White-matter abnormalities in the right posterior hemisphere in generalized anxiety disorder: a diffusion imaging study

Brambilla, Paolo; Como, Giuseppe; Isola, Miriam; Taboga, F.; Zuliani, Riccardo; Goljevscek, Serena; Ragogna, M.; Brondani, Giovanni; Baiano, Monica; Perini, Laura; Ferro, Adele; Bazzocchi, Massimo; Zuiani, Chiara; Balestrieri, Matteo

doi:10.1017/s0033291711001255

Cited by 29 publications

(17 citation statements)

References 79 publications

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“…Of note, a recent DTI study of GAD did not report on FA for the uncinate fasciculus, but instead used a method assessing apparent diffusion coefficient (ADC), which is equivalent to MD, for circular ROIs in each of the four major brain lobes and the corpus callosum, and found no group differences for either the frontal or temporal lobe. 42 The uncinate fasciculus findings here provide complementary support for past fMRI studies in GAD that have noted hyperactivity of the amygdala relative to healthy controls while participants are involved in processes such as implicit emotion regulation and conflict monitoring, 9 the anticipation of emotional (and non-emotional) images, 4 and viewing emotional faces. 10,11 One interpretation of the amygdala hyperactivity that has frequently been observed in GAD is that patients fail to effectively recruit prefrontal circuitry that serves to regulate amygdala responses.…”

Section: Discussionsupporting

confidence: 77%

“…The null findings for MD in the uncinate fasciculus are consistent with the only previously published MD findings for GAD. 42 Although the precise biological characteristics associated with different DTI measures are not fully known, 63 FA and MD likely quantify complementary aspects of brain microstructure. Differences in FA may reflect alterations in either myelination or axonal density, whereas MD reflects the overall density of tissue membranes irrespective of fiber orientation.…”

Section: Discussionmentioning

confidence: 99%

“…31–37 Recent studies using diffusion tensor imaging (DTI) indicate a promising role for the uncinate fasciculus as a candidate marker of regulation deficits in GAD, as reduced structural integrity of the uncinate fasciculus has been implicated in social anxiety disorder, 38 bipolar disorder, 39 trait anxiety, 40 and individuals with low-expressing 5-HTTLPR alleles. 41 The sole prior report on white matter in GAD 42 did not specifically investigate the uncinate fasciculus and used a different measure of diffusion than in the above reports. 38–41 …”

Section: Introductionmentioning

confidence: 99%

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Reduced Structural Connectivity of a Major Frontolimbic Pathway in Generalized Anxiety Disorder

Tromp

Grupe²,

Oathes³

et al. 2012

Arch Gen Psychiatry

157

129

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Context Emotion regulation deficits figure prominently in generalized anxiety disorder (GAD), as well as other anxiety and mood disorders. Research examining emotion regulation and top-down modulation has implicated reduced coupling of the amygdala with prefrontal and anterior cingulate cortex (ACC), suggesting altered frontolimbic white matter connectivity in GAD. Objective To investigate structural connectivity between ventral prefrontal/ACC areas and the amygdala in GAD, and to assess associations with functional connectivity between those areas. Design Participants underwent diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) scans. Setting University magnetic resonance imaging facility. Participants Forty-nine GAD patients and 39 healthy volunteers, including a subset of 21 patients without comorbid Axis I diagnoses and 21 healthy volunteers matched for age, sex, and education. Main Outcome Measure Mean fractional anisotropy (FA) values in the left and right uncinate fasciculus, as measured by tract-based analysis for DTI data. Results Lower mean FA values in bilateral uncinate fasciculus indicated reduced frontolimbic structural connectivity in GAD. This reduction in uncinate fasciculus integrity was most pronounced for patients without comorbidity and was not observed in other white matter tracts. Across all subjects, higher FA values were associated with more negative functional coupling between the pregenual ACC and amygdala during the anticipation of aversion. Conclusions Decreased frontolimbic structural connectivity suggests a neural basis for emotion regulation deficits in GAD. The functional significance of these structural differences is underscored by decreased functional connectivity between the ACC and amygdala in subjects with reduced structural integrity of the uncinate fasciculus.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reduced Structural Connectivity of a Major Frontolimbic Pathway in Generalized Anxiety Disorder

