Abstract
Neuropeptide Y (NPY) is a neurotransmitter that has been implicated in the development of anxiety and mood disorders. Low levels of NPY have been associated with risk for these disorders, and high levels with resilience. Anxiety and depression are associated with altered intrinsic functional connectivity of brain networks, but the effect of NPY on functional connectivity is not known. Here, we test the hypothesis that individual differences in NPY expression affect resting functional connectivity of the default mode and salience networks. We evaluated static connectivity using graph theoretical techniques and dynamic connectivity with Leading Eigenvector Dynamics Analysis (LEiDA). To increase our power of detecting NPY effects, we genotyped 221 individuals and identified 29 healthy subjects at the extremes of genetically predicted NPY expression (12 high, 17 low). Static connectivity analysis revealed that lower levels of NPY were associated with shorter path lengths, higher global efficiency, higher clustering, higher small-worldness, and average higher node strength within the salience network, whereas subjects with high NPY expression displayed higher modularity and node eccentricity within the salience network. Dynamic connectivity analysis showed that the salience network of low-NPY subjects spent more time in a highly coordinated state relative to high-NPY subjects, and the salience network of high-NPY subjects switched between states more frequently. No group differences were found for static or dynamic connectivity of the default mode network. These findings suggest that genetically driven individual differences in NPY expression influence risk of mood and anxiety disorders by altering the intrinsic functional connectivity of the salience network.
Highlights
Neuropeptide Y (NPY) is among the most abundantly expressed peptides in the brain (Tatemoto et al, 1982; Adrian et al, 1983; Allen et al, 1983), and is known to affect the neural processing of emotion, appetite, and stress (Morgan et al, 2002; Van Den Heuvel et al, 2015; Reichmann and Holzer, 2016)
We recently showed that healthy individuals with genetically driven low NPY expression exhibit heightened activation of the nucleus accumbens in response to salient stimuli (Warthen et al, 2018)
In this paper we investigate how NPY expression effects both the static and dynamic connectivity of the brain using graph theoretical methods and Leading Eigenvector Dynamics Analysis (LEiDA) (Cabral et al, 2017), respectively
Summary
Neuropeptide Y (NPY) is among the most abundantly expressed peptides in the brain (Tatemoto et al, 1982; Adrian et al, 1983; Allen et al, 1983), and is known to affect the neural processing of emotion, appetite, and stress (Morgan et al, 2002; Van Den Heuvel et al, 2015; Reichmann and Holzer, 2016) Individuals vary in their expression of NPY, and low levels of NPY have been associated with the development of anxiety (Reichmann and Holzer, 2016), depression. In this paper we investigate how NPY expression effects both the static and dynamic connectivity of the brain using graph theoretical methods and Leading Eigenvector Dynamics Analysis (LEiDA) (Cabral et al, 2017), respectively
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