Social cognition in anorexia nervosa: Evidence of preserved Theory of Mind and impaired emotional functioning.

The findings of the few studies that have to date investigated the way in which individuals with Anorexia Nervosa (AN) navigate their social environment are somewhat contradictory. We undertook this study to shed new light on the social-cognitive profile of patients with AN, analysing Theory of Mind and emotional functioning. Starting from previous evidence on the role of the amygdala in the neurobiology of AN and in the social cognition, we hypothesise preserved Theory of Mind and impaired emotional functioning in patients with AN.Thirty women diagnosed with AN and thirty-two women matched for education and age were involved in the study. Theory of Mind and emotional functioning were assessed with a set of validated experimental tasks. A measure of perceived social support was also used to test the correlations between this dimension and the social-cognitive profile of AN patients.The performance of patients with AN is significantly worse than that of healthy controls on tasks assessing emotional functioning, whereas patients’ performance is comparable to that of healthy controls on the Theory of Mind task. Correlation analyses showed no relationship between scores on any of the social-cognition tasks and either age of onset or duration of illness. A correlation between social support and emotional functioning was found. This latter result seems to suggest a potential role of social support in the treatment and recovery of AN.The pattern of results followed the experimental hypothesis. They may be useful to help us better understand the social-cognitive profile of patients with AN and to contribute to the development of effective interventions based on the ways in which patients with AN actually perceive their social environment

Altered social attention in anorexia nervosa during real social interaction

The capacity to devote attentional resources in response to body-related signals provided by others is still largely unexplored in individuals with Anorexia Nervosa (AN). Here, we tested this capacity through a novel paradigm that mimics a social interaction with a real partner. Healthy individuals (Experiment 1) and individuals with AN (Experiment 2) completed a task with another person which consisted in performing, alternatively, rapid aiming movements to lateralised targets. Generally, this task leads to a form of Inhibition of Return (IOR), which consists of longer reaction times when an individual has to respond to a location previously searched by either himself (individual IOR) or by the partner (social IOR) as compared to previously unexplored locations. IOR is considered as an important attentional mechanism that promotes an effective exploration of the environment during social interaction. Here, healthy individuals displayed both individual and social IOR that were both reliable and of the same magnitude. Individuals with AN displayed a non-significant individual IOR but a reliable social IOR that was also significantly stronger than individual IOR. These results suggest the presence of a reduced sensitivity in processing body-related stimuli conveyed by oneself in individuals with AN which is reflected in action-based attentional processes

Linguistic embodiment in typical and atypical anorexia nervosa: Evidence from an image-word matching task

Objective: The integration of sensory, motor, and cognitive systems is embodied cognition, according to which mind and body are not separate and distinct, and our body (and our brain, as part of the body) contributes to determining our mental and cognitive processes. In spite of limited data available, Anorexia nervosa (AN) appears as a condition in which embodied cognition is altered, in particular, if we consider bodily sensations and visuospatial information processing. We aimed to evaluate the ability to correctly identify body parts and actions in both full (AN) and atypical AN (AAN), looking at the role of the underweight status. Method: A group of 143 females (AN = 45, AAN = 43, unaffected women = 55) was enrolled. All participants performed a linguistic embodied task to evaluate the association between a picture-showing a bodily action-and a written verb. Additionally, a subsample of 24 AN participants performed a retest after stable weight recovery. Results: Both AN and AAN demonstrated an abnormal ability to evaluate the picture-written verb associations, especially if the involved bodily effectors were the same in both stimuli (i.e., pictorial and verbal) and needed a longer response time. Conclusions: Specific embodied cognition linked to body schema seems to be impaired in persons with AN. The longitudinal analysis showed a difference between AN and AAN only in the underweight condition, suggesting the presence of an abnormal linguistic embodiment. More attention should be devoted to embodiment during AN treatment to improve bodily cognition, which might, in turn, diminish body misperception

