Enhanced interhemispheric resting-state functional connectivity of the visual network is an early treatment response of paroxetine in patients with panic disorder.

This study aimed to detect alterations in interhemispheric interactions in patients with panic disorder (PD), determine whether such alterations could serve as biomarkers for the diagnosis and prediction of therapeutic outcomes, and map dynamic changes in interhemispheric interactions in patients with PD after treatment. Fifty-four patients with PD and 54 healthy controls (HCs) were enrolled in this study. All participants underwent clinical assessment and a resting-state functional magnetic resonance imaging scan at (i) baseline and (ii) after paroxetine treatment for 4 weeks. A voxel-mirrored homotopic connectivity (VMHC) indicator, support vector machine (SVM), and support vector regression (SVR) were used in this study. Patients with PD showed reduced VMHC in the fusiform, middle temporal/occipital, and postcentral/precentral gyri, relative to those of HCs. After treatment, the patients exhibited enhanced VMHC in the lingual gyrus, relative to the baseline data. The VMHC of the fusiform and postcentral/precentral gyri contributed most to the classification (accuracy = 87.04%). The predicted changes were accessed from the SVR using the aberrant VMHC as features. Positive correlations (p < 0.001) were indicated between the actual and predicted changes in the severity of anxiety. These findings suggest that impaired interhemispheric coordination in the cognitive-sensory network characterized PD and that VMHC can serve as biomarkers and predictors of the efficiency of PD treatment. Enhanced VMHC in the lingual gyrus of patients with PD after treatment implied that pharmacotherapy recruited the visual network in the early stages.

Resting-state cortico-limbic functional connectivity pattern in panic disorder: Relationships with emotion regulation strategy use and symptom severity.

Cognitive reappraisal is an effective emotion regulation strategy involving prefrontal cortex (PFC) control of the amygdala. Its aberrant functioning is closely associated with panic disorder (PD). However, the resting-state functional connectivity (rsFC) between the PFC, implicated in cognitive reappraisal, and the amygdala in PD has not been studied. Thus, this study aims to investigate the rsFC patterns and their association with cognitive reappraisal and PD. This study involved 51 participants, including 26 untreated patients with PD and 25 healthy controls (HC). We evaluated the habit of cognitive reappraisal assessment and the severity of PD using neuropsychological and clinical measures. Resting-state fMRI was utilized to evaluate the rsFC pattern between the PFC, engaged in cognitive reappraisal, and the amygdala. Mediation analysis was performed to explore the role of this rsFC in the relationship between cognitive reappraisal and PD severity. PD patients showed reduced rsFC between the PFC and the amygdala compared to HC. This weakened rsFC was associated with the severity of PD symptoms. Moreover, cognitive reappraisal was negatively correlated with PD severity, and mediation analysis indicated that the rsFC of the PFC-amygdala played a mediating role in this association. Abnormal PFC-amygdala rsFC may play a pivotal role in PD development and/or manifestation and mediate the association between cognitive reappraisal and PD severity, potentially serving as a clinical indicator for monitoring and intervention.

Cerebral Hypoperfusion Detected by Arterial Spine-Labelled MR Imaging in a Patient Presenting with Migraine and Panic Attacks.

I report a case of arterial spine-labelled MR imaging (ASL)-detected cerebral hypoperfusion during migraine and panic attacks. A 20-year-old woman with a history of headache for 6 years and independent panic attacks for 3 years was transferred to Okayama Kyokuto Hospital for panic attacks. On that day, she had had severe headache that was improved by taking non-steroidal anti-inflammatory drug, but panic attacks initiated. On arrival, she also complained of a mild headache. ASL revealed cerebral hypoperfusion in the right temporo-occipital region. The threshold to induce panic attacks in migraine patients could be lowered by the physiopathology underlying migraine attacks.

Altered DNA Methylation of the Serotonin Transporter Gene Associated with Early Life Stress and White Matter Microalterations in Korean Patients with Panic Disorder.

