Comparisons of the amplitude of low-frequency fluctuation and functional connectivity in major depressive disorder and social anxiety disorder: A resting-state fMRI study.

BACKGROUND: Studies comparing the brain functions of major depressive disorder (MDD) and social anxiety disorder (SAD) at the regional and network levels remain scarce. This study aimed to elucidate their pathogenesis using neuroimaging techniques and explore biomarkers that can differentiate these disorders. METHODS: Resting-state fMRI data were collected from 48 patients with MDD, 41 patients with SAD, and 82 healthy controls. Differences in the amplitude of low-frequency fluctuations (ALFF) among the three groups were examined to identify regions showing abnormal regional spontaneous activity. A seed-based functional connectivity (FC) analysis was conducted using ALFF results as seeds and different connections were identified between regions showing abnormal local spontaneous activity and other regions. The correlation between abnormal brain function and clinical symptoms was analyzed. RESULTS: Patients with MDD and SAD exhibited similar abnormal ALFF and FC in several brain regions; notably, FC between the right superior frontal gyrus (SFG) and the right posterior supramarginal gyrus (pSMG) in patients with SAD was negatively correlated with depressive symptoms. Furthermore, patients with MDD showed higher ALFF in the right SFG than HCs and those with SAD. LIMITATION: Potential effects of medications, comorbidities, and data type could not be ignored. CONCLUSION: MDD and SAD showed common and distinct aberrant brain function patterns at the regional and network levels. At the regional level, we found that the ALFF in the right SFG was different between patients with MDD and those with SAD. At the network level, we did not find any differences between these disorders.

Comprehensive elucidation of resting-state functional connectivity in anorexia nervosa by a multicenter cross-sectional study.

BACKGROUND: Previous research on the changes in resting-state functional connectivity (rsFC) in anorexia nervosa (AN) has been limited by an insufficient sample size, which reduced the reliability of the results and made it difficult to set the whole brain as regions of interest (ROIs). METHODS: We analyzed functional magnetic resonance imaging data from 114 female AN patients and 135 healthy controls (HC) and obtained self-reported psychological scales, including eating disorder examination questionnaire 6.0. One hundred sixty-four cortical, subcortical, cerebellar, and network parcellation regions were considered as ROIs. We calculated the ROI-to-ROI rsFCs and performed group comparisons. RESULTS: Compared to HC, AN patients showed 12 stronger rsFCs mainly in regions containing dorsolateral prefrontal cortex (DLPFC), and 33 weaker rsFCs primarily in regions containing cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between anterior cingulate cortex (ACC) and thalamus (p < 0.01, false discovery rate [FDR] correction). Comparisons between AN subtypes showed that there were stronger rsFCs between right lingual gyrus and right supracalcarine cortex and between left temporal occipital fusiform cortex and medial part of visual network in the restricting type compared to the binge/purging type (p < 0.01, FDR correction). CONCLUSION: Stronger rsFCs in regions containing mainly DLPFC, and weaker rsFCs in regions containing primarily cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between ACC and thalamus, may represent categorical diagnostic markers discriminating AN patients from HC.

Long-term effects of integrated cognitive behavioral therapy for chronic pain: A qualitative and quantitative study.

