Prefrontal and amygdala engagement during emotional reactivity and regulation in generalized anxiety disorder

Fitzgerald, Jacklynn M.; Phan, K. Luan; Kennedy, Amy E.; Shankman, Stewart A.; Langenecker, Scott A.; Klumpp, Heide

doi:10.1016/j.jad.2017.05.013

Cited by 49 publications

(48 citation statements)

References 86 publications

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“… 68 Normal activation in the dlPFC may not be affected because of help from other brain areas of the frontoparietal network. Behavior studies have shown that patients with anxiety disorder can successfully down-regulate their negative emotion, 43 , 44 which may be in line with the above putative mechanism by which the activity of the dlPFC is not affected. Second, although in their review Zilverstand et al 3 reported abnormal activity in the dlPFC in anxiety disorders, they did not conduct a meta-analysis to provide a comprehensive description of the neurobiological underpinnings of cognitive emotion dysregulation.…”

Section: Discussionsupporting

confidence: 59%

Prefrontoparietal dysfunction during emotion regulation in anxiety disorder: a meta-analysis of functional magnetic resonance imaging studies

Wang¹,

Zhang²,

Si³

et al. 2018

NDT

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ObjectiveImpairments in emotion regulation, and more specifically in cognitive reappraisal, are thought to play a key role in the pathogenesis of anxiety disorders. However, the available evidence on such deficits is inconsistent. To further illustrate the neurobiological underpinnings of anxiety disorder, the present meta-analysis summarizes functional magnetic resonance imaging (fMRI) findings for cognitive reappraisal tasks and investigates related brain areas.MethodsWe performed a comprehensive series of meta-analyses of cognitive reappraisal fMRI studies contrasting patients with anxiety disorder with healthy control (HC) subjects, employing an anisotropic effect-size signed differential mapping approach. We also conducted a subgroup analysis of medication status, anxiety disorder subtype, data-processing software, and MRI field strengths. Meta-regression was used to explore the effects of demographics and clinical characteristics. Eight studies, with 11 datasets including 219 patients with anxiety disorder and 227 HC, were identified.ResultsCompared with HC, patients with anxiety disorder showed relatively decreased activation of the bilateral dorsomedial prefrontal cortex (dmPFC), bilateral dorsal anterior cingulate cortex (dACC), bilateral supplementary motor area (SMA), left ventromedial prefrontal cortex (vmPFC), bilateral parietal cortex, and left fusiform gyrus during cognitive reappraisal. The subgroup analysis, jackknife sensitivity analysis, heterogeneity analysis, and Egger’s tests further confirmed these findings.ConclusionsImpaired cognitive reappraisal in anxiety disorder may be the consequence of hypo-activation of the prefrontoparietal network, consistent with insufficient top-down control. Our findings provide robust evidence that functional impairment in prefrontoparietal neuronal circuits may have a significant role in the pathogenesis of anxiety disorder.

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Section: Discussionsupporting

confidence: 59%

Prefrontoparietal dysfunction during emotion regulation in anxiety disorder: a meta-analysis of functional magnetic resonance imaging studies

Wang¹,

Zhang²,

Si³

et al. 2018

NDT

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“…While one study showed reduced effective connectivity in the amygdala (Qiao et al., 2017 [frontal gyrus seeds]), and another observed reduced FC between the right and left amygdala (Liu et al., 2015), all other FC results were greater for GAD (albeit with inconsistent seed regions; Andreescu et al., 2015; Buff et al., 2016; Liu et al., 2015; Mohlman et al., 2017; Qiao et al., 2017) and spanning all age groups. Finally, the majority of task results ( n = 11) indicated greater amygdala activity for subjects with GAD for passive (Fitzgerald et al., 2017; Hölzel et al., 2013; McClure et al., 2007; Nitschke et al., 2009), congruency (Etkin et al., 2010; Etkin and Schatzberg, 2011; Fonzo et al., 2015, 2014; Monk et al., 2008; Price et al., 2011), and emotion modulation (Mohlman et al., 2017) tasks, while only a few studies in adults ( n = 2) showed reduced activity for subjects with GAD in passive (Carlson et al., 2017) and congruency (Blair et al., 2012) tasks. One study investigating high uncertainty observed both increased and decreased activity in the amygdala (Yassa et al., 2012).…”

Section: Resultsmentioning

confidence: 93%

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

Kolesar

Bilevicius

Wilson

et al. 2019

NeuroImage: Clinical

102

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“…Fitzgerald et al114 demonstrated that emotion regulation disturbances in GAD involve excessive reactivity to negative stimuli and a failure to effectively downregulate negative affective states. The authors reported that GAD patients engaged the left amygdala to a greater extent while viewing negative images, which suggests that these patients are more responsive to negative stimuli.…”

Section: Methodsmentioning

confidence: 99%

Structural and functional neuroimaging studies in generalized anxiety disorder: a systematic review

Madonna

Delvecchio

Soares

et al. 2019

Braz. J. Psychiatry

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Objectives:Brain imaging studies carried out in patients suffering from generalized anxiety disorder (GAD) have contributed to better characterize the pathophysiological mechanisms underlying this disorder. The present study reviews the available functional and structural brain imaging evidence on GAD, and suggests further strategies for investigations in this field.Methods:A systematic literature review was performed in PubMed, PsycINFO, and Google Scholar, aiming to identify original research evaluating GAD patients with the use of structural and functional magnetic resonance imaging as well as diffusion tensor imaging.Results:The available studies have shown impairments in ventrolateral and dorsolateral prefrontal cortex, anterior cingulate, posterior parietal regions, and amygdala in both pediatric and adult GAD patients, mostly in the right hemisphere. However, the literature is often tentative, given that most studies have employed small samples and included patients with comorbidities or in current use of various medications. Finally, different methodological aspects, such as the type of imaging equipment used, also complicate the generalizability of the findings.Conclusions:Longitudinal neuroimaging studies with larger samples of both juvenile and adult GAD patients, as well as at risk individuals and unaffected relatives, should be carried out in order to shed light on the specific biological signature of GAD.

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Prefrontal and amygdala engagement during emotional reactivity and regulation in generalized anxiety disorder

Cited by 49 publications

References 86 publications

Prefrontoparietal dysfunction during emotion regulation in anxiety disorder: a meta-analysis of functional magnetic resonance imaging studies

Prefrontoparietal dysfunction during emotion regulation in anxiety disorder: a meta-analysis of functional magnetic resonance imaging studies

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

Structural and functional neuroimaging studies in generalized anxiety disorder: a systematic review

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