Central amygdala CRF+ neurons promote heightened threat reactivity following early life adversity in mice.

Failure to appropriately predict and titrate reactivity to threat is a core feature of fear and anxiety-related disorders and is common following early life adversity (ELA). A population of neurons in the lateral central amygdala (CeAL) expressing corticotropin releasing factor (CRF) have been proposed to be key in processing threat of different intensities to mediate active fear expression. Here, we use in vivo fiber photometry to show that ELA results in sex-specific changes in the activity of CeAL CRF+ neurons, yielding divergent mechanisms underlying the augmented startle in ELA mice, a translationally relevant behavior indicative of heightened threat reactivity and hypervigilance. Further, chemogenic inhibition of CeAL CRF+ neurons selectively diminishes startle and produces a long-lasting suppression of threat reactivity. These findings identify a mechanism for sex-differences in susceptibility for anxiety following ELA and have broad implications for understanding the neural circuitry that encodes and gates the behavioral expression of fear.

State mechanisms of change in eating disorder symptoms and fears during an online imaginal exposure treatment for eating disorders.

Anxiety and fear are key characteristics of eating disorders (EDs). Exposure therapy is a specific type of intervention aimed at reducing fear and anxiety and is efficacious in treating a variety of anxiety and related disorders. A growing body of research suggests that exposure therapy is also efficacious for the treatment of EDs. However, there is currently little research investigating mechanisms of change during exposure therapy for EDs. The current study (N = 143) expanded on an open series trial of imaginal exposure for EDs that found significant reductions in ED symptoms and core ED fears. In the current study we investigated change in state drive for thinness, body dissatisfaction, and anxiety as mechanisms underpinning change in ED symptoms and core ED fears during four sessions of online imaginal exposure treatment for EDs. We found that state body dissatisfaction, but not state drive for thinness or anxiety, was a mechanism of change for ED symptoms and some core ED fears. Our findings suggest that body dissatisfaction may be a mechanism driving change during exposure therapy for EDs. Optimizing exposure treatments to focus on body dissatisfaction may improve treatment outcomes for EDs.

Comparisons between atypical anorexia nervosa and anorexia nervosa: Psychological and comorbidity patterns.

OBJECTIVE: Literature comparing "atypical" anorexia nervosa (atypical AN) and anorexia nervosa (AN) suggests these diagnoses share significant similarities in eating disorder (ED) pathology and psychiatric comorbidities. This study evaluated potential differences in ED pathology, psychiatric comorbidity, associated mechanisms (i.e., ED fears and perfectionism), and demographic factors (i.e., ethnicity and age) between individuals with atypical AN and AN. METHOD: Data from seven protocols were combined for a total 464 individuals diagnosed with atypical AN (n = 215) or AN (n = 249). Between-group differences in ED severity and behaviors, psychiatric comorbidities, ED fears, perfectionism, and demographic factors were assessed using t-tests, Wilcoxon rank-sum tests, and Fisher's exact test. RESULTS: Participants with atypical AN reported higher levels of overvaluation of weight and shape than those with AN. Participants with AN scored higher on food-related fears (anxiety about eating, food avoidance behaviors, and feared concerns) and fears of social eating, as well as obsessive-compulsive symptoms. Participants with AN were more likely to identify as Asian or Pacific Islander. No other statistically significant differences were found between groups for overall ED severity, ED behaviors, psychiatric comorbidities, general ED fears, perfectionism, or demographic factors. DISCUSSION: Overall, results support previous literature indicating limited differences between individuals with atypical AN and AN, though individuals with atypical AN reported more overvaluation of weight and shape and those with AN reported higher food and social eating fears and obsessive-compulsive symptoms. Relatively few overall differences between atypical AN and AN highlight the importance of exploring dimensional conceptualizations of AN as an alternative to the current categorical conceptualization. PUBLIC SIGNIFICANCE: This study assessed differences among individuals with atypical anorexia nervosa and anorexia nervosa in eating disorder severity and behaviors, comorbid psychiatric diagnoses, associated mechanisms, and demographic factors. Few differences emerged, though participants with atypical anorexia nervosa reported more overvaluation of weight and shape, while those with anorexia nervosa reported more food and social eating fears and higher obsessive-compulsive symptoms. Results support exploration of these diagnoses as a spectrum disorder.

