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Related Experiment Video

Updated: Mar 10, 2026

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
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Schizophrenia copy number variants and associative learning.

N E Clifton1, A J Pocklington1,2, B Scholz1

  • 1Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.

Molecular Psychiatry
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Summary

Schizophrenia genetic risk variants, specifically copy number variants (CNVs), are linked to impaired fear extinction learning. This suggests CNVs may impact inhibitory learning, contributing to schizophrenia symptoms.

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Area of Science:

  • Neurogenetics
  • Psychiatric Genetics
  • Cognitive Neuroscience

Background:

  • Large-scale genomic studies identify copy number variants (CNVs) as significant risk factors for schizophrenia.
  • The precise mechanisms by which CNVs contribute to schizophrenia pathogenesis are not fully understood.
  • Abnormalities in associative learning processes are a long-recognized feature of schizophrenia.

Purpose of the Study:

  • To investigate the impact of schizophrenia-associated CNVs on specific phases of associative learning.
  • To determine if genes within schizophrenia risk CNVs are preferentially expressed during memory consolidation, retrieval, or extinction.

Main Methods:

  • Analysis of CNVs in a large cohort of schizophrenia cases (11,917) and controls (16,416).
  • Integration of human genetic data with experimental gene expression studies in animal models.
  • Examination of gene enrichment for CNVs during distinct associative learning phases (consolidation, retrieval, extinction).

Main Results:

  • Schizophrenia risk CNVs were significantly enriched for genes expressed during fear extinction in the hippocampus.
  • No enrichment was observed for genes involved in memory consolidation or retrieval.
  • This points to a specific impairment in inhibitory learning associated with CNVs in schizophrenia.

Conclusions:

  • Schizophrenia-associated CNVs may impair inhibitory learning by affecting genes crucial for fear extinction.
  • This impairment in inhibitory learning could be a key mechanism contributing to the core symptoms of schizophrenia.
  • Findings highlight the role of specific learning deficits in the genetic etiology of schizophrenia.