Reduced dorsal fronto-striatal connectivity at rest in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a serious psychiatric illness that remains difficult to treat. Elucidating the neural mechanisms of AN is necessary to identify novel treatment targets and improve outcomes. A growing body of literature points to a role for dorsal fronto-striatal circuitry in the pathophysiology of AN, with increasing evidence of abnormal task-based fMRI activation within this network among patients with AN. Whether these abnormalities are present at rest and reflect fundamental differences in brain organization is unclear. METHODS: The current study combined resting-state fMRI data from patients with AN (n = 89) and healthy controls (HC; n = 92) across four studies, removing site effects using ComBat harmonization. First, the a priori hypothesis that dorsal fronto-striatal connectivity strength - specifically between the anterior caudate and dlPFC - differed between patients and HC was tested using seed-based functional connectivity analysis with small-volume correction. To assess specificity of effects, exploratory analyses examined anterior caudate whole-brain connectivity, amplitude of low-frequency fluctuations (ALFF), and node centrality. RESULTS: Compared to HC, patients showed significantly reduced right, but not left, anterior caudate-dlPFC connectivity (p = 0.002) in small-volume corrected analyses. Whole-brain analyses also identified reduced connectivity between the right anterior caudate and left superior frontal and middle frontal gyri (p = 0.028) and increased connectivity between the right anterior caudate and right occipital cortex (p = 0.038). No group differences were found in analyses of anterior caudate ALFF and node centrality. CONCLUSIONS: Decreased coupling of dorsal fronto-striatal regions indicates that circuit-based abnormalities persist at rest and suggests this network may be a potential treatment target.

Prefrontal cortex activation by binge-eating status in individuals with obesity while attempting to reappraise responses to food using functional near infrared spectroscopy.

PURPOSE: Difficulty reappraising drives to consume palatable foods may promote poorer inhibition and binge eating (BE) in adults with obesity, but neural underpinnings of food-related reappraisal are underexamined. METHODS: To examine neural correlates of food-related reappraisal, adults with obesity with and without BE wore a portable neuroimaging tool, functional near-infrared spectroscopy (fNIRS). fNIRS measured activity in the prefrontal cortex while participants watched videos of food and attempt to "resist" the food stimuli (i.e., "consider the negative consequences of eating the food"). RESULTS: Participants (N = 32, 62.5% female; BMI 38.6 [Formula: see text] 7.1; 43.5 [Formula: see text] 13.4 y) had a BMI > 30 kg/m2. Eighteen adults (67.0% female; BMI 38.2 [Formula: see text] 7.6) reported BE (≥ 12 BE-episodes in preceding 3 months). The control group comprised 14 adults who denied BE (64.0% female; BMI 39.2 [Formula: see text] 6.6). Among the entire sample, mixed models showed significant, small hyperactivation during crave and resist compared to watch (relax) condition bilaterally in the medial superior frontal gyrus, dorsolateral areas, and middle frontal gyrus (optodes 5, 7, 9, 10, 11, and 12) in the total sample. No statistically significant differences in neural activation were observed between the BE and control group. Moreover, there were no significant group by condition interactions on neural activation. CONCLUSION: Among adults with obesity, BE status was not linked to differential activation in inhibitory prefrontal cortex areas during a food-related reappraisal task. Future research is needed with larger samples, adults without obesity, and inhibition paradigms with both behavioral and cognitive components. LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies. TRIAL REGISTRATION: # NCT03113669, date April 13, 2017.

Large-Scale Exploration of Whole-Brain Structural Connectivity in Anorexia Nervosa: Alterations in the Connectivity of Frontal and Subcortical Networks.

BACKGROUND: Anorexia nervosa (AN) is characterized by disturbances in cognition and behavior surrounding eating and weight. The severity of AN combined with the absence of localized brain abnormalities suggests distributed, systemic underpinnings that may be identified using diffusion-weighted magnetic resonance imaging and tractography to reconstruct white matter pathways. METHODS: Diffusion-weighted magnetic resonance imaging data acquired from female patients with AN (n= 147) and female healthy control (HC) participants (n = 119), ages 12 to 40 years, were combined across 5 studies. Probabilistic tractography was completed, and full-cortex connectomes describing streamline counts between 84 brain regions were generated and harmonized. Graph theory methods were used to describe alterations in network organization in AN. The network-based statistic tested between-group differences in brain subnetwork connectivity. The metrics strength and efficiency indexed the connectivity of brain regions (network nodes) and were compared between groups using multiple linear regression. RESULTS: Individuals with AN, relative to HC peers, had reduced connectivity in a network comprising subcortical regions and greater connectivity between frontal cortical regions (p < .05, familywise error corrected). Node-based analyses indicated reduced connectivity of the left hippocampus in patients relative to HC peers (p < .05, permutation corrected). Severity of illness, assessed by body mass index, was associated with subcortical connectivity (p < .05, uncorrected). CONCLUSIONS: Analyses identified reduced structural connectivity of subcortical networks and regions, and stronger cortical network connectivity, among individuals with AN relative to HC peers. These findings are consistent with alterations in feeding, emotion, and executive control circuits in AN, and may direct hypothesis-driven research into mechanisms of persistent restrictive eating behavior.