Investigating the Theory of Clinical Perfectionism in a Transdiagnostic Eating Disorder Sample Using Network Analysis.

Eating disorders are deadly psychiatric illnesses, with treatments working for less than half of individuals who seek treatment. The transdiagnostic theory of eating disorders proposes that eating disorders share similar maintaining symptoms, such as what this theory calls clinical perfectionism (i.e., high levels of concern over mistakes and personal standards). However, it has been difficult to examine the interrelationship of specific aspects of perfectionism, beyond assessing moderation effects, which have generally not found support for the theory of clinical perfectionism in eating disorders. Thus, we used network analysis to test the theory of perfectionism by testing the interrelationships between maladaptive perfectionism facets (concern over mistakes, personal standards, parental criticism, parental expectations, and personal standards) and eating disorder symptoms in 397 individuals diagnosed with an eating disorder. Concern over mistakes was a central symptom and demonstrated the strongest interrelationships with eating disorder symptoms compared to the other aspects of perfectionism, connecting to eating concerns and cognitive restraint. Objective binge eating had a strong negative connection to personal standards. We identified specific central symptoms and illness pathways of perfectionism, which partially supports the theory of clinical perfectionism. Results, if replicated, may suggest that concern over mistakes might be best reconceptualized as part of eating disorder pathology and be targeted to improve treatment outcomes for eating disorders.

A tale of two receptors: simultaneous targeting of NMDARs and 5-HT 4 Rs exerts additive effects against stress.

BACKGROUND: Serotonin (5-HT) receptors and N -methyl-D-aspartate receptors (NMDARs) have both been implicated in the pathophysiology of depression and anxiety disorders. Here, we evaluated whether targeting both receptors through combined dosing of ( R , S )-ketamine, an NMDAR antagonist, and prucalopride, a serotonin type IV receptor (5-HT 4 R) agonist, would have additive effects, resulting in reductions in stress-induced fear, behavioral despair, and hyponeophagia. METHODS: A single injection of saline (Sal), ( R , S )-ketamine (K), prucalopride (P), or a combined dose of ( R , S )-ketamine and prucalopride (K+P) was administered before or after contextual fear conditioning (CFC) stress in both sexes. Drug efficacy was assayed using the forced swim test (FST), elevated plus maze (EPM), open field (OF), marble burying (MB), and novelty-suppressed feeding (NSF). Patch clamp electrophysiology was used to measure the effects of combined drug on neural activity in hippocampal CA3. c-fos and parvalbumin (PV) expression in the hippocampus (HPC) and medial prefrontal cortex (mPFC) was examined using immunohistochemistry and network analysis. RESULTS: We found that a combination of K+P, given before or after stress, exerted additive effects, compared to either drug alone, in reducing a variety of stress-induced behaviors in both sexes. Combined K+P administration significantly altered c-fos and PV expression and network activity in the HPC and mPFC. CONCLUSIONS: Our results indicate that combined K+P has additive benefits for combating stress-induced pathophysiology, both at the behavioral and neural level. Our findings provide preliminary evidence that future clinical studies using this combined treatment strategy may prove advantageous in protecting against a broader range of stress-induced psychiatric disorders.

Binge Eating, Purging, and Restriction Symptoms: Increasing Accuracy of Prediction Using Machine Learning.

Eating disorders are severe mental illnesses characterized by the hallmark behaviors of binge eating, restriction, and purging. These disordered eating behaviors carry extreme impairment and medical complications, regardless of eating disorder diagnosis. Despite the importance of these disordered behaviors to every eating disorder diagnosis, our current models are not able to accurately predict behavior occurrence. The current study utilized machine learning to develop longitudinal predictive models of binge eating, purging, and restriction in an eating disorder sample (N = 60) using real-time intensive longitudinal data. Participants completed four daily assessments of eating disorder symptoms and emotions for 25 days on a smartphone (total data points per participant = 100). Using data, we were able to compute highly accurate prediction models for binge eating, restriction, and purging (.76-.96 accuracy). The ability to accurately predict the occurrence of binge eating, restriction, and purging has crucial implications for the development of preventative interventions for the eating disorders. Machine learning models may be able to accurately predict onset of problematic psychiatric behaviors leading to preventative interventions designed to disrupt engagement in such behaviors.

An examination of eating disorder fears in imaginal exposure scripts.