INTRODUCTION: Changes in the DNA methylation of 5-HTTLPR are associated with the pathophysiology of panic disorder (PD). This study was conducted to investigate the association between stressful life events and the level of 5-HTTLPR methylation in patients with PD. We also examined whether these factors were associated with white matter alterations in psychological trauma-related regions. METHODS: The participants comprised 232 patients with PD and 93 healthy adults of Korean descent. DNA methylation levels of five cytosine-phosphate-guanine (CpG) sites in the 5-HTTLPR region were analyzed. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the trauma-related regions. RESULTS: PD patients showed significantly lower levels of the DNA methylation at 5-HTTLPR 5 CpG sites than healthy controls. In patients with PD, the DNA methylation levels at 5-HTTLPR 5 CpG sites showed significant negative association with the parental separation-related psychological distress, and positive correlations with the fractional anisotropy values of the superior longitudinal fasciculus (SLF) which might be related to trait anxiety. CONCLUSION: Early life stress was significantly associated with DNA methylation levels at 5-HTTLPR related to the decreased white matter integrity in the SLF region in PD. Decreased white matter connectivity in the SLF might be related to trait anxiety and is vital to the pathophysiology of PD.

Impact of childhood trauma on the abnormal functional connectivity of brain regions in the fear network model of panic disorder.

BACKGROUND: People who have suffered childhood trauma may be more susceptible to panic disorder (PD). Existing evidence indicates that childhood trauma can significantly impact brain function. Meanwhile, the brain regions involved in the fear network model (FNM) of PD highly overlap with the brain regions affected by childhood trauma. However, it remains unclear whether functional connections between brain regions associated with the FNM in patients with PD are affected by childhood trauma. This study aimed to investigate the effects of childhood trauma on the functional connectivity (FC) of brain regions associated with the FNM in patients with PD. METHOD: This study recruited 62 patients with PD, including 21 with a high level of childhood trauma (PD_HCT), 41 with a low level of childhood trauma (PD_LCT), and 40 healthy controls (HCs). The patients underwent magnetic resonance imaging resting-state scanning. The amygdala, anterior cingulate, thalamus, and hippocampus were chosen as regions of interest (ROIs) to examine group differences in ROIs and whole-brain resting-state FC (rsFC). RESULTS: Compared with PD_HCT patients, PD_LCT patients exhibited significantly increased rsFC in the right thalamus, right temporo-occipital middle temporal gyrus, left thalamus, and right temporo-occipital middle temporal gyrus. Compared with HCs, PD_LCT patients had increased rsFC between the right thalamus and the right temporo-occipital middle temporal gyrus. CONCLUSION: Patients with PD who had suffered high and low levels of childhood trauma were found to exhibit different pathological rsFC alterations in the FNM, suggesting that childhood trauma may be an important risk factor for the development of PD symptoms.

Can the aberrant occipital-cerebellum network be a predictor of treatment in panic disorder?

BACKGROUND: This study aimed to detect altered brain activation pattern of patients with panic disorder (PD) and its changes after treatment. The possibilities of diagnosis and prediction of treatment response based on the aberrant brain activity were tested. METHODS: Fifty-four PD patients and 54 healthy controls (HCs) were recruited. Clinical assessment and resting-state functional magnetic resonance imaging scans were conducted. Then, patients received a 4-week paroxetine treatment and underwent a second clinical assessment and scan. The fractional amplitude of low-frequency fluctuations (fALFF) was measured. Support vector machine (SVM) and support vector regression (SVR) analyses were conducted. RESULTS: Lower fALFF values in the right calcarine/lingual gyrus and left lingual gyrus/cerebellum IV/V, whereas higher fALFF values in right cerebellum Crus II were observed in patients related to HCs at baseline. After treatment, patients with PD exhibited significant clinical improvement, and the abnormal lower fALFF values in the right lingual gyrus exhibited a great increase. The abnormal fALFF at pretreatment can distinguish patients from HCs with 80 % accuracy and predict treatment response which was reflected in the significant correlation between the predicted and actual treatment responses. LIMITATIONS: The impacts of ethnic, cultural, and other regional differences on PD were not considered for it was a single-center study. CONCLUSIONS: The occipital-cerebellum network played an important role in the pathophysiology of PD and should be a part of the fear network. The abnormal fALFF values in patients with PD at pretreatment could serve as biomarkers of PD and predict the early treatment response of paroxetine.

