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.

Early Trauma Is Associated With Suicidal Ideation in Patients With Panic Disorder.

ABSTRACT: There are several predictors of suicidality in patients with panic disorder (PD). Being a woman, younger age, low education level, unmarried status, and symptom severity have been suggested. This study aimed to examine whether early trauma is associated with suicidal ideation in patients with PD. Our study included 267 patients with PD and 105 controls. Data on sociodemographic variables and data from the Early Trauma Inventory Self Report-Short Form, Beck Depression Inventory, Panic Disorder Severity Scale, Anxiety Sensitivity Inventory-Revised, Coping Scales, and Scale for Suicide Ideation were collected, and correlation and regression analyses were performed. This study suggests that clinicians should consider early trauma when assessing suicidal ideation in patients with PD. Clinicians could consider alternative treatments, such as trauma-focused cognitive-behavioral therapy, eye movement desensitization, reprocessing approaches, and classical pharmacological and psychological treatments for patients with PD who have a history of early trauma and are expected to be at high risk for suicide.

Cognitive Behavioral Therapy and Mindfulness-Based Cognitive Therapy for Depressive Disorders.

Recently, the importance of cognitive behavioral therapy (CBT) in the treatment of depression is gradually emerging. Particularly, mindfulness meditation has various approaches related to dialectical behavioral therapy (DBT), acceptance and commitment therapy (ACT), mindfulness-based stress reduction (MBSR), and mindfulness-based cognitive therapy (MBCT), and evidence has been provided that they alleviate depressive symptoms. In particular, as MBCT increases the level of evidence in the treatment of repetitive depressive disorders, guidelines are being recommended to prevent recurrence. Mindfulness may also contribute to improving the patient's symptoms as well as improving the therapeutic relationship with the therapist. For both mindful patients and therapists, positive awareness of internal experiences can be a good way to enrich the mind and overcome depressive disorders.

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.

Association between mental illness and COVID-19 susceptibility and clinical outcomes in South Korea: a nationwide cohort study.

BACKGROUND: Evidence for the associations between mental illness and the likelihood of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and the clinical outcomes of COVID-19 is scarce. We aimed to investigate these associations with data from a national register in South Korea. METHODS: A nationwide cohort study with propensity score matching was done in South Korea using data collected from the Health Insurance Review and Assessment Service of Korea. We defined mental illness as present if one of the relevant ICD-10 codes was recorded at least twice within 1 year for an outpatient or inpatient. Severe mental illness was considered as non-affective or affective disorders with psychotic features. We included all patients aged older than 20 years who were tested for SARS-CoV-2 through services facilitated by the Korea Centers for Disease Control and Prevention, the Health Insurance Review and Assessment Service of Korea, and the Ministry of Health and Welfare, South Korea. We investigated the primary outcome (SARS-CoV-2 test positivity) in the entire cohort and the secondary outcomes (severe clinical outcomes of COVID-19: death, admission to the intensive care unit, or invasive ventilation) among those who tested positive. FINDINGS: Between Jan 1 and May 15, 2020, 216 418 people were tested for SARS-CoV-2, of whom 7160 (3·3%) tested positive. In the entire cohort with propensity score matching, 1391 (3·0%) of 47 058 patients without a mental illness tested positive for SARS-CoV-2, compared with 1383 (2·9%) of 48 058 with a mental illness (adjusted odds ratio [OR] 1·00, 95% CI 0·93-1·08). Among the patients who tested positive for SARS-CoV-2, after propensity score matching, 109 (8·3%) of 1320 patients without a mental illness had severe clinical outcomes of COVID-19 compared with 128 (9·7%) of 1320 with a mental illness (adjusted OR 1·27, 95% CI 1·01-1·66). INTERPRETATION: Diagnosis of a mental illness was not associated with increased likelihood of testing positive for SARS-CoV-2. Patients with a severe mental illness had a slightly higher risk for severe clinical outcomes of COVID-19 than patients without a history of mental illness. Clinicians treating patients with COVID-19 should be aware of the risk associated with pre-existing mental illness. FUNDING: National Research Foundation of Korea.

Biosynthesis of (-)-5-Hydroxy-equol and 5-Hydroxy-dehydroequol from Soy Isoflavone, Genistein Using Microbial Whole Cell Bioconversion.

