Evaluating the predictions of an interoceptive inference model of bulimia nervosa.

OBJECTIVE: Bulimia nervosa (BN) is associated with loss-of-control (LOC) eating episodes that frequently occur in response to negative emotions. According to recent neurocomputational models, this link could be explained by a failure to accurately update beliefs about the body in states of high arousal. Specifically, these interoceptive inference models suggest that under-relying on signals from one's body about sensory experience ("low sensory precision") and/or over-relying on previously held beliefs ("excessively precise priors") lead to inaccurate perception and maladaptive behaviors. We conducted an initial test of these core predictions of the interoceptive inference model in BN using self-report measures. METHODS: We compared women with BN (n = 30) and age-, BMI-, and full-scale IQ-matched controls (n = 31) on trust in sensory information from the body and two types of beliefs about what can be done to regulate high negative affect. Within the BN group, we tested interrelations among these measures and explored their associations with LOC eating frequency. RESULTS: Compared with healthy controls, the BN group reported lower levels of trust in sensory information and stronger beliefs that once upset, there is little one can do, apart from eating, to self-regulate. These beliefs were associated with each other and with lower body trust. Beliefs about the uncontrollability of emotion were associated with more frequent subjective binge-eating episodes. CONCLUSIONS: Findings provide initial support for the core predictions of an interoceptive inference account of BN: low trust in sensory information ("sensory precision") may promote an overreliance on maladaptive "prior beliefs" about the effects of eating on negative emotions, ultimately interfering with accurate updating of beliefs about other strategies that could regulate emotions and maintain LOC eating. Low body trust, strong expectations about emotions, and their neurocomputational underpinnings could be promising combined treatment targets for BN.

Interoception, the brain's processing of bodily signals, is critical for emotional and behavioral control. Disturbances in interoception may contribute to emotion dysregulation and problematic behaviors across a range of psychiatric disorders, including eating disorders, but the exact mechanisms remain unclear. Recent "interoceptive inference" models of psychopathology propose that dysregulated emotions and maladaptive behaviors persist because, during intense emotional states, individuals under-rely on information from bodily signals and over-rely on pre-existing expectations ("prior beliefs"). In this study, we tested these core predictions among individuals with bulimia nervosa (BN). We compared women with BN and healthy controls on self-reported measures of bodily trust and two types of pre-existing beliefs about responses to negative emotions. We found the first evidence of lower trust in bodily signals in individuals with BN compared to controls. This reduced trust was linked to stronger beliefs that there is little one can do, apart from eating, to regulate emotions. These beliefs, in turn, were associated with more frequent eating episodes characterized by loss of control. Though more research is needed to replicate these results, they provide preliminary support for a model that could explain why individuals with BN are more likely to have uncontrolled eating in the context of strong negative emotions.

Early change in gastric-specific anxiety sensitivity as a predictor of eating disorder treatment outcome.

Eating disorders (EDs) are often accompanied by gastrointestinal (GI) distress. Anxiety sensitivity is the tendency to interpret sensations of anxiety as threatening or dangerous, and includes both broad physical symptoms (e.g., elevated heartrate) and GI-specific symptoms. Physical and GI-specific anxiety sensitivity may be important risk and maintaining factors in EDs. This study tested the hypothesis that greater reductions in both types of anxiety sensitivity during the first month of treatment would predict lower ED symptoms and trait anxiety at discharge and 6-month follow-up. Patients (n = 424) in ED treatment reported physical and GI-specific anxiety sensitivity, ED symptoms, and trait anxiety at treatment admission, 1-month into treatment, discharge, and 6-month follow-up. Analyses were conducted with hierarchical linear regression with imputation, controlling for relevant covariates. Results indicated that early reduction in GI-specific but not general physical anxiety sensitivity predicted both lower ED symptoms and lower trait anxiety at discharge and 6-month follow-up. These findings demonstrate the importance of GI-specific anxiety sensitivity as a potential maintaining factor in EDs. Developing and refining treatments to target GI-specific anxiety sensitivity may have promise in improving the treatment not only of EDs, but also of commonly co-morbid anxiety disorders.

Weight gained during treatment predicts 6-month body mass index in a large sample of patients with anorexia nervosa using ensemble machine learning.

