Localized gray matter volume abnormalities in generalized anxiety disorder

Department of Clinical Psychology, University of Graz, Universitätsplatz 2/III, 8010, Graz, Austria, .
European Archives of Psychiatry and Clinical Neuroscience (Impact Factor: 3.53). 06/2011; 261(4):303-7. DOI: 10.1007/s00406-010-0147-5
Source: PubMed


Generalized anxiety disorder (GAD) is characterized by excessive and persistent worrying. Neural substrates of this disorder are insufficiently understood, which relates to functional as well as to structural brain abnormalities. Especially, findings on the neuroanatomy of GAD have been inconsistent and were predominantly derived from pediatric samples. Therefore, we studied adult patients. Thirty-one women (16 patients with GAD and 15 healthy control participants) underwent structural MRI scanning. Gray matter volumes for specific brain regions involved in worrying, anticipatory anxiety, and emotion regulation were analyzed by means of voxel-based morphometry. Relative to controls, patients with GAD had larger volumes of the amygdala and the dorsomedial prefrontal cortex (DMPFC). Moreover, patients' self-reports on symptom severity were positively correlated with volumes of the DMPFC and the anterior cingulate cortex. Patients with GAD show localized gray matter volume differences in brain regions associated with anticipatory anxiety and emotion regulation. This abnormality may represent either a predisposition for GAD or a consequence of disorder-specific behavior, such as chronic worrying. This issue should be addressed in future MRI studies.

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    • "No volumetric differences were detected for other regions such as the amygdala. While not all investigations of GM volume differences in GAD report higher amygdala volumes, these were nevertheless found in a number of studies (De Bellis et al., 2000; Etkin et al., 2009; Schienle et al., 2011). On the contrary, amygdala GM decreases were shown for major depression in a number of meta-analyses (Hamilton et al., 2008; Sacher et al., 2012; Bora et al., 2012a). "
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    ABSTRACT: Increasing efforts have been made to investigate the underlying pathophysiology of generalized anxiety disorder (GAD), but only limited consistent information is available on gray (GM) and white matter (WM) volume changes in affected adults. Additionally, few studies employed dimensional approaches to GAD pathology. This study compares structural brain imaging data from n=19 GAD subjects and n=24 healthy comparison (HC) subjects, all medication-free and matched on age, sex and education. Separate categorical and dimensional models were employed using voxel-based morphometry for GM and WM. Significantly higher GM volumes were found in GAD subjects mainly in basal ganglia structures and less consistently in the superior temporal pole. For WM, GAD subjects showed significantly lower volumes in the dlPFC. Largely consistent findings in dimensional and categorical models point toward these structural alterations being reliable and of importance for GAD. While lower volume in the dlPFC could reflect impaired emotional processing and control over worry in GAD, basal ganglia alterations may be linked to disturbed gain and loss anticipation as implicated in previous functional GAD studies. As perturbations in anticipation processes are central to GAD, these areas may warrant greater attention in future studies.
    10/2015; DOI:10.1016/j.pscychresns.2015.10.009
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    • "In particular, Greenberg et al. (2013) showed an abnormal functional response of the ACC in patients with GAD during fear generalization tasks. Schienle et al. (2011) described a positive relationship between GM volume of this area and the self-reporting on the degree of worrying in a GAD group. Another study found an inverse correlation between thickness of the ACC and the severity of the social anxiety symptoms in patients with SAD (Frick et al. 2013). "
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    ABSTRACT: Objectives The State-Trait Anxiety Inventory (STAI) and the Hamilton scale for anxiety (HARS) are two of the most important scales employed in clinical and psychological realms for the evaluation of anxiety. Although the reliability and sensibility of these scales are widely demonstrated there is an open debate on what exactly their scores reflect. Neuroimaging provides the potential to validate the quality and reliability of clinical scales through the identification of specific biomarkers. For this reason, we evaluated the neural correlates of these two scales in a large cohort of healthy individuals using structural neuroimaging methods.Case reportNeuroimaging analysis included thickness/volume estimation of cortical and subcortical limbic structures, which were regressed on anxiety inventory scores with age and gender used for assessing discriminant validity. A total of 121 healthy subjects were evaluated. Despite the two anxiety scales, at a behavioral level, displaying significant correlations among them (HARS with STAI-state (r = 0.24; P = 0.006) and HARS with STAI-trait (r = 0.42; P < 0.001)), multivariate neuroimaging analyses demonstrated that anatomical variability in the anterior cingulate cortex was the best predictor of the HARS scores (all β's ≥ 0.31 and P's ≤ 0.01), whereas STAI-related measures did not show any significant relationship with regions of limbic circuits, but their scores were predicted by gender (all β's ≥ 0.23 and P's ≤ 0.02).Conclusion Although the purpose of HARS and STAI is to quantify the degree and characteristics of anxiety-like behaviors, our neuroimaging data indicated that these scales are neurobiologically different, confirming that their scores might reflect different aspects of anxiety: the HARS is more related to subclinical expression of anxiety disorders, whereas the STAI captures sub-dimensions of personality linked to anxiety.
    Brain and Behavior 07/2014; 4(4). DOI:10.1002/brb3.232 · 2.24 Impact Factor
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    • "One study [14] found that adult GAD patients exhibited increased activation to angry expressions in the lateral frontal cortex, whereas another study [22] suggested that adult GAD patients showed decreased activation to emotional conflict in the dorsomedial prefrontal cortex compared with healthy controls. The limited structural neuroimaging studies have shown a sub-threshold decrease of gray matter volume in bilateral ventrolateral cortex in pediatric anxiety patients [18], and a larger volume of the dorsomedial prefrontal cortex in adult GAD patients [15]. In addition, a functional connectivity study [22] has revealed the aberrant functional connection between amygdala and the prefrontal cortex, suggesting neural correlates for emotion regulation deficits in adults with GAD. "
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    ABSTRACT: Previous neuroimaging studies have suggested an abnormal neural circuitry of emotion regulation including the amygdala and prefrontal cortex in both adult and adolescent generalized anxiety disorder (GAD) patients. Aberrant integrity of white matter in this neural circuitry has been verified in adult GAD patients. White matter abnormalities in adolescent GAD patients have not been detected. Twenty-five adolescents with GAD and 24 healthy controls underwent a diffusion tensor imaging scan. Fractional anisotropy (FA) was compared between groups with a voxel-wise Tract-Based Spatial Statistics (TBSS) analysis method. Compared with healthy controls, adolescents with GAD showed significantly reduced FA in bilateral uncinate fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and corona radiata. The findings in the present study suggest a neural basis of emotion dysregulation in adolescent GAD patients.
    BMC Psychiatry 02/2014; 14(1):41. DOI:10.1186/1471-244X-14-41 · 2.21 Impact Factor
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