Updating Prospective Self-Efficacy Beliefs About Cardiac Interoception in Anorexia Nervosa: An Experimental and Computational Study.

Patients with anorexia nervosa (AN) typically hold altered beliefs about their body that they struggle to update, including global, prospective beliefs about their ability to know and regulate their body and particularly their interoceptive states. While clinical questionnaire studies have provided ample evidence on the role of such beliefs in the onset, maintenance, and treatment of AN, psychophysical studies have typically focused on perceptual and 'local' beliefs. Across two experiments, we examined how women at the acute AN (N = 86) and post-acute AN state (N = 87), compared to matched healthy controls (N = 180) formed and updated their self-efficacy beliefs retrospectively (Experiment 1) and prospectively (Experiment 2) about their heartbeat counting abilities in an adapted heartbeat counting task. As preregistered, while AN patients did not differ from controls in interoceptive accuracy per se, they hold and maintain 'pessimistic' interoceptive, metacognitive self-efficacy beliefs after performance. Modelling using a simplified computational Bayesian learning framework showed that neither local evidence from performance, nor retrospective beliefs following that performance (that themselves were suboptimally updated) seem to be sufficient to counter and update pessimistic, self-efficacy beliefs in AN. AN patients showed lower learning rates than controls, revealing a tendency to base their posterior beliefs more on prior beliefs rather than prediction errors in both retrospective and prospective belief updating. Further explorations showed that while these differences in both explicit beliefs, and the latent mechanisms of belief updating, were not explained by general cognitive flexibility differences, they were explained by negative mood comorbidity, even after the acute stage of illness.

Interactomic exploration of LRRC8A in volume-regulated anion channels.

Ion channels are critical in enabling ion movement into and within cells and are important targets for pharmacological interventions in different human diseases. In addition to their ion transport abilities, ion channels interact with signalling and scaffolding proteins, which affects their function, cellular positioning, and links to intracellular signalling pathways. The study of "channelosomes" within cells has the potential to uncover their involvement in human diseases, although this field of research is still emerging. LRRC8A is the gene that encodes a crucial protein involved in the formation of volume-regulated anion channels (VRACs). Some studies suggest that LRRC8A could be a valuable prognostic tool in different types of cancer, serving as a biomarker for predicting patients' outcomes. LRRC8A expression levels might be linked to tumour progression, metastasis, and treatment response, although its implications in different cancer types can be varied. Here, publicly accessible databases of cancer patients were systematically analysed to determine if a correlation between VRAC channel expression and survival rate exists across distinct cancer types. Moreover, we re-evaluated the impact of LRRC8A on cellular proliferation and migration in colon cancer via HCT116 LRRC8A-KO cells, which is a current topic of debate in the literature. In addition, to investigate the role of LRRC8A in cellular signalling, we conducted biotin proximity-dependent identification (BioID) analysis, revealing a correlation between VRAC channels and cell-cell junctions, mechanisms that govern cellular calcium homeostasis, kinases, and GTPase signalling. Overall, this dataset improves our understanding of LRRC8A/VRAC and explores new research avenues while identifying promising therapeutic targets and promoting inventive methods for disease treatment.

An optogenetic method for the controlled release of single molecules.

We developed a system for optogenetic release of single molecules in cells. We confined soluble and transmembrane proteins to the Golgi apparatus via a photocleavable protein and released them by short pulses of light. Our method allows for a light dose-dependent delivery of functional proteins to the cytosol and plasma membrane in amounts compatible with single-molecule imaging, greatly simplifying access to single-molecule microscopy of any protein in live cells. We were able to reconstitute ion conductance by delivering BK and LRRC8/volume-regulated anion channels to the plasma membrane. Finally we were able to induce NF-kB signaling in T lymphoblasts stimulated by interleukin-1 by controlled release of a signaling protein that had been knocked out. We observed light-induced formation of functional inflammatory signaling complexes that triggered phosphorylation of the inhibitor of nuclear factor kappa-B kinase only in activated cells. We thus developed an optogenetic method for the reconstitution and investigation of cellular function at the single-molecule level.

Early identification of risk for eating disorders in Italian secondary school students: a cross-sectional study.

