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Updated: Feb 14, 2026
13:08
Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia
Published on: December 2, 2015
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Schizophrenia polygenic risk score predicts mnemonic hippocampal activity
Qiang Chen1, Gianluca Ursini1,2, Adrienne L Romer3
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, 855 North Wolfe Street, MD, USA.
Brain : a Journal of Neurology
|February 8, 2018
Summary
Higher schizophrenia polygenic risk scores are linked to reduced hippocampal activity during memory encoding in healthy individuals. This finding supports hippocampal function as a key intermediate phenotype for schizophrenia risk.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Polygenic risk scores (PRS) are used to study schizophrenia's genetic basis.
- Research linking PRS to specific pathophysiological aspects of schizophrenia is limited.
- Hippocampal activity during memory encoding is a potential intermediate phenotype for schizophrenia.
Purpose of the Study:
- To investigate if schizophrenia PRS predicts hippocampal activity during memory encoding in healthy volunteers.
- To validate hippocampal activity as a genetic risk-associated intermediate phenotype for schizophrenia.
Main Methods:
- Analyzed PRS and hippocampal activity in discovery (n=191) and replication (n=76, n=137) samples of healthy volunteers.
- Calculated PRS using genome-wide association study data.
- Assessed hippocampal activity using blood oxygen level-dependent functional MRI during memory encoding of visual stimuli.
Main Results:
- Schizophrenia PRS were significantly associated with hippocampal activity in all samples.
- The association was consistently negative: higher PRS correlated with lower hippocampal activity.
- PRS explained over 8% of the variance in hippocampal activity during memory encoding in the discovery sample.
Conclusions:
- Schizophrenia PRS predict variability in hippocampal activity during memory encoding in healthy individuals.
- Hippocampal activity during memory encoding is a validated intermediate phenotype for schizophrenia.
- Schizophrenia risk alleles converge on this pattern of neural activity, impacting memory function.
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