Long-term benefits of mindfulness on white matter tracts underlying the cortical midline structures in panic disorder: A 2-year longitudinal study.

AIMS: We aimed to examine the long-term benefits of mindfulness-based cognitive therapy (MBCT) on white matter plasticity in the cortical midline structures (CMS) for a period of 2 years in patients with panic disorder and the relationships between white matter changes in the CMS and severity of state and trait symptoms. METHODS: Seventy-one participants were enrolled and underwent diffusion tensor imaging at baseline and after 2 years (26 who received MBCT as an adjunct to pharmacotherapy [MBCT+PT], 20 treated with pharmacotherapy alone [PT-alone], and 25 healthy controls [HCs]). The severity of symptoms and fractional anisotropy (FA) in white matter regions underlying the CMS were assessed at baseline and 2-year follow-up. RESULTS: The MBCT+PT group showed better outcomes after 2 years than the PT-alone group. The groups showed different FA changes: the MBCT+PT group showed decreased FA in the left anterior cingulate cortex (ACC); the PT-alone group showed increased FA in the bilateral dorsomedial prefrontal cortex, posterior cingulate cortex (PCC), and precuneus. Decreased white matter FA in the ACC, PCC, and precuneus was associated with improvements in the severity of state and trait symptoms in patients with panic disorder. CONCLUSION: Alleviation of excessive white matter connectivity in the CMS after MBCT leads to improvements in clinical symptoms and trait vulnerability in patients with panic disorder. Our study provides new evidence for the long-term benefits of MBCT on white matter plasticity and its clinical applicability as a robust treatment for panic disorder.

Specific and common functional connectivity deficits in drug-free generalized anxiety disorder and panic disorder: A data-driven analysis.

Evidence of comparing neural network differences between anxiety disorder subtypes is limited, while it is crucial to reveal the pathogenesis of anxiety disorders. The present study aimed to investigate specific and common resting-state functional connectivity (FC) networks in generalized anxiety disorder (GAD), panic disorder (PD), and healthy controls (HC). We employed the gRAICAR algorithm to decompose the resting-state fMRI into independent components and align the components across 61 subjects (22 GAD, 18 PD and 21 HC). The default mode network and precuneus network exhibited GAD-specific aberrance, the anterior default mode network showed atypicality specific to PD, and the right fronto-parietal network showed aberrance common to GAD and PD. Between GAD-specific networks, FC between bilateral dorsolateral prefrontal cortex (DLPFC) was positively correlated with interoceptive sensitivity. In the common network, altered FCs between DLPFC and angular gyrus, and between orbitofrontal cortex and precuneus, were positively correlated with anxiety severity and interoceptive sensitivity. The pathological mechanism of PD could closely relate to the dysfunction of prefrontal cortex, while GAD could involve more extensive brain areas, which may be related to fear generalization.

Prediction of prognosis in patients with panic disorder using pre-treatment brain white matter features.

BACKGROUND: The early identification of patients with panic disorder (PD) with a poor prognosis is important for improving treatment outcomes; however, it is challenging due to a lack of objective biomarkers. We investigated the reliability of characterizing structural white matter (WM) connectivity and its ability to predict PD prognosis after pharmacotherapy. METHODS: A total of 138 patients (59 men) with PD and 153 healthy controls (HCs; 73 men) participated in this study. PD symptom severity was measured using the Panic Disorder Severity Scale (PDSS) at baseline and follow-up periods of 8 weeks, 6 months, and 1 year. The least absolute shrinkage and selection operator (Lasso) was utilized to identify prognosis-related WM regions on diffusion imaging features. RESULTS: Lasso identified seven prognosis-related WM regions: the bilateral posterior corona radiata, bilateral posterior limb of the internal capsule, the left retrolenticular part of the internal capsule, the left sagittal stratum, and the right fornix/stria terminalis. Some of these regions showed lower mean fractional anisotropy (FA) values in patients with PD than in HCs. The predicted PDSS scores using FA from these regions consistently correlated with the actual prognosis in all periods. LIMITATIONS: This study had limited ability to evaluate individual longitudinal changes in detail owing to the data acquisition time and brain atlas resolution. CONCLUSIONS: Our findings suggest the possibility of using structural WM connectivity as a biomarker for the clinical characterization of PD. Our findings will expand our understanding of the neurobiology of PD and improve biomarker-based prognosis prediction in clinical practice.