Mentalizing Subtypes in Eating Disorders: A Latent Profile Analysis

Background: Mentalizing, the mental capacity to understand oneself and others in terms of mental states, has been found to be reduced in several mental disorders. Some studies have suggested that eating disorders (EDs) may also be associated with impairments in mentalizing. The aim of this work is to investigate the possible presence of mentalizing subtypes in a sample of patients with EDs. Method: A sample of patients with eating disorders (N = 157) completed a battery of measures assessing mentalization and related variables, including the Reflective Functioning Questionnaire (RFQ), the Difficulties in Emotion Regulation Strategies (DERS), the Interpersonal Reactivity Index (IRI). Clinicians rated patients in relation to imbalances in different dimensions of mentalization to prementalizing modes and attachment style by using the Mentalization Imbalances Scale, the Modes of Mentalization Scale (MMS), and the Adult Attachment Questionnaire. A latent profile analysis was conducted to test the possible presence of different subgroups. MANOVA was used to test the possible differences between the four mentalizing profiles in relation to emotion dysregulation (DERS), empathy (IRI), and adequate and impairments in mentalizing (MMS and RFQ). Results: The latent profile analysis suggested the presence of four different profiles in relation to impairments in the dimensions of mentalization: (1) affective/self/automatic imbalances, (2) external imbalance, (3) cognitive/self/automatic imbalances, and (4) cognitive/other/automatic imbalances. Patients belonging to profile 1 are characterized by the prevalence of affective mentalization that overwhelms the capacity to reflect on mental states with an imbalance on the self-dimension; profile 2 patients are excessively focused on the external cues of mentalization; profile 3 patients are characterized by an over-involvement on the cognitive and self-facets of mentalization, with an impairment in adopting the other mind perspective; and profile 4 patients have similar impairments compared to profile 3 patients but with an excessive focus on others and deficits in self-reflection. These profiles were heterogeneous in terms of EDs represented in each group and presented significant differences on various variables such as attachment style, emotion dysregulation, empathy, interpersonal reactivity, and reflective function. This study represents, so far, the first work that confirms the presence of different mentalizing patterns in ED patients. Conclusions: ED patients can be classified in relation to impairments in different dimensions of mentalization above and beyond ED diagnosis

Mitochondrial Role in Intrinsic Apoptosis Induced by a New Synthesized Chalcone in Hepatocellular Carcinoma Cells

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the fourth cause of cancer-related deaths worldwide. Presently, a few drugs are available for HCC treatment and prevention, including both natural and synthetic compounds. In this study, a new chalcone, (E)-1-(2,4,6-triethoxyphenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (ETTC), was synthesized and its effects and mechanisms of action over human hepatoma cells were investigated. Cytotoxic activity was revealed in HCC cells, while no effects were observed in normal hepatocytes. In HCC cells, ETTC caused subG1 cell cycle arrest and apoptosis, characterized by nuclear fragmentation. The activation of caspases 3/7 and 9, the increase in pro-apoptotic BAX, and the decrease in anti-apoptotic BCL-2 suggest the activation of the intrinsic pathway of apoptosis. ETTC mitochondrial targeting is confirmed by the reduction in mitochondrial membrane potential and Complex I activity together with levels of superoxide anion increasing. Our outcomes prove the potential mitochondria-mediated antitumor effect of newly synthesized chalcone ETTC in HCC

The impact of COVID-19 lockdown and of the following "re-opening" period on specific and general psychopathology in people with Eating Disorders: the emergent role of internalizing symptoms

BACKGROUND: We assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on specific Eating Disorder (ED) and general psychopathology in people with an ED diagnosis during the lockdown period and after the end of the related containment measures.METHODS: People with clinically defined diagnosis and undergoing treatment for an ED completed an online survey, which included adapted questions from standardized psychometric scales. Data relative to three different time periods (before, during and after the end of lockdown) were collected. Psychopathological changes over these periods were investigated and compared through one-way analysis of variance or covariance with repeated measures.RESULTS: Three hundred twelve people completed the survey (57.4% diagnosed with Anorexia Nervosa (AN) or atypical AN, 20.2% with Bulimia Nervosa, 15.4% with Binge Eating Disorder, 7.05% with Other Specified Feeding or Eating Disorders). The severity of both specific and general psychopathology increased during the lockdown and the rise of general symptoms persisted in the following re-opening phase, except for suicide ideation. Almost all of these findings were not affected by ED diagnosis, participants' age and illness duration.LIMITATIONS: The retrospective nature of data collection is the main limitation of the study.CONCLUSIONS: People with EDs showed a COVID-19 emergency-induced worsening of both general and specific psychopathology. The effect on general psychopathology persisted in the re-opening period. These findings suggest a high stress vulnerability of ED individuals with important effects on internalizing symptoms, which are worth of attention by clinicians