Cognitive behavioral therapy (CBT) is known to improve chronic pain management. However, past studies revealed only small to moderate benefits in short-term results, and long-term follow-up studies are lacking. This study aimed to follow an integrated CBT program's effectiveness 1.5 years after its completion. This observational study was the follow-up on the data collected from our CBT sessions conducted under 3 different studies in 2018 to 2019. Seven assessment items (Numerical Rating Scale, Pain Catastrophizing Scale [PCS], Pain Disability Assessment Scale [PDAS], Patient Health Questionnaire-9 items, Generalized Anxiety Disorder 7, European quality of life 5-dimensions 5-level, and Beck Depression Inventory [BDI]) were statistically analyzed. Thematic analysis was conducted in semi structured interviews. PCS ( F  = 6.52, P  = .003), PDAS ( F  = 5.68, P  = .01), European quality of life 5-dimensions 5-level ( F  = 3.82, P  = .03), and BDI ( F  = 4.61, P  = .01) exhibited significant changes ( P  < .05), confirmed by pairwise t test, revealing a moderate to large effect size. From post-treatment to follow-up, all scores showed no significant changes ( P  > .1). In the qualitative study, the analysis revealed 3 subthemes: "Autonomy," "Understanding of yourself and pain," and "Acceptance of pain." Our study suggests that integrated CBT may reduce the scores of PCS, PDAS and BDI, and this effect lasts for at least 1 year. Identified themes support the relevance of mitigative factors in managing chronic pain.

Child Developmental MRI (CDM) project: protocol for a multi-centre, cross-sectional study on elucidating the pathophysiology of attention-deficit/hyperactivity disorder and autism spectrum disorder through a multi-dimensional approach.

INTRODUCTION: Neuroimaging studies on attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have demonstrated differences in extensive brain structure, activity and network. However, there remains heterogeneity and inconsistency across these findings, presumably because of the diversity of the disorders themselves, small sample sizes, and site and parameter differences in MRI scanners, and their overall pathogenesis remains unclear. To address these gaps in the literature, we will apply the travelling-subject approach to correct site differences in MRI scanners and clarify brain structure and network characteristics of children with ADHD and ASD using large samples collected in a multi-centre collaboration. In addition, we will investigate the relationship between these characteristics and genetic, epigenetic, biochemical markers, and behavioural and psychological measures. METHODS AND ANALYSIS: We will collect resting-state functional MRI (fMRI) and T1-weighted and diffusion-weighted MRI data from 15 healthy adults as travelling subjects and 300 children (ADHD, n=100; ASD, n=100; and typical development, n=100) with multi-dimensional assessments. We will also apply data from more than 1000 samples acquired in our previous neuroimaging studies on ADHD and ASD. ETHICS AND DISSEMINATION: The study protocol has been approved by the Research Ethics Committee of the University of Fukui Hospital (approval no: 20220601). Our study findings will be submitted to scientific peer-reviewed journals and conferences.

Clinical Effectiveness and Cost-effectiveness of Videoconference-Based Integrated Cognitive Behavioral Therapy for Chronic Pain: Randomized Controlled Trial.

BACKGROUND: Cognitive behavioral therapy is known to improve the management of chronic pain. However, the components of this therapy are still being investigated and debated. OBJECTIVE: This study aimed to examine the effectiveness of an integrated cognitive behavioral therapy program with new components (attention-shift, memory work, video feedback, and image training) delivered via videoconferencing. METHODS: This study was unblinded and participants were recruited and assessed face-to-face in the outpatient department. We conducted a randomized controlled trial for chronic pain to compare 16 weekly videoconference-based cognitive behavioral therapy (vCBT) sessions provided by a therapist with treatment as usual (TAU). Thirty patients (age range, 22-75 years) with chronic pain were randomly assigned to either vCBT (n=15) or TAU (n=15). Patients were evaluated at week 1 (baseline), week 8 (midintervention), and week 16 (postintervention). The primary outcome was the change in pain intensity, which was recorded using the numerical rating scale at 16 weeks from the baseline. Secondary outcomes were pain severity and pain interference, which were assessed using the Brief Pain Inventory. Additionally, we evaluated disability, pain catastrophizing cognition, depression, anxiety, quality of life, and cost utility. RESULTS: In the eligibility assessment, 30 patients were eventually randomized and enrolled; finally, 15 patients in the vCBT and 14 patients in the TAU group were analyzed. Although no significant difference was found between the 2 groups in terms of changes in pain intensity by the numerical rating scale scores at week 16 from baseline (P=.36), there was a significant improvement in the comprehensive evaluation of pain by total score of Brief Pain Inventory (-1.43, 95% CI -2.49 to -0.37, df=24; P=.01). Further, significant improvement was seen in pain interference by using the Brief Pain Inventory (-9.42, 95% CI -14.47 to -4.36, df=25; P=.001) and in disability by using the Pain Disability Assessment Scale (-1.95, 95% CI -3.33 to -0.56, df=24; P=.008) compared with TAU. As for the Medical Economic Evaluation, the incremental cost-effectiveness ratio for 1 year was estimated at 2.9 million yen (about US $25,000) per quality-adjusted life year gained. CONCLUSIONS: The findings of our study suggest that integrated cognitive behavioral therapy delivered by videoconferencing in regular medical care may reduce pain interference but not pain intensity. Further, this treatment method may be cost-effective, although this needs to be further verified using a larger sample size. TRIAL REGISTRATION: University Hospital Medical Information Network UMIN000031124; https://tinyurl.com/2pr3xszb.