Retinal Changes in Panic Disorder Patients.

AIM: Optical coherence tomography (OCT) is a novel method that allows high resolution cross-sectional imaging of biological tissues. It was suggested that changes in the cranial structure or functions would be reflected in the retina. OCT has been an important method in the diagnosis and follow-up of diseases via morphometric or quantitative retinal measurements. Panic disorder (PD) is an anxiety disorder, where free radicals, inflammatory processes and neurotransmitter transmission disorders play a role in the etiology. The present study aimed to demonstrate neurodegeneration in PD by the comparison of PD patient and control OCT data. MATERIAL AND METHOD: The study group included 21 PD patients who met the study criteria. The control group included 21 healthy individuals without any known psychiatric or organic disease, including eye disease, and gender-matched to the patient group. All participants underwent detailed psychiatric and eye examinations. Central macular thickness (CMT), macular volume (MV), mean and retinal nerve fiber layer thickness (RNFL), ganglion cell layer thickness (GCLT), and central choroidal thickness (CCT) were measured in both eyes of all participants with OCT. A sociodemographic data form, Clinical Global Impression Scale (CGIS), and Panic Disorder Severity Scale (PDSS) were administered to the participants. RESULTS: In the study, it was determined that the CMT values of the PD patients were lower when compared to the controls in the OCT examination. There was a statistically significant difference between the CMT of the PD patient group and the control group; the CMT was lower in the patient group. There were no significant differences between the groups based on GCLT, RNFL superior, RNFL inferior, RNFL nasal, RNFL temporal, and CCT. There was no significant correlation between CGIS, PDSS scores and OCT measurements. CONCLUSION: This is the first study in the literature where patients with a PD diagnosis were analyzed based on the OCT method. OCT, which is a simple, noninvasive and relatively inexpensive method that the patient could easily adapt to during imaging, could be employed as a supplementary method in the diagnosis and follow-up of PD patients.

Abnormal functional connectivity of brain regions associated with fear network model in panic disorder.

Background: Patients with panic disorder (PD) have an abnormal function in brain regions related to fear network is well recognised. However, the traditional fear network model (FNM) which was based on animals' horrible behaviours has been found that it's not enough to explain the pathological mechanism of PD. This study aims to explore brain regions' abnormalities in the new advanced FNM, and estimate whether it can better explain PD.Methods: Magnetic resonance imaging resting-state scans were acquired in 40 patients with PD (35 drug-naïve and 5 drug-free) and 40 healthy controls (HCs). Twelve brain regions in the advanced FNM were chosen as regions of interest (ROIs) to examine the group difference in the ROIs and whole-brain resting-state functional connectivity (rsFC).Results: We found significantly increased thalamic rsFC with the insula, compared with HCs. And it was significantly correlated with HAMA-somatic score. We also found increased thalamic rsFC with occipital gyrus, temporal gyrus, and frontal gyrus when compared with HCs.Conclusions: Taken together, PD patients exhibit abnormal rsFC alterations within the advanced FNM, especially the increased rsFC within thalamus-insula loop, suggesting that excessive sensitivity to external information plays an important role in PD. The advanced FNM may provide a fuller explanation about PD.

An interpretable radiomics model for the diagnosis of panic disorder with or without agoraphobia using magnetic resonance imaging.

