POSADA-PEREZ M, KARVELA E, et al. Bi-allelic NRXN1alpha deletion in microglia derived from iPSC of an autistic patient increases interleukin-6 production and impairs supporting function on neuronal networking[J]. Brain Behav Immun, 2025, 123: 28-42. DOI: 10.1016/j.bbi.2024.09.001.
[42]
DIAS C, MO A, CAI C, et al. Cell-type-specific effects of autism-associated 15q duplication syndrome in the human brain[J]. Am J Hum Genet, 2024, 111(8): 1544-1558. DOI: 10.1016/j.ajhg.2024.07.002.
[43]
HSU T T, HUANG T N, WANG C Y, et al. Deep brain stimulation of the Tbr1-deficient mouse model of autism spectrum disorder at the basolateral amygdala alters amygdalar connectivity, whole-brain synchronization, and social behaviors[J/OL]. PLoS Biol, 2024, 22(7): e3002646 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/39012916/. DOI: 10.1371/journal.pbio.3002646.
[44]
GELMEZ P, KARAKOC T E, ULUCAN O. Autism spectrum disorder and atypical brain connectivity: Novel insights from brain connectivity-associated genes by combining random forest and support vector machine algorithm[J]. OMICS, 2024, 28(11): 563-572. DOI: 10.1089/omi.2024.0167.
[45]
LI X, ZHANG K, HE X, et al. Structural, functional, and molecular imaging of autism spectrum disorder[J]. Neurosci Bull, 2021, 37(7): 1051-1071. DOI: 10.1007/s12264-021-00673-0.
[46]
TSURUGIZAWA T. Translational magnetic resonance imaging in autism spectrum disorder from the mouse model to human[J/OL]. Front Neurosci, 2022, 16: 872036 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/35585926/. DOI: 10.3389/fnins.2022.872036.
[47]
GAO J, XU Y, LI Y, et al. Comprehensive exploration of multi-modal and multi-branch imaging markers for autism diagnosis and interpretation: insights from an advanced deep learning model[J/OL]. Cereb Cortex, 2024, 34(2): bhad521 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/38220572/. DOI: 10.1093/cercor/bhad521.
[48]
LI X, RUAN C, ZIBRILA A I, et al. Children with autism spectrum disorder present glymphatic system dysfunction evidenced by diffusion tensor imaging along the perivascular space[J/OL]. Medicine (Baltimore), 2022, 101(48): e32061 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/36482590/. DOI: 10.1097/MD.0000000000032061.
[49]
XU Y Y, SU X, JI Z Z, et al. The exploration of glymphatic system alteration in patients with autism spectrum disorder aged 9-18 years using DTI-ALPS method[J]. Radiol Practice, 2024, 39(9): 1117-1121. DOI: 10.13609/j.cnki.1000-0313.2024.09.001.
[50]
TANG S, NIE L, LIU X, et al. Application of quantitative magnetic resonance imaging in the diagnosis of autism in children[J/OL]. Front Med (Lausanne), 2022, 9: 818404 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/35646984/. DOI: 10.3389/fmed.2022.818404.
[51]
TANG S, XU Y, LIU X, et al. Quantitative susceptibility mapping shows lower brain iron content in children with autism[J]. Eur Radiol, 2021, 31(4): 2073-2083. DOI: 10.1007/s00330-020-07267-w.
[52]
DU L, YE F, GAO W, et al. Decreased brain iron deposition based on quantitative susceptibility mapping correlates with reduced neurodevelopmental status in children with autism spectrum disorder[J]. Cereb Cortex, 2024, 34(13): 63-71. DOI: 10.1093/cercor/bhae081.
[53]
WANG M, XU D, ZHANG L, et al. Application of multimodal MRI in the early diagnosis of autism spectrum disorders: A review[J/OL]. Diagnostics (Basel), 2023, 13(19): 3027 [2024-08-19]. https://www.ncbi.nlm.nih.gov/pubmed/37835770/. DOI: 10.3390/diagnostics13193027.

PREV A case of MRI of placental infarction complicated with fetal ischemic stroke
NEXT Research progress of magnetic resonance imaging in epileptic thalamus
  


LINK


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