Integrated cognitive behavioral therapy for chronic pain: An open-labeled prospective single-arm trial.

BACKGROUND: We aimed to examine the feasibility of our newly-developed, integrated, and high-intensity individual cognitive behavioral therapy (CBT) protocol for treatment-resistant chronic pain. METHODS: We conducted an open-labeled prospective single-arm trial for patients aged 18 years and above, suffering from chronic pain, and diagnosed with somatic symptom disorder with predominant pain. We provided 16 weekly sessions of CBT, each lasting for 50 minutes, which included 4 new strategies: attention shift, memory work, mental practice, and video feedback. For comparison, the study had a pre-test post-test design. The primary outcome was the change from baseline (week 1) to 16, as indicated by the Numerical Rating Scale and Pain Catastrophizing Scale. In addition, we evaluated depression, anxiety, disability, and quality of life as secondary outcomes. RESULTS: Sixteen patients with chronic pain underwent our CBT program. Though there was no reduction in pain intensity, catastrophic cognition showed statistically significant improvement with a large effect size. Depression, anxiety, and disability demonstrated statistically significant improvements, with small to moderate effect sizes. No adverse events were reported. CONCLUSION: Our newly integrated CBT program for chronic pain may improve catastrophic cognition, depression, anxiety, and disability. Large-scale randomized controlled studies are necessary to investigate the program's effectiveness in the future.

Neuropsychological Comparison Between Patients with Social Anxiety and Healthy Controls: Weak Central Coherence and Visual Scanning Deficit.

INTRODUCTION: Although deficits in neuropsychological functioning have been reported in social anxiety disorder (SAD), studies focusing on neuropsychological dysfunction in SAD are limited, and the evidence is still lacking. The purpose of this study was to examine the deficits in neuropsychological functioning in patients with SAD by comparing SAD patients and a healthy control (HC) group. MATERIALS AND METHODS: A total of 72 participants (20 in the SAD group and 52 in the HC group) were assessed with neuropsychological tests, consisting of the Rey Complex Figure Test (RCFT) to measure central coherence and the Trail Making Test A and B (TMT-A; TMT-B) to measure visual scanning and executive functioning. RESULTS: Analysis of covariance with depressive symptoms as a covariate revealed that central coherence (RCFT) and visual scanning (TMT-A) were significantly lower in the SAD group than in the HC group. No difference was found in executive functioning (TMT-B) when the effect of visual scanning was considered. DISCUSSION: Our findings suggest that SAD patients have weak central coherence and deficits in visual scanning compared to healthy controls. The clinical implications of these neuropsychological functioning deficits in SAD patients are discussed.

Cognitive-behavioral family therapy as psychoeducation for adolescents with high-functioning autism spectrum disorders: Aware and Care for my Autistic Traits (ACAT) program study protocol for a pragmatic multisite randomized controlled trial.

