White matter correlates of anxiety sensitivity in panic disorder.

Anxiety sensitivity (AS) refers to a fear of anxiety-related sensations and is a dispositional variable especially elevated in patients with panic disorder (PD). Although several functional imaging studies of AS in patients with PD have suggested the presence of altered neural activity in paralimbic areas such as the insula, no study has investigated white matter (WM) alterations in patients with PD in relation to AS. The objective of this study was to investigate the WM correlates of AS in patients with PD. One-hundred and twelve right-handed patients with PD and 48 healthy control (HC) subjects were enrolled in this study. The Anxiety Sensitivity Inventory-Revised (ASI-R), the Panic Disorder Severity Scale (PDSS), the Albany Panic and Phobia Questionnaire (APPQ), the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) were administered. Tract-based spatial statistics were used for diffusion tensor magnetic resonance imaging analysis. Among the patients with PD, the ASI-R total scores were significantly correlated with the fractional anisotropy values of the WM regions near the insula, the splenium of the corpus callosum, the tapetum, the fornix/stria terminalis, the posterior limb of the internal capsule, the retrolenticular part of the internal capsule, the posterior thalamic radiation, the sagittal striatum, and the posterior corona radiata located in temporo-parieto-limbic regions and are involved in interoceptive processing (p<0.01; threshold-free cluster enhancement [TFCE]-corrected). These WM regions were also significantly correlated with the APPQ interoceptive avoidance subscale and BDI scores in patients with PD (p<0.01, TFCE-corrected). Correlation analysis among the HC subjects revealed no significant findings. There has been no comparative study on the structural neural correlates of AS in PD. The current study suggests that the WM correlates of AS in patients with PD may be associated with the insula and the adjacent temporo-parieto-limbic WM regions, which may play important roles in interoceptive processing in the brain and in depression in PD.

Kim MK ，Kim B ，Kiu Choi T ，Lee SH ... -  《-》

White matter connectivity differences between treatment responders and non-responders in patients with panic disorder.

Panic disorder (PD) is a prevalent and highly disabling mental condition. However, less is known about relationships between biomarkers that may together predict a better response to pharmacological treatment. The objective of the present study was to compare the brain white matter (WM) connectivity between treatment-responsive patients with panic disorder (RPD) and non-responsive patients with panic disorder (NRPD) after 12 weeks of pharmacotherapy. Sixty-four patients with PD were enrolled in this study (RPD, n = 37; NRPD, n = 27). All patients were examined by using magnetic resonance imaging at 3 Tesla. The Panic Disorder Severity Scale (PDSS), Albany Panic and Phobia Questionnaire (APPQ), Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) were administered at baseline of the study. Fractional anisotropy (FA) data were compared using tract-based spatial statistics (TBSS). TBSS results showed that the FA values of the patients with NRPD were significantly higher than of those with RPD in the WM regions such as the precentral gyrus, parahippocampal gyrus, posterior corona radiata, posterior thalamic radiation, posterior parts of the corpus callosum, and precuneus. Symptom severity scales, such as ASI-R scores, showed significant positive correlations of the FA values with the fronto-temporal WM regions in NRPD. These results suggest that structural changes to areas such as the fronto-limbic regions and the posterior part of default mode network, could influence medication response in PD. Further studies with a larger number of patients should be performed to confirm our findings.

Kim SW ，Kim MK ，Kim B ，Choi TK ，Lee SH ... -  《-》

White matter alterations are associated with suicide attempt in patients with panic disorder.

Panic disorder (PD) is associated with an increased risk of suicide attempt (SA). However, no study has examined the neural correlates of SA in PD. The goal of this study was to evaluate alterations in white matter (WM) and gray matter (GM) in patients with PD with and without a history of SA. Twelve patients with PD and a history of SA (PD+SA) and 24 patients with PD and no history of SA (PD-SA) underwent magnetic resonance imaging (MRI). All patients completed the Scale for Suicide Ideation (SSI), the Panic Disorder Severity Scale (PDSS), and the Beck Depression Inventory (BDI). The groups were matched for age, sex, and BDI and PDSS scores. Voxel-based morphometry and tract-based spatial statistics were used for the imaging analysis. Although no GM or WM volume differences were observed, increased fractional anisotropy (FA) values were found in the WM tracts of the PD+SA group compared with the PD-SA group. The regions with increased FA included the internal capsule, splenium of the corpus callosum, superior and posterior corona radiata, thalamic radiations, sagittal stratum, and superior longitudinal fasciculus. The FA values for the internal capsule and thalamic radiations were significantly correlated with the SSI scores in the PD+SA group. The results should be considered preliminary due to the relatively small sample size. Our data suggest that the aberrant WM integrity of the internal capsule and thalamic radiations may be the significant neural correlate of SA in patients with PD.

Kim B ，Oh J ，Kim MK ，Lee S ，Tae WS ，Kim CM ，Choi TK ，Lee SH ... -  《-》

White matter microstructural changes are associated with alcohol use in patients with panic disorder.

A close relationship between panic disorder (PD) and alcohol use disorder (AUD) has been suggested. We aimed to investigate alterations in white matter (WM) volume or integrity in patients with PD comorbid with AUD. Forty-nine patients with PD, free of comorbid AUD (PD-AUD), and 20 patients with PD comorbid with AUD (PD+AUD) were investigated. All subjects were assessed using the Panic Disorder Severity Scale, Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Depression Inventory, and CAGE questionnaire. Voxel-based morphometry and tract-based spatial statistics were used for imaging analysis. Increased fractional anisotropy (FA), as well as decreased mean diffusivity and radial diffusivity were observed in multiple WM tracts, including the body and splenium of the corpus callosum and the retrolenticular part of the internal capsule, in the PD+AUD group compared to the PD-AUD group. CAGE scores in the PD+AUD group and ASI-R scores in the PD-AUD group were significantly correlated with FA values for the corpus callosum. No WM volume differences were found. The present study should be considered preliminary due to relatively small sample size. Our findings revealed microstructural changes in multiple WM tracts, including the corpus callosum and internal capsule, suggesting they could be significant neural correlates of AUD in patients with PD.

Kim B ，Shin WS ，Kim MK ，Lee SH ... -  《-》

Fornix microalterations associated with early trauma in panic disorder.

It is well accepted that panic disorder (PD) is associated with early trauma, and that the limbic systems are one of the main structures involved in PD pathophysiology. However, previous studies have not addressed the relationship between early trauma and major limbic white-matter (WM) structures in PD. Participants enrolled in the study consisted of 53 right-handed patients with PD and 21 healthy controls (HC). The Early Trauma Inventory Self Report-Short Form (ETISR-SF), Anxiety Sensitivity Inventory-Revised (ASI-R), and the Albany Panic and Phobia Questionnaire (APPQ) were applied in the study. Tract-based spatial statistics were used for diffusion tensor magnetic resonance imaging analysis. Among the patients with PD, the fractional anisotropy (FA) values of the fornix body in major limbic WM regions showed significant negative correlation with the ETISR-SF total score, while the scores of mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the same region of fornix had significant positive correlation with those scores (p<0.05; FWE corrected). Further significant correlation was observed between these four scores and the measures of symptom severity in PD, such as that in ASI-R and APPQ in the same region. Recall bias is possible in evaluating early trauma in the participants. The current study suggests a significant association of early trauma with the fornix body possibly through axons and myelin disruptions within major limbic structures in PD. A multi-centered large sample will be needed to confirm these findings.

Yu ST ，Lee KS ，Lee SH 《-》