BACKGROUND: Early and accurate diagnosis of panic disorder with or without agoraphobia (PDA) is crucial to reducing disease burden and individual suffering. However, its diagnosis is challenging for lack of validated biomarkers. This study aimed to investigate whether radiomic features extracted from T1-weighted images (T1) of major fear-circuit structures (amygdala, insula, and anterior cingulate cortex [ACC]) could differentiate patients with PDA from healthy controls (HCs). METHODS: The 213 participants (93 PDA, 120 HCs) were allocated to training (n = 149) and test (n = 64) sets after undergoing magnetic resonance imaging. Radiomic features (n = 1498) were extracted from T1 of the studied structures. Machine learning models were trained after feature selection and then validated in the test set. SHapley Additive exPlanations (SHAP) explored the model interpretability. RESULTS: We identified 29 radiomic features to differentiate participants with PDA from HCs. The area under the curve, accuracy, sensitivity, and specificity of the best performing radiomics model in the test set were 0.84 (95% confidence interval: 0.74-0.95), 81.3%, 75.0%, and 86.1%, respectively. The SHAP model explanation suggested that the energy features extracted from the bilateral long insula gyrus and central sulcus of the insula and right ACC were highly associated with the risk of PDA. LIMITATIONS: This was a cross-sectional study with a relatively small sample size, and the causality of changes in radiomic features and their biological and clinical meanings remained to be elucidated. CONCLUSIONS: Our findings suggest that radiomic features from the fear-circuit structures could unveil hidden microstructural aberrations underlying the pathogenesis of PDA that could help identify PDA.

The alterations of degree centrality in the frontal lobe of patients with panic disorder.

Objective: The brain network in panic disorder (PD) is still an intriguing issue for research. In this study, we hoped to investigate the role of DC (degree centrality) for the pathophysiology of PD, especially for the fear network. Methods: We enrolled 60 patients with PD and 60 controls in the current study. The gender and age were matched for two groups. All participants received the resting-state functional magnetic resonance imaging to survey the baseline brain activity. Then the DC values of all participants were using REST toolbox. We also compared the DC values between PD and controls. The statistical threshold was set as FDR (false discovery rate) < 0.05. Results: The DC values were significantly lower in the right superior frontal gyrus of PD patients compared to controls (FDR < 0.05). In addition, a negative correlation between the DC values and panic severity was observed in the right superior frontal gyrus and left inferior frontal gyrus. However, there was no significant association between the DC values and illness duration. Conclusion: The DC seemed significantly altered in the frontal lobe of PD patients. The role of the frontal lobe might be more emphasized in the pathophysiology research for PD.

Disrupted fronto-temporal function in panic disorder: a resting-state connectome study.

Recent neuroimaging studies have identified alterations in activity and connectivity among many brain regions as potential biomarkers for panic disorder. However, the functional connectome of panic disorder is not well understood. Therefore, a graph-theoretical approach was applied in this study to construct functional networks of patients and healthy controls in order to discover topological changes in panic disorder. 31 patients and 33 age and sex matched healthy controls underwent resting-state functional magnetic resonance imaging. Brain networks for each participant were structured using nodes from the Anatomical Automatic Labeling template and edges from connectivity matrices. Then, topological organizations of networks were calculated. Network-based statistical analysis was conducted, and global and nodal properties were compared between patients and controls. Unlike controls, patients with panic disorder displayed a small-world network. Patients also revealed decreased nodal efficiency in right superior frontal gyrus (SFG), middle frontal gyrus (MFG), right superior temporal gyrus (STG), and left middle temporal gyrus (MTG). Decreased functional connectivity was found in panic disorder between right MTG and extensive temporal regions. Among these disrupted regions, the decreased nodal efficiency of SFG showed a positive correlation with clinical symptoms while nodal betweenness centrality in angular gyrus showed a negative correlation. Our results indicated decreased function of global and regional information transmission in panic disorder and emphasized the role of temporal regions in its pathology.

Neural correlates of emotional processing in panic disorder.