Equols are isoflavandiols formed by reduction of soy isoflavones such as daidzein and genistein by gut microorganisms. These phytoestrogens are of interest for their various biological effects. We report biosynthesis from genistein to (-)-5-hydroxy-equol in recombinant E. coli expressing three reductases (daidzein reductase DZNR, dihidrodaidzein reductase DHDR, tetrahydrodaidzein reductase THDR) and a racemase (dihydrodaidzein racemase, DDRC) originating from the gut bacterium, Slackia isoflavoniconvertens. The biosynthesized 5-hydroxy-equol proved as an optically negative enantiomer, nonetheless it displayed an inverse circular dichroism spectrum to (S)-equol. Compartmentalized expression of DZNR and DDRC in one E. coli strain and DHDR and THDR in another increased the yield to 230 mg/L and the productivity to 38 mg/L/h. If the last reductase was missing, the intermediate spontaneously dehydrated to 5-hydroxy-dehydroequol in up to 99 mg/L yield. This novel isoflavene, previously not known to be synthesized in nature, was also detected in this biotransformation system. Although (S)-equol favors binding to human estrogen receptor (hER) ß over hERα, (-)-5-hydroxy-equol showed the opposite preference. This study provides elucidation of the biosynthetic route of (-)-5-hydroxy-equol and measurement of its potent antagonistic character as a phytoestrogen for the first time.

Impact of Mindfulness-Based Cognitive Therapy on Intolerance of Uncertainty in Patients with Panic Disorder.

OBJECTIVE: Intolerance of uncertainty (IU) is a transdiagnostic construct in various anxiety and depressive disorders. However, the relationship between IU and panic symptom severity is not yet fully understood. We examined the relationship between IU, panic, and depressive symptoms during mindfulness-based cognitive therapy (MBCT) in patients with panic disorder. METHODS: We screened 83 patients with panic disorder and subsequently enrolled 69 of them in the present study. Patients participating in MBCT for panic disorder were evaluated at baseline and at 8 weeks using the Intolerance of Uncertainty Scale (IUS), Panic Disorder Severity Scale-Self Report (PDSS-SR), and Beck Depression Inventory (BDI). RESULTS: There was a significant decrease in scores on the IUS (p<0.001), PDSS (p<0.001), and BDI (p<0.001) following MBCT for panic disorder. Pre-treatment IUS scores significantly correlated with pre-treatment PDSS (p=0.003) and BDI (p=0.003) scores. We also found a significant association between the reduction in IU and PDSS after controlling for the reduction in the BDI score (p<0.001). CONCLUSION: IU may play a critical role in the diagnosis and treatment of panic disorder. MBCT is effective in lowering IU in patients with panic disorder.

Factors associated with treatment outcomes in mindfulness-based cognitive therapy for panic disorder.

PURPOSE: Although the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) for panic disorder (PD) has been studied previously, data on the predictors of treatment outcomes in MBCT for PD are scarce. MATERIALS AND METHODS: Eighty patients with PD were screened to analyze treatment outcomes such as MBCT completion, treatment response, and remission after undergoing MBCT for PD. Sociodemographic characteristics, comorbid personality disorders, and baseline medication doses were examined. The study administered the Panic Disorder Severity Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale and Anxiety Sensitivity Inventory-Revised to patients at baseline and at eight weeks. RESULTS: Sixty-five participants were enrolled in the present study. Comorbid personality disorder was significantly associated with MBCT non-completion. We found that anxiety sensitivity (AS) improvement after an eight week MBCT program was a statistically significant factor associated with treatment response. Using logistic regression analysis, AS improvement after MBCT showed significant association with PD remission after MBCT. CONCLUSION: Comorbid personality disorders of participants could be a potential predictor of MBCT non-completion. Furthermore, AS improvement after MBCT may predict treatment response and remission after MBCT for PD. However, better designed studies with a larger number of patients are needed to confirm our findings.

Effects of surface treatments on the susceptibilities of low temperature degradation by autoclaving in zirconia.

The aim of this study was to investigate the effect of surface treatments on the aging susceptibilities by autoclaving in zirconia ceramics. Four commercially available tetragonal zirconia polycrystals and one zirconia-alumina composite were tested. Disk-shaped specimens were prepared and the grain sizes were analyzed using a scanning electron microscope and image analyzer. The specimens were divided into three groups based on surface treatments including heat treatment subsequent to mirror polishing, grinding, and sandblasting. Specimens in each group were autoclaved at 134°C for 1, 3, 5, 10, and 15 h. The phases of the specimens were analyzed using an X-ray diffractometer, and the relative amount of the monoclinic phase was calculated and analyzed using Student's t-test and Newman-Keuls multiple comparisons test. Single routine autoclave treatment for sterilization did not promote the phase transformation in zirconia. The phase transformations of all specimens by autoclaving were correlated with grain size, except for the zirconia-alumina composite. Grinding or sandblasting treatments gave rise to increased formation of the monoclinic phase, especially for the zirconia-alumina composite, which showed the highest fraction for the monoclinic phase. The effects of surface treatments on the aging susceptibilities by autoclaving were different in the experimental groups. It is notable that not all zirconia ceramics show similar phase transformation by autoclaving after surface treatments.

