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<p>Schizophrenia (SZ), a severe disorder with hallucinations, delusions, disorganized thinking, and negative symptoms, has ~ 80% heritability. Genomic studies revealed a polygenic basis: common variants and rare, high-risk CNVs like 22q11.2 deletion implicate neurodevelopmental, and synaptic pathways, offering etiologically clear models. Traditional cell and animal models poorly capture human brain development. Cerebral organoids—3D neural tissues from human induced pluripotent stem cells (iPSCs)—recapitulate early corticogenesis, forming cortical zones, neuronal migration, and network activity. Building on this, multi-regional assembloids fuse brain regions to model complex interactions like GABAergic interneuron migration and cortico-subcortical circuits—key to schizophrenia’s cognitive deficits. This review synthesizes advances in 3D models of schizophrenia, highlighting convergent mechanisms and their clinical implications. We outline where human neural systems inform clinical practices such as linking genetic risk to cognitive symptoms—and what innovations (e.g., larger cohorts, polygenic modeling) are needed to translate these insights into personalized care for schizophrenia’s diverse presentations.</p>

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Modeling schizophrenia in three dimensions: cerebral organoids and assembloids

  • 期刊论文

  • 发表日期：

    2025年11月8日

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  • Artemiy O. Kurishev,
  • Vera E. Golimbet

摘要

Schizophrenia (SZ), a severe disorder with hallucinations, delusions, disorganized thinking, and negative symptoms, has ~ 80% heritability. Genomic studies revealed a polygenic basis: common variants and rare, high-risk CNVs like 22q11.2 deletion implicate neurodevelopmental, and synaptic pathways, offering etiologically clear models. Traditional cell and animal models poorly capture human brain development. Cerebral organoids—3D neural tissues from human induced pluripotent stem cells (iPSCs)—recapitulate early corticogenesis, forming cortical zones, neuronal migration, and network activity. Building on this, multi-regional assembloids fuse brain regions to model complex interactions like GABAergic interneuron migration and cortico-subcortical circuits—key to schizophrenia’s cognitive deficits. This review synthesizes advances in 3D models of schizophrenia, highlighting convergent mechanisms and their clinical implications. We outline where human neural systems inform clinical practices such as linking genetic risk to cognitive symptoms—and what innovations (e.g., larger cohorts, polygenic modeling) are needed to translate these insights into personalized care for schizophrenia’s diverse presentations.