A consensus document on definition and diagnostic criteria for orthorexia nervosa

Purpose: Since the term orthorexia nervosa (ON) was coined from the Greek (ὀρθός, right and ὄρεξις, appetite) in 1997 to describe an obsession with “correct” eating, it has been used worldwide without a consistent definition. Although multiple authors have proposed diagnostic criteria, and many theoretical papers have been published, no consensus definition of ON exists, empirical primary evidence is limited, and ON is not a standardized diagnosis. These gaps prevent research to identify risk and protective factors, pathophysiology, functional consequences, and evidence-based therapeutic treatments. The aims of the current study are to categorize the common observations and presentations of ON pathology among experts in the eating disorder field, propose tentative diagnostic criteria, and consider which DSM chapter and category would be most appropriate for ON should it be included. Methods: 47 eating disorder researchers and multidisciplinary treatment specialists from 14 different countries across four continents completed a three-phase modified Delphi process, with 75% agreement determined as the threshold for a statement to be included in the final consensus document. In phase I, participants were asked via online survey to agree or disagree with 67 statements about ON in four categories: A–Definition, Clinical Aspects, Duration; B–Consequences; C–Onset; D–Exclusion Criteria, and comment on their rationale. Responses were used to modify the statements which were then provided to the same participants for phase II, a second round of feedback, again in online survey form. Responses to phase II were used to modify and improve the statements for phase III, in which statements that met the predetermined 75% of agreement threshold were provided for review and commentary by all participants. Results: 27 statements met or exceeded the consensus threshold and were compiled into proposed diagnostic criteria for ON. Conclusions: This is the first time a standardized definition of ON has been developed from a worldwide, multidisciplinary cohort of experts. It represents a summary of observations, clinical expertise, and research findings from a wide base of knowledge. It may be used as a base for diagnosis, treatment protocols, and further research to answer the open questions that remain, particularly the functional consequences of ON and how it might be prevented or identified and intervened upon in its early stages. Although the participants encompass many countries and disciplines, further research will be needed to determine if these diagnostic criteria are applicable to the experience of ON in geographic areas not represented in the current expert panel. Level of evidence_ Level V: opinions of expert committee

Interoception and Autonomic Correlates during Social Interactions. Implications for Anorexia

The aim of this study is to investigate the bodily-self in Restrictive Anorexia, focusing on two basic aspects related to the bodily self: autonomic strategies in social behavior, in which others’ social desirability features, and social cues (e.g., gaze) are modulated, and interoception (i.e., the sensitivity to stimuli originating inside the body). Furthermore, since previous studies carried out on healthy individuals found that interoception seems to contribute to the autonomic regulation of social behavior, as measured by Respiratory Sinus Arrhythmia (RSA), we aimed to explore this link in anorexia patients, whose ability to perceive their bodily signal seems to be impaired. To this purpose, we compared a group of anorexia patients (ANg; restrictive type) with a group of Healthy Controls (HCg) for RSA responses during both a resting state and a social proxemics task, for their explicit judgments of comfort in social distances during a behavioral proxemics task, and for their Interoceptive Accuracy (IA). The results showed that ANg displayed significantly lower social disposition and a flattened autonomic reactivity during the proxemics task, irrespective of the presence of others’ socially desirable features or social cues. Moreover, unlike HCg, the autonomic arousal of ANg did not guide behavioral judgments of social distances. Finally, IA was strictly related to social disposition in both groups, but with opposite trends in ANg. We conclude that autonomic imbalance and its altered relationship with interoception might have a crucial role in anorexia disturbances

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982