BACKGROUND: Deficits in emotional processing are conceptualized in prevailing models of anxiety to underpin key symptoms of panic disorder (PD). Neuroimaging studies show evidence of aberrant neural functioning in PD patients during emotional processing, however little is understood about how non-conscious emotional processing impacts neural processes. METHOD: We examined activation and functional connectivity differences in brain regions involved in emotional processing between PD and healthy controls (HC) during subliminal and supraliminal presentations of facial emotions. Twenty-two PD and 33 HC participants were shown happy, sad, neutral, fear, anger and disgust facial expressions during functional magnetic resonance imaging using a 3T MRI scanner. We performed voxelwise ROI analyses at FWE-corrected p < 0.05 for main effects of group and group*emotion interactions. RESULTS: There was less pregenual anterior cingulate cortex (pgACC) activation to subliminal presentations of happy and sad faces in PD compared to HC participants (group*emotion). In addition, PD patients had less pgACC - right amygdala connectivity than HC participants during sad and fear subliminal processing (group*emotion). PD patients also exhibited lower right cerebellum activity across all supraliminal presentations of facial expressions compared to HC. CONCLUSION: These findings suggest that there is aberrant neural processing in PD patients during both conscious and preconscious processing of both positive and negative stimuli, suggesting impaired recruitment of implicit regulatory networks during affective processing. It appears that PD patients may experience deficits in key regulatory connections between inhibitory and emotional neural networks at very early stages of processing of negative affective states.

Neural basis of implicit cognitive reappraisal in panic disorder: an event-related fMRI study.

BACKGROUND: Panic disorder (PD) is thought to be related with deficits in emotion regulation, especially in cognitive reappraisal. According to the cognitive model, PD patients' intrinsic and unconscious misappraisal strategies are the cause of panic attacks. However, no studies have yet been performed to explore the underlying neuromechanism of cognitive reappraisal that occur on an unconscious level in PD patients. METHODS: Twenty-six patients with PD and 25 healthy controls (HC) performed a fully-verified event-block design emotional regulation task aimed at investigating responses of implicit cognitive reappraisal during an fMRI scan. Participants passively viewed negatively valanced pictures that were beforehand neutrally, positively, or adversely portrayed in the task. RESULTS: Whole-brain analysis of fMRI data showed that PD patients exhibited less activation in the right dorsolateral prefrontal cortex (dlPFC) and right dorsomedial prefrontal cortex (dmPFC) compared to HC, but presented greater activation in parietal cortex when negative pictures were preceded by positive/neutral vs negative descriptions. Simultaneously, interactive effects of Group × Condition were observed in the right amygdala across both groups. Furthermore, activation in dlPFC and dmPFC was is negatively correlated to severity of anxiety and panic in PD when negative images were preceded by non-negative vs negative descriptions. CONCLUSIONS: Emotional dysregulation in PD is likely the result of deficient activation in dlPFC and dmPFC during implicit cognitive reappraisal, in line with impaired automatic top-down regulation. Correlations between severity of anxiety and panic attack and activation of right dlPFC and dmPFC suggest that the failure to engage prefrontal region during implicit cognitive reappraisal might be associated wtih the severity of anxiety and panic; such functional patterns might be the target of possible treatments.

Emotional processing in panic disorder and its subtypes: An fMRI study using emotional faces.

BACKGROUND: Inconsistent findings regarding the pathophysiology of panic disorder (PD) could result from clinical heterogeneity. Identifying subtypes could enhance insights into the neurobiological substrates of PD. METHODS: An emotional faces fMRI paradigm was used in a group of PD patients (n = 73) and healthy controls (n = 58). The overall PD group was further divided into three previously identified subtypes: a cognitive-autonomic (n = 22), an autonomic (n = 16) and an aspecific (n = 35) subtype. Differences in brain activity levels in response to emotional facial expressions between groups were examined for six regions of interests, namely the amygdala, ventromedial prefrontal cortex, anterior cingulate, fusiform gyrus, lingual gyrus and insula. RESULTS: PD patients showed lower activity in the rostral anterior cingulate in response to angry faces than healthy controls, which was mainly driven by the autonomic subtype. No significant differences were found in other brain regions when comparing PD patients with controls or when comparing across PD subtypes. LIMITATIONS: Sample sizes in subgroups were relatively small CONCLUSIONS: The role of the rostral anterior cingulate cortex for emotional processes critical in panic disorder is highlighted by this study and provides, albeit preliminary, evidence for the use of a subtype approach to advance our neurobiological insights in PD considering its involvement in the appraisal of autonomic viscero-sensory symptoms.

The interaction effect of early trauma exposure and a diagnosis of panic disorder on cortical thickness.

