First Clinical Report on the Treatment of Parkinson's Disease with Fetal Midbrain Precursor Cells.

BACKGROUND: Because human fetal ventral mesencephalic tissue grafts provide promising results in ameliorating Parkinson's disease-implicated motor dysfunctions, human fetal midbrain-derived dopamine neuronal precursor cells are considered good candidates for cell-based therapy for Parkinson's disease in that large quantities of cells can be supplied through a good manufacturing practice-compliant system. OBJECTIVE: We conducted a prospective, phase I/IIa, dose-escalation, open-label "first-in-human" clinical trial with fetal neural precursor cells to assess their safety and therapeutic efficacy in patients with idiopathic Parkinson's disease. METHODS: Fifteen patients were assigned to receive three different doses of cells (4 × 106 , 12 × 106 , and 40 × 106 cells) and completed a 12-month follow-up. The primary outcome was safety, by measuring the presence of grade 3 or higher cells according to National Cancer Institute guidelines and any contaminated cells. Secondary outcomes assessed motor and neurocognitive function, as well as the level of dopamine transporters, by positron emission tomography-computed tomography. RESULTS: Although a pronation-supination and hand/arm movement performance was remarkably enhanced in all three groups (all P < 0.05), the medium- and high-dose-treated groups exhibited significant improvement in Unified Parkinson's Disease Rating Scale Part III only up to 26.16% and 40%, respectively, at 12 months after transplantation without any serious clinical complications or graft-induced dyskinesia in all patients. However, the motor improvements did not correlate with increase in the dopamine transporter on positron emission tomography images. CONCLUSIONS: Our results primarily demonstrate the safety and plausible dose-dependent efficacy of human fetal midbrain-derived dopamine neuronal precursor cells for idiopathic Parkinson's disease. © 2023 International Parkinson and Movement Disorder Society.

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.

Serotonin Transporter and COMT Polymorphisms as Independent Predictors of Health-related Quality of Life in Patients with Panic Disorder.

There is growing evidence of poor health-related quality of life (HRQOL) in patients with panic disorder (PD). However, little is known about the factors affecting HRQOL in patients with PD. The authors examined whether 5-HTTLPR tri-allelic approach and Cathechol-O-methyltransferase (COMT) Val(158)Met polymorphism can predict HRQOL in patients with PD controlling for sociodemographic factors and disorder-related symptom levels. The sample consisted of 179 patients with PD consecutively recruited from an outpatient clinic and age- and gender ratio-matched 110 healthy controls. The SF-36 was used to assess multiple domains of HRQOL. Hierarchical multiple regression analysis was performed to determine the independent effect of the 5-HTTLPR and COMT Val(158)Met on the SF-36 in panic patients. Patients with PD showed lowered HRQOL in all sub-domains of the SF-36 compared to healthy controls. The 5-HTTLPR independently and additively accounted for 2.2% of variation (6.7% of inherited variance) of perceived general health and the COMT Val(158)Met independently and additively accounted for 1.5% of variation (5.0% of inherited variance) of role limitation due to emotional problems in patient group. The present study suggests that specific genetic polymorphisms are associated with certain domains of HRQOL and provides a new insight on exploring the factors that predict HRQOL in patients with PD.

Serotonergic genes (5-HTT and HTR1A) and separation life events: gene-by-environment interaction for panic disorder.

BACKGROUND: The polymorphisms of serotonergic genes (5-HTTLPR and HTR1A rs6295) and separation life events have been studied to find an association with panic disorder, respectively. However, there are no studies that have yet evaluated the interaction effect between serotonergic genes and separation life events for panic disorder. METHODS: For this study, 194 panic disorder patients and 172 healthy controls were included for genotyping and environmental factor analysis. Separation life events were assessed using the Stressful Life Events Scale and clinical interviews. To evaluate the potential endophenotypes of panic disorder, the Anxiety Sensitivity Index-revised (ASI-R), harm avoidance in the Temperament and Character Inventory (HA), and neuroticism in the Eysenck Personality Questionnaire (neuroticism) scales were administered. RESULTS: For 5-HTTLPR and HTR1A rs6295, there was no significant main effect of each genotype on panic disorder alone. However, the number of separation life events and their interaction with 5-HTTLPR showed a statistically significant effect on panic disorder. In addition, the interaction between 5-HTTLPR and the number of separation life events significantly affected the HA for potential endophenotypes. CONCLUSION: This study could suggest the effect of the interaction between 5-HTTLPR and separation life events on panic disorder and its potential endophenotype.

