A systematic review of fMRI studies in generalized anxiety disorder: Evaluating its neural and cognitive basis

Mochcovitch, Marina Dyskant; Freire, Rafael C.; Garcia, Rafael Ferreira; Nardi, Antônio Egídio

doi:10.1016/j.jad.2014.06.041

Cited by 163 publications

(126 citation statements)

References 31 publications

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“…CBD produced no changes in predicted areas (relative to placebo) but reduced activation in the left insula, superior temporal gyrus, and transverse temporal gyrus. The fearful faces task activates the amygdala, and other medial temporal areas involved in [107] Varying in schizotypy and cannabis use, DBP Inhaled, 16 mg, acute Baseline VAS anxiety No significant effect of CBD HV = healthy volunteers; DBP = double-blind placebo; SAD = social anxiety disorder; HC = healthy controls; THC = Δ 9-tetrahydrocannabinol; STAI = Spielberger's state trait anxiety inventory; VAMS = visual analog mood scale; BP = blood pressure; SPST = simulated public speaking test; SCR = skin conductance response; SPECT = single-photon emission computed tomography; SSPS-N = negative self-evaluation subscale; HR = heart rate; VAS = visual analog scale, CBD = cannabidiol ↑ rCBF in the right posterior cingulate gyrus CBD = cannabidiol; HV = healthy controls; DBP = double-blind placebo; SAD = social anxiety disorder; HC = healthy controls; SPECT = single-photo emission computed tomography; rCBF = regional cerebral blood flow; fMRI = functional magnetic resonance imaging; HPC = hippocampus; HYP = hypothalamus; PHG = parahippocampal gyrus; STG = superior temporal gyrus; MTG = medial temporal gyrus; ACC = anterior cingulate cortex; PCC = posterior cingulate cortex emotion processing, and heightened amygdala response activation has been reported in anxiety disorders, including GAD and PTSD [113,114]. CBD attenuated blood-oxygen-level dependent activation in the left amygdala, and the anterior and posterior cingulate cortex in response to intensely fearful faces, and also reduced amplitude in skin conductance fluctuation, which was highly correlated with amygdala activation [109].…”

Section: Evidence From Neuroimaging Studiesmentioning

confidence: 99%

Cannabidiol as a Potential Treatment for Anxiety Disorders

et al. 2015

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Cannabidiol (CBD), a Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a range of neuropsychiatric disorders. The purpose of the current review is to determine CBD's potential as a treatment for anxiety-related disorders, by assessing evidence from preclinical, human experimental, clinical, and epidemiological studies. We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely; however, few studies have investigated chronic CBD dosing. Likewise, evidence from human studies supports an anxiolytic role of CBD, but is currently limited to acute dosing, also with few studies in clinical populations. Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with need for further study of chronic and therapeutic effects in relevant clinical populations.

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Section: Evidence From Neuroimaging Studiesmentioning

confidence: 99%

Cannabidiol as a Potential Treatment for Anxiety Disorders

et al. 2015

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“…There are a number of distinct brain regions within the PFC that are dysregulated in anxiety and mood disorders, including the orbitofrontal (OFC), ventrolateral prefrontal (vlPFC), and medial prefrontal (mPFC) cortices (3)(4)(5). Of these, a region within mPFC (pregenual cingulate cortex) has been implicated in regulating negative emotional valence in decision making (6), but the contribution of the other regions remains unknown.…”

mentioning

confidence: 99%

Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making

Clarke

Horst

Roberts

2015

Proc. Natl. Acad. Sci. U.S.A.

