Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems

Hahn, Lisa; Schroeter, Matthias L.; Eickhoff, Simon; Otto, Markus; Dukart, Jürgen

Poster (After Call)

FZJ-2022-00661

Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems

Hahn, L. (First author)FZJ* ; Eickhoff, S.FZJ* ; Otto, M. ; Dukart, J. (Corresponding author)FZJ* ; Schroeter, M. L. (Corresponding author)

2021

Society of Biological Psychiatry 2021 Annual Meeting, SOBP, Online, USA, 28 Apr 2021 - 1 May 2021

Please use a persistent id in citations: http://hdl.handle.net/2128/30340

Abstract: Background: Behavioral variant frontotemporal dementia (bvFTD) is characterized by changes in personality and behavior and by progressive structural and functional alterations in frontal and temporal regions. Only little is known about the relationship of these alterations with the underlying pathophysiology. Here, we explored if these alterations follow the distribution of specific neurotransmitter systems.Methods: We evaluated if resting state activity alterations in bvFTD are associated with the known in vivo distribution of specific neurotransmitter systems. For this, maps of fractional amplitude of low frequency fluctuations (fALFF) as derived from resting-state functional magnetic resonance imaging were computed for 52 bvFTD patients relative to 22 healthy controls (HC). We tested if these maps co-localize with the non-pathological distribution of specific neurotransmitter systems and their coding mRNA gene expression.Results: Compared to HC, patients displayed significantly reduced fALFF in fronto-temporal and fronto-parietal regions. These alterations significantly co-localized with the distribution of serotonin (5HT1b, 5HT2a), dopamine (D2), and gamma-aminobutyric acid type A (GABAa) receptors, and the noradrenaline transporter (NAT) (all p≤.001). Significant co-localization of fALFF alterations was also observed with mRNA expression of genes encoding the respective receptors and transporters.Conclusion: We showed that fALFF reduction in bvFTD co-localize with the spatial distribution of serotonergic, dopaminergic, GABAergic, and noradrenalinergic systems, and their coding mRNA gene expression. These findings provide novel insight into neuropathophysiological mechanisms underlying functional alterations in bvFTD.

Contributing Institute(s):