eprintid: 10204366
rev_number: 8
eprint_status: archive
userid: 699
dir: disk0/10/20/43/66
datestamp: 2025-02-06 09:23:18
lastmod: 2025-02-06 09:25:43
status_changed: 2025-02-06 09:23:18
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Jun, Suhnyoung
creators_name: Altmann, Andre
creators_name: Sadaghiani, Sepideh
title: Modulatory neurotransmitter genotypes shape dynamic functional connectome reconfigurations
ispublished: inpress
divisions: UCL
divisions: B04
divisions: F42
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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.
date: 2025-01-22
date_type: published
publisher: Society for Neuroscience
official_url: https://doi.org/10.1523/jneurosci.1939-24.2025
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2357748
doi: 10.1523/JNEUROSCI.1939-24.2025
medium: Print-Electronic
pii: JNEUROSCI.1939-24.2025
lyricists_name: Altmann, Andre
lyricists_id: AALTM39
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
funding_acknowledgements: 1R01MH11622 [HHS | NIH | National Institute of Mental Health]
full_text_status: public
publication: The Journal of Neuroscience
article_number: e1939242025
event_location: United States
issn: 0270-6474
citation:        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 <https://doi.org/10.1523/JNEUROSCI.1939-24.2025>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10204366/1/JNEUROSCI.1939-24.2025.full.pdf