OBJECTIVE: Eating disorders (EDs) are maintained by fear and anxiety, which lead to disordered eating behaviors thought to prevent the occurrence of feared outcomes. Fear of weight gain and food are among the most common fears present in the EDs. However, theory and clinical observation suggest that the feared consequences of eating or weight gain are diverse and individualized. Further research is needed to delineate specific fears underlying ED pathology. METHOD: 167 participants with any ED participated in an online four-session imaginal exposure intervention. Imaginal exposure scripts were rated by trained coders using items derived from the Eating Disorder Fear Interview to identify fears present. Frequencies of fears present in scripts were quantified. RESULTS: Two-thirds of scripts mentioned fears of food and weight or body-related fears. In over half of scripts, fear of judgment and fear of loss of control were identified. Diagnostic differences were found, including that those with anorexia nervosa (AN) and bulimia nervosa (BN) had highest fears of food, whereas those with AN and other specified feeding and eating disorder (OSFED) had higher weight gain/body-focused fears. LIMITATIONS: We were underpowered to make comparisons between ED diagnoses other than AN, BN, and OSFED. CONCLUSIONS: Imaginal exposure scripts contained a large number of fears related to food, weight/shape, judgment, and loss of control, among others. These findings extend the current understanding of ED fears and provide evidence for the individualized and varied nature of fears. Identification of ED fears can further inform research on designing personalized, exposure-based treatment approaches.

Personalizing eating disorder treatment using idiographic models: An open series trial.

OBJECTIVE: Treatments for adults with eating disorders (EDs) only work in about 50% of individuals, and for some diagnoses (e.g., anorexia nervosa; atypical anorexia nervosa), there are no existing evidence-based treatments. Part of the reason that treatments may only work in a subset of individuals is because of the high heterogeneity present in the EDs, even within diagnoses. Manualized treatments delivered in a standard format may not always address the most relevant symptoms for a specific individual. METHOD: The current open series trial recruited participants with transdiagnostic ED diagnoses (N = 79) to investigate the feasibility, acceptability, and initial clinical efficacy of a 10-session network-informed personalized treatment for eating disorders. This treatment uses idiographic (i.e., one-person) network models of ecological momentary assessment symptom data to match participants to evidence-based modules of treatment. RESULTS: We found that network-informed personalized treatment was highly feasible with low dropout rates, was rated as highly acceptable, and had strong initial clinical efficacy. ED severity decreased from pre- to posttreatment and at 1-year follow-up with a large effect size. ED cognitions, behaviors, clinical impairment, worry, and depression also decreased from pre- to posttreatment. CONCLUSIONS: These data suggest that network-informed personalized treatment has high acceptability and feasibility and can decrease ED and related pathology, possibly serving as a feasible alternative to existing treatments. Future randomized controlled trials comparing network-informed personalized treatment for ED to existing gold standard treatments are needed. Additionally, more research is needed on this type of personalized treatment both in the EDs, as well as in additional forms of psychopathology, such as depression. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Psychiatric Comorbidity Among Eating Disorders and Obsessive-Compulsive Disorder and Underlying Shared Mechanisms and Features: An Updated Review.

Eating disorders (EDs) are highly comorbid with obsessive-compulsive disorder (OCD), with comorbidity rates as high as 41%. In the current review, we summarize the literature regarding the prevalence of ED-OCD comorbidity. We also identify and review the literature assessing shared features (i.e., shared characteristics or symptoms) and mechanisms (i.e., variables that may explain ED or OCD symptoms) of EDs and OCD. Potential shared features of EDs and OCD include age of onset, course of illness, obsessions, compulsions and ritualistic behaviors, and thought action fusion. Shared mechanisms that may explain ED-OCD comorbidity include genetic and neurobiological mechanisms, anxiety and fear, repetitive negative thinking, perfectionism, intolerance of uncertainty, distress tolerance, and impulsivity. Based on these shared features and mechanisms, a theoretical conceptualization of ED and OCD comorbidity is developed, and outline considerations for assessment, differential diagnosis, treatment, and future research regarding ED-OCD comorbidity are described.

A Network Analysis Investigation of Disordered Eating Across Demographic and Developmental Subpopulations Using a National Epidemiological Sample of High School Students.