Psychopharmacologic Management of Eating Disorders.

PURPOSE OF REVIEW: Identifying medications that may be used as therapeutic agents for eating disorders is a longstanding focus of research, with varying degrees of success. The present review consolidates the most recent findings on pharmacological treatment of three eating disorders, including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). RECENT FINDINGS: Recent research suggests that olanzapine demonstrates positive effects on weight gain among outpatients with AN. There are fewer recent advances in psychopharmacological treatment for BN and BED, likely due to the relative success of prior medication trials. Olanzapine is the first medication to safely promote weight gain among individuals with AN. Fluoxetine is FDA-approved for BN treatment, and lisdexamfetamine is FDA-approved for BED treatment. BN and BED also generally respond well to SSRIs prescribed off-label. Research on psychopharmacological treatments for other eating disorders, such as avoidant-restrictive food intake disorder and other specified feeding and eating disorders, are sorely needed.

Use of high-frequency repetitive transcranial magnetic stimulation to probe the neural circuitry of food choice in anorexia nervosa: A proof-of-concept study.

Repetitive transcranial magnetic stimulation (rTMS) is used to modulate neural systems and provides the opportunity for experimental tests of hypotheses regarding mechanisms underlying anorexia nervosa (AN). The present pilot study has investigated whether high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to a region of the right dorsolateral prefrontal cortex (DLPFC) might be associated with change in food selection among adult inpatients with AN. Ten women received one session of sham and one session of HF-rTMS targeting the right DLPFC while completing a computerized Food Choice Task. Compared to sham, HF-rTMS was associated with changes in food ratings and food choice: inpatients reported higher healthiness ratings of low- and high-fat foods and selected a significantly greater proportion of high-fat foods over a neutrally rated reference item while receiving HF-rTMS. Findings suggest that HF-rTMS to the right DLPFC was associated with a reduction of fat avoidance on a food choice task among inpatients with AN and provide additional support for the possibility that this region, and related neural circuits, may underlie restrictive food choice. Research using rTMS to experimentally test neural mechanisms is needed to elucidate the underpinnings of AN and supports the development of novel treatment targets.

Current Therapeutic Approaches to Anorexia Nervosa: State of the Art.

Anorexia nervosa (AN) is a devastating psychiatric disorder characterized by extreme restriction of food intake and low body weight, both associated with significant medical and psychological morbidity. The clinical severity of AN has prompted the consideration and study of behavioral and pharmacological treatments in efforts to establish empirically based methods to reduce the burden of the disorder. Among adolescents, family-based treatment is considered a first-line behavioral treatment. Research continues to explore the efficacy of family-based treatment and predictors of treatment response to further improve outcomes. Several behavioral treatments for adults also exist, including cognitive-behavioral therapy, exposure and response prevention, third-wave acceptance-based treatments, and supportive psychotherapy, all of which help to improve symptoms and promote modest weight gain. Despite this, no one treatment is considered superior, and all existing behavioral approaches leave a proportion of adults symptomatic or at a high risk of relapse. As such, among adults, there is continued need for development of novel, mechanism-based approaches to better target the core symptoms of AN. Although antidepressants impart little benefit on weight or symptoms, the second-generation antipsychotic olanzapine has shown ability to promote modest weight gain in outpatients with AN. Most recently, the field's evolving conceptualization of AN as a biologically based disorder coupled with technological advancements has led to consideration of varying neuromodulation strategies as a potential therapeutic approach that remains under investigation.