OBJECTIVE: This study used machine learning methods to analyze data on treatment outcomes from individuals with anorexia nervosa admitted to a specialized eating disorders treatment program. METHODS: Of 368 individuals with anorexia nervosa (209 adolescents and 159 adults), 160 individuals had data available for a 6-month follow-up analysis. Participants were treated in a 6-day-per-week partial-hospital program. Participants were assessed for eating disorder-specific and non-specific psychopathology. The analyses used established machine learning procedures combined in an ensemble model from support vector machine learning, random forest prediction, and the elastic net regularized regression with an exploration (training; 75%) and confirmation (test; 25%) split of the data. RESULTS: The models predicting body mass index (BMI) at 6-month follow-up explained a 28.6% variance in the training set (n = 120). The model had good performance in predicting 6-month BMI in the test dataset (n = 40), with predicted BMI significantly correlating with actual BMI (r = .51, p = 0.01). The change in BMI from admission to discharge was the most important predictor, strongly correlating with reported BMI at 6-month follow-up (r = .55). Behavioral variables were much less predictive of BMI outcome. Results were similar for z-transformed BMI in the adolescent-only group. Length of stay was most predictive of weight gain in treatment (r = .56) but did not predict longer-term BMI. CONCLUSIONS: This study, using an agnostic ensemble machine learning approach in the largest to-date sample of individuals with anorexia nervosa, suggests that achieving weight gain goals in treatment predicts longer-term weight-related outcomes. Other potential predictors, personality, mood, or eating disorder-specific symptoms were relatively much less predictive. PUBLIC SIGNIFICANCE: The results from this study indicate that the amount of weight gained during treatment predicts BMI 6 months after discharge from a high level of care. This suggests that patients require sufficient time in a higher level of care treatment to meet their specific weight goals and be able to maintain normal weight.

Comparing changes in eating disorder psychopathology and comorbid symptoms over treatment in anorexia nervosa and atypical anorexia nervosa in a partial hospitalization program.

OBJECTIVE: The objective of this study is to compare treatment trajectories in anorexia nervosa (AN) and atypical AN. METHOD: Adolescents and adults with AN (n = 319) or atypical AN (n = 67) in a partial hospitalization program (PHP) completed diagnostic interviews and self-report questionnaires measuring eating disorder (ED), depression, and anxiety symptoms throughout treatment. RESULTS: Premorbid weight loss did not differ between diagnoses. Individuals with atypical AN had more comorbid diagnoses, but groups did not differ on specific diagnoses. ED psychopathology and comorbid symptoms of depression/anxiety did not differ at admission between groups nor did rate of change in ED psychopathology and comorbid symptoms of depression/anxiety from admission to 1-month. From admission to discharge, individuals with atypical AN had a faster reduction in ED psychopathology and comorbid symptoms of depression and anxiety (ps < 0.05; rs = 0.01-0.32); however, there were no group differences in ED psychopathology or depression symptoms at discharge (ps>.50; ds = .01-.30). Individuals with atypical AN had lower anxiety at discharge compared to individuals with AN (p = 0.05; d = .4). Length of stay did not differ between groups (p = 0.11; d = .21). DISCUSSION: Groups had similar ED treatment trajectories, suggesting more similarities than differences. PHP may also be effective for AAN. PUBLIC SIGNIFICANCE: This study supports previous research that individuals with AN and atypical AN have more similarities than differences. Results from this study indicate that individuals with AN and atypical AN have similar treatment outcomes for both ED psychopathology and depressive symptoms; however, individuals with atypical AN have lower anxiety symptoms at discharge compared to individuals with AN. AN and atypical AN also have more symptom similarity at admission and throughout treatment, which challenges their current designation as distinct disorders.

Expanding considerations for treating avoidant/restrictive food intake disorder at a higher level of care.

Existing descriptions of the treatment of avoidant/restrictive food intake disorder (ARFID) at higher levels of care (HLOC) for eating disorders are limited, despite HLOC settings frequently serving patients with ARFID. The purpose of this commentary is to expand on the preliminary literature that describes pediatric ARFID treatment at HLOC by describing two specific components of our approach to treating pediatric ARFID that may not yet have traction in the current literature. Specifically, we highlight the utility of (1) treatment accommodations that appropriately account for patients' neurodevelopmental needs (e.g., executive functioning, sensory processing) and (2) the adjunctive use of Dialectical Behavior Therapy (DBT) elements within family-based pediatric ARFID treatment. We also describe necessary future directions for research in these domains to clarify if incorporating these considerations and approaches into pediatric ARFID treatment at HLOC does indeed improve treatment outcomes.