AIM: Eating disorders are major illnesses that primarily affect adolescents and young adults and seriously threaten public health. Early identification of at-risk individuals and timely initiation of treatment is crucial to improve outcomes. The Inside Out Institute Screener (IOI-S) is a rapid self-administration screening tool for high-risk and early-stage eating disorders. This study aimed to investigate the risk of having an eating disorder in a sample of Italian students by testing the Italian version of the IOI-S. METHODS: A multicentre cross-sectional study was conducted in a population of students aged 12-19 years; validity and reliability of the IOI-Sita were investigated. RESULTS: Four-hundred and ninety-one (81.97%) students were enrolled, 24.85% of whom were found to be at "very high risk" of an eating disorder, according to IOI-Sita. Younger (p<0.001) and female (p<0.001) students had higher risk scores. The EFA confirmed the original monodimensional structure of the tool, S-CVI=0.95%. The Content Validity Index of the scale (S-CVI) was 0.95, ω coefficient was 0.927. DISCUSSION AND CONCLUSIONS: This research confirms the need to screen for eating disorders in Italian youth adequately; the psychometric properties of the IOI-Sita confirm it as a valid and reliable tool for screening high-risk and early-stage eating disorders.

Eye movement desensitisation and reprocessing as add-on treatment to enhanced cognitive behaviour therapy for patients with anorexia nervosa reporting childhood maltreatment: A quasi-experimental multicenter study.

OBJECTIVE: This quasi-experimental study aimed to compare the outcome of patients with Anorexia Nervosa (AN) reporting moderate/severe childhood maltreatment (CM) treated exclusively with Enhanced Cognitive Behaviour Therapy (CBT-E) or with CBT-E plus Eye Movement Desensitisation and Reprocessing (EMDR). METHOD: A total of 75 patients with AN reporting moderate/severe CM were initially assessed regarding body mass index (BMI), general and eating disorder (ED)-specific psychopathology, and dissociative symptoms, and re-evaluated after 40 CBT-E sessions (T1). Then, 18 patients received EMDR, whereas the others were placed on a waiting list and continued CBT-E. T2 assessment was performed after 20-25 sessions of EMDR or CBT-E. A control group of 67 patients without CM was also enroled and treated with CBT-E. RESULTS: Contrary to patients without CM, neither of the traumatised groups improved in BMI, general and ED psychopathology, or dissociation at T1. However, at T2, both traumatised groups improved in BMI and ED-specific psychopathology, with the CBT + EMDR group demonstrating greater improvements. Moreover, only the CBT + EMDR group improved in general psychopathology and dissociative symptoms. The reduction of ED symptoms in traumatised patients was mediated by the amelioration of dissociation. DISCUSSION: The addition of EMDR to CBT-E may benefit patients with AN reporting moderate/severe CM.

State of Mind Assessment in Relation to Adult Attachment and Text Analysis of Adult Attachment Interviews in a Sample of Patients with Anorexia Nervosa.

BACKGROUND: Attachment theory represents one of the most important references for the study of the development of an individual throughout their life cycle and provides the clinician with a profound key for the purposes of understanding the suffering that underlies severe psychopathologies such as eating disorders. As such, we conducted a cross-sectional study with a mixed-methods analysis on a sample of 32 young women with anorexia nervosa (AN); this study was embedded in the utilized theoretical framework with the following aims: 1. to evaluate the state of mind (SoM) in relation to adult attachment, assuming a prevalence of the dismissing (DS) SoM and 2. to analyze the linguistic attachment profile emerging from the transcripts of the AAIs. METHODS: Interviews were transcribed verbatim, coded, and analyzed using the linguistic inquiry and word count (LIWC) method. RESULTS: The results were observed to be consistent with the referenced literature. The prevalence of a DS SoM (68.75%) is observed in the study sample, whereas the results of the lexical analysis of the stories deviate from expectations. Notably, the lexical results indicate the coexistence of the dismissing and entangled aspects at the representational level. CONCLUSIONS: The study results suggest a high level of specificity in the emotional functioning of patients with AN, with a focusing on a pervasive control of emotions that is well illustrated by the avoidant/ambivalent (A/C) strategy described in Crittenden's dynamic-maturational model. These findings and considerations have important implications for clinical work and treatment, which we believe must be structured on the basis of starting from a reappraisal of emotional content.

Molecular determinants underlying volume-regulated anion channel subunit-dependent oxidation sensitivity.