Predictors of illness course and health maintenance following inpatient treatment among patients with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a life-threatening psychiatric disorder associated with significant medical and psychosocial impairment. Hospital-based behavioral treatment is an effective intervention in the short-term. However, relapse rates following discharge are high and thus, there is a need to identify predictors of longitudinal outcome. The current study provides information regarding illness course and health maintenance among patients with AN over 5 years following discharge from an eating disorder inpatient unit. METHODS: Participants were individuals with AN who were discharged from a specialized, inpatient behaviorally-based unit. Prior to discharge, height and weight were measured and participants completed self-report measures of eating disorder severity and general psychopathology (depression, anxiety, harm avoidance). Participants were contacted annually for self-report measures of weight, eating disorder severity and clinical impairment. Outcome was defined by illness course (body mass index (BMI) and clinical impairment during the 5 years) and health maintenance (categories of weight and eating disorder symptom severity) across follow-up, using all available data. Linear mixed models were used to examine whether demographic and clinical parameters at discharge predicted BMI and clinical impairment over time. Additional analyses examined whether these variables significantly influenced an individual's likelihood of maintaining inpatient treatment gains. RESULTS: One-hundred and sixty-eight individuals contributed data. Higher trait anxiety at discharge was associated with a lower BMI during follow-up (p = 0.012). There was a significant interaction between duration of illness and time, whereby duration of illness was associated with a faster rate of weight loss (p = 0.003) during follow-up. As duration of illness increased, there was a greater increase in self-reported clinical impairment (p = 0.011). Increased eating disorder severity at discharge was also associated with greater clinical impairment at follow-up (p = 0.004). Higher BMI at discharge was significantly associated with maintaining healthy weight across a priori BMI-based definitions of health maintenance. CONCLUSIONS: Weight status (higher BMI) and duration of illness are key factors in the prognosis of AN. Higher weight targets in intensive treatments may be of value in improving outcomes.

Developing an Acceptance-Based Behavioral Weight Loss Treatment for Individuals With Binge Eating Pathology: A Preliminary Proof of Concept Study and Clinical Case Series.

Binge eating (BE; i.e., the consumption of a large amount of food in a discrete time period, accompanied by a sense of loss of control) is highly comorbid with overweight or obesity and is the primary symptom of binge eating disorder (BED). Current gold-standard treatment for BED (i.e., CBT) does not produce meaningful weight loss, thus failing to address a critical treatment target. This article describes the development of a novel acceptance-based behavioral treatment (ABBT) for individuals with clinically significant BE desiring to reduce BE symptoms and achieve concurrent weight loss. We discuss the development and structure of the novel treatment approach, and describe the test of a proof of concept version of the treatment in a clinical case series of four individuals. In the context of each clinical case description, we present initial acceptability of the treatment and challenges faced in treatment development and delivery. Finally, we discuss future research directions for the treatment, which could improve BE symptoms and weight loss outcomes for individuals with BE pathology.

Mediating role of experiential avoidance in the relationship between anxiety sensitivity and eating disorder psychopathology: A clinical replication.

OBJECTIVE: This study sought to examine whether anxiety sensitivity was associated with eating disorder (ED) symptom severity among patients with severe EDs, and to determine whether this relationship was mediated by experiential avoidance. METHOD: Adolescent and adult females (N = 625) seeking residential ED treatment completed self-report measures of anxiety sensitivity, experiential avoidance, and ED psychopathology. Linear regression evaluated the cross-sectional association between ED symptom severity and three dimensions of anxiety sensitivity (social, physical, and cognitive). Regression-based mediation analysis with bootstrapping tested the associations among the three dimensions of anxiety sensitivity and ED symptom severity through experiential avoidance. RESULTS: The social dimension of anxiety sensitivity was positively associated with severity of ED psychopathology. Experiential avoidance mediated this association. DISCUSSION: ED symptoms in this sample were more severe among patients who endorsed greater concern about appearing nervous or anxious to others. The current results indicate that this relationship was driven by a tendency to avoid experiences that evoke emotional discomfort. If replicated, these findings suggest that targeting both social anxiety sensitivity and experiential avoidance may improve ED treatment outcomes. Further study of the mechanistic relationships among social anxiety sensitivity, experiential avoidance, and ED psychopathology, is warranted.

Why is premorbid BMI consistently elevated in clinical samples, but not in risk factor samples, of individuals with eating disorders?

Body image disturbance is widely viewed as contributing to the development and maintenance of disordered eating. Yet this perspective is not inconsistent with the possibility that elevated premorbid BMIs also increase the risk of developing eating disorders. Research examining whether actual body size may play a role in eating disorder development reveals a curious pattern of findings. Few prospective risk factor studies conducted with community-based samples found a relationship between premorbid BMI and subsequent eating disorder pathology whereas retrospective research conducted with clinical samples indicates a consistent pattern of elevated premorbid BMIs relative to population norms or control groups. This study documents these disparate findings, considers potential explanations for them and proposes further study of premorbid BMI as a factor contributing to the psychopathology of eating disorders, particularly among those who come to the attention of treatment providers.

Body concerns and BMI as predictors of disordered eating and body mass in girls: An 18-year longitudinal investigation.

