Prefrontal-amygdala connectivity in trait anxiety and generalized anxiety disorder: Testing the boundaries between healthy and pathological worries

• Published in: Journal of affective disorders 2020-04, Vol.267, p.211-219
• Main Authors: Porta-Casteràs, D, Fullana, MA, Tinoco, D, Martínez-Zalacaín, I, Pujol, J, Palao, DJ, Soriano-Mas, C, Harrison, BJ, Via, E, Cardoner, N
• Format: Article
• Language: English
• Subjects: Amygdala - diagnostic imaging; Amygdala; ventromedial prefrontal cortex; Anxiety - diagnostic imaging; Anxiety Disorders - diagnostic imaging; Cross-Sectional Studies; Functional magnetic resonance imaging; Generalized anxiety disorder; Humans; Magnetic Resonance Imaging; Prefrontal Cortex - diagnostic imaging; Resting state; Trait anxiety
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2020.02.029

•GAD participants presented an increased resting-state functional connectivity between left basolateral amygdala and vmPFC.•Non-GAD participants with low and high tendency to worry did not differ in amygala-vmPFC connectivity.•Cognitive anxiety sensitivity was a significant predictor of this circuit connectivity, above the effect of GAD diagnosis.•Our data suggest a categorical differentiation, at a neural level, between pathological and healthy worries. Current brain-based theoretical models of generalized anxiety disorder (GAD) suggest a dysfunction of amygdala-ventromedial prefrontal cortex emotional regulatory mechanisms. These alterations might be reflected by an altered resting state functional connectivity between both areas and could extend to vulnerable non-clinical samples such as high worriers without a GAD diagnosis. However, there is a lack of information in this regard. We investigated differences in resting state functional connectivity between the basolateral amygdala and the ventromedial prefrontal cortex (amygdala-vmPFC) in 28 unmedicated participants with GAD, 28 high-worriers and 28 low-worriers. We additionally explored selected clinical variables as predictors of amygdala-vmPFC connectivity, including anxiety sensitivity. GAD participants presented higher left amygdala-vmPFC connectivity compared to both groups of non-GAD participants, and there were no differences between the latter two groups. In our exploratory analyses, concerns about the cognitive consequences of anxiety (the cognitive dimension of anxiety sensitivity) were found to be a significant predictor of the left amygdala-vmPFC connectivity. The cross-sectional nature of our study preclude us from assessing if functional connectivity measures and anxiety sensitivity scores entail an increased risk of GAD. These results suggest a neurobiological qualitative distinction at the level of the amygdala-vmPFC emotional-regulatory system in GAD compared to non-GAD participants, either high- or low-worriers. At this neural level, they question previous hypotheses of continuity between high worries and GAD development. Instead, other anxiety traits such as anxiety sensitivity might confer a greater proneness to the amygdala-vmPFC connectivity alterations observed in GAD.