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

Background

Maladaptive 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.

Methods

Amplitude 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).

Results

Trait-anxiety was positively associated with LC’s fALFF and negatively with VTA’s 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 VTA’s 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.

Limitations

Use of external molecular datasets and need for replication in patients.

Conclusions

Noradrenergic 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.

Highlights

• Trait-anxiety shows a positive association with the activity of locus coeruleus

• Trait-anxiety and emotional regulation are linked to VTA-frontoparietal connectivity

• Trait-anxiety fully mediates emotion regulation’s effect on VTA’s connectivity

• Strength of connectivity with VTA is positively linked to the frontal ALFF and fALFF