Anatomical Insights into Cerebral and Craniofacial Morphology in ASD Using Anthropometric Measurements

Pashmina  Shaikh; Sana Kashif; Iqra  Khalid; Shahida  Hingoro; Sameena  Gul; Hifsa  Baloch

doi:10.36283/ziun-pjmd14-3/008

Authors

Pashmina Shaikh Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan. https://orcid.org/0009-0002-0487-2546
Sana Kashif Chandka Medical College/Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, Sindh, Pakistan.
Iqra Khalid Liaquat Institute of Medical and Health Sciences, Thatta,Pakistan.
Shahida Hingoro Liaquat Institute of Medical & Health Sciences,Thatta, Sindh, Pakistan.
Sameena Gul Bilawal Medical College, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh,Pakistan.
Hifsa Baloch Liaquat Institute of Medical and Health sciences, Thatta, Pakistan.

DOI:

https://doi.org/10.36283/ziun-pjmd14-3/008

Keywords:

Autism Spectrum Disorder, Craniofacial Abnormalities, Anthropometry, Animal Model, Cerebrum & Propionic Acid

Abstract

Background: The association of neurodevelopmental and craniofacial anomalies with Autism Spectrum Disorder (ASD) is indicative of cerebral abnormalities. To examine cerebral and craniofacial anatomical variations in a rodent model of ASD using defined anthropometric measures.

Methods: This in vivo study was performed in an animal research facility and analysis was done (Ref#18/05/223) at Liaquat University of Medical & Health Sciences (LUMHS), Jamshoro and Continental Medical College, Lahore (CMC) from June to December 2023. Twenty Albino Wistar rats were allocated into two groups. Control (n=6) and ASD-imposed (n = 14) under the administration of propionic acid (PPA) using a random sampling technique. OpenEpi 3.0.0 was used for sample size calculation. The craniofacial and cerebral markers were measured using the calipers and stereotactic referencing after euthanasia. The skull length, intercanthal width, head circumference, and cranial index were considered. H&E staining was also performed to view histological patterns in certain brain tissues. Statistical analysis was done using SPSS version 26. Independent t-tests and Chi-square tests were performed. A p-value of <0.05 was considered statistically significant.

Results: The ASD-induced group exhibited significantly reduced skull length (29.3 ± 2.1 mm vs. 32.8 ± 1.5 mm; p = 0.002) and head circumference (40.2 ± 2.7 mm vs. 42.5 ± 2.2 mm; p = 0.041), alongside increased intercanthal distance (7.8 ± 0.6 mm vs. 6.2 ± 0.4 mm; p = 0.0001) and cranial index (81.9% vs. 75.3%; p = 0.003). Histologically, cortical layering was disrupted in 10 of 14 ASD rats, and ventricular enlargement was observed in 12 of 14, compared to none in controls (all p < 0.01).

Conclusion: Craniofacial morphometric studies of ASD rodent models show quantifiable anatomical differences associated with neurodevelopmental compromising. This strategy can act as a translational model for grasping structural markers of early ASD detection and pathogenesis.

Author Biographies

Pashmina Shaikh, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan.

Department of Anatomy,
Sana Kashif, Chandka Medical College/Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, Sindh, Pakistan.

Department of Anatomy,
Iqra Khalid, Liaquat Institute of Medical and Health Sciences, Thatta,Pakistan.

Department of Anatomy,
Shahida Hingoro, Liaquat Institute of Medical & Health Sciences,Thatta, Sindh, Pakistan.

Department of Anatomy,
Sameena Gul, Bilawal Medical College, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh,Pakistan.

Department of Anatomy,
Hifsa Baloch, Liaquat Institute of Medical and Health sciences, Thatta, Pakistan.

Department of Anatomy,

References

1. Maenner MJ, Warren Z, Williams AR, Amoakohene E, Bakian AV, Bilder DA, 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. MMWR Surveill Summ. 2023 Mar 24;72(2):1-14. doi: 10.15585/mmwr.ss7202a1.

2. Solmi M, Song M, Yon DK, Lee SW, Fombonne E, Kim MS, et al. Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries. Mol Psychiatry. 2022 Oct;27(10):4172-4180. doi: 10.1038/s41380-022-01630-7.

3. Kaplan ZB, Pearce EN, Lee SY, Shin HM, Schmidt RJ. Maternal Thyroid Dysfunction During Pregnancy as an Etiologic Factor in Autism Spectrum Disorder: Challenges and Opportunities for Research. Thyroid. 2024 Feb;34(2):144-157. doi: 10.1089/thy.2023.0391.

4. Zhuang H, Liang Z, Ma G, Qureshi A, Ran X, Feng C, et al. Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy. MedComm (2020). 2024 Mar 2;5(3):e497. doi: 10.1002/mco2.497.

5. Junaid M, Slack-Smith L, Wong K, Bourke J, Baynam G, Calache H, et al. Association between craniofacial anomalies, intellectual disability and autism spectrum disorder: Western Australian population-based study. Pediatr Res. 2022 Dec;92(6):1795-1804. doi: 10.1038/s41390-022-02024-9.

6. Pretzsch CM, Schäfer T, Lombardo MV, Warrier V, Mann C, Bletsch A, et al. Neurobiological Correlates of Change in Adaptive Behavior in Autism. Am J Psychiatry. 2022 May;179(5):336-349. doi: 10.1176/appi.ajp.21070711.

7. Silverman JL, Thurm A, Ethridge SB, Soller MM, Petkova SP, Abel T, et al. Reconsidering animal models used to study autism spectrum disorder: Current state and optimizing future. Genes Brain Behav. 2022 Jun;21(5):e12803. doi: 10.1111/gbb.12803.