Elevated interoceptive deficits in individuals with eating disorders and self-injurious thoughts and behaviors: A replication and extension.

INTRODUCTION: People with eating disorders (EDs) frequently report self-injurious thoughts and behaviors (SITBs). We aimed to replicate and extend findings demonstrating greater interoceptive deficits according to SITB severity. We predicted that interoceptive deficits would be greater among people with versus without lifetime SITBs and among those with multiple suicide attempts compared with single attempts or nonsuicidal self-injury. We also predicted that interoception would be increasingly impaired with greater current suicidality severity. METHOD: Adults (N = 118) seeking ED treatment reported current and lifetime SITBs upon admission to treatment. We used planned contrasts to compare interoceptive deficits (self-reported using the Eating Disorders Inventory) by SITB and current suicidality groups (assessed by self-report and clinical interview). RESULTS: Interoceptive deficits were greater among people with any SITB history compared to those without. People with multiple suicide attempts did not differ in interoceptive deficits from those with single attempts or only nonsuicidal self-injury. Interoceptive deficits were elevated among those with any current suicidality compared to those with no suicidal symptoms; interoceptive deficits did not differ according to severity of suicidality. CONCLUSION: Among those with EDs, interoceptive deficits are elevated among those with concurrent SITBs. Interventions aimed at improving interoception may reduce the risk for SITBs.

Effects of borderline personality disorder symptoms on dialectical behavior therapy outcomes for eating disorders.

Existing literature on the effects of borderline personality disorder (BPD) and eating disorder (ED) comorbidity in terms of clinical presentation and treatment outcome has been limited and inconclusive. The present study examined whether clients with EDs and varying levels of BPD symptoms presented with more severe ED symptoms at admission, and whether they responded to dialectical behavior therapy (DBT)-based treatment. Participants (N = 176) were adults in a DBT-based partial hospitalization program for EDs at an academic medical center. Participants completed self-report measures at admission, 1-month postadmission, discharge, and 6-month follow-up. Results suggested that patients with elevated BPD symptoms at admission had greater ED symptoms during treatment, evidenced by small to moderate effect sizes. However, patients with high BPD symptoms demonstrated steeper declines in binge eating, fasting, and parasuicidal behavior early during treatment compared to patients with low BPD symptoms. Individuals with high BPD symptoms at admission (i.e., probable BPD diagnosis) were as likely to meet remission criteria and relapse as individuals with low BPD symptoms, though this null finding may be influenced by small cell sizes. Our findings also suggest that DBT skills use does not predict changes in symptoms. In sum, our findings suggest that while clients with higher BPD symptoms may improve during DBT-based partial hospitalization, their ED symptoms may remain more severe. Future studies are needed to determine whether adjunctive treatments improve outcomes for clients with EDs and comorbid BPD symptoms in DBT programs and whether skills use quality is a better predictor of ED symptom changes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study.

Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m-2; s.d. 3.7) who met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AN or pAN (partial remission) were recruited to a study conducted at an academic clinical research institute. Participants received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support. The primary aim was to assess safety, tolerability and feasibility at post-treatment by incidences and occurrences of adverse events (AEs) and clinically significant changes in electrocardiogram (ECG), laboratory tests, vital signs and suicidality. No clinically significant changes were observed in ECG, vital signs or suicidality. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 h. No other clinically significant changes were observed in laboratory values. All AEs were mild and transient in nature. Participants' qualitative perceptions suggest that the treatment was acceptable for most participants. Results suggest that psilocybin therapy is safe, tolerable and acceptable for female AN, which is a promising finding given physiological dangers and problems with treatment engagement. ClinicalTrials.gov identifier NCT04661514 .

State-specific alterations in the neural computations underlying inhibitory control in women remitted from bulimia nervosa.