Loss of heterozygosity of tumor suppressor genes (p16, Rb, E-cadherin, p53) in hypopharynx squamous cell carcinoma.

OBJECTIVE: Microsatellite alterations, especially those that cause loss of heterozygosity (LOH), have recently been postulated as a novel mechanism of carcinogenesis and a useful prognostic factor in many kinds of malignant tumors. However, few studies have focused on a specific site, hypopharynx. The aim of this study was to evaluate the relationship between LOH and hypopharyngeal squamous cell carcinoma (HPSCC). STUDY DESIGN: Laboratory-based study. SETTING: Integrated health care system. SUBJECTS AND METHODS: Matched normal and cancerous tissues from 30 patients with HPSCC were examined for LOH in 4 tumor suppressor genes (TSGs) (p16, Rb, E-cadherin, and p53) at loci 9p21, 13q21, 6q22, and 17p13, respectively, using microsatellite markers amplified by polymerase chain reaction. The results for each loci were compared with clinicopathological features. RESULTS: Among the 30 cases, 26 (86.7%) exhibited LOH, with the most common alteration being LOH at p53 (52.6%). Significantly higher rates of LOH detection were seen in Rb, p53, and the LOH-high group (cases where 2 or more loci with LOH were found) in cases of lymph node metastasis. Compared with stage I and II carcinoma, tumors of stages III and IV had significantly higher frequencies of LOH in Rb, p53, and the LOH-high group. However, the presence of LOH was not significantly correlated with survival. CONCLUSION: These results suggest that LOH in TSGs such as Rb and p53 may contribute to the development and progression of HPSCC. The presence of LOH in the primary tumor may also be predictive of lymph node metastasis.

Effectiveness of a mindfulness-based cognitive therapy program as an adjunct to pharmacotherapy in patients with panic disorder.

Mindfulness-based cognitive therapy (MBCT) has been studied to treat patients with depressive or anxiety disorders. The aim of this study was to examine whether MBCT is effective as an adjunct to pharmacotherapy in the treatment of patients with panic disorder. Twenty-three patients with panic disorder were included in a MBCT program for a period of 8 weeks. The Hamilton Anxiety Rating Scale (HAM-A), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Anxiety Sensitivity Index-Revised (ASI-R), Albany Panic and Phobia Questionnaire (APPQ), and Panic Disorder Severity Scale (PDSS) were used to assess the patients during the MBCT program. Both HAM-A and PDSS scores were significantly decreased at the 2nd, 4th and 8th weeks compared to baseline in the patients with panic disorder (HAM-A, p<0.01; PDSS, p<0.01). Also, BAI, APPQ and ASI-R were improved significantly after MBCT program (BAI, p<0.01; APPQ, p<0.01; ASI-R, p<0.01). In addition, all subscale scores of ASI-R decreased significantly. MBCT could be effective as an adjunct to pharmacotherapy in patients with panic disorder. However, randomized controlled trials are needed.

Effectiveness of mindfulness-based cognitive therapy as an adjuvant to pharmacotherapy in patients with panic disorder or generalized anxiety disorder.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) has been widely used to treat patients with depressive disorder to prevent relapse. The objective of this study was to examine the effectiveness of newly developed MBCT program as an adjuvant to pharmacotherapy in the treatment of patients with panic disorder or generalized anxiety disorder. METHODS: Forty-six patients with panic disorder or generalized anxiety disorder were assigned to either MBCT or an anxiety disorder education (ADE) program for a period of 8 weeks. The Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Symptom Checklist-90-Revised (SCL-90-R) were used to assess the patients at 0 week and after the two programs had been running for 2, 4, and 8 weeks. RESULTS: The MBCT group demonstrated significantly more improvement than the ADE group according to all anxiety (HAM-A, p<0.01; BAI, p<0.01; anxiety subscale of SCL-90-R, p=0.01) and depression (HAM-D, p<0.01; BDI, p<0.01; depression subscale of SCL-90-R, p<0.01) scale scores. The obsessive-compulsive and phobic subscales of the SCL-90-R also showed significantly more improvement in the MBCT group. However, no significant improvement was observed in the MBCT group versus the ADE group in terms of the somatization, interpersonal sensitivity, paranoid ideation, or psychoticism subscale scores of the SCL-90-R. CONCLUSIONS: MBCT may be effective at relieving anxiety and depressive symptoms in patients with panic disorder or generalized anxiety disorder. However, well-designed, randomized controlled trials are needed.

