Systematic reduction of gray matter volume in anorexia nervosa, but relative enlargement with clinical symptoms in the prefrontal and posterior insular cortices: a multicenter neuroimaging study.

Although brain morphological abnormalities have been reported in anorexia nervosa (AN), the reliability and reproducibility of previous studies were limited due to insufficient sample sizes, which prevented exploratory analysis of the whole brain as opposed to regions of interest (ROIs). Objective was to identify brain morphological abnormalities in AN and the association with severity of AN by brain structural magnetic resonance imaging (MRI) in a multicenter study, and to conduct exploratory analysis of the whole brain. Here, we conducted a cross-sectional multicenter study using T1-weighted imaging (T1WI) data collected between May 2014 and February 2019 in Japan. We analyzed MRI data from 103 female AN patients (58 anorexia nervosa restricting type [ANR] and 45 anorexia nervosa binge-purging type [ANBP]) and 102 age-matched female healthy controls (HC). MRI data from five centers were preprocessed using the latest harmonization method to correct for intercenter differences. Gray matter volume (GMV) was calculated from T1WI data of all participants. Of the 205 participants, we obtained severity of eating disorder symptom scores from 179 participants, including 87 in the AN group (51 ANR, 36 ANBP) and 92 HC using the Eating Disorder Examination Questionnaire (EDE-Q) 6.0. GMV reduction were observed in the AN brain, including the bilateral cerebellum, middle and posterior cingulate gyrus, supplementary motor cortex, precentral gyrus medial segment, and thalamus. In addition, the orbitofrontal cortex (OFC), ventromedial prefrontal cortex (vmPFC), rostral anterior cingulate cortex (ACC), and posterior insula volumes showed positive correlations with severity of symptoms. This multicenter study was conducted with a large sample size to identify brain morphological abnormalities in AN. The findings provide a better understanding of the pathogenesis of AN and have potential for the development of brain imaging biomarkers of AN. Trial Registration: UMIN000017456. https://center6.umin.ac.jp/cgi-open-bin/icdr/ctr_view.cgi?recptno=R000019303 .

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.

Atypical social cognition processing in bulimia nervosa: an fMRI study of patients thinking of others' mental states.

BACKGROUND: Feeding and eating disorders are severe mental disorders that gravely affect patients' lives. In particular, patients with anorexia nervosa (AN) or bulimia nervosa (BN) appear to have poor social cognition. Many studies have shown the relationship between poor social cognition and brain responses in AN. However, few studies have examined the relationship between social cognition and BN. Therefore, we examined which brain regions impact the ability for social cognition in patients with BN. METHODS: We used task-based functional magnetic resonance imaging (fMRI) to examine brain responses during a social cognition task and the Reading Mind in the Eyes Test (RMET). During the fMRI, 22 women with BN and 22 healthy women (HW) took the RMET. Participants also completed the eating disorder clinical measures Bulimic Investigatory Test, Edinburgh (BITE) and Eating Disorders Examination Questionnaire (EDE-Q), the Patient Health Questionnaire (PHQ-9) measure of depression; and the Generalized Anxiety Disorder (GAD-7) measure of anxiety. RESULTS: No difference was observed in the RMET scores between women with BN and HW. Both groups showed activation in brain regions specific to social cognition. During the task, no differences were shown between the groups in the BOLD signal (p < 0.05, familywise error corrected for multiple comparisons). However, there was a tendency of more robust activation in the right angular gyrus, ventral diencephalon, thalamus proper, temporal pole, and middle temporal gyrus in BN (p < 0.001, uncorrected for multiple comparisons). Moreover, HW showed a positive correlation between RMET scores and the activation of two regions: medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC); however, no significant correlation was observed in women with BN. CONCLUSIONS: While activation in the mPFC and ACC positively correlated to the RMET scores in HW, no correlation was observed in BN patients. Therefore, women with BN might display modulated neural processing when thinking of others' mental states. Further examination is needed to investigate neural processing in BN patients to better understand their social cognition abilities. TRIAL REGISTRATION: UMIN, UMIN000010220. Registered 13 March 2013, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000010220.

Guided Internet-Based Cognitive Behavioral Therapy for Women With Bulimia Nervosa: Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Individual face-to-face cognitive behavioral therapy is known to be effective for bulimia nervosa (BN). Since foods vary considerably between regions and cultures in which patients live, cultural adaptation of the treatment program is particularly important in cognitive behavioral therapy for BN. Recently, an internet-based cognitive behavioral therapy (ICBT) program was developed for Japanese women with BN, adapted to the Japanese food culture. However, no previous randomized controlled trial has examined the effectiveness of ICBT. OBJECTIVE: This paper presents a research protocol for strategies to examine the effects of guided ICBT. METHODS: This study is designed as a multicenter, prospective, assessor-blinded randomized controlled trial. The treatment groups will be divided into treatment as usual (TAU) alone as the control group and ICBT combined with TAU as the intervention group. The primary outcome is the total of binge eating and purging behaviors assessed before and after treatment by an independent assessor. Secondary outcomes will include measures of eating disorder severity, depression, anxiety, quality of life, treatment satisfaction, and working alliances. Treatment satisfaction and working alliances will be measured post assessment only. Other measures will be assessed at baseline, post intervention, and follow-up, and the outcomes will be analyzed on an intention-to-treat basis. RESULTS: This study will be conducted at 7 different medical institutions in Japan from August 2022 to October 2026. Recruitment of participants began on August 19, 2022, and recruitment is scheduled to continue until July 2024. The first participants were registered on September 8, 2022. CONCLUSIONS: This is the first multicenter randomized controlled trial in Japan comparing the effectiveness of ICBT and TAU in patients with BN. TRIAL REGISTRATION: University Hospital Medical Information Network UMIN000048732; https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055522. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49828.