The neurocomputational processes underlying bulimia nervosa and its primary symptoms, out-of-control overeating and purging, are poorly understood. Research suggests that the brains of healthy individuals form a dynamic internal model to predict whether control is needed in each moment. This study tested the hypothesis that this computational process of inhibitory control is abnormally affected by metabolic state (being fasted or fed) in bulimia nervosa. A Bayesian ideal observer model was fit to behavioral data acquired from 22 women remitted from bulimia nervosa and 20 group-matched controls who completed a stop-signal task during two counterbalanced functional MRI sessions, one after a 16 h fast and one after a meal. This model estimates participants' trial-by-trial updating of the probability of a stop signal based on their experienced trial history. Neural analyses focused on control-related Bayesian prediction errors, which quantify the direction and degree of "surprise" an individual experiences on any given trial. Regardless of group, metabolic state did not affect behavioral performance on the task. However, metabolic state modulated group differences in neural activation. In the fed state, women remitted from bulimia nervosa had attenuated prediction-error-dependent activation in the left dorsal caudate. This fed-state activation was lower among women with more frequent past binge eating and self-induced vomiting. When they are in a fed state, individuals with bulimia nervosa may not effectively process unexpected information needed to engage inhibitory control. This may explain the difficulties these individuals have stopping eating after it begins.

Using clinical cutoff scores on the eating disorder examination-questionnaire to evaluate eating disorder symptoms during and after naturalistic intensive treatment.

Clinical cutoff scores for self-report measures provide a means of evaluating clinically significant pathology during and after treatment. A cutoff of 2.8 on the Eating Disorder Examination-Questionnaire (EDE-Q) has been recommended to screen for eating disorders (ED). We used this cutoff to assess ED symptoms in adolescents (n = 444) and adults (n = 592) through ED treatment and follow-up. Most patients scored above 2.8 at intake (adolescents 67%, M = 3.21; adults 78%, M = 4.20) and below 2.8 at discharge (adolescents 65%, M = 1.87; adults 66%, M = 2.67), with gains often maintained through follow-up (40% of adolescents and 35% of adults at 12-month follow-up). EDE-Q scores were higher in adults than adolescents and in patients with binge/purge disorders. Results suggest a cutoff of 2.8 on the EDE-Q effectively tracks ED symptom improvement through treatment and discharge. This supports the need for the development of culture-specific and empirically developed clinical cutoffs and their widespread use to evaluate program effectiveness.

Confirmatory factor analysis of Acute Suicidal Affective Disturbance in a sample of treatment-seeking eating disorder patients.

INTRODUCTION: We examined the factor structure of Acute Suicidal Affective Disturbance (ASAD) in individuals with eating disorders. ASAD is a proposed diagnosis with four symptoms: rapidly increasing suicidal intent, social or self-alienation, hopelessness regarding the previous symptoms, and overarousal. METHODS: Patients with eating disorders (N = 378) completed self-report symptom questionnaires at admission to a partial hospitalization program for eating disorders. Using proxy measures, we conducted a confirmatory factor analysis (CFA) of the one-factor model of ASAD. RESULTS: Initial model fit was poor. We iteratively revised the model to include theoretically-justified correlated residuals (i.e., those between items intended to measure the same ASAD symptom). After these modifications, model fit remained mediocre. We next conducted a multiple-group CFA to compare ASAD between individuals with the restricting subtype of anorexia nervosa (the "ANR" model, n = 145) and individuals with binge/purge disorders (i.e., bulimia nervosa and the binge-purge subtype of anorexia nervosa; the "BP" model, n = 234). The final model had mediocre fit with partial invariance between subgroups; the ASAD factor mean was higher in the BP model. We additionally tested a bifactor model, with similar findings. LIMITATIONS: Our use of proxy measures of ASAD items may have resulted in imprecise measurement of ASAD symptoms, pointing to the importance of future research using validated measures of ASAD. CONCLUSIONS: We found moderate support for ASAD in an eating disorder sample, with invariance between eating disorder phenotypes. Our findings suggest that the ASAD diagnosis may not fully generalize to eating disorder samples.

Impaired belief updating and devaluation in adult women with bulimia nervosa.