The volume-regulated anion channel (VRAC) is formed by LRRC8 subunits. Besides their role in the maintenance of cell homeostasis, VRACs are critically involved in oxidative stress mechanisms: reactive oxygen species directly modulate VRACs in a subunit-dependent manner. It was reported that LRRC8A-LRRC8E heteromeric channels are activated by oxidation, whereas LRRC8A-LRRC8C heteromers are inhibited. Here we adopted chimeric- as well as concatemeric-based strategies to identify residues responsible for the divergent effect of oxidants. We identified two cysteines in the first two leucine rich repeats of LRRC8E, C424 and C448, as the targets of oxidation. Oxidation likely results in the formation of a disulfide bond between the two cysteines, which in turn induces a conformational change leading to channel activation. Additionally, we found that LRRC8C inhibition is caused by oxidation of the first methionine. We thus identified crucial molecular elements involved in channel activation, which are conceivably relevant in determining physiological ROS effects. KEY POINTS: Volume-regulated anion channels (VRACs) are heterohexameric complexes composed of an essential LRRC8A subunit and a variable number of LRRC8B-E subunits. VRACs are directly regulated by oxidation, with LRRC8A-LRRC8E heteromers being potentiated and LRRC8A-LRRC8C heteromers being inhibited by oxidation. We identified two LRRC8E specific intracellular cysteines that form a disulfide bond upon oxidation leading to LRRC8A-LRRC8E potentiation. Inhibition of LRRC8A-LRRC8C heteromers is mediated by the oxidation of the start methionine, being additionally dependent on the identity of the LRR domain. Besides providing physiological insights concerning the outcome of reactive oxygen species modulation, the results point to key structural elements involved in VRAC activation.

Adaptation and validation of the Caregiver Burden Inventory in eating disorders.

BACKGROUND: Living with people diagnosed with a mental disorder is known to increase the risk of developing high levels of so-called "caregiver burden" in informal caregivers. In-depth analysis of this phenomenon and specific assessment tools for caregivers of patients diagnosed with Eating Disorders (EDs) are lacking. In this study, we aimed to evaluate the psychometric properties of the Caregiver Burden Inventory in EDs and employ this adapted tool in this category of caregivers. METHODS: A cross-sectional study was conducted in the Eating Disorders outpatient unit of an Italian University hospital. Face and content validity were investigated by calculating standard Content Validity Indices (CVI-I and CVI-S) after administering the Inventory to 6 expert nurses with at least 5 years of experience in mental health services assisting people diagnosed with Eating Disorders. Internal consistency was evaluated with Cronbach's α coefficient for the overall scale and subscales. An exploratory factor analysis (EFA) was performed to explore latent constructs. The adapted CBI was then administered to 62 informal caregivers of ED patients. RESULTS: The EFA yielded a 5-factor structure. The CVI-S was 97.2%; the Cronbach α coefficient was 0,90 (> 0.74 in each subscale). The median burden level in the experimental population was 40.0 [range = 21 to 54], in a theoretical range from 0 (no burden) to 96 (highest level of burden). CONCLUSION: The Caregiver Burden Inventory appears to be a valid and reliable instrument to assess caregiver burden in individuals diagnosed with Eating Disorders. Further research is needed to evaluate this tool's efficiency in improving individually tailored interventions on families.

Eating disorders (EDs) are characterized by the development of abnormal eating habits, dysregulation of body weight and/or body image distortion. The pervasiveness of EDs may significantly affect the life of patients' caregivers in terms of emotional load, termed Caregiver Burden (CB). This may impact the quality of life of the entire family and promote conflicts which may in turn exacerbate ED behaviours. Among several international assessment tools to measure CB, the Caregiver Burden Inventory (CBI) is perhaps the most widely employed. However, this tool has never been specifically tested in caregivers of ED patients. Here we show that CBI can adequately quantify burden in this category of caregivers. Systematic use of this instrument can support healthcare workers who aim to address the carer's discomfort and promote a focused monitoring of subjects with increased risk, in order to adequately plan targeted intervention programs.

The VRAC blocker DCPIB directly gates the BK channels and increases intracellular Ca2+ in melanoma and pancreatic duct adenocarcinoma cell lines.

