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

Kolesar, Tiffany A.; Bilevicius, Elena; Wilson, Alyssia; Kornelsen, Jennifer

doi:10.1016/j.nicl.2019.102016

Cited by 103 publications

(95 citation statements)

References 128 publications

(363 reference statements)

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“…These changes have been detected in PD‐ANX patients compared to both PD‐noANX patients and HCs and have been shown to correlate with anxiety severity, further corroborating the crucial pathophysiological role of these areas. This parallels with several functional connectivity studies in anxiety patients not affected by PD 29,30 . The insula is proposed to integrate external and internal stimuli, 31 identifying the most relevant ones to guide attention and motor behaviors.…”

Section: Discussionsupporting

confidence: 69%

“…This parallels with several functional connectivity studies in anxiety patients not affected by PD. 29,30 The insula is proposed to integrate external and internal stimuli, 31 identifying the most relevant ones to guide attention and motor behaviors. With its functional connections with the ACC, this system may regulate and activate responses to salience stimuli.…”

Section: Discussionmentioning

confidence: 99%

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Connectivity Correlates of Anxiety Symptoms in Drug‐Naive Parkinson's Disease Patients

et al. 2020

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Background Anxiety symptoms are common in Parkinson's disease (PD). A link between anxiety and cognitive impairment in PD has been demonstrated. Objectives Using resting‐state functional magnetic resonance imaging, we investigated intrinsic brain network connectivity correlates of anxiety symptoms in a cohort of drug‐naive, cognitively unimpaired patients with PD. Methods The intrinsic functional brain connectivity of 25 drug‐naive, cognitively unimpaired PD patients with anxiety, 25 without anxiety, and 20 matched healthy controls was compared. All patients underwent a detailed behavioral and neuropsychological evaluation. Anxiety presence and severity were assessed using the Parkinson's Disease Anxiety Scale. Single‐subject and group‐level independent component analyses were used to investigate functional connectivity differences within and between the major resting‐state networks. Results Decreased connectivity within the default‐mode and sensorimotor networks (SMN), increased connectivity within the executive‐control network (ECN), and divergent connectivity measures within salience and frontoparietal networks (SN and FPN) were detected in PD patients with anxiety compared with those without anxiety. Moreover, patients with anxiety showed a disrupted inter‐network connectivity between SN and SMN, ECN, and FPN. Anxiety severity was correlated with functional abnormalities within these networks. Conclusions Our findings demonstrated that an abnormal intrinsic connectivity within and between the most reported large‐scale networks may represent a potential neural correlate of anxiety symptoms in drug‐naive PD patients even in the absence of clinically relevant cognitive impairment. We hypothesize that these specific cognitive and limbic network architecture changes may represent a potential biomarker of treatment response in clinical trials. © 2020 International Parkinson and Movement Disorder Society

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Connectivity Correlates of Anxiety Symptoms in Drug‐Naive Parkinson's Disease Patients

et al. 2020

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“…Magnetic resonance imaging (MRI), in particular, offers a non-invasive means to measure diverse properties of the human brain, including regional volume, functional responsivity to psychological tasks, functional architecture at rest, and connectivity. Naturally, an abundance of MRI studies of GAD has been made available over the past 20 years (see [ 6 , 7 ] for recent reviews of the literature).…”

Section: Introductionmentioning

confidence: 99%

Altered Task-Evoked Corticolimbic Responsivity in Generalized Anxiety Disorder

Kim

2021

IJMS

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Generalized anxiety disorder (GAD) is marked by uncontrollable, persistent worry and exaggerated response to uncertainty. Here, we review and summarize the findings from the GAD literature that employs functional neuroimaging methods. In particular, the present review focuses on task-based blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. We find that select brain regions often regarded as a part of a corticolimbic circuit (e.g., amygdala, anterior cingulate cortex, prefrontal cortex) are consistently targeted for a priori hypothesis-driven analyses, which, in turn, shows varying degrees of abnormal BOLD responsivity in GAD. Data-driven whole-brain analyses show the insula and the hippocampus, among other regions, to be affected by GAD, depending on the task used in each individual study. Overall, while the heterogeneity of the tasks and sample size limits the generalizability of the findings thus far, some promising convergence can be observed in the form of the altered BOLD responsivity of the corticolimbic circuitry in GAD.

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“…This is important knowledge with potentially far reaching consequences. Volume loss might lead to cognitive deficits and a higher chance of developing mental illness, given that smaller volume of the amygdala and hippocampus has been implicated in the most common psychiatric disorders 50,51 . For instance, it is thought plausible that smoking-related structural brain changes in regions that connect fear response areas (e.g.…”

Section: Discussionmentioning

confidence: 99%

Investigating the causal nature of the relationship of subcortical brain volume with smoking and alcohol use

Logtenberg¹,

Overbeek²,

Pasman

et al. 2020

Preprint

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Background: Structural variation in subcortical brain regions has been linked to substance use, including the most prevalent substances nicotine and alcohol. It may be that pre-existing differences in subcortical brain volume affect smoking and alcohol use, but there is also evidence that smoking and alcohol use can lead to structural changes. We assess the causal nature of this complex relationship with bi-directional Mendelian randomization (MR). Methods: MR uses genetic variants predictive of a certain trait (exposure) as instrumental variables to test causal effects on a certain outcome. Due to random assortment at meiosis, genetic variants shouldnt be associated with confounders, allowing less biased causal inference. We employed summary-level data of the largest available genome-wide association studies of subcortical brain region volumes (nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen, and thalamus; n=50,290) and smoking and alcohol use (smoking initiation, n=848,460; cigarettes per day, n=216,590; smoking cessation, n=378,249; alcohol drinks per week, n=630,154; alcohol dependence, n=46,568). The main analysis, inverse-variance weighted regression, was verified by a wide range of sensitivity methods. Results: There was strong evidence that alcohol dependence decreased amygdala and hippocampal volume and that smoking more cigarettes per day decreased hippocampal volume. From subcortical brain volumes to substance use, there was no or weak evidence for causal effects. Conclusions: Our findings suggest that heavy alcohol use and smoking can causally reduce subcortical brain volume. This adds to accumulating evidence that alcohol and smoking affect the brain, and most likely mental health, warranting more recognition in public health efforts.

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

Abstract: HighlightsPFC-amygdala FC is altered in GAD, indicating top-down processing deficits.GAD had reduced activity for emotion regulation and working memory in the culmen.Salience, default, and central executive nodes have altered structure and function.

Cited by 103 publications

References 128 publications

Connectivity Correlates of Anxiety Symptoms in Drug‐Naive Parkinson's Disease Patients

Connectivity Correlates of Anxiety Symptoms in Drug‐Naive Parkinson's Disease Patients

Altered Task-Evoked Corticolimbic Responsivity in Generalized Anxiety Disorder

Investigating the causal nature of the relationship of subcortical brain volume with smoking and alcohol use

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