Noradrenergic and Dopaminergic Neural Correlates of Trait Anxiety: Unveiling the Impact of Maladaptive Emotion Regulation

BackgroundMaladaptive emotion regulation plays a crucial role in the development and maintenance of elevated anxiety levels, both in patients and in individuals with subclinical symptomatology. While pharmacological treatments for anxiety target the emotion dysregulation through dopaminergic, noradrenergic and serotonergic systems, little is known about the underlying mechanisms. Therefore, the current study depicts the association of these neuromodulatory systems resting-state functioning with trait-anxiety, investigating the role of maladaptive emotion regulation. MethodsAmplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), and whole-brain resting-state functional connectivity (rs-FC) were obtained from the ventral tegmental area (VTA), locus coeruleus (LC) and dorsal raphe, and correlated with trait-anxiety and self-reported maladaptive emotion regulation (N = 60). ResultsTrait-anxiety was positively associated with LCs fALFF and negatively with VTAs whole-brain rs-FC with the left inferior parietal lobule (L-IPL) and the left superior frontal gyrus (L-SFG). Maladaptive emotion regulation was negatively associated with VTAs rs-FC with these regions, with trait-anxiety fully mediating this association. VTA connectivity with the frontal region, but not parietal, positively predicted its amplitude of neural oscillations, an effect that was paralleled by stronger frontal dopaminergic innervation. LimitationsUse of external molecular datasets and need for replication in patients. ConclusionsNoradrenergic and dopaminergic systems appear to contribute differently to subclinical anxiety. While noradrenaline likely acts through a more general mechanism, the dopaminergic dysconnectivity with the frontoparietal control network may act as one of the mechanisms of maladaptive emotion regulation, informing the models on the disorder development. HighlightsO_LITrait-anxiety shows a positive association with the activity of locus coeruleus C_LIO_LITrait-anxiety and emotional regulation are linked to VTA-frontoparietal connectivity C_LIO_LITrait-anxiety fully mediates emotion regulations effect on VTAs connectivity C_LIO_LIStrength of connectivity with VTA is positively linked to the frontal ALFF and fALFF C_LI