Usefulness of mindfulness-based cognitive therapy for treating insomnia in patients with anxiety disorders: a pilot study.

The objective of this study was to examine the usefulness of a mindfulness-based cognitive therapy (MBCT) for treating insomnia symptoms in patients with anxiety disorder. Nineteen patients with anxiety disorder were assigned to an 8-week MBCT clinical trial. Participants showed significant improvement in Pittsburgh Sleep Quality Index (Z = -3.46, p = 0.00), Penn State Worry Questionnaire (Z = -3.83, p = 0.00), Ruminative Response Scale (Z = -3.83, p = 0.00), Hamilton Anxiety Rating Scale (Z = -3.73, p = 0.00), and Hamilton Depression Rating Scale scores (Z = -3.06, p = 0.00) at the end of the 8-week program as compared with baseline. Multiple regression analysis showed that baseline Penn State Worry Questionnaire scores were associated with baseline Pittsburgh Sleep Quality Index scores. These findings suggest that MBCT can be effective at relieving insomnia symptoms by reducing worry associated sleep disturbances in patients with anxiety disorder. However, well-designed, randomized, controlled trials are needed to confirm our findings.

Transcutaneous injection laryngoplasty through the cricothyroid space in the sitting position: anatomical information and technique.

A variety of approaches have been introduced to perform injection laryngoplasty under local anesthesia. Among these reported methods, transcutaneous injection through the cricothyroid space offers many advantages, but it possesses some technical difficulties during access to the vocal fold. The aim of this study was to assess the anatomic references related to transcutaneous injection laryngoplasty through cricothyroid space using 3-dimensionally reconstructed computed tomography to provide guidelines and to achieve higher efficacy during the procedure. The study group consisted of 14 patients (7 male, 7 female) with unilateral vocal fold paralysis and who had undergone multi-detector array computed tomography (MDCT) between January 2004 and December 2005. Assumption was made that transcutaneous injection is approached from the surface at lower margin of the thyroid cartilage and 7 mm lateral to the midline through the cricothyroid membrane and spot at the posterior 1/3 of true vocal cord is the target for injection laryngoplasty. From the surface of the injection point to the target, a line was drawn. Its length and the angle formed between it and the approach direction of needle was measured. Based on these measurements, 15 patients (8 male, 7 female) with unilateral vocal fold paralysis received 15 trials of transcutaneous injection laryngoplasty through the cricothyroid space. The average length from the surface of the injection point (7 mm lateral to the midline) to the posterior 1/3 of the true vocal cord (target of the injection) was 15.75 mm in men and 13.91 mm in women. The average of the angle in medial direction at the surface needed to reach the target of the injection was 10.57 degrees in men and 12.71 degrees in women, and in superior direction was 47.57 degrees in men and 47.43 degrees in women. Injection laryngoplasty performed under acquired reference measurements were successful in 14 trials (93.3%) out of 15 trials in 15 patients. We suggest that knowledge of the anatomic references regarding the transcutaneous injection laryngoplasty through cricothyroid space will provide guidelines for beginners and improve the understanding of the procedure, eventually leading to easier and more precise access to the vocal cord.

Effectiveness of a meditation-based stress management program as an adjunct to pharmacotherapy in patients with anxiety disorder.

OBJECTIVE: The objective of this study was to examine the effectiveness of a meditation-based stress management program in patients with anxiety disorder. METHODS: Patients with anxiety disorder were randomly assigned to an 8-week clinical trial of either a meditation-based stress management program or an anxiety disorder education program. The Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory, and the Symptom Checklist--90-Revised (SCL-90-R) were used to measure outcome at 0, 2, 4, and 8 weeks of the program. RESULTS: Compared to the education group, the meditation-based stress management group showed significant improvement in scores on all anxiety scales (HAM-A, P=.00; STAI state, P=.00; STAI trait, P=.00; anxiety subscale of SCL-90-R, P=.00) and in the SCL-90-R hostility subscale (P=.01). Findings on depression measures were inconsistent, with no significant improvement shown by subjects in the meditation-based stress management group compared to those in the education group. The meditation-based stress management group did not show significant improvement in somatization, obsessive-compulsive symptoms, and interpersonal sensitivity scores, or in the SCL-90-R phobic anxiety subscale compared to the education group. CONCLUSIONS: A meditation-based stress management program can be effective in relieving anxiety symptoms in patients with anxiety disorder. However, well-designed, randomized, and controlled trials are needed to scientifically prove the worth of this intervention prior to treatment.