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.

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 .

Neural correlates of a mindfulness-based intervention in anorexia nervosa.

We examined the neural underpinnings of the effects of mindfulness on anxiety in anorexia nervosa using functional magnetic resonance imaging in 21 anorexia patients. We used a functional magnetic resonance imaging task designed to induce weight-related anxiety and asked participants to regulate their anxiety either using or not using an acceptance strategy. Our results showed reduced activity in the amygdala, anterior cingulate cortex, putamen, caudate, orbital gyrus, middle frontal gyrus, posterior cingulate cortex and precuneus following a mindfulness-based intervention. The present study provides new insight regarding the neural mechanisms underlying the effect of mindfulness-based intervention in ameliorating anorexia nervosa.

Structural brain changes in severe and enduring anorexia nervosa: A multimodal magnetic resonance imaging study of gray matter volume, cortical thickness, and white matter integrity.

Whole-brain T1-weighted imaging and diffusion tensor imaging was performed in 35 adult women with anorexia nervosa (AN) and 35 healthy controls. We conducted voxel-based group comparisons for gray matter volume (GMV), cortical thickness (CT), and fractional anisotropy (FA) values, using age and total intracranial volume as nuisance covariates. We then conducted the same group comparisons for these three measures, but this time also controlled for the following global pathological measures: total GMV, mean CT across the whole brain, and mean FA across the entire white matter skeleton. Compared with the healthy controls, AN patients had lower GMV and CT in widespread cortical regions, and smaller FA values in widespread white matter regions. After controlling for global parameters, almost all of the differences between the two groups disappeared, except for higher CT in the medial orbital gyrus and parietal operculum in the AN group. Structural brain changes in AN are likely to be composed of both global and region-specific changes. The former changes are likely to have a dominant impact, while the latter changes might in part explain the disease-specific pathophysiology of AN.

The relationship between attention and avoidance coping in anorexia nervosa: functional magnetic resonance imaging study.

BACKGROUND: Numerous studies have demonstrated attentional control difficulties and high avoidance coping in patients with anorexia nervosa. Attention is a critical coping resource because it enables individuals to demonstrate self-control and complete goal-directed behaviours. AIMS: We aimed to examine whether attentional control difficulty is related to high avoidance coping, and investigate the neural underpinnings of attentional control difficulties in individuals with anorexia nervosa. METHOD: Twenty-three patients with anorexia nervosa and 17 healthy controls completed questionnaires that assessed attention and coping, and underwent functional magnetic resonance imaging while performing a go/no-go task. RESULTS: Patients with anorexia nervosa showed weaker attentional control, higher omission error rates and higher avoidance coping compared with healthy controls. Attentional control difficulty was associated with higher avoidance coping in both groups. Functional magnetic resonance imaging analysis showed less deactivation in regions representing internal mental processing, such as the praecuneus, cuneus and left lingual gyrus, during the no-go condition. Moreover, weakened deactivation of the left lingual gyrus was associated with higher commission error rate in the anorexia nervosa group. CONCLUSIONS: Our results suggest that patients with anorexia nervosa may have difficulty in maintaining attention to external ongoing events because of disturbance from internal self-related thought, and support the notion that attentional control difficulties underlie the frequent use of avoidance coping in anorexia nervosa.

Eating Disorder Neuroimaging Initiative (EDNI): a multicentre prospective cohort study protocol for elucidating the neural effects of cognitive-behavioural therapy for eating disorders.