White Matter Alterations Associated with Pro-inflammatory Cytokines in Patients with Major Depressive Disorder.

OBJECTIVE: Regarding the neuroinflammatory theory of major depressive disorder (MDD), little is known about the effect of pro-inflammatory cytokines on white matter (WM) changes in MDD. We aimed to investigate the relationship between pro-inflammatory cytokines and WM alterations in patients with MDD. METHODS: Twenty-two patients with MDD and 22 healthy controls (HC) were evaluated for brain imaging and pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6, IL-8, interferon-γ and tumor necrosis factor (TNF)-α. Tract-based spatial statistics and FreeSurfer were used for brain image analysis. RESULTS: The levels of TNF-α and IL-8 were significantly higher in the MDD group than in HC. Compared to HC, lower fractional anisotropy (FA), and higher median diffusivity (MD) and radial diffusivity (RD) values were found in the MDD group for several WM regions. Voxel-wise correlation analysis showed that the level of TNF-α was negatively correlated with FA, and positively correlated with MD and RD in the left body and genu of the corpus callosum, left anterior corona radiata, and left superior corona radiata. CONCLUSION: Our findings suggest that TNF-α may play an important role in the WM alterations in depression, possibly through demyelination.

Effectiveness of a psychosocial intervention for relapse prevention in patients with schizophrenia receiving risperidone via long-acting injection.

Schizophrenia is a chronic disorder that is usually characterized by relapses alternating with periods of full or partial remission. We examined whether combined therapy with a psychosocial intervention for relapse prevention (PIRP) and risperidone administered by long-acting injection (RLAI) would be more effective in reducing relapses than RLAI with treatment-as-usual (TAU) among outpatients with schizophrenia. We conducted a prospective, controlled study over 2 years in 46 patients with schizophrenia receiving RLAI, of which 21 and 25 patients were assigned to the PIRP and TAU control groups, respectively. The 1- and 2-year relapse rates were lower and medication compliance was higher in the PIRP group than in the TAU group. Cox proportional analysis revealed that time from baseline to relapse was associated with RLAI discontinuation. These results indicate that PIRP can be effective in maintaining medication compliance, and that discontinuation of long-acting atypical antipsychotics might be predictive of the next relapse. However, these results need to be replicated in studies with larger samples.

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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Effects of transcranial direct current stimulation using miniaturized devices vs sertraline for depression in Korea: A 6 week, multicenter, randomized, double blind, active-controlled study.

We compared the efficacy and safety of transcranial direct current stimulation (tDCS) vs. Sertraline in the treatment of Major Depressive Disorder (MDD) in South Korean participants. This was a multi-center, double blind, active controlled study with non-inferiority testing. Patients were randomly assigned to receive tDCS (n = 45) or Sertraline (n = 47). tDCS was administered in 30-min, 2 mA prefrontal stimulation sessions for 10 consecutive weekdays, followed by 2 treatments at 4 and 6 weeks. Sertraline was administered at a dose of 50 mg per day for 6 weeks. The primary outcome measure was a change in the Montgomery-Asberg Depression Rating Scale (MADRS) score at six weeks. Mean MADRS scores decreased by 14.58 ± 8.51 points in the tDCS group and 12.32 ± 8.56 points in the Sertraline group. There was no significant main effect of group (p = 0.5877) or time by group interaction across weeks 0, 3, and 6 (p = 0.1539). Noninferiority of tDCS compared with Sertraline was not demonstrated. The mean difference between the Sertraline and tDCS group was -2.258 (95% confidence interval [CI], -5.795 to 1.27811), and the lower boundary of the CI was lower than the prespecified noninferiority margin of -3.56. There were no significant group differences in the rate of adverse events. In the present study, the noninferiority of tDCS to Sertraline for the treatment of depression was not found in this Korean population.

Human umbilical cord-derived mesenchymal stem cells alleviate schizophrenia-relevant behaviors in amphetamine-sensitized mice by inhibiting neuroinflammation.

