The 5-HTTLPR Polymorphism Affects Network-Based Functional Connectivity in the Visual-Limbic System in Healthy Adults
Hengyi Cao1, Anais Harneit1, Henrik Walter2
1Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Summary
The serotonin transporter gene variant (5-HTTLPR) did not affect amygdala activation but was linked to altered visual-limbic network connectivity, impacting emotion regulation in healthy adults.
Area of Science:
- Neuroscience
- Genetics
- Psychology
Background:
- The serotonin transporter-linked polymorphic region (5-HTTLPR) is a genetic variant influencing serotonin transporter expression.
- The short allele (S) of 5-HTTLPR has been linked to emotion dysregulation, but its neural mechanisms remain unclear.
- Previous studies on 5-HTTLPR's effect on amygdala activation during emotional processing have yielded conflicting results.
Purpose of the Study:
- To re-evaluate the association between 5-HTTLPR and amygdala activation in a healthy cohort.
- To investigate potential network-based functional connectivity phenotypes associated with 5-HTTLPR.
- To assess the reliability, behavioral significance, and structural independence of identified network phenotypes.
Main Methods:
- Functional magnetic resonance imaging (fMRI) was used during an emotional face processing task in 223 healthy subjects.
- Analysis focused on amygdala activation and functional connectivity within a visual-limbic subnetwork.
- Emotion suppression scores were collected, and test-retest reliability of connectivity metrics was evaluated.
Main Results:
- No significant association was found between 5-HTTLPR genotype and amygdala activation.
- The number of S alleles in 5-HTTLPR significantly correlated with reduced functional connectivity in a visual-limbic subnetwork (PFWE=0.03).
- Lower subnetwork connectivity was associated with higher emotion suppression scores (P=0.01) and was reliable and independent of structural factors.
Conclusions:
- Genetic variation in 5-HTTLPR is associated with functional connectivity within a visual-limbic network, not directly with amygdala activation.
- This network-based phenotype links 5-HTTLPR to emotion regulation, suggesting a more complex neural mechanism than previously thought.
- Further research is needed to critically evaluate the association between 5-HTTLPR and amygdala activation.
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