Disordered eating (DE) poses a large societal burden, yet limited research has examined DE from a developmental epidemiological perspective. It is important to consider how demographics influence DE symptoms to inform prevention and early intervention programs across diverse subpopulations. Therefore, we conducted network analyses using a large nationally representative epidemiological sample of high school students (Youth Risk Behavior Survey, United States; n = 59,582) to identify the most important symptoms and symptom relationships among six DE behaviors. We compared networks by sex, grade, and race to identify differences in symptom networks. Dieting for weight loss was highly central across networks. Networks significantly differed across sex, grade, and race. Our results suggest that dieting for weight loss may be an early intervention target for eating disorders, regardless of demographic and developmental factors. In addition, sex, race, and age should be accounted for when researching and developing prevention programs for DE and eating disorders. Public health officials, as well as mental health professionals, should present a more balanced message about dieting and weight loss to high school students to prevent the detrimental impact of DE on physical and mental health. Notably, this study is the first large, nationwide epidemiological sample using DE symptoms in network analysis.

Functional Genomic Analysis of Amphetamine Sensitivity in Drosophila.

Abuse of psychostimulants, including amphetamines (AMPHs), is a major public health problem with profound psychiatric, medical, and psychosocial complications. The actions of these drugs at the dopamine transporter (DAT) play a critical role in their therapeutic efficacy as well as their liability for abuse and dependence. To date, however, the mechanisms that mediate these actions are not well-understood, and therapeutic interventions for AMPH abuse have been limited. Drug exposure can induce broad changes in gene expression that can contribute to neuroplasticity and effect long-lasting changes in neuronal function. Identifying genes and gene pathways perturbed by drug exposure is essential to our understanding of the molecular basis of drug addiction. In this study, we used Drosophila as a model to examine AMPH-induced transcriptional changes that are DAT-dependent, as those would be the most relevant to the stimulatory effects of the drug. Using this approach, we found genes involved in the control of mRNA translation to be significantly upregulated in response to AMPH in a DAT-dependent manner. To further prioritize genes for validation, we explored functional convergence between these genes and genes we identified in a genome-wide association study of AMPH sensitivity using the Drosophila Genetic Reference Panel. We validated a number of these genes by showing that they act specifically in dopamine neurons to mediate the behavioral effects of AMPH. Taken together, our data establish Drosophila as a powerful model that enables the integration of behavioral, genomic and transcriptomic data, followed by rapid gene validation, to investigate the molecular underpinnings of psychostimulant action.

Longitudinal group and individual networks of eating disorder symptoms in individuals diagnosed with an eating disorder.

Eating disorders (EDs) are serious psychiatric illnesses with high mortality and societal cost. Despite their severity, there are few evidence-based treatments, and only 50% of individuals respond to existing treatments. This low response rate may be due to the fact that EDs are highly heterogeneous disorders. Precision treatments are needed that can intervene on individual maintenance factors. The first step in such treatment development is identification of central treatment targets, both at the group (i.e., on average) and individual level. The current study (N = 102 individuals with an ED) utilized intensive longitudinal data to model several types of group-level and individual network models. Overall, we identified several group-level central symptoms, with the most common central symptoms of fear of weight gain, desire for thinness, feeling like one is overeating, thinking about dieting, and feeling guilty. We also found that these symptoms, specifically fear of weight gain, a desire to be thinner, thinking about dieting, feeling like one is overeating, and feeling guilty, predicted ED severity at a 1- and 6-month follow-up. We modeled 97 individual networks and found that central symptoms were highly heterogeneous, regardless of ED diagnosis. This work adds to the growing literature using intensive longitudinal data to model ED pathology and implicates fear of weight gain, thinking about dieting, and feelings of guilt as symptoms needing further treatment development work. Additionally, this work contributes essential knowledge on how group and individual network modeling can be used to conceptualize the maintenance of EDs on average and at the individual level. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Testing intrusive thoughts as illness pathways between eating disorders and obsessive-compulsive disorder symptoms: a network analysis.