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Dysregulation of the orbitofrontal and ventrolateral prefrontal cortices is implicated in anxiety and mood disorders, but the specific contributions of each region are unknown, including how they gate the impact of threat on decision making. To address this, the effects of GABAergic inactivation of these regions were studied in marmoset monkeys performing an instrumental approach–avoidance decision-making task that is sensitive to changes in anxiety. Inactivation of either region induced a negative bias away from punishment that could be ameliorated with anxiolytic treatment. However, whereas the effects of ventrolateral prefrontal cortex inactivation on punishment avoidance were seen immediately, those of orbitofrontal cortex inactivation were delayed and their expression was dependent upon an amygdala–anterior hippocampal circuit. We propose that these negative biases result from deficits in attentional control and punishment prediction, respectively, and that they provide the basis for understanding how distinct regional prefrontal dysregulation contributes to the heterogeneity of anxiety disorders with implications for cognitive-behavioral treatment strategies.

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“…Decreased PFC‐amygdala connectivity is perhaps the most consistent FC abnormality reported for these regions in GAD (Hilbert et al., 2014; Mochcovitch et al., 2014; Taylor & Whalen, 2015). In HCs these regions are anticorrelated, which is often interpreted as PFC inhibiting amygdala (Banks, Eddy, Angstadt, Nathan, & Phan, 2007; Etkin, Egner, Peraza, Kandel, & Hirsch, 2006; Kim et al., 2011; Ochsner et al., 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Patients with GAD are characterized by abnormal neural activity , in prefrontal cortical (PFC) and limbic regions, including anterior cingulate cortex (ACC), anterior insula (AI) and amygdala (Hilbert, Lueken, & Beesdo‐Baum, 2014; Mochcovitch, da Rocha Freire, Garcia, & Nardi, 2014; Taylor & Whalen, 2015). PFC‐amygdala coupling (or functional connectivity (FC); Friston, 2011), has also been shown to be weaker in GAD, and has demonstrated association with symptom severity.…”

Section: Introductionmentioning

confidence: 99%

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Neural functional architecture and modulation during decision making under uncertainty in individuals with generalized anxiety disorder

et al. 2018

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BackgroundRecent evidence suggests that repetitive transcranial magnetic stimulation (rTMS) might be effective in treating generalized anxiety disorder (GAD). Cognitive models of GAD highlight the role of intolerance of uncertainty (IU) in precipitating and maintaining worry, and it has been hypothesized that patients with GAD exhibit decision‐making deficits under uncertain conditions. Improving understanding of the neural mechanisms underlying cognitive deficits associated with IU may lead to the identification of novel rTMS treatment targets and optimization of treatment parameters. The current report describes two interrelated studies designed to identify and verify a potential neural target for rTMS treatment of GAD.MethodsStudy I explored the integrity of prefrontal cortex (PFC) and amygdala neural networks, which underlie decision making under conditions of uncertainty, in GAD. Individuals diagnosed with GAD (n = 31) and healthy controls (n = 20) completed a functional magnetic resonance imaging (fMRI) gambling task that manipulated uncertainty using high versus low error rates. In a subsequent randomized‐controlled trial (Study II), a subset of the GAD sample (n = 16) completed the fMRI gambling task again after 30 sessions of active versus sham rTMS (1 Hz, right dorsolateral prefrontal cortex) to investigate the modulation of functional networks and symptoms.ResultsIn Study I, participants with GAD demonstrated impairments in PFC‐PFC and PFC‐amygdala functional connectivity (FC) mostly during the high uncertainty condition. In Study II, one region of interest pair, dorsal anterior cingulate (ACC) – subgenual ACC, showed “normalization” of FC following active, but not sham, rTMS, and neural changes were associated with improvement in worry symptoms.ConclusionsThese results outline a possible treatment mechanism of rTMS in GAD, and pave the way for future studies of treatment optimization.

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A systematic review of fMRI studies in generalized anxiety disorder: Evaluating its neural and cognitive basis

Cited by 163 publications

References 31 publications

Cannabidiol as a Potential Treatment for Anxiety Disorders

Cannabidiol as a Potential Treatment for Anxiety Disorders

Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making

Neural functional architecture and modulation during decision making under uncertainty in individuals with generalized anxiety disorder

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