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Serotonin-1A receptor C-1019G polymorphism affects brain functional networks.

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • The serotonin-1A (5-HT1A) receptor influences serotonin neuron activity, a key factor in affective disorders.
  • Clinical studies link the 5-HT1A receptor -1019G allele to increased susceptibility to affective disorders, but the mechanism is unclear.

Purpose of the Study:

  • To investigate how serotonin-1A receptor genetic polymorphism affects resting-state functional connectivity (FC) in healthy human subjects.
  • To explore the neural underpinnings of affective disorder predisposition associated with the 5-HT1A receptor.

Main Methods:

  • Functional magnetic resonance imaging (fMRI) was used in 99 healthy participants.
  • A seed-based approach identified resting-state functional connectivity (FC) within the default mode network (DMN), salience network (SN), and central executive network.
  • Participants were genotyped for the serotonin-1A receptor -1019 polymorphism.

Main Results:

  • G-allele carriers showed decreased FC in the DMN within the dorsolateral and ventromedial prefrontal cortices compared to C-homozygotes.
  • G-allele carriers exhibited reduced SN connectivity in the ventromedial prefrontal cortex and subgenual anterior cingulate cortex.
  • Serotonin-1A receptor polymorphism significantly modulated resting-state FC within the DMN and SN.

Conclusions:

  • Genetic variations in the serotonin-1A receptor influence brain network functional connectivity.
  • Altered DMN and SN connectivity in G-allele carriers may contribute to the neural mechanisms underlying predisposition to affective disorders.