Recent models of bulimia nervosa (BN) propose that binge-purge episodes ultimately become automatic in response to cues and insensitive to negative outcomes. Here, we examined whether women with BN show alterations in instrumental learning and devaluation sensitivity using traditional and computational modeling analyses of behavioral data. Adult women with BN (n = 30) and group-matched healthy controls (n = 31) completed a task in which they first learned stimulus-response-outcome associations. Then, participants were required to repeatedly adjust their responses in a "baseline test", when different sets of stimuli were explicitly devalued, and in a "slips-of-action test", when outcomes instead of stimuli were devalued. The BN group showed intact behavioral sensitivity to outcome devaluation during the slips-of-action test, but showed difficulty overriding previously learned stimulus-response associations on the baseline test. Results from a Bayesian learner model indicated that this impaired performance could be accounted for by a slower pace of belief updating when a new set of previously learned responses had to be inhibited (p = 0.036). Worse performance and a slower belief update in the baseline test were each associated with more frequent binge eating (p = 0.012) and purging (p = 0.002). Our findings suggest that BN diagnosis and severity are associated with deficits in flexibly updating beliefs to withhold previously learned responses to cues. Additional research is needed to determine whether this impaired ability to adjust behavior is responsible for maintaining automatic and persistent binge eating and purging in response to internal and environmental cues.

Integrating evidence-based PTSD treatment into intensive eating disorders treatment: a preliminary investigation.

PURPOSE: Given data suggesting common co-occurrence and worse outcomes for individuals with eating disorders (EDs) and post-traumatic stress disorder (PTSD), it is critical to identify integrated treatment approaches for this group of patients. Past work has explored the feasibility and initial efficacy of intervention approaches that draw on evidence-based treatments for both EDs and PTSD; however, this work remains limited in scope. In the current study, we explored the feasibility and naturalistic outcomes of PTSD treatment delivered within the context of intensive ED treatment. METHOD: Participants were 57 adult men and women with DSM-5 EDs and comorbid PTSD who completed a course of either Prolonged Exposure (PE; n = 22) or Cognitive Processing Therapy (CPT; n = 35) (Msessions = 10.40; SD = 5.13) and weekly validated measurements of clinical symptoms while enrolled in ED programming. RESULTS: Multi-level models for PTSD symptoms indicated a significant linear effect of time, such that participants demonstrated significant decreases over time in PTSD symptoms, regardless of treatment modality. CONCLUSION: Our preliminary investigation provides support for the feasibility and efficacy of an integrated approach to treating EDs and PTSD. It is critical for future work to undertake randomized tests of this integrated approach using large, heterogeneous samples. LEVEL OF EVIDENCE: Level IV, multiple time series with intervention.

Research in eating disorders: the misunderstanding of supposing serious mental illnesses as a niche specialty.

PURPOSE: Eating disorders (EDs) are mental illnesses with severe consequences and high mortality rates. Notwithstanding, EDs are considered a niche specialty making it often difficult for researchers to publish in high-impact journals. Subsequently, research on EDs receives less funding than other fields of psychiatry potentially slowing treatment progress. This study aimed to compare research vitality between EDs and schizophrenia focusing on: number and type of publications; top-cited articles; geographical distribution of top-ten publishing countries; journal distribution of scientific production as measured by bibliometric analysis; funded research and collaborations. METHODS: We used the Scopus database, then we adopted the Bibliometrix R-package software with the web interface app Biblioshiny. We included in the analyses 1,916 papers on EDs and 6491 on schizophrenia. RESULTS: The ED field published three times less than schizophrenia in top-ranking journals - with letters and notes particularly lacking-notwithstanding a comparable number of papers published per author. Only 50% of top-cited articles focused on EDs and a smaller pool of journals available for ED research (i.e., Zones 1 and 2 according to Bradford's law) emerged; journals publishing on EDs showed an overall lower rank compared to the schizophrenia field. Schizophrenia research was more geographically distributed and more funded; in contrast, a comparable collaboration index was found between the fields. CONCLUSION: These data show that research on EDs is currently marginalized and top-rank journals are seldom achievable by researchers in EDs. Such difficulties in research dissemination entail potentially serious repercussions on clinical advancements. LEVEL OF EVIDENCE: Level V: opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Associations of suicide risk with emotional reactivity, dysregulation, and eating disorder treatment outcomes.

