Emotion Reactivity and Regulation in Late-Life Generalized Anxiety Disorder: Functional Connectivity at Baseline and Post-Treatment

Generalized anxiety disorder (GAD) is one of the most prevalent mental disorders in the elderly, but its functional neuroanatomy is not well understood. Given the role of emotion dysregulation in GAD, we sought to describe the neural bases of emotion regulation in late-life GAD by analyzing the functional connectivity (FC) in the Salience Network and the Executive Control Network during worry induction and worry reappraisal. Methods: The study included 28 elderly GAD and 31 non-anxious comparison participants. Twelve elderly GAD completed a 12-week pharmacotherapy trial. We used an in-scanner worry script that alternates blocks of worry induction and reappraisal. We assessed network FC, using the following seeds: anterior insula (AI), dorsolateral prefrontal cortex (dlPFC), the bed nucleus of stria terminalis (BNST), and the paraventricular nucleus (PVN). Results: GAD participants exhibited greater FC during worry induction between the left AI and the right orbitofrontal cortex, and between the BNST and the subgenual cingulate. During worry reappraisal, the non-anxious participants had greater FC between the left dlPFC and the medial PFC, as well as between the left AI and the medial PFC, and elderly GAD patients had greater FC between the PVN and the amygdala. Following 12 weeks of pharmacotherapy, GAD participants had greater connectivity between the dlPFC and several prefrontal regions during worry reappraisal. Conclusion: FC during worry induction and reappraisal points toward abnormalities in both worry generation and worry reappraisal. Following successful pharmacologic treatment, we observed greater connectivity in the prefrontal nodes of the Executive Control Network during reappraisal of worry.