INTRODUCTION: Anorexia nervosa is a refractory psychiatric disorder with a mortality rate of 5.9% and standardised mortality ratio of 5.35, which is much higher than other psychiatric disorders. The standardised mortality ratio of bulimia nervosa is 1.49; however, it is characterised by suicidality resulting in a shorter time to death. While there is no current validated drug treatment for eating disorders in Japan, cognitive-behavioural therapy (CBT) is a well-established and commonly used treatment. CBT is also recommended in the Japanese Guidelines for the Treatment of Eating Disorders (2012) and has been covered by insurance since 2018. However, the neural mechanisms responsible for the effect of CBT have not been elucidated, and the use of biomarkers such as neuroimaging data would be beneficial. METHODS AND ANALYSIS: The Eating Disorder Neuroimaging Initiative is a multisite prospective cohort study. We will longitudinally collect data from 72 patients with eating disorders (anorexia nervosa and bulimia nervosa) and 70 controls. Data will be collected at baseline, after 21-41 sessions of CBT and 12 months later. We will assess longitudinal changes in neural circuit function, clinical data, gene expression and psychological measures by therapeutic intervention and analyse the relationship among them using machine learning methods. ETHICS AND DISSEMINATION: The study was approved by The Ethical Committee of the National Center of Neurology and Psychiatry (A2019-072). We will obtain written informed consent from all patients who participate in the study after they had been fully informed about the study protocol. All imaging, demographic and clinical data are shared between the participating sites and will be made publicly available in 2024. TRIAL REGISTRATION NUMBER: UMIN000039841.

Exaggerated envy and guilt measured by economic games in Japanese women with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) patients are assumed to express high levels of guilt and envy. Ultimatum game (UG) is a standard behavioral task that focuses on interpersonal behavior when splitting a sum of money between two players. UG studies consistently demonstrate that people tend to decrease their inequity in outcomes, one explanation being that economically irrational decision-making may partly arise from the emotions guilt and envy. We assumed that AN patients would perform excessively fair in UG, reflecting high guilt and envy. METHODS: We utilized UG to investigate the characteristics of guilt and envy among 24 Japanese AN patients and 22 age-matched healthy controls (HC). The relation between the outcome of UG and decision strategy confirmed by post-experimental questionnaires was analyzed. RESULTS: As proposer, AN offered a larger amount to the responder compared with HC (p = 0.002) while, on the other hand, as responder, AN demanded much higher allocation to accept the offer compared with HC (p = 0.026). Regarding the strategy as responder, AN put more emphasis on fairness and less emphasis on monetary reward compared with HC (p = 0.046, p = 0.042, respectively). CONCLUSIONS: The results indicate that Japanese AN patients demonstrate strong preference for fairness, with high guilt and high envy. High sensitivity to guilt and envy of AN patients can affect not only their own behavior concerning eating attitude and body shape, but also decision-making in interpersonal situations. Behavioral experimental settings among social situations will enable us to evaluate and help actual decision-making in the real life of patients.

Differences in neural responses to reward and punishment processing between anorexia nervosa subtypes: An fMRI study.

AIM: Anorexia nervosa (AN) includes the restricting (AN-r) and binge-eating/purging (AN-bp) subtypes, which have been reported to differ regarding their underlying pathophysiologies as well as their behavioral patterns. However, the differences in neural mechanisms of reward systems between AN subtypes remain unclear. The aim of the present study was to explore differences in the neural processing of reward and punishment between AN subtypes. METHODS: Twenty-three female patients with AN (11 AN-r and 12 AN-bp) and 20 healthy women underwent functional magnetic resonance imaging while performing a monetary incentive delay task. Whole-brain one-way analysis of variance was conducted to test between-group differences. RESULTS: There were significant group differences in brain activation in the rostral anterior cingulate cortex and right posterior insula during loss anticipation, with increased brain activation in the AN-bp group relative to the AN-r and healthy women groups. No significant differences were found during gain anticipation. CONCLUSION: AN-bp patients showed altered neural responses to punishment in brain regions implicated in emotional arousal. Our findings suggest that individuals with AN-bp are more sensitive to potential punishment than individuals with AN-r and healthy individuals at the neural level. The present study provides preliminary evidence that there are neurobiological differences between AN subtypes with regard to the reward system, especially punishment processing.

Establishment and characterization of the RMG-V cell line from human ovarian clear cell adenocarcinoma.

A cell line, designated as RMG-V, was established from a patient with clear cell adenocarcinoma of the ovary. The cell line has grown without interruption and has been propagated continuously by serial passaging (more than 36 times) over 5 years. The cells are spindle-shaped, display neoplastic and pleomorphic features, and grow in a jigsaw puzzle-like arrangement while forming monolayers without contact inhibition. These cells proliferate rapidly, and the population doubling time is about 15.5 hours. The number of chromosomes ranges between 77 and 85, with a modal number of 83.