Obsessive-compulsive disorder (OCD) and eating disorders (EDs) frequently co-occur. Intrusive thoughts are a mechanism that may maintain this comorbidity. This study used network analysis to identify central ED-related intrusive thoughts and tested which intrusive thoughts connected ED and OCD symptoms. Two cross-sectional graphical LASSO networks were computed using a sample of 353 non-clinical participants (mean age = 35.38, SD = 9.9, 40% female, 81.6% Caucasian) with elevated disordered eating symptoms. Model 1 included just ED-related intrusive thoughts, and Model 2 included ED-related intrusive thoughts, ED, and OCD symptoms. In Model 1, we found that thoughts about one's bodily appearance (i.e., looking horrible, getting fat, gaining weight) were most central. In Model 2, we found that desire to lose weight, eating in secret, and shape dissatisfaction were most central. We identified one illness pathway (i.e., difficulty concentrating due to thoughts of food/calories) connecting intrusive thoughts, ED symptoms, and OCD symptoms. However, intrusive thoughts did not bridge ED and OCD symptoms. Hence, we found some evidence that ED-related intrusive thoughts may contribute to ED and OCD symptoms based on thought content and frequency. However, other aspects of intrusive thoughts should be considered to ascertain whether they do in fact significantly contribute to ED and OCD comorbidity. Prevention efforts targeting ED-related intrusive thoughts may attenuate ED and OCD symptoms among subclinical individuals.

The Role of the Dopamine Transporter in the Effects of Amphetamine on Sleep and Sleep Architecture in Drosophila.

The dopamine transporter (DAT) mediates the inactivation of released dopamine (DA) through its reuptake, and thereby plays an important homeostatic role in dopaminergic neurotransmission. Amphetamines exert their stimulant effects by targeting DAT and inducing the reverse transport of DA, leading to a dramatic increase of extracellular DA. Animal models have proven critical to investigating the molecular and cellular mechanisms underlying transporter function and its modulation by psychostimulants such as amphetamine. Here we establish a behavioral model for amphetamine action using adult Drosophila melanogaster. We use it to characterize the effects of amphetamine on sleep and sleep architecture. Our data show that amphetamine induces hyperactivity and disrupts sleep in a DA-dependent manner. Flies that do not express a functional DAT (dDAT null mutants) have been shown to be hyperactive and to exhibit significantly reduced sleep at baseline. Our data show that, in contrast to its action in control flies, amphetamine decreases the locomotor activity of dDAT null mutants and restores their sleep by modulating distinct aspects of sleep structure. To begin to explore the circuitry involved in the actions of amphetamine on sleep, we also describe the localization of dDAT throughout the fly brain, particularly in neuropils known to regulate sleep. Together, our data establish Drosophila as a robust model for studying the regulatory mechanisms that govern DAT function and psychostimulant action.

Using individual networks to identify treatment targets for eating disorder treatment: a proof-of-concept study and initial data.

BACKGROUND: Eating disorders (EDs) are severe mental illnesses, with high morbidity, mortality, and societal burden. EDs are extremely heterogenous, and only 50% of patients currently respond to first-line treatments. Personalized and effective treatments for EDs are drastically needed. METHODS: The current study (N = 34 participants with an ED diagnosis collected throughout the United States) aimed to investigate best methods informing how to select personalized treatment targets utilizing idiographic network analysis, which could then be used for evidence based personalized treatment development. We present initial data collected via experience sampling (i.e., ecological momentary assessment) over the course of 15 days, 5 times a day (75 total measurement points) that were used to select treatment targets for a personalized treatment for EDs. RESULTS: Overall, we found that treatment targets were highly variable, with less than 50% of individuals endorsing central symptoms related to weight and shape, consistent with current treatment response rates for treatments designed to target those symptoms. We also found that different aspects of selection methods (e.g., number of items, type of centrality measure) impacted treatment target selection. CONCLUSIONS: We discuss implications of these data, how to use idiographic network analysis to personalize treatment, and identify areas that need future research. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04183894. Registered 3 December 2019-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04183894 . NCT04183894 (ClinicalTrials.gov identifier).

Eating disorders are severe psychiatric illnesses that carry high mortality, morbidity, and societal and personal burden. Treatments for eating disorders only work in 50% of patients, signifying a great need to improve treatments. One reason that treatments may not work, is because eating disorders vary substantially from one individual to the next, which existing treatments do not fully consider. The current study (N = 34 participants with an eating disorder diagnosis) uses a new modeling technique to identify which symptoms should be targeted in treatment in a personalized manner. As expected, we found that, using this modeling technique, symptoms that should be targeted in treatment vary considerably. We discuss how to use this modeling technique to identify individual treatment targets and ways in which the field can use this strategy to improve existing and create new treatments.

Pinpointing core and pathway symptoms among sleep disturbance, anxiety, worry, and eating disorder symptoms in anorexia nervosa and atypical anorexia nervosa.