INTRODUCTION: Emotional processes play a role in both suicide risk and eating disorders (EDs), which are often comorbid. However, limited research has explored how emotional processes relate to suicide risk in EDs and the prognostic value of suicide risk for ED treatment. Thus, the current study examined associations between emotion dysregulation and reactivity with suicide risk in patients with EDs, and determined if suicide risk predicts ED treatment outcomes. METHODS: Participants (n = 201) were adults in an ED partial hospitalization program who completed measures at admission, 1-month post-admission, and discharge. RESULTS: When controlling for depressive symptoms, limited access to adaptive emotion regulation strategies, difficulties engaging in goal-oriented behaviors, and engaging in impulsive behavior when experiencing negative emotions (i.e., emotion dysregulation) were associated with suicide attempt frequency. Depressive symptoms were associated with suicide risk severity, while emotion dysregulation and reactivity were not. Importantly, patients with elevated suicide risk at admission improved comparably to other risk categories across treatment, despite presenting with greater ED symptoms at admission. CONCLUSION: Emotion dysregulation and depression are salient factors when examining suicide risk in patients with EDs. Suicide risk and attempt history may not negatively impact ED treatment outcomes when using emotion-focused treatment.

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group.

BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

Family functioning and eating disorders treatment in a partial hospitalization program in adolescent females with eating disorders.

OBJECTIVE: Previous research examining family functioning in eating disorder (ED) treatment has focused primarily on outpatient settings. However, few studies have examined this aspect in partial hospitalization programs. To address this gap, this study examined family functioning over the course of an ED partial hospitalization program (PHP) in adolescent females (M(SD) age = 15.66 (1.50)). METHOD: Participants (n = 105) completed the Family Assessment Device and Eating Disorder Examination Questionnaire at treatment admission, 1-month post-admission, and discharge. RESULTS: Results from repeated measures analysis of variance indicated adolescents perceived an improvement in family functioning regarding Communication, Affective Responsiveness, and Behavioral Control through 1-year follow-up (p values < .05). Neither family functioning at admission nor change in family functioning in the first month correlated with any outcomes (weight, ED symptoms, and remission). DISCUSSION: Results support that family functioning does not contribute to ED severity, and that treatment can improve adolescent perception of family functioning. Given the importance of involving the family in ED treatment, identifying mediators of treatment outcomes is critical to improve treatment efficacy. PUBLIC SIGNIFICANCE: Adolescents in a partial hospital program (PHP) for eating disorders (EDs) perceived improvements in their family communication, behavior, and ability to process appropriate emotions from admission to 1-year post-treatment, although these aspects did not significantly predict treatment outcomes. The findings provide helpful information for future research on adolescents with EDs in higher levels of care and underscore the importance of exploring mechanisms of family-based treatment in PHP.

Evaluating the use of lamotrigine to reduce mood lability and impulsive behaviors in adults with chronic and severe eating disorders.

BACKGROUND: Gold-standard psychological and pharmacological treatments for bulimic-spectrum eating disorders only result in remission for around 50% of patients; patients with affective lability and impulsivity represent a subgroup with particularly poor outcomes. Both dialectical behavior therapy (DBT), a treatment for emotion dysregulation, and lamotrigine, a mood stabilizer, have demonstrated promise for targeting affective lability and impulsivity; however, data exploring the combination of these interventions remain limited. OBJECTIVE: We followed a group of women with recurrent dysregulated eating behaviors (N = 62) throughout intensive DBT treatment and compared the symptom trajectory of those prescribed lamotrigine (n = 28) and those who were not (n = 34). METHOD: Participants completed surveys every 2 weeks throughout treatment. RESULTS: Group analyses suggested that all participants self-reported decreases in emotional reactivity, negative urgency, and symptoms of borderline personality disorder (BPD). The lamotrigine group reported greater elevations in BPD symptoms at baseline, but demonstrated steeper decreases in emotion and behavioral dysregulation than the non-matched comparison group. Within-subject analyses suggested that within the lamotrigine group, subjects reported greater decreases in symptoms following prescription of lamotrigine. CONCLUSIONS: Findings provide initial data suggesting that lamotrigine could be useful as an adjunctive treatment for patients with affective lability and impulsivity. LEVEL OF EVIDENCE: IV, time series without randomization.

Association of Generalized Anxiety Disorder With Autonomic Hypersensitivity and Blunted Ventromedial Prefrontal Cortex Activity During Peripheral Adrenergic Stimulation: A Randomized Clinical Trial.