BACKGROUND AND PURPOSE: The volume regulated anion channel (VRAC) is known to be involved in different aspects of cancer cell behaviour and response to therapies. For this reason, we investigated the effect of DCPIB, a presumably specific blocker of VRAC, in two types of cancer: pancreatic duct adenocarcinoma (PDAC) and melanoma. EXPERIMENTAL APPROACH: We used patch-clamp electrophysiology, supported by Ca2+ imaging, gene expression analysis, docking simulation and mutagenesis. We employed two PDAC lines (Panc-1 and MiaPaCa-2), as well as a primary (IGR39) and a metastatic (IGR37) melanoma line. KEY RESULTS: DCPIB markedly increased whole-cell currents in Panc-1, MiaPaca2 and IGR39, but not in IGR37 cells. The currents were mostly mediated by KCa 1.1 channels, commonly known as BK channels. We confirmed DCPIB activation of BK channels also in HEK293 cells transfected with α subunits of this channel. Further experiments showed that in IGR39, and to a smaller degree also in Panc-1 cells, DCPIB induced a rapid Ca2+ influx. This, in turn, indirectly potentiated BK channels and, in IGR39 cells, additionally activated other Ca2+ -dependent channels. However, Ca2+ influx was not required for activation of BK channels by DCPIB, as such activation involved the extracellular part of the protein and we have identified a residue crucial for binding. CONCLUSION AND IMPLICATIONS: DCPIB directly targeted BK channels and, also, acutely increased intracellular Ca2+ . Our findings extend the list of DCPIB effects that should be taken into consideration for future development of DCPIB-based modulators of ion channels and other membrane proteins.

Eating disturbances in eating disorders and in high-functioning autism spectrum disorders: a preliminary study.

PURPOSE: The relationship between autism spectrum disorders (ASDs) and eating disorders (EDs) has been widely studied in the last decades. We aimed to directly compare patients with EDs, individuals with high-functioning ASDs (HF-ASDs) and healthy controls (HC) at measures detecting: (1) symptoms of eating disorders, (2) eating disturbances known to be characteristic of autism. METHODS: Thirty-four patients with EDs, 34 individuals with HF-ASDs and 35 HC, all females, completed the eating attitude test (EAT-26) and the Swedish eating assessment for autism spectrum disorders (SWEAA), two self-report questionnaires assessing, respectively, symptoms and concerns characteristic of eating disorders and ASD-related eating disturbances. RESULTS: At the EAT-26, patients with EDs scored significantly higher than individuals with HF-ASDs, and both of them scored higher than HC (p < 0.05, ηp2 = 0.283). Conversely, at the SWEAA, no differences between individuals with HF-ASDs and patients with EDs emerged (p = 901), but they both scored higher than HC (p < 0.05, ηp2 = 0.247). CONCLUSION: Individuals with HF-ASDs did not seem to reach the same level of EDs symptomatology as patients with EDs. Patients with EDs did not seem to present a different amount of autistic-eating behaviours than subjects with HF-ASDs. Patients with EDs and individuals with HF-ASDs scored higher than HC at both scales. Our results give further preliminary evidence of the overlap between autistic traits and EDs symptomatology, and should be taken into account in the definition of a shared model between EDs and ASDs. LEVEL OF EVIDENCE: Level II; Evidence obtained from controlled trial without randomization.

How Is the History of Early Traumatic Exposure Associated With the Psychopathological Outcomes of COVID-19 Related Lockdown and Subsequent Re-opening in People With Eating Disorders?

The negative impact of COVID-19 pandemic on people with Eating Disorders (EDs) has been documented. The aim of this study was to evaluate whether a history of traumatic experiences during childhood or adolescence was associated with a higher degree of psychopathological worsening during COVID-19 related lockdown and in the following re-opening period in this group of people. People with EDs undergoing a specialist ED treatment in different Italian services before the spreading of COVID-19 pandemic (n = 312) filled in an online survey to retrospectively evaluate ED specific and general psychopathology changes after COVID-19 quarantine. Based on the presence of self-reported traumatic experiences, the participants were split into three groups: patients with EDs and no traumatic experiences, patients with EDs and childhood traumatic experiences, patients with EDs and adolescent traumatic experiences. Both people with or without early traumatic experiences reported retrospectively a worsening of general and ED-specific psychopathology during the COVID 19-induced lockdown and in the following re-opening period. Compared to ED participants without early traumatic experiences, those with a self-reported history of early traumatic experiences reported heightened anxious and post-traumatic stress symptoms, ineffectiveness, body dissatisfaction, and purging behaviors. These differences were seen before COVID-19 related restrictions as well as during the lockdown period and after the easing of COVID-19 related restrictions. In line with the "maltreated ecophenotype" theory, these results may suggest a clinical vulnerability of maltreated people with EDs leading to a greater severity in both general and ED-specific symptomatology experienced during the exposure to the COVID-19 pandemic.