Body concerns (e.g., body dissatisfaction and weight preoccupation) are well-supported prospective risk factors for the development of eating disorders in women. Body concerns are psychological variables but they are partly based on actual body mass. This study tested whether (a) body concerns predict increases in eating disorder characteristics measured both continuously (via subscale scores on the Minnesota Eating Behavior Survey (MEBS) and categorically (via transition to a probable or definite eating disorder), (b) body concerns predict changes in BMI, and (c) BMI predicts changes in eating disorder symptoms or development of an eating disorder. Beginning with 762 girls at age 11, the MEBS' Body Dissatisfaction (BD) and Weight Preoccupation (WP) scales were used to predict change in the MEBS' Bulimic Behavior scale (the sum of the Binge Eating and Compensatory Behaviors scales), in BD and WP themselves and in BMI over 18 years of follow up. Baseline BMI was also used to predict BMI and MEBS change. Contrary to expectations, BD and WP predicted significantly reduced growth in all MEBS scales and also predicted significantly reduced growth in BMI. BD, WP and BMI did not predict development of an ED. This pattern was strengthened when predictors were measured at age 17 instead of 11. We consider the possibility that the divergence between the current findings and past findings on eating disorder risk factors may stem from the unusually long developmental period studied, ranging from age 11 (or 17) through age 29. Additional longitudinal research that spans a similar developmental period could shed light on the plausibility of this explanation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Addressing Weight Suppression to Improve Treatment Outcome for Bulimia Nervosa.

Cognitive behavioral therapy (CBT) is regarded as the gold-standard treatment for bulimia nervosa (BN), yet despite impressive empirical support for its effectiveness, over 50% of patients fail to achieve abstinence from binge eating and purging by the end of treatment. One factor that may contribute to reduced efficacy rates in CBT is weight suppression (WS; the difference between a person's highest weight ever at their adult height and current weight). A growing body of research indicates that WS in patients with BN may have a clinically significant effect on symptomatology and prognosis. However, the current cognitive behavioral framework for BN does not explicitly acknowledge the role of WS in the onset or maintenance of BN symptoms and does not provide guidance for clinicians on how to address WS during treatment. The relationship between WS, biological pressure to regain lost weight, and the maintenance of BN symptoms suggest that current cognitive behavioral models of BN may be improved by considering the role of WS and exploring needed treatment modifications. Indeed, a reconceptualization of existing models may offer insight into potential strategies that can be used to reduce the susceptibility to treatment dropout, nonresponse, and relapse. It is therefore necessary to consider whether, and how, clinicians' consideration of WS during case conceptualization and treatment planning could serve to improve CBT outcomes. The current review explores ways in which high WS could contribute to poor CBT outcomes, provides preliminary clinical recommendations for incorporating WS into existing cognitive behavioral treatments based on extant data and clinical wisdom, and proposes suggestions for future research needed in this domain.

Neural correlates of interoception: Effects of interoceptive focus and relationship to dimensional measures of body awareness.

Interoception has been defined as the sensing of the physiological condition of the body, with interoceptive sensibility (IS) characterizing an individual's self-reported awareness of internal sensation. IS is a multidimensional construct including not only the tendency to be aware of sensation but also how sensations are interpreted, regulated, and used to inform behavior, with different dimensions relating to different aspects of health and disease. Here we investigated neural mechanisms of interoception when healthy individuals attended to their heartbeat and skin temperature, and examined the relationship between neural activity during interoception and individual differences in self-reported IS using the Multidimensional Scale of Interoceptive Awareness (MAIA). Consistent with prior work, interoception activated a network involving insula and sensorimotor regions but also including occipital, temporal, and prefrontal cortex. Differences based on interoceptive focus (heartbeat vs skin temperature) were found in insula, sensorimotor regions, occipital cortex, and limbic areas. Factor analysis of MAIA dimensions revealed 3 dissociable components of IS in our dataset, only one of which was related to neural activity during interoception. Reduced scores on the third factor, which reflected reduced ability to control attention to body sensation and increased tendency to distract from and worry about aversive sensations, was associated with greater activation in many of the same regions as those involved in interoception, including insula, sensorimotor, anterior cingulate, and temporal cortex. These data suggest that self-rated interoceptive sensibility is related to altered activation in regions involved in monitoring body state, which has implications for disorders associated with abnormality of interoception. Hum Brain Mapp 38:6068-6082, 2017. © 2017 Wiley Periodicals, Inc.

An investigation of two dimensions of impulsivity as predictors of loss-of-control eating severity and frequency.