BACKGROUND: One aim of an autism spectrum disorder (ASD) diagnosis is to obtain special support for the disorder, though this does not guarantee practical support. We developed a psychoeducational program using cognitive-behavioral therapy (CBT) and Aware and Care for my Autistic Traits (ACAT) for Japanese adolescents with high-functioning ASD and their parents. METHODS: This multisite study is a randomized controlled trial. In total, 24 participants will be assigned to the ACAT group and 24 to the treatment-as-usual (TAU) group. The ACAT group will receive a weekly 100-min session for 6 weeks, regular medical care, and one follow-up session. In this ongoing clinical trial, we will compare the scores of the measures recorded in the pre- and post-intervention stages between the ACAT and TAU groups. A total of 41 patients out of a target of 48 have participated in the trial to date. The primary outcome measure is the Autism Knowledge Questionnaire. Secondary outcome measures include Barriers to Access to Care Evaluation 3rd Edition, the Strengths and Difficulties Questionnaire, the Vineland Adaptive Behavior Scales second edition, the Parenting Resilience Elements Questionnaire, the General Health Questionnaire 12, and the Depression Self-Rating Scale for Children assessments, as well as an electroencephalographic recording. DISCUSSION: It is expected that participants in the ACAT group will significantly increase their self-understanding and awareness of ASD symptoms compared to those in the TAU group. Additionally, the ACAT group is expected to exhibit improved social adaptation and mental health if children and parents are able to better understand the ASD characteristics through sessions. This intervention will contribute to the establishment of an effective evidence-based treatment strategy for adolescents with ASD. TRIAL REGISTRATION: UMIN Register 000029851 . Registered on January 06, 2018.

Predictors of response to exposure and response prevention-based cognitive behavioral therapy for obsessive-compulsive disorder.

BACKGROUND: Cognitive behavioral therapy (CBT), which includes exposure and response prevention (ERP), is effective in improving symptoms of obsessive-compulsive disorder (OCD). However, whether poor cognitive functions and autism spectrum disorder (ASD) traits affect the therapeutic response of patients with OCD to ERP-based CBT remains unclear. This study aimed to identify factors predictive of the therapeutic response of Japanese patients with OCD to ERP-based CBT. METHODS: Forty-two Japanese outpatients with OCD were assessed using the Wechsler Adult Intelligence Scale-III (WAIS-III), Yale-Brown Obsessive-Compulsive Scale, Patient Health Questionnaire 9-item scale, and Autism Spectrum Quotient (AQ) at pre- and post-treatment. We used multiple regression analyses to estimate the effect on therapeutic response change. The treatment response change was set as a dependent variable in multiple regression analyses. RESULTS: Multiple regression analyses showed that among independent variables, communication as an AQ sub-scale and Letter Number Sequencing as a WAIS-III sub-test predict the therapeutic response to ERP-based CBT . CONCLUSIONS: Our results suggest that diminished working memory (Letter Number Sequencing), poor communication skill (AQ sub-scale) may undermine responsiveness to ERP-based CBT among patients with OCD. TRIAL REGISTRATION: UMIN, UMIN00024087 . Registered 20 September 2016 - Retrospectively registered (including retrospective data).

Developmental changes in attention to social information from childhood to adolescence in autism spectrum disorders: a comparative study.

