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Modulatory Neurotransmitter Genotypes Shape Dynamic Functional Connectome Reconfigurations.

Suhnyoung Jun1,2, Andre Altmann3, Sepideh Sadaghiani4,2,5

  • 1Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 suhnyoung.jun@gmail.com.

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Specific gene variants influence brain network dynamics. Noradrenergic and cholinergic system polymorphisms impact how the brain occupies and transitions between states, offering insights into mental health.

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Dynamic functional connectome reconfigurations are highly heritable and linked to cognition and mental health.
  • The specific genetic underpinnings of connectome dynamics remain largely unknown.
  • Modulatory neurotransmitter systems significantly impact functional connectivity.

Purpose of the Study:

  • To comprehensively investigate single nucleotide polymorphisms (SNPs) in modulatory neurotransmitter systems.
  • To identify genetic contributions to individual differences in dynamic connectome features.
  • To link specific neurotransmitter pathways to distinct temporal phenotypes of brain connectivity.

Main Methods:

  • Analysis of a large set of SNPs related to neurotransmitter receptors, enzymes, and transporters.
  • Utilized data from 674 healthy adult subjects from the Human Connectome Project.
  • Employed Stability Selection with resampling to identify significant SNP-connectome associations.

Main Results:

  • Specific subsets of modulatory neurotransmitter SNPs explain individual differences in temporal connectome dynamics.
  • Noradrenergic polymorphisms were associated with Fractional Occupancy (time spent in states).
  • Cholinergic polymorphisms were associated with Transition Probability (state transitions).

Conclusions:

  • Identified specific genetic effects of modulatory neurotransmitter systems on connectome dynamics.
  • Demonstrated that dynamic connectome features can serve as endophenotypes.
  • Highlighted potential for neurotransmitter-targeted precision psychiatry.