The promises and challenges of human brain organoids as models of neuropsychiatric disease
Abstract
Neuropsychiatric disorders such as autism spectrum disorder (ASD), schizophrenia (SCZ) and bipolar disorder (BPD) are of great societal and medical importance, but the complexity of these diseases and the challenges of modeling the development and function of the human brain have made these disorders difficult to study experimentally. The recent development of 3D brain organoids derived from human pluripotent stem cells offers a promising approach for investigating the phenotypic underpinnings of these highly polygenic disorders and for understanding the contribution of individual risk variants and complex genetic background to human pathology. Here we discuss the advantages, limitations and future applications of human brain organoids as in vitro models of neuropsychiatric disease.
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Human brain organoids can fully replicate human biology and potentially reduce translational barriers from experimental findings to therapeutic applications.
“Meanwhile, being entirely derived from human cells, these organoids can fully replicate human biology and potentially reduce the translational barriers from experimental findings to therapeutic applications (20–22), offering advantages over animal models (23–25).”
From Understanding monocyte-driven neuroinflammation in Alzheimer’s disease using human cortical organoid microphysiological systems (2025) · cites this paper as [22]
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- Authors
- Quadrato, G., Brown, J., & Arlotta, P.
- Affiliations
- Harvard University (US)
- Corresponding author
- Arlotta, Paola
- Venue
- Nature Medicine
- Published
- 2016-10-26
- Volume
- 22
- Issue
- 11
- Pages
- 1220-1228
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2545768818
- Cited by
- 304
- References
- 100
- Citations by year
- 2026: 21 · 2025: 29 · 2024: 29 · 2023: 26 · 2022: 27 · 2021: 29 · 2020: 44 · 2019: 38 · 2018: 35 · 2017: 26
- FWCI
- 17.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Broad Institute
- National Institutes of Health
- Stanley Center for Psychiatric Research, Broad Institute
- National Institute of Mental Health (R01MH101268)
- National Institute of Neurological Disorders and Stroke (R01NS078164)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- brain organoids, neuropsychiatric disorders, autism spectrum disorder, schizophrenia, bipolar disorder, human pluripotent stem cells, in vitro disease model, polygenic disease, genetic risk variants, 3D brain models
- MeSH terms
- Autism Spectrum Disorder, Mental Disorders, Bipolar Disorder, Brain, Humans, Models, Neurological, Models, Psychological, Nerve Net, Organoids, Schizophrenia, Pluripotent Stem Cells, Neurogenesis, Induced Pluripotent Stem Cells, In Vitro Techniques
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