Loss-of-control (LOC) eating episodes represent one form of dysregulated eating common to full- and sub-threshold eating disorders. Extensive evidence suggests that impulsivity, particularly in the context of negative affect and/or depression, may play an important etiological role in the development and maintenance of LOC eating. However, most prior studies have considered LOC eating as a dichotomous rather than dimensional construct, and few studies have considered the interaction of multiple dimensions of impulsivity while also accounting for the role of depressive symptoms. The present study examined the independent and interacting effects of two facets of impulsivity-response inhibition and negative urgency-on LOC eating episode severity and frequency among college women (N = 102). Depressive symptom severity was included as a covariate. Results indicated that greater negative urgency was associated with greater LOC severity; this effect was moderated by response inhibition, such that the effect of urgency was particularly pronounced for individuals with higher response inhibition capacity. Negative urgency was the only significant predictor of LOC frequency. Depression had no significant effect on either LOC severity or frequency (ps ≥ 0.16). Results support the importance of considering multiple facets of impulsivity in predicting LOC eating behavior, and further indicate that factors influencing subjective severity and frequency of LOC may be distinct.

Switching between internally and externally focused attention in obsessive-compulsive disorder: Abnormal visual cortex activation and connectivity.

Obsessive-compulsive disorder (OCD) is characterized by excessive absorption with internally-generated distressing thoughts and urges, with difficulty incorporating external information running counter to their fears and concerns. In the present study, we experimentally probed this core feature of OCD through the use of a novel attention switching task that investigates transitions between internally focused (IF) and externally focused (EF) attentional states. Eighteen OCD patients and 18 controls imagined positive and negative personal event scenarios (IF state) or performed a color-word Stroop task (EF state). The IF/EF states were followed by a target detection (TD) task requiring responses to external stimuli. Compared to controls, OCD patients made significantly more errors and showed reduced activation of superior and inferior occipital cortex, thalamus, and putamen during TD following negative IF, with the inferior occipital hypoactivation being significantly greater for TD following negative IF compared to TD following the other conditions. Patients showed stronger functional connectivity between the inferior occipital region and dorsomedial prefrontal cortex. These findings point to an OCD-related impairment in the visual processing of external stimuli specifically when they follow a period of negative internal focus, and suggest that future treatments may wish to target the transition between attentional states.

Effects of context on risk taking and decision times in obsessive-compulsive disorder.

Despite the fact that OCD patients show altered decision making in everyday life, few studies have investigated how patients make risky decisions and what contextual factors impact choices. We investigated cognitive context with the use of the "framing effect" task, which investigates decision making based on whether monetarily equivalent choice options are framed in terms of a potential to either lose (lose $20 out of $50) or gain (gain $30 out of $50) money. In addition, we manipulated social context by providing positive or neutral feedback on subjects' choices. Overall, participants were risk taking for options framed in terms of potential loss and risk averse for options framed in terms of potential gain (the classic framing effect). Although OCD patients were generally more risk averse, the effect of the frame on choices did not differ significantly from healthy participants and choices were not impacted by social context. Within OCD patients, greater self-reported indecisiveness was associated with a larger effect of the frame on choices. OCD patients were also significantly slower to make choices in the loss compared to gain frame, an effect that was not observed among healthy participants. Overall, our results suggest that the framing of choice options has a differential effect on decision times but not the actual choices made by OCD patients, and that patients are not sensitive to social feedback when making choices. The correlation between indecisiveness and the framing effect in OCD suggests that further work interrogating the relationship between specific symptoms and decision making among patients may yield new insights into the disorder.

The Persistence of Experience: Prior Attentional and Emotional State Affects Network Functioning in a Target Detection Task.

Efficient, adaptive behavior relies on the ability to flexibly move between internally focused (IF) and externally focused (EF) attentional states. Despite evidence that IF cognitive processes such as event imagination comprise a significant amount of awake cognition, the consequences of internal absorption on the subsequent recruitment of brain networks during EF tasks are unknown. The present functional magnetic resonance imaging (fMRI) study employed a novel attentional state switching task. Subjects imagined positive and negative events (IF task) or performed a working memory task (EF task) before switching to a target detection (TD) task also requiring attention to external information, allowing for the investigation of neural functioning during external attention based on prior attentional state. There was a robust increase of activity in frontal, parietal, and temporal regions during TD when subjects were previously performing the EF compared with IF task, an effect that was most pronounced following negative IF. Additionally, dorsolateral prefrontal cortex was less negatively coupled with ventromedial prefrontal and posterior cingulate cortices during TD following IF compared with EF. These findings reveal the striking consequences for brain activity following immersion in an IF attentional state, which have strong implications for psychiatric disorders characterized by excessive internal focus.