8. Li Z, Zhu YX, Gu LJ, Cheng Y. Understanding autism spectrum disorders with animal models: applications, insights, and perspectives. Zool Res. 2021 Nov 18;42(6):800-824. doi: 10.24272/j.issn.2095-8137.2021.251.

9. Lagod PP, Abdelli LS, Naser SA. An In Vivo Model of Propionic Acid-Rich Diet-Induced Gliosis and Neuro-Inflammation in Mice (FVB/N-Tg(GFAPGFP)14Mes/J): A Potential Link to Autism Spectrum Disorder. Int J Mol Sci. 2024 Jul 25;25(15):8093. doi: 10.3390/ijms25158093.

10. Bhardwaj R, Agrawal U, Vashist P, Manna S. Determination of sample size for various study designs in medical research: A practical primer. J Family Med Prim Care. 2024 Jul;13(7):2555-2561. doi: 10.4103/jfmpc.jfmpc_1675_23.

11. Rahi S, Gupta R, Sharma A, Mehan S. Smo-Shh signaling activator purmorphamine ameliorates neurobehavioral, molecular, and morphological alterations in an intracerebroventricular propionic acid-induced experimental model of autism. Hum Exp Toxicol. 2021 Nov;40(11):1880-1898. doi: 10.1177/09603271211013456.

12. Quatrosi G, Genovese D, Galliano G, Zoppé H, Amodio E, Bonnet-Brilhault F, et al. Cranio-Facial Characteristics in Autism Spectrum Disorder: A Scoping Review. J Clin Med. 2024 Jan 26;13(3):729. doi: 10.3390/jcm13030729.

13. Exposito-Alonso D, Rico B. Mechanisms Underlying Circuit Dysfunction in Neurodevelopmental Disorders. Annu Rev Genet. 2022 Nov 30;56:391-422. doi: 10.1146/annurev-genet-072820-023642.

14. Guerra M, Medici V, La Sala G, Farini D. Unravelling the Cerebellar Involvement in Autism Spectrum Disorders: Insights into Genetic Mechanisms and Developmental Pathways. Cells. 2024 Jul 10;13(14):1176. doi: 10.3390/cells13141176.

15. Kyriakopoulou V, Davidson A, Chew A, Gupta N, Arichi T, Nosarti C, et al. Characterisation of ASD traits among a cohort of children with isolated fetal ventriculomegaly. Nat Commun. 2023 Mar 21;14(1):1550. doi: 10.1038/s41467-023-37242-0.

16. Ellingford RA, Panasiuk MJ, de Meritens ER, Shaunak R, Naybour L, Browne L, et al. Cell-type-specific synaptic imbalance and disrupted homeostatic plasticity in cortical circuits of ASD-associated Chd8 haploinsufficient mice. Mol Psychiatry. 2021 Jul;26(7):3614-3624. doi: 10.1038/s41380-021-01070-9.

17. Rozhkova IN, Okotrub SV, Brusentsev EY, Uldanova EE, Chuyko EА, Lipina TV, et al. Neuronal density in the brain cortex and hippocampus in Clsnt2-KO mouse strain modeling autistic spectrum disorder. Vavilovskii Zhurnal Genet Selektsii. 2022 Jul;26(4):365-370. doi: 10.18699/VJGB-22-44.

18. Usui N, Kobayashi H, Shimada S. Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder. Int J Mol Sci. 2023 Mar 13;24(6):5487. doi: 10.3390/ijms24065487. PMID: 36982559; PMCID: PMC10049423.

19. Sharma AR, Batra G, Saini L, Sharma S, Mishra A, Singla R, et al. Valproic Acid and Propionic Acid Modulated Mechanical Pathways Associated with Autism Spectrum Disorder at Prenatal and Neonatal Exposure. CNS Neurol Disord Drug Targets. 2022;21(5):399-408. doi: 10.2174/1871527320666210806165430.

20. Themistocleous CK, Andreou M, Peristeri E. Autism Detection in Children: Integrating Machine Learning and Natural Language Processing in Narrative Analysis. Behav Sci (Basel). 2024 May 29;14(6):459. doi: 10.3390/bs14060459.

21. Kasherman MA, Currey L, Kurniawan ND, Zalucki O, Vega MS, Jolly LA, et al. Abnormal Behavior and Cortical Connectivity Deficits in Mice Lacking Usp9x. Cereb Cortex. 2021 Feb 5;31(3):1763-1775. doi: 10.1093/cercor/bhaa324.

22. Nisar S, Haris M. Neuroimaging genetics approaches to identify new biomarkers for the early diagnosis of autism spectrum disorder. Mol Psychiatry. 2023 Dec;28(12):4995-5008. doi: 10.1038/s41380-023-02060-9.

23. Matthews H, de Jong G, Maal T, Claes P. Static and Motion Facial Analysis for Craniofacial Assessment and Diagnosing Diseases. Annu Rev Biomed Data Sci. 2022 Aug 10;5:19-42. doi: 10.1146/annurev-biodatasci-122120-111413.

24. Carroll L, Braeutigam S, Dawes JM, Krsnik Z, Kostovic I, Coutinho E, et al. Autism Spectrum Disorders: Multiple Routes to, and Multiple Consequences of, Abnormal Synaptic Function and Connectivity. Neuroscientist. 2021 Feb;27(1):10-29. doi: 10.1177/1073858420921378.

25. Derkowski W, Kędzia A, Dudek K, Glonek M. Morphometric evaluation of the anterior cranial fossa during the prenatal stage in humans and its clinical implications. PLoS One. 2024 Dec 27;19(12):e0309184. doi: 10.1371/journal.pone.0309184.