Amygdala functional connectivity as a longitudinal biomarker of symptom changes in generalized anxiety

Elena Makovac, David R. Watson, Frances Meeten, Sarah N. Garfinkel, Mara Cercignani, Hugo D. Critchley, Cristina Ottaviani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)
66 Downloads (Pure)


Generalized anxiety disorder (GAD) is characterized by excessive worry, autonomic dysregulation and functional amygdala dysconnectivity, yet these illness markers have rarely been considered together, nor their interrelationship tested longitudinally. We hypothesized that an individual's capacity for emotion regulation predicts longer-term changes in amygdala functional connectivity, supporting the modification of GAD core symptoms. Sixteen patients with GAD (14 women) and individually matched controls were studied at two time points separated by 1 year. Resting-state fMRI data and concurrent measurement of vagally mediated heart rate variability were obtained before and after the induction of perseverative cognition. A greater rise in levels of worry following the induction predicted a stronger reduction in connectivity between right amygdala and ventromedial prefrontal cortex, and enhanced coupling between left amygdala and ventral tegmental area at follow-up. Similarly, amplified physiological responses to the induction predicted increased connectivity between right amygdala and thalamus. Longitudinal shifts in a distinct set of functional connectivity scores were associated with concomitant changes in GAD symptomatology over the course of the year. Results highlight the prognostic value of indices of emotional dysregulation and emphasize the integral role of the amygdala as a critical hub in functional neural circuitry underlying the progression of GAD symptomatology.

Original languageEnglish
Pages (from-to)1719-1728
Number of pages10
JournalSocial Cognitive and Affective Neuroscience
Issue number11
Early online date30 Jun 2016
Publication statusPublished - 1 Nov 2016


  • Amygdala functional connectivity
  • Emotion regulation
  • Generalized anxiety disorder
  • Heart rate variability
  • Longitudinal
  • Perseverative cognition


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