BACKGROUND: Sleep, anxiety, and worry are strongly related to psychiatric illness and in particular to eating disorder (ED) symptoms. However, it is unclear how these specific sleep and anxiety symptoms are interrelated with anorexia nervosa (AN) pathology. METHODS: We utilized network analysis to test our theoretically-based conceptual model, by identifying core features and illness (i.e., bridge) pathways among sleep disturbance, anxiety, worry, and ED symptoms in 267 participants with a diagnosis of AN or atypical AN. RESULTS: The following core symptoms were identified: shape judgement, restriction, and feeling tired. The strongest bridge symptoms included worry, feeling tired, loss of energy, and physical anxiety. Worry was connected positively to fasting, fear of gaining weight or becoming fat, loss of energy, and feeling tired, and negatively to changes in sleeping patterns. Feeling tired was connected to restriction, fasting, binge eating, and worry. Loss of energy was connected to loss of control over eating and worry. Physical anxiety was negatively connected to restriction. CONCLUSIONS: We identified specific core symptoms and illness pathways supporting our theoretical conceptual model of how ED symptoms, anxiety, worry, and sleep disturbances inter-relate in AN and atypical AN. In particular we found that symptoms associated with sleep and anxiety were central and had strong connections with AN symptoms. In addition to targeting AN symptoms, these data suggest that targeting sleep disturbance, anxiety, and worry could improve treatment for AN.

A network investigation of core symptoms and pathways across duration of illness using a comprehensive cognitive-behavioral model of eating-disorder symptoms.

BACKGROUND: In the past decade, network analysis (NA) has been applied to psychopathology to quantify complex symptom relationships. This statistical technique has demonstrated much promise, as it provides researchers the ability to identify relationships across many symptoms in one model and can identify central symptoms that may predict important clinical outcomes. However, network models are highly influenced by node selection, which could limit the generalizability of findings. The current study (N = 6850) tests a comprehensive, cognitive-behavioral model of eating-disorder symptoms using items from two, widely used measures (Eating Disorder Examination Questionnaire and Eating Pathology Symptoms Inventory). METHODS: We used NA to identify central symptoms and compared networks across the duration of illness (DOI), as chronicity is one of the only known predictors of poor outcome in eating disorders (EDs). RESULTS: Our results suggest that eating when not hungry and feeling fat were the most central symptoms across groups. There were no significant differences in network structure across DOI, meaning the connections between symptoms remained relatively consistent. However, differences emerged in central symptoms, such that cognitive symptoms related to overvaluation of weight/shape were central in individuals with shorter DOI, and behavioral central symptoms emerged more in medium and long DOI. CONCLUSIONS: Our results have important implications for the treatment of individuals with enduring EDs, as they may have a different core, maintaining symptoms. Additionally, our findings highlight the importance of using comprehensive, theoretically- or empirically-derived models for NA.

Disordered eating, self-esteem, and depression symptoms in Iranian adolescents and young adults: A network analysis.

OBJECTIVE: The network theory of psychopathology examines networks of interconnections across symptoms. Several network studies of disordered eating have identified central and bridge symptoms in Western samples, yet network models of disordered eating have not been tested in non-Western samples. The current study tested a network model of disordered eating in Iranian adolescents and college students, as well as models of co-occurring depression and self-esteem. METHOD: Participants were Iranian college students (n= 637) and adolescents (n = 1,111) who completed the Eating Disorder Examination-Questionnaire (EDE-Q), Rosenberg Self-Esteem Scale (RSES) and Beck Depression Inventory, Second Edition (BDI-II). We computed six Glasso networks and identified central and bridge symptoms. RESULTS: Central disordered eating nodes in most models were a desire to lose weight and discomfort when seeing one's own body. Central self-esteem and depression nodes were feeling useless and self-dislike, respectively. Feeling like a failure was the most common bridge symptom between disordered eating and depression symptoms. With exception of a few differences in some edges, networks did not significantly differ in structure. DISCUSSION: Desire to lose weight was the most central node in the networks, which is consistent with sociocultural theories of disordered eating development, as well as prior network models from Western-culture samples. Feeling like a failure was the most central bridge symptom between depression and disordered eating, suggesting that very low self-esteem may be a shared correlate or risk factor for disordered eating and depression in Iranian adolescents and young adults.