At present, therapeutic options available for treating schizophrenia are limited to monoamine-based antipsychotic drugs. Recent genome wide association study (GWAS) indicated a close relationship between immune system and schizophrenia. To leverage the GWAS finding for therapeutic strategy, we conducted a mechanism and effect study on application of human umbilical cord-derived mesenchymal stem cells (hUC-MSC) with potent immune-modulatory effect in an animal model useful for the study of schizophrenia. Schizophrenia-relevant behaviors were induced by amphetamine administration (amphetamine-sensitized mice) and the effect of a single intravenous administration of hUC-MSC was examined in the amphetamine-sensitized mice. Schizophrenia-relevant behaviors were assessed by open field test, light/dark box, social interaction test, latent inhibition, prepulse inhibition, tail suspension test, and forced swimming test. Our results indicated that neuroinflammation along with peripheral TNF-α elevation is associated with schizophrenia-relevant behaviors in amphetamine-sensitized mice. In addition, hUC-MSC inhibited schizophrenia-relevant and the neuroinflammatory changes. The main mechanism of hUC-MSC was associated with the induction of Treg and production of the anti-inflammatory cytokine, IL-10 in periphery. In vitro study revealed that amphetamine did not directly induce a neuroinflammatory reaction, while recombinant TNF-α (rTNF-α) increased mRNA expression of TNF-α, KMO, and IL-1ß in several microglial cell lines. Moreover, recombinant IL-10 (rIL-10) and MSC conditioned media inhibited the inflammatory response in rTNF-α-treated microglial cells. Assuming that hUC-MSCs rarely reach the CNS and do not remain in the body for an extended time, these findings suggest that a single hUC-MSC infusion have long-term beneficial effect via regulatory T cell induction and secretion of IL-10 in amphetamine-sensitized mice.

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.

Effectiveness of risperidone long-acting injection in first-episode schizophrenia: in naturalistic setting.

Patients with first-episode schizophrenia frequently relapse during the first years of the illness. This may be associated with clinical deterioration. It is important to prevent relapses in first-episode schizophrenia. We examine whether risperidone long-acting injection (RLAI) could effectively act to prevent relapse in first-episode schizophrenia. We conducted a prospective, naturalistic, controlled, and open-label study over 2 years in 50 patients with first-episode schizophrenia. 22 patients with schizophrenia were assigned to the RLAI group and 28 patients with schizophrenia to the oral risperidone group as control. We compared medication adherence, time to non-adherence, and relapse rate between the RLAI and control groups. There were no significant difference in sociodemographic findings and initial psychometric measures between two groups. The RLAI group showed significantly lower relapse rate and higher medication adherence than the control group. The result demonstrated by Kaplan-Meier survival analysis that time to non-adherence is associated with the difference in the groups. Cox proportional survival analysis revealed that time from baseline to relapse was associated with time to non-adherence. This result showed that RLAI could be effective in maintaining medication adherence and preventing relapse. However, studies with a larger sample size will be needed to examine whether these results are applicable to schizophrenic population.

Association between anger and first-onset primary spontaneous pneumothorax.

OBJECTIVE: Primary spontaneous pneumothorax (PSP) is a frequent and problematic disease, but its underlying causes and pathophysiology remain unclear. This study examined whether anger, which is related to many psychosomatic diseases, is a psychosocial factor associated with first-onset PSP. METHOD: We administered the State-Trait Anger Expression Inventory, Stress Response Inventory, Coping Scale, Beck Depression Inventory and Global Assessment of Recent Stress to 91 patients with first-onset PSP and to 77 patients with recent minor trauma as controls. RESULTS: The scores on anger-in, anger-out, state anger and trait anger were significantly higher in the PSP group than in the control group. Logistic regression analysis revealed that low body mass index and trait anger could be associated with PSP. CONCLUSION: We hypothesize that anger could play a role in the pathophysiology of PSP.

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.

Effects of Uric Acid on the Alterations of White Matter Connectivity in Patients with Major Depression.

OBJECTIVE: Uric acid is a non-enzymatic antioxidant associated with depression. Despite its known protective role in other brain disorders, little is known about its influence on the structural characteristics of brains of patients with major depressive disorder (MDD). This study explored the association between uric acid and characteristics of white matter (WM) in patients with MDD. METHODS: A total of 32 patients with MDD and 23 healthy controls (HCs) were examined. All participants were scored based on the Beck Depression Inventory and Beck Anxiety Inventory at baseline. All patients were also rated with the Hamilton Depression Rating Scale. We collected blood samples from all participants immediately after their enrollment and before the initiation of antidepressants in case of patients. Tract-based spatial statistics were used for all imaging analyses. RESULTS: Lower fractional anisotropy (FA) and higher radial diffusivity (RD) values were found in the MDD group than in the HC group. Voxelwise correlation analysis revealed that the serum uric acid levels positively correlated with the FA and negatively with the RD in WM regions that previously showed significant group differences in the MDD group. The correlated areas were located in the left anterior corona radiata, left frontal lobe WM, and left anterior cingulate cortex WM. CONCLUSION: The present study suggests a significant association between altered WM connectivity and serum uric acid levels in patients with MDD, possibly through demyelination.

