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Linking genes, circuits, and behavior: network connectivity as a novel endophenotype of externalizing
Naomi Sadeh1, Jeffrey M Spielberg1, Mark W Logue2
1Department of Psychological and Brain Sciences,University of Delaware,Newark, DE,USA.
Psychological Medicine
|September 13, 2018
Summary
Genetic risk for externalizing disorders is linked to altered brain connectivity in networks crucial for emotion and impulse control. This study identifies specific neural phenotypes associated with this genetic vulnerability.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Externalizing disorders have a partial genetic basis, but the underlying biological mechanisms are not fully understood.
- Identifying neural phenotypes linked to genetic risk is crucial for understanding the development of these disorders.
Purpose of the Study:
- To identify neural phenotypes associated with genomic vulnerability for externalizing disorders.
- To investigate the relationship between polygenic risk scores for externalizing disorders and brain functional connectivity.
Main Methods:
- 155 participants underwent genome-wide genotyping and resting-state functional MRI.
- A polygenic score (PS) for externalizing was calculated, and network analysis was used to identify functional neural networks.
- Inhibitory control tasks and psychiatric diagnoses were used to phenotype externalizing behaviors.
Main Results:
- An externalizing polygenic score (PS) predicted connectivity in a left amygdala-centered circuit, including the inferior frontal gyrus (IFG) and rostral anterior cingulate cortex (rACC).
- Amygdala influenced prefrontal cortex connectivity differently based on PS levels, indicating gene-environment interactions.
- Higher PS was associated with increased hub-like function in the amygdala and rACC, suggesting genetic modulation of network communication.
Conclusions:
- Externalizing polygenic risk is associated with disrupted connectivity in neural networks involved in emotion regulation and impulse control.
- These findings provide evidence for a genetically associated neurobiological vulnerability network for externalizing disorders.
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