Effect of schizophrenia common variants on infant brain volumes: cross-sectional study in 207 term neonates in
Hai Le1, Konstantina Dimitrakopoulou2, Hamel Patel3
1Centre for the Developing Brain, Perinatal Imaging and Health Department, King's College London, London, UK. Le.hai@kcl.ac.uk.
Insights
Schizophrenia risk genes may impact early brain development, showing reduced grey and white matter volumes in infants. These findings suggest potential structural alterations years before the typical onset of schizophrenia.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Schizophrenia onset typically occurs in adolescence/young adulthood.
- Early developmental deviations are implicated in schizophrenia.
- Few studies link schizophrenia genetic risk to neonatal brain imaging.
Purpose of the Study:
- Investigate brain imaging changes in neonates related to schizophrenia.
- Examine associations between schizophrenia polygenic risk scores (PRS) and neonatal brain volumes.
Main Methods:
- Compared brain volumes (grey and white matter) with schizophrenia PRS in 207 healthy infants.
- Utilized linear regression, controlling for gestational age, scan age, ancestry, sex, and intracranial volume.
- Included individuals of Asian ancestry to confirm robustness.
Main Results:
- Schizophrenia PRS negatively associated with superior temporal gyrus grey and white matter volumes.
- PRS also linked to reduced white frontal lobe and total white matter volumes.
- Functional analysis revealed enrichment in neurodevelopmental pathways for associated risk variants.
Conclusions:
- Schizophrenia risk genes may influence early brain growth.
- Potential for early-life structural alterations preceding schizophrenia onset.
- Suggests a possible neurodevelopmental origin of schizophrenia detectable in infancy.
Abstract:
Increasing lines of evidence suggest deviations from the normal early developmental trajectory could give rise to the onset of schizophrenia during adolescence and young adulthood, but few studies have investigated brain imaging changes associated with schizophrenia common variants in neonates. This study compared the brain volumes of both grey and white matter regions with schizophrenia polygenic risk scores (PRS) for 207 healthy term-born infants of European ancestry. Linear regression was used to estimate the relationship between PRS and brain volumes, with gestational age at birth, postmenstrual age at scan, ancestral principal components, sex and intracranial volumes as covariates. The schizophrenia PRS were negatively associated with the grey (β = -0.08, p = 4.2 × 10-3) and white (β = -0.13, p = 9.4 × 10-3) matter superior temporal gyrus volumes, white frontal lobe volume (β = -0.09, p = 1.5 × 10-3) and the total white matter volume (β = -0.062, p = 1.66 × 10-2). This result also remained robust when incorporating individuals of Asian ancestry. Explorative functional analysis of the schizophrenia risk variants associated with the right frontal lobe white matter volume found enrichment in neurodevelopmental pathways. This preliminary result suggests possible involvement of schizophrenia risk genes in early brain growth, and potential early life structural alterations long before the average age of onset of the disease.
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