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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.

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.

BackgroundGold-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.ObjectiveWe 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).MethodParticipants completed surveys every 2 weeks throughout treatment.ResultsGroup 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.ConclusionsFindings provide initial data suggesting that lamotrigine could be useful as an adjunctive treatment for patients with affective lability and impulsivity.Level of evidenceIV, time series without randomization.

PurposeAdults with bulimia nervosa (BN) and co-occurring emotional dysregulation and multiple impulsive behaviors are less responsive to existing interventions. Initial data suggest that the combination of Dialectical Behavior Therapy (DBT) and a mood stabilizer, lamotrigine, significantly reduces symptoms of affective and behavioral dysregulation in these patients. Identifying candidate neurobiological mechanisms of change for this novel treatment combination may help guide future randomized controlled trials and inform new and targeted treatment development. Here, we examined neurocognitive and symptom changes in a female patient with BN and severe affective and behavioral dysregulation who received DBT and lamotrigine.MethodsGo/no-go task performance data and resting-state functional MRI scans were acquired before the initiation of lamotrigine (after 6 weeks in an intensive DBT program), and again after reaching and maintaining a stable dose of lamotrigine. The patient completed a battery of symptom measures biweekly for 18 weeks over the course of treatment.ResultsAfter lamotrigine initiation, the patient made fewer errors on a response inhibition task and showed increased and new connectivity within frontoparietal and frontolimbic networks involved in behavioral and affective control. Accompanying this symptom improvement, the patient reported marked reductions in bulimic symptoms, behavioral dysregulation, and reactivity to negative affect, along with increases in DBT skills use.ConclusionImproved response inhibition and cognitive control network connectivity should be further investigated as neurocognitive mechanisms of change with combined DBT and lamotrigine for eating disorders. Longitudinal, controlled trials integrating neuroimaging and symptom measures are needed to fully evaluate the effects of this treatment.Level of evidenceIV: Evidence obtained from multiple time series with or without the intervention, such as case studies.

ObjectiveBinge-eating and purging behaviors commonly co-occur with overweight. However, little is known about the potential associations of elevated weight status with eating disorder severity or treatment outcomes. Thus, the present study compared binge-eating and purging patients with low, normal, and high weight statuses on eating disorder and mood symptoms at treatment admission, and tested whether weight status was associated with symptom change over treatment.MethodThe sample included 135 adult female patients in an intensive outpatient program, who completed self-assessments at admission and discharge. MANOVAs compared the groups at treatment admission, and multilevel models examined changes over time.ResultsAt admission, the high-weight group reported greater fasting frequency than the normal-weight group, and higher shape and weight concerns than the low-weight group. Over time, the high-