IMPORTANCE: ß-Adrenergic stimulation elicits heart palpitations and dyspnea, key features of acute anxiety and sympathetic arousal, yet no neuroimaging studies have examined how the pharmacologic modulation of interoceptive signals is associated with fear-related neurocircuitry in individuals with generalized anxiety disorder (GAD). OBJECTIVE: To examine the neural circuitry underlying autonomic arousal induced via isoproterenol, a rapidly acting, peripheral ß-adrenergic agonist akin to adrenaline. DESIGN, SETTING, AND PARTICIPANTS: This crossover randomized clinical trial of 58 women with artifact-free data was conducted from January 1, 2017, to November 31, 2019, at the Laureate Institute for Brain Research in Tulsa, Oklahoma. EXPOSURES: Functional magnetic resonance imaging was used to assess neural responses during randomized intravenous bolus infusions of isoproterenol (0.5 and 2.0 µg) and saline, each administered twice in a double-blind fashion. MAIN OUTCOMES AND MEASURES: Blood oxygen level-dependent responses across the whole brain during isoproterenol administration in patients with GAD vs healthy comparators. Cardiac and respiratory responses, as well as interoceptive awareness and anxiety, were also measured during the infusion protocol. RESULTS: Of the 58 female study participants, 29 had GAD (mean [SD] age, 26.9 [6.8] years) and 29 were matched healthy comparators (mean [SD] age, 24.4 [5.0] years). During the 0.5-µg dose of isoproterenol, the GAD group exhibited higher heart rate responses (b = 5.34; 95% CI, 2.06-8.61; P = .002), higher intensity ratings of cardiorespiratory sensations (b = 8.38; 95% CI, 2.05-14.71; P = .01), higher levels of self-reported anxiety (b = 1.04; 95% CI, 0.33-1.76; P = .005), and significant hypoactivation in the ventromedial prefrontal cortex (vmPFC) that was evident throughout peak response (Cohen d = 1.55; P < .001) and early recovery (Cohen d = 1.52; P < .001) periods. Correlational analysis of physiological and subjective indexes and percentage of signal change extracted during the 0.5-µg dose revealed that vmPFC hypoactivation was inversely correlated with heart rate (r56 = -0.51, adjusted P = .001) and retrospective intensity of both heartbeat (r56 = -0.50, adjusted P = .002) and breathing (r56 = -0.44, adjusted P = .01) sensations. Ventromedial prefrontal cortex hypoactivation correlated inversely with continuous dial ratings at a trend level (r56 = -0.38, adjusted P = .051), whereas anxiety (r56 = -0.28, adjusted P = .27) and chronotropic dose 25 (r56 = -0.14, adjusted P = .72) showed no such association. CONCLUSIONS AND RELEVANCE: In this crossover randomized clinical trial, women with GAD exhibited autonomic hypersensitivity during low levels of adrenergic stimulation characterized by elevated heart rate, heightened interoceptive awareness, increased anxiety, and a blunted neural response localized to the vmPFC. These findings support the notion that autonomic hyperarousal may be associated with regulatory dysfunctions in the vmPFC, which could serve as a treatment target to help patients with GAD more appropriately appraise and regulate signals of sympathetic arousal. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02615119.

Pilot study of a water load test as a measure of gastric interoception in anorexia nervosa.

PURPOSE: Research and clinical experience suggest that individuals with anorexia nervosa (AN) have deficits in gastric interoception, which has been hypothesized to maintain restrictive eating. Behavioral water load tasks (WLTs) have the capability to noninvasively assess gastric interoception; however, to date, no studies have examined WLTs in AN. Thus, the present proof-of-concept pilot study explored the preliminary validity of a WLT in individuals with AN. METHODS: Participants were n = 10 individuals with AN and n = 10 matched-control women (CW). Participants completed self-report questionnaires before and after a WLT, in which participants were asked to drink water until "completely full". RESULTS: Participants with AN drank significantly less water than CW (AN = 240(109.14) milliliters (ml), CW = 398.00(149.21) ml, p = 0.02, Cohen's d = 1.21), but reported greater increases in negative affect pre- to-post-WLT (p = 0.04, partial eta2 = 0.21). Correlations between WLT performance and interoceptive sensibility in AN and CW participants supported the convergent validity of the WLT. CONCLUSION: Preliminary results support the potential utility of the WLT as a behavioral measure of gastric interoception in patients with AN. Future research should examine how response to the WLT changes over the course of intervention and how results are related to treatment outcome. LEVEL OF EVIDENCE: Level IV: Evidence obtained from multiple time series analysis such as case studies. (NB: Dramatic results in uncontrolled trials might also be regarded as this type of evidence).