TY  - INPR
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
TI  - Modulatory neurotransmitter genotypes shape dynamic functional connectome reconfigurations
Y1  - 2025/01/22/
AV  - public
JF  - The Journal of Neuroscience
A1  - Jun, Suhnyoung
A1  - Altmann, Andre
A1  - Sadaghiani, Sepideh
N2  - 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.
ID  - discovery10204366
PB  - Society for Neuroscience
UR  - https://doi.org/10.1523/jneurosci.1939-24.2025
SN  - 0270-6474
ER  -