BACKGROUND: Elucidating developmental changes in the symptoms of autism spectrum disorder (ASD) is important to support individuals with ASD. However, no report has clarified the developmental changes in attention to social information for a broad age range. The aim of this study was to investigate the developmental changes in attention to social information from early childhood to adolescence in individuals with ASD and typically developed (TD) children. METHODS: We recruited children with ASD (n = 83) and TD participants (n = 307) between 2 and 18 years of age. Using the all-in-one-eye-tracking system, Gazefinder, we measured the percentage fixation time allocated to areas of interest (AoIs) depicted in movies (the eyes and mouth in movies of a human face with/without mouth motion, upright and inverted biological motion in movies showing these stimuli simultaneously, people and geometry in preference paradigm movies showing these stimuli simultaneously, and objects with/without finger-pointing in a movie showing a woman pointing toward an object). We conducted a three-way analysis of variance, 2 (diagnosis: ASD and TD) by 2 (sex: male and female) by 3 (age group: 0-5, 6-11, and 12-18 years) and locally weighted the scatterplot smoothing (LOESS) regression curve on each AoI. RESULTS: In the face stimuli, the percentage fixation time to the eye region for the TD group increased with age, whereas the one for the ASD group did not. In the ASD group, the LOESS curves of the gaze ratios at the eye region increased up to approximately 10 years of age and thereafter tended to decrease. For the percentage fixation time to the people region in the preference paradigm, the ASD group gazed more briefly at people than did the TD group. LIMITATIONS: It is possible that due to the cross-sectional design, the degree of severity and of social interest might have differed according to the subjects' age. CONCLUSIONS: There may be qualitative differences in abnormal eye contact in ASD between individuals in early childhood and those older than 10 years.

Prognosis Prediction Using Therapeutic Agreement of Video Conference-Delivered Cognitive Behavioral Therapy: Retrospective Secondary Analysis of a Single-Arm Pilot Trial.

BACKGROUND: The therapist-patient therapeutic alliance is known to be an important factor in cognitive behavioral therapy (CBT). However, findings by previous studies for obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD) have not been consistent regarding whether this alliance provides symptomatic improvements. OBJECTIVE: This study investigated predictors of symptom improvement in patients receiving CBT via video conferencing. METHODS: A total of 29 patients who participated in a previous clinical trial were recruited for the current study. Therapeutic alliance and clinical background in patients with OCD, PD, and SAD were measured at first session or the eighth session, which were calculated by multiple regression analyses to estimate the impact on therapeutic response percentage change. RESULTS: The multiple regression analyses showed that, among the independent variables, only patients' agreement in the therapeutic alliance remained viable, as other variables were a best fit for the excluded model (P=.002). The results show that patients' agreement on therapeutic goals and tasks explains the prognosis, as the normalization factor beta was 0.54 (SE 32.73; 95% CI 1.23-5.17; P=.002) and the adjusted R2 was .266. CONCLUSIONS: Patients' agreement on therapeutic goals and tasks predicts improvement after CBT via video conferencing. TRIAL REGISTRATION: UMIN Clinical Trial Repository UMIN000026609; https://tinyurl.com/ye6dcbwt.

Internet-Based Cognitive Behavioral Therapy With Real-Time Therapist Support via Videoconference for Patients With Obsessive-Compulsive Disorder, Panic Disorder, and Social Anxiety Disorder: Pilot Single-Arm Trial.

