Prefrontal-limbic connectivity during worry in older adults with generalized anxiety disorder

Abstract

Objectives: Although generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders in older adults, very little is known about the neurobiology of worry, the hallmark symptom of GAD in adults over the age of 60. This study investigated the neurobiology and neural circuitry of worry in older GAD patients and controls.

Method: Twenty older GAD patients and 16 age-matched controls (mean age = 67.88) were compared on clinical measures and neural activity during worry using functional magnetic resonance imaging.

Results: As expected, worry elicited activation in frontal regions, amygdala, and insula within the GAD group, with a similar but less prominent frontal pattern was observed in controls. Effective connectivity analyses revealed a positive directional circuit in the GAD group extending from ventromedial through dorsolateral prefrontal cortices, converging on the amygdala. A less complex circuit was observed in controls with only dorsolateral prefrontal regions converging on the amygdala; however, a separate circuit passing through the orbitofrontal cortex converged on the insula.

Conclusion: Results elucidate a different neurobiology of pathological versus normal worry in later life. A limited resource model is implicated wherein worry in GAD competes for the same neural resources (e.g. prefrontal cortical areas) that are involved in the adaptive regulation of emotion through cognitive and behavioral strategies.

Keywords:

• generalized anxiety disorder
• GAD
• aging
• neurobiology
• worry
• prefrontal-limbic connectivity

Acknowledgements

The authors would like to thank Dr Jack B. Nitschke for comments on an earlier version of this manuscript. This research was supported by a NARSAD Young Investigator Grant, a Busch Biomedical Grant from Rutgers, and an NIH Center for Clinical and Translational Science Pilot Award from UMDNJ/RWJ Medical University awarded to the first author.

Disclosure statement

No potential conflict of interest was reported by the authors.