White matter correlates of anxiety sensitivity in panic disorder.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: There has been no comparative study on the structural neural correlates of AS in PD. CONCLUSIONS: 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.

Chronic high dose of captopril induces depressive-like behaviors in mice: possible mechanism of regulatory T cell in depression.

Major depression has various types of symptoms and disease courses with inconsistent response to monoamine-related antidepressants. Thus, monoamine theory may not be the only pathophysiologic pathway relevant to depression. Recently, it has been suggested that regulatory T cell (Treg) is associated with depression. Based on our previous study that showed decreased regulatory T cell (Treg) population following chronic high-dose captopril (CHC, 40 mg/kg/day * 21 days) administration, we examined whether CHC alone can induce depressive-like behaviors in mice even without stressful stimuli. In this study, we found that CHC induced depressive-like behaviors in tail suspension test (TST) and forced swimming test (FST) without systemic illness, while it did not induce anhedonic behavior, anxiety-like behaviors, or sociality-related behavior. The depressive-like behaviors were rescued by either CHC washout or antidepressant. CHC caused reduction in foxp3 and gata3 mRNA expression in the lymph nodes with elevation in plasma IL-1ß and IL-6. Interestingly, CHC increased serum angiotensin II level. In the hippocampus, CHC increased TNF-α and IL-6 mRNA expression with microglia activation while reduced glucocorticoid receptor expression. However, CHC did not affect to hippocampal kynurenine pathway, serotonin level, hypothalamic corticotropin-releasing hormone mRNA level, or serum corticosterone level. Consequently, we propose that CHC may induce a specific form of depressive-like behaviors via Treg reduction and microglial activation.

Induced Pluripotent Stem Cells as a Novel Tool in Psychiatric Research.

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a valuable opportunity to study neurodevelopmental and neurodegenerative psychiatric diseases by offering an unlimited source for patient-specific neuronal and glial cells. The present review focuses on the recent advancements in modeling psychiatric disorders such as Phelan-McDermid syndrome, Timothy syndrome, Rett syndrome, schizophrenia, bipolar disorder, and dementia. The treatment effects identified in studies on iPSCs using known therapeutic compounds are also summarized in this review. Here we discuss validation of cellular models and explore iPSCs as a novel drug screening tool. Although there are several limitations associated with the current methods used to study mental disorders, using iPSCs as a model system provides the advantage of rewinding and reviewing the development and degeneration of human neural cells.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: The present study should be considered preliminary due to relatively small sample size. CONCLUSIONS: 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.

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.

White matter alterations associated with suicide in patients with schizophrenia or schizophreniform disorder.

The risk of suicide is disproportionately high among people diagnosed with schizophrenia or schizophreniform disorder. Brain imaging studies have shown a few relationships between neuroanatomy and suicide. This study examines the relationship between alterations in brain white matter (WM) and suicidal behavior in people with schizophrenia or schizophreniform disorder. The study participants were 56 patients with schizophrenia or schizophreniform disorder, with (n=15) and without (n=41) a history of suicide attempts. Fractional anisotropy (FA) values were compared between suicide attempters and non-attempters using Tract-Based Spatial Statistics (TBSS). Attempters showed significantly higher FA values than non-attempters in the left corona radiata, the superior longitudinal fasciculus, the posterior limb and retrolenticular part of the internal capsule, the external capsule, the insula, the posterior thalamic radiation, the cerebral peduncle, the sagittal stratum, and temporal lobe WM. Scores of the picture arrangement test showed a significant positive correlation with FA values of the right corona radiata, the right superior longitudinal fasciculus, the body of the corpus callosum, and the left corona radiata in attempters but not in non-attempters. These findings suggest that fronto-temporo-limbic circuits can be associated mainly with suicidal behavior in people with schizophrenia or schizophreniform disorder.