Jun, Suhnyoung;
Altmann, Andre;
Sadaghiani, Sepideh;
(2025)
Modulatory neurotransmitter genotypes shape dynamic functional connectome reconfigurations.
The Journal of Neuroscience
, Article e1939242025. 10.1523/JNEUROSCI.1939-24.2025.
(In press).
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Abstract
Dynamic reconfigurations of the functional connectome across different connectivity states are highly heritable, predictive of cognitive abilities, and linked to mental health. Despite their established heritability, the specific polymorphisms that shape connectome dynamics are largely unknown. Given the widespread regulatory impact of modulatory neurotransmitters on functional connectivity, we comprehensively investigated a large set of single nucleotide polymorphisms (SNPs) of their receptors, metabolic enzymes, and transporters in 674 healthy adult subjects (347 females) from the Human Connectome Project. Pre-registered modulatory neurotransmitter SNPs and dynamic connectome features entered a Stability Selection procedure with resampling. We found that specific subsets of these SNPs explain individual differences in temporal phenotypes of fMRI-derived connectome dynamics for which we previously established heritability. Specifically, noradrenergic polymorphisms explained Fractional Occupancy, i.e., the proportion of time spent in each connectome state, and cholinergic polymorphisms explained Transition Probability, i.e., the probability to transition between state pairs, respectively. This work identifies specific genetic effects on connectome dynamics via the regulatory impact of modulatory neurotransmitter systems. Our observations highlight the potential of dynamic connectome features as endophenotypes for neurotransmitter-focused precision psychiatry.
| Type: | Article |
|---|---|
| Title: | Modulatory neurotransmitter genotypes shape dynamic functional connectome reconfigurations |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1523/JNEUROSCI.1939-24.2025 |
| Publisher version: | https://doi.org/10.1523/jneurosci.1939-24.2025 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10204366 |
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