Hyperexcitable interneurons trigger cortical spreading depression in an Scn1a migraine model.

Cortical spreading depression (CSD), a wave of depolarization followed by depression of cortical activity, is a pathophysiological process implicated in migraine with aura and various other brain pathologies, such as ischemic stroke and traumatic brain injury. To gain insight into the pathophysiology of CSD, we generated a mouse model for a severe monogenic subtype of migraine with aura, familial hemiplegic migraine type 3 (FHM3). FHM3 is caused by mutations in SCN1A, encoding the voltage-gated Na+ channel NaV1.1 predominantly expressed in inhibitory interneurons. Homozygous Scn1aL1649Q knock-in mice died prematurely, whereas heterozygous mice had a normal lifespan. Heterozygous Scn1aL1649Q knock-in mice compared with WT mice displayed a significantly enhanced susceptibility to CSD. We found L1649Q to cause a gain-of-function effect with an impaired Na+-channel inactivation and increased ramp Na+ currents leading to hyperactivity of fast-spiking inhibitory interneurons. Brain slice recordings using K+-sensitive electrodes revealed an increase in extracellular K+ in the early phase of CSD in heterozygous mice, likely representing the mechanistic link between interneuron hyperactivity and CSD initiation. The neuronal phenotype and premature death of homozygous Scn1aL1649Q knock-in mice was partially rescued by GS967, a blocker of persistent Na+ currents. Collectively, our findings identify interneuron hyperactivity as a mechanism to trigger CSD.

TRPM2 Oxidation Activates Two Distinct Potassium Channels in Melanoma Cells through Intracellular Calcium Increase.

Tumor microenvironments are often characterized by an increase in oxidative stress levels. We studied the response to oxidative stimulation in human primary (IGR39) or metastatic (IGR37) cell lines obtained from the same patient, performing patch-clamp recordings, intracellular calcium ([Ca2+]i) imaging, and RT-qPCR gene expression analysis. In IGR39 cells, chloramine-T (Chl-T) activated large K+ currents (KROS) that were partially sensitive to tetraethylammonium (TEA). A large fraction of KROS was inhibited by paxilline-a specific inhibitor of large-conductance Ca2+-activated BK channels. The TEA-insensitive component was inhibited by senicapoc-a specific inhibitor of the Ca2+-activated KCa3.1 channel. Both BK and KCa3.1 activation were mediated by an increase in [Ca2+]i induced by Chl-T. Both KROS and [Ca2+]i increase were inhibited by ACA and clotrimazole-two different inhibitors of the calcium-permeable TRPM2 channel. Surprisingly, IGR37 cells did not exhibit current increase upon the application of Chl-T. Expression analysis confirmed that the genes encoding BK, KCa3.1, and TRPM2 are much more expressed in IGR39 than in IGR37. The potassium currents and [Ca2+]i increase observed in response to the oxidizing agent strongly suggest that these three molecular entities play a major role in the progression of melanoma. Pharmacological targeting of either of these ion channels could be a new strategy to reduce the metastatic potential of melanoma cells, and could complement classical radio- or chemotherapeutic treatments.

Unique variants in CLCN3, encoding an endosomal anion/proton exchanger, underlie a spectrum of neurodevelopmental disorders.