BACKGROUND: Cognitive behavioral therapy (CBT) is the first-line treatment for adults with obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). Patients in rural areas can access CBT via the internet. The effectiveness of internet-delivered cognitive behavioral therapy (ICBT) has been consistently shown, but no clinical studies have demonstrated the feasibility of ICBT with real-time therapist support via videoconference for OCD, PD, and SAD at the same time. OBJECTIVES: This study aimed to evaluate the feasibility of videoconference-delivered CBT for patients with OCD, PD, or SAD. METHODS: A total of 30 Japanese participants (mean age 35.4 years, SD 9.2) with OCD, SAD, or PD received 16 sessions of individualized videoconference-delivered CBT with real-time support of a therapist, using tablet personal computer (Apple iPad Mini 2). Treatment involved individualized CBT formulations specific to the presenting diagnosis; all sessions were provided by the same therapist. The primary outcomes were reduction in symptomatology, using the Yale-Brown obsessive-compulsive scale (Y-BOCS) for OCD, Panic Disorder Severity Scale (PDSS) for PD, and Liebowitz Social Anxiety Scale (LSAS) for SAD. The secondary outcomes included the EuroQol-5 Dimension (EQ-5D) for Quality of Life, the Patient Health Questionnaire (PHQ-9) for depression, the Generalized Anxiety Disorder (GAD-7) questionnaire for anxiety, and Working Alliance Inventory-Short Form (WAI-SF). All primary outcomes were assessed at baseline and at weeks 1 (baseline), 8 (midintervention), and 16 (postintervention) face-to-face during therapy. The occurrence of adverse events was observed after each session. For the primary analysis comparing between pre- and posttreatments, the participants' points and 95% CIs were estimated by the paired t tests with the change between pre- and posttreatment. RESULTS: A significant reduction in symptom of obsession-compulsion (Y-BOCS=-6.2; Cohen d=0.74; 95% CI -9.4 to -3.0, P=.002), panic (PDSS=-5.6; Cohen d=0.89; 95% CI -9.83 to -1.37; P=.02), social anxiety (LSAS=-33.6; Cohen d=1.10; 95% CI -59.62 to -7.49, P=.02) were observed. In addition, depression (PHQ-9=-1.72; Cohen d=0.27; 95% CI -3.26 to -0.19; P=.03) and general anxiety (GAD-7=-3.03; Cohen d=0.61; 95% CI -4.57 to -1.49, P<.001) were significantly improved. Although there were no significant changes at 16 weeks from baseline in EQ-5D (0.0336; Cohen d=-0.202; 95% CI -0.0198 to 0.00869; P=.21), there were high therapeutic alliance (ie, WAI-SF) scores (from 68.0 to 73.7) throughout treatment, which significantly increased (4.14; 95% CI 1.24 to 7.04; P=.007). Of the participants, 86% (25/29) were satisfied with videoconference-delivered CBT, and 83% (24/29) preferred videoconference-delivered CBT to face-to-face CBT. An adverse event occurred to a patient with SAD; the incidence was 3% (1/30). CONCLUSIONS: Videoconference-delivered CBT for patients with OCD, SAD, and SAD may be feasible and acceptable.

Case of bullous pemphigoid coexisting with anti-desmoglein autoantibodies.

A 79-year-old Japanese woman had clinical and histopathological features of bullous pemphigoid, while direct immunofluorescence test revealed C3 and immunoglobulin G depositions in the lower cell surfaces of the epidermis in addition to those in the dermoepidermal junction. Chemiluminescent enzyme immunoassays were positive for desmoglein-1 and -3 antibodies in addition to anti-BP180 antibodies. In an immunoblotting study, antibodies against both 180-kDa bullous pemphigoid antigen and 130-kDa pemphigus vulgaris antigen were detected. Based on these results, bullous pemphigoid coexisting with anti-desmoglein autoantibodies was diagnosed in this case.

Development of rhabdomyolysis in a child after norovirus gastroenteritis.

BACKGROUND: In children, the most significant cause of rhabdomyolysis or muscle breakdown is viral infection. However, there are no reports that norovirus, a gastroenteric virus that commonly infects children, specifically causes rhabdomyolysis. Here, we report the first pediatric case of norovirus-associated rhabdomyolysis. CASE PRESENTATION: The patient, a 2-year-old boy with fever, diarrhea, and vomiting, was referred to our hospital with dysstasia and transaminitis. He was diagnosed with rhabdomyolysis. Additionally, norovirus genogroup GII was detected from stool samples by real-time quantitative reverse transcription Polymerase Chain Reaction, and thereafter, the norovirus GII.4 variant was identified. CONCLUSION: However, the association between rhabdomyolysis and the isolated norovirus variant was not clarified. After treatment the patient recovered without renal failure or disseminated intravascular coagulation. Rhabdomyolysis is a disease for which there is a need for early detection and treatment. If abnormal posture or muscle weakness is observed during the course of gastroenteritis, blood and urinary tests should be performed to rule out rhabdomyolysis.