Systematic review and meta-analyses of neural structural and functional differences in generalized anxiety disorder and healthy controls using magnetic resonance imaging

Tiffany A Kolesar; Elena Bilevicius; Alyssia D Wilson; Jennifer Kornelsen

doi:10.1016/j.nicl.2019.102016

Systematic review and meta-analyses of neural structural and functional differences in generalized anxiety disorder and healthy controls using magnetic resonance imaging

Neuroimage Clin. 2019:24:102016. doi: 10.1016/j.nicl.2019.102016. Epub 2019 Oct 14.

Authors

Tiffany A Kolesar¹, Elena Bilevicius², Alyssia D Wilson³, Jennifer Kornelsen⁴

Affiliations

¹ Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada.
² Department of Psychology, University of Manitoba, Winnipeg, MB, Canada.
³ Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁴ Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada; Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada; Department of Radiology, University of Manitoba, Winnipeg, MB, Canada. Electronic address: Jennifer.Kornelsen@umanitoba.ca.

Abstract

Objective: To compare structure, functional connectivity (FC) and task-based neural differences in subjects with generalized anxiety disorder (GAD) compared to healthy controls (HC).

Methods: The Embase, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched from inception until March 12, 2018. Two reviewers independently screened titles, abstracts, and full-text articles. Data were extracted from records directly contrasting GAD and HC that included structure (connectivity and local indices such as volume, etc.), FC, or task-based magnetic resonance imaging data. Meta-analyses were conducted, as applicable, using AES-SDM software.

Results: The literature search produced 4,645 total records, of which 85 met the inclusion criteria for the systematic review. Records included structural (n = 35), FC (n = 33), and task-based (n = 42) findings. Meta-analyses were conducted on voxel-based morphometry and task-based results.

Discussion: The systematic review confirms and extends findings from previous reviews. Although few whole-brain resting state studies were conducted, key nodes of resting state networks have altered physiology: the hippocampus (default network), ACC and amygdala (salience network), have reduced volume, and the dlPFC (central executive network) and ACC have reduced FC with the amygdala in GAD. Nodes in the sensorimotor network are also altered with greater pre- and postcentral volume, reduced supplementary motor area volume, and reduced FC in anterior and increased FC in posterior cerebellum.

Conclusions: Despite limitations due to sample size, the meta-analyses highly agree with the systematic review and provide evidence of widely distributed neural differences in subjects with GAD, compared to HC. Further research optimized for meta-analyses would greatly improve large-scale comparisons.

Keywords: Functional magnetic resonance imaging; Generalized anxiety disorder; Meta-analysis; Systematic review.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Amygdala* / diagnostic imaging
Amygdala* / pathology
Amygdala* / physiopathology
Anxiety Disorders* / diagnostic imaging
Anxiety Disorders* / pathology
Anxiety Disorders* / physiopathology
Cerebral Cortex* / diagnostic imaging
Cerebral Cortex* / pathology
Cerebral Cortex* / physiopathology
Connectome*
Humans
Magnetic Resonance Imaging*
Nerve Net* / diagnostic imaging
Nerve Net* / pathology
Nerve Net* / physiopathology