The genetic causes of global developmental delay (GDD) and intellectual disability (ID) are diverse and include variants in numerous ion channels and transporters. Loss-of-function variants in all five endosomal/lysosomal members of the CLC family of Cl- channels and Cl-/H+ exchangers lead to pathology in mice, humans, or both. We have identified nine variants in CLCN3, the gene encoding CIC-3, in 11 individuals with GDD/ID and neurodevelopmental disorders of varying severity. In addition to a homozygous frameshift variant in two siblings, we identified eight different heterozygous de novo missense variants. All have GDD/ID, mood or behavioral disorders, and dysmorphic features; 9/11 have structural brain abnormalities; and 6/11 have seizures. The homozygous variants are predicted to cause loss of ClC-3 function, resulting in severe neurological disease similar to the phenotype observed in Clcn3-/- mice. Their MRIs show possible neurodegeneration with thin corpora callosa and decreased white matter volumes. Individuals with heterozygous variants had a range of neurodevelopmental anomalies including agenesis of the corpus callosum, pons hypoplasia, and increased gyral folding. To characterize the altered function of the exchanger, electrophysiological analyses were performed in Xenopus oocytes and mammalian cells. Two variants, p.Ile607Thr and p.Thr570Ile, had increased currents at negative cytoplasmic voltages and loss of inhibition by luminal acidic pH. In contrast, two other variants showed no significant difference in the current properties. Overall, our work establishes a role for CLCN3 in human neurodevelopment and shows that both homozygous loss of ClC-3 and heterozygous variants can lead to GDD/ID and neuroanatomical abnormalities.

Functional and Structural Characterization of ClC-1 and Nav1.4 Channels Resulting from CLCN1 and SCN4A Mutations Identified Alone and Coexisting in Myotonic Patients.

Non-dystrophic myotonias have been linked to loss-of-function mutations in the ClC-1 chloride channel or gain-of-function mutations in the Nav1.4 sodium channel. Here, we describe a family with members diagnosed with Thomsen's disease. One novel mutation (p.W322*) in CLCN1 and one undescribed mutation (p.R1463H) in SCN4A are segregating in this family. The CLCN1-p.W322* was also found in an unrelated family, in compound heterozygosity with the known CLCN1-p.G355R mutation. One reported mutation, SCN4A-p.T1313M, was found in a third family. Both CLCN1 mutations exhibited loss-of-function: CLCN1-p.W322* probably leads to a non-viable truncated protein; for CLCN1-p.G355R, we predict structural damage, triggering important steric clashes. The SCN4A-p.R1463H produced a positive shift in the steady-state inactivation increasing window currents and a faster recovery from inactivation. These gain-of-function effects are probably due to a disruption of interaction R1463-D1356, which destabilizes the voltage sensor domain (VSD) IV and increases the flexibility of the S4-S5 linker. Finally, modelling suggested that the p.T1313M induces a strong decrease in protein flexibility on the III-IV linker. This study demonstrates that CLCN1-p.W322* and SCN4A-p.R1463H mutations can act alone or in combination as inducers of myotonia. Their co-segregation highlights the necessity for carrying out deep genetic analysis to provide accurate genetic counseling and management of patients.

The psychological impact of COVID-19-related lockdown measures among a sample of Italian patients with eating disorders: a preliminary longitudinal study.

PURPOSE: To explore the prevalence of symptoms of anxiety and depression, along with PTSD- and ED-related symptoms, across a sample of patients with Eating Disorders (EDs) compared to a group of healthy controls (HC) during the lockdown period in Italy; to assess whether patients' reported aforementioned psychiatric symptoms improved, remained stable or worsened with the easing of the lockdown measures. METHODS: t0 assessment (during lockdown): 59 ED patients and 43 HC completed an online survey, including the Depression, Anxiety and Stress Scale-21 items (DASS-21), the Impact of Event Scale-Revised (IES-R), the Perceived Stress Scale (PSS), and specific ad-hoc questions extracted from the Eating Disorder Examination-Questionnaire; t1 assessment (post-lockdown): 40 EDs patients, a subset of the t0 sample, completed the same assessment 2 months after t0. RESULTS: EDs patients scored higher than HC at the DASS-21, IES-R and PSS. At t1, levels of stress, anxiety and depression were not different than at t0, but symptoms related to post-traumatic stress disorder (PTSD), patients' reported level of psychological wellbeing and specific EDs symptomatology improved. DISCUSSION: During the lockdown, EDs patients presented significantly higher levels of stress, anxiety, depression, PTSD- and ED-related symptoms than HC. With the easing of the lockdown, PTSD- and ED-related symptoms improved, but high levels of stress, anxiety and depression persisted. LEVEL OF EVIDENCE: Level I, experimental study.

