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Cited by 7Down syndrome and intellectual disability researchGenetics and Neurodevelopmental DisordersAutism Spectrum Disorder Research

Meta-Analysis of Down Syndrome Cortical Development Reveals Underdeveloped State of the Science

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Risgaard, Kirstin A., Sorci, Isabella A., Mohan, Sruti, Bhattacharyya, Anita·2022·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2022.915272PMC PMC9234119
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Abstract

Neurodevelopmental impairment contributes to the hallmark cognitive disability in individuals with Down syndrome (DS, trisomy 21, T21). The appearance of cognitive deficits in infancy suggests that alterations emerge during the earliest stages of neural development and continue throughout the lifespan in DS. Neural correlates of intellectual and language function include cortical structures, specifically temporal and frontal lobes that are smaller in DS. Yet, despite increased understanding of the DS cognitive-behavioral phenotype in childhood, there is very little structural and histological information to help explain the deficits. Consequently, attempts to effectively design therapeutic targets or interventions are limited. We present a systematic review of published research on cortical development in DS that reveals a paucity of studies that rigorously identify cellular features that may underlie the gross morphological deficits of the developing DS brain. We assessed 115 published reports retrieved through PubMed and other sources and found that only 23 reported histological and/or immunohistochemical data to define cell composition affected in DS post-mortem brain. Further, our analysis reveals that many reports have limited samples sizes and few DS samples, making it difficult to draw conclusions that are generally applicable to the DS population. Thus, the lack of replication and limited number of studies indicate that more developmentally focused research, ideally using equal numbers of age-matched samples in analyses, is needed to elucidate the cellular nature of smaller brain size in DS.

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  • Studies on the post-mortem Down syndrome brain are often underpowered because of limited availability of human brain tissue, especially from prenatal developmental periods.

    “Because of the limited availability of human brain tissue, especially from prenatal developmental periods, studies on the post-mortem DS brain are often underpowered17.”

    From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [17]

  • The fetal cortex, cerebellum and hippocampus have all been shown to contain fewer neurons in individuals with Down syndrome than in controls, albeit based on small sample sizes.

    “The fetal cortex, cerebellum and hippocampus have all been shown to contain fewer neurons in individuals with DS than in controls40–48, albeit based on small sample sizes17.”

    From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [17]

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Authors
Risgaard, K. A., Sorci, I. A., Mohan, S., & Bhattacharyya, A.
Affiliations
University of Wisconsin–Madison (US)
Corresponding author
Bhattacharyya, Anita
ORCID
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2022-06-13
Volume
16
Pages
915272-915272
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2022.915272
PMC
PMC9234119
OpenAlex
W4282591939
Cited by
7
References
55
Citations by year
2026: 1 · 2025: 4 · 2024: 2
FWCI
0.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords
Down syndrome, cortical development, neurodevelopmental impairment, brain size, immunohistochemistry, cognitive disability, temporal lobe, frontal lobe, sample size limitations, replication

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