BACKGROUND: Early trauma (ET) is a risk factor for adult psychiatric disorders. ET exposure is known to cause structural brain alterations, particularly in the fronto-temporo-limbic circuitry. ET-related effects on brain development may differ based on individual characteristics and cause different psychiatric outcomes. We investigated the interaction effect of ET exposure and panic disorder (PD) on cortical thickness. METHODS: Sixty-six participants with PD and 66 healthy controls were enrolled. High-resolution T1-weighted images were acquired, and a whole-brain vertex-based analysis was performed to estimate cortical thickness. The Early Trauma Inventory Self Report-Short Form, Anxiety Sensitivity Inventory-Revised, Panic Disorder Severity Scale, Beck Depression Inventory-II, and Beck Anxiety Inventory were administered. RESULTS: There was a significant interaction between ET exposure and PD on the mean cortical thickness in the bilateral insula and right pars triangularis. An exploratory correlational analysis revealed a positive correlation between the mean cortical thickness in the left insula and severity of anxiety sensitivity to cardiovascular symptoms in participants with PD. LIMITATIONS: Our findings may be affected by recall bias because this study is limited by its retrospective cross-sectional design. CONCLUSIONS: Our findings suggest that ET exposure may affect brain structures differently based on a diagnosis of PD. Furthermore, individual variations in brain alterations after ET may confer trait vulnerability that triggers the development of PD. Future longitudinal studies are warranted to elucidate the neurobiological mechanisms underlying ET and psychiatric outcomes.

Initial white matter connectivity differences between remitters and non-remitters of patients with panic disorder after 6 months of pharmacotherapy.

Panic disorder (PD) is a harmful mental condition that causes relapsed and persistent impairment. In the treatment of PD, the prognosis for PD should be considered. However, the relationship between pharmacotherapy and biomarkers, for predicting a better response through neuroimaging, is a little known. The purpose of the present study was to examine whether there would be the initial white matter (WM) regions associated with the remission in 6 months. A total of 104 patients with PD were investigated in the study. After six months, there were 17 remission patients with PD and 81 non-remission patients. The Panic Disorder Severity Scale, Albany Panic and Phobia Questionnaire, Anxiety Sensitivity Inventory-Revised, Beck Anxiety Inventory, and Beck Depression Inventory were assessed for all patients at baseline. We compared the diffusion indices between remission and non-remission group at 6 months using Tract-Based Spatial Statistics. The results showed that the fractional anisotropy (FA) values were significantly higher in the non-remitter group compared with those in the remitter group in the WM regions, such as the posterior corona radiata and superior longitudinal fasciculus, at the 6 month evaluation. The logistic regression analysis with clinical symptom severity and FA values of the WM regions as covariates showed that FA values in those regions and the Beck Depression Inventory-II predicted poor remission. This study suggests that posterior corona radiata and superior longitudinal fasciculus are related to potential predictive factors of 6-month remission in patients with PD. WM regions associated with the long-term remission should be verified with further investigations.

Neural correlates of negative and disease-specific emotional stimuli in panic disorder: a functional magnetic resonance imaging study.

OBJECTIVE: Decades of research have highlighted the involvement of the prefrontal cortex, anterior cingulated cortex, and limbic areas (amygdala) in panic disorder (PD). However, little attention has been given specifically to the inferior frontal gyrus. The current study aimed to investigate the neural substrates, including the inferior frontal gyrus, of both panic-related and negative conditions among individuals with PD and healthy controls. METHODS: We examined 13 medication-free PD patients and 14 healthy controls with functional magnetic resonance imaging (fMRI) during exposure to negative and neutral pictures and a set of specific panic-related pictures. RESULTS: Subtraction between the conditions indicated activation of the left amygdala region and the right inferior frontal gyrus in PD patients during the specific panic-related condition, whereas the left amygdalar region and left inferior frontal gyrus were activated during the negative condition in controls. CONCLUSION: These results suggest that in patients with PD, a prominent bottom-up process is involved in specific panic-related conditions, which might be associated with weak modulation of the left frontal area. These data add to our current understanding of the neural correlates of PD and can contribute to future clinical interventions targeting the functional reestablishment of these regions.