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.

Mechanisms of Activation of LRRC8 Volume Regulated Anion Channels.

Volume regulated anion channels (VRACs) are ubiquitously expressed in all vertebrate cells. Despite many years of research, the fundamental mechanisms underlying VRAC activation are not understood. The recent molecular identification of the LRRC8 genes underlying VRAC revealed that VRACs are formed by a hexameric assembly of members of the LRRC8 gene family. Knowing the genes underlying VRACs allowed the discovery of novel VRAC functions into cell volume regulation, and first structure function studies revealed important insight in channel activation mechanisms. The determination of cryo-EM structures of homomeric LRRC8A and LRRC8D complexes provide a framework for a rational approach to investigate biophysical mechanisms. We discuss several recent advances within the structural framework, and we critically review the literature on the main mechanisms proposed to be involved in VRAC activation, including low intracellular ionic strength, membrane unfolding, oxidation, phosphorylation and G-protein coupling.

Risk and resilience factors for specific and general psychopathology worsening in people with Eating Disorders during COVID-19 pandemic: a retrospective Italian multicentre study.

PURPOSE: The COVID-19 pandemic restrictions had negative impact on the psychopathology of people with Eating Disorders (EDs). Factors involved in the vulnerability to stressful events have been under-investigated in this population. We aimed to assess which factors contributed to COVID-19-induced worsening in both general and specific psychopathology. METHODS: Three-hundred and twelve people with a clinically defined diagnosis of an ED and undergoing a specialist ED treatment in different Italian ED services before the spreading of COVID-19 pandemic filled in an online survey. ED specific and general psychopathology changes after COVID-19 quarantine were retrospectively evaluated. Factors related to COVID-19 concerns (financial condition, fear of contagion, perceived social isolation/support, satisfaction in peer, family or sentimental relationships), illness duration and treatment-related variables (type of treatment provided, type of access to care, satisfaction with therapeutic relationships) were included as predicting factors in a structural equational model, which included latent variables consisting of general and ED psychopathology items as outcomes. RESULTS: A perceived low quality of therapeutic relationships, fear of contagion and increased isolation were positively associated with psychopathology worsening. Reduced satisfaction with family and with friends' relationships and reduced perceived social support were associated with ED and general symptoms deterioration, respectively. No significant effect emerged for intimate relationships, illness duration, economic condition and type of treatment. CONCLUSIONS: This study provides a comprehensive evaluation of clinical variables associated with psychopathological changes during the COVID-19 lockdown period highlighting potential risk and resilience factors and, possibly, informing treatment as well as prevention strategies for EDs. LEVEL OF EVIDENCE IV: Evidence obtained from multiple time series analysis such as case studies.

The Anticipation and Perception of Affective Touch in Women with and Recovered from Anorexia Nervosa.

Disruptions in reward processing and anhedonia have long been observed in Anorexia Nervosa (AN). Interoceptive deficits have also been observed in AN, including reduced tactile pleasure. However, the extent to which this tactile anhedonia is specifically liked to an impairment in a specialised, interoceptive C-tactile system originating at the periphery, or a more top-down mechanism in the processing of tactile pleasantness remains debated. Here, we investigated differences between patients with and recovered from AN (RAN) and healthy controls (HC) in the perception of pleasantness of touch delivered in a CT-optimal versus a CT-non-optimal manner, and in their top-down, anticipatory beliefs about the perceived pleasantness of touch. To this end, we measured the anticipated pleasantness of various materials touching the skin and the perceived pleasantness of light, dynamic touch applied to the forearm of 27 women with AN, 24 women who have recovered and 30 HCs using C Tactile (CT) afferents-optimal (slow) and non-optimal (fast) velocities. Our results showed that both clinical groups anticipated tactile experiences and rated delivered tactile stimuli as less pleasant than HCs, but the latter difference was not related to the CT optimality of the stimulation. Instead, differences in the perception of CT-optimal touch were predicted by differences in top-down beliefs, alexithymia and interoceptive sensibility. Thus, tactile anhedonia in AN might persist as a trait even after otherwise successful recovery of AN and it is not linked to a bottom-up interoceptive deficit in the CT system, but rather to a learned, defective top-down anticipation of tactile pleasantness.