Tromp

Grupe²,

Oathes³

et al. 2012

Arch Gen Psychiatry

157

129

View full text Add to dashboard Cite

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“…In our sample, we found overall that the left hippocampus was larger than the right; hence, our hippocampal laterality ratio indicates that participants where the right hemisphere may be approaching symmetry with the left or overtaking it in terms of size may have a more hyperactive BIS. Consistent with this, some researchers have suggested that some aspects of anxiety may be lateralized to the right hemisphere [71-73], and heightened right hemisphere activity [74], and structural changes [75] in general has been reported for clinical anxiety populations.…”

Section: Discussionmentioning

confidence: 63%

The Behavioural Inhibition System, anxiety and hippocampal volume in a non-clinical population

Levita

Bois

Healey

et al. 2014

Biol Mood Anxiety Disord

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BackgroundAnimal studies have suggested that the hippocampus may play an important role in anxiety as part of the Behavioural Inhibition System (BIS), which mediates reactivity to threat and punishment and can predict an individual’s response to anxiety-relevant cues in a given environment. The aim of the present structural magnetic resonance imaging (MRI) study was to examine the relationship between individual differences in BIS and hippocampal structure, since this has not received sufficient attention in non-clinical populations. Thirty healthy right-handed participants with no history of alcohol or drug abuse, neurological or psychiatric disorders, or traumatic brain injury were recruited (16 male, 14 female, age 18 to 32 years). T1-weighted structural MRI scans were used to derive estimates of total intracranial volume, and hippocampal and amygdala gray matter volume using FreeSurfer. To relate brain structure to Gray’s BIS, participants completed the Sensitivity to Punishment questionnaire. They also completed questionnaires assessing other measures potentially associated with hippocampal volume (Beck Depression Inventory, Negative Life Experience Survey), and two other measures of anxiety (Spielberger Trait Anxiety Inventory and the Beck Anxiety Inventory).ResultsWe found that high scores on the Sensitivity to Punishment scale were positively associated with hippocampal volume, and that this phenomenon was lateralized to the right side. In other words, greater levels of behavioural inhibition (BIS) were positively associated with right hippocampal volume.ConclusionsOur data suggest that hippocampal volume is related to the cognitive and affective dimensions of anxiety indexed by the Sensitivity to Punishment, and support the idea that morphological differences in the hippocampal formation may be associated with behavioural inhibition contributions to anxiety.

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“…The interpretation of these WM differences is limited as only few studies so far reported WM volume in GAD (De Bellis et al, 2002; Strawn et al, 2013). However, while relatively little WM volume data in GAD are available, a range of diffusion tensor imaging studies already demonstrated the importance of pathological changes in WM tracts and microstructure for GAD (Brambilla et al, 2012; Tromp et al, 2012; Zhang et al, 2013), with some of these findings being related to the PFC as well (Tromp et al, 2012). The results reported here might provide another target for such investigations in the future.…”

Section: Discussionmentioning

confidence: 99%

Gray and white matter volume abnormalities in generalized anxiety disorder by categorical and dimensional characterization

Hilbert

Pine

Muehlhan

et al. 2015

Psychiatry Research: Neuroimaging

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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.

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White-matter abnormalities in the right posterior hemisphere in generalized anxiety disorder: a diffusion imaging study

Cited by 29 publications

References 79 publications

Reduced Structural Connectivity of a Major Frontolimbic Pathway in Generalized Anxiety Disorder

Reduced Structural Connectivity of a Major Frontolimbic Pathway in Generalized Anxiety Disorder

The Behavioural Inhibition System, anxiety and hippocampal volume in a non-clinical population

Gray and white matter volume abnormalities in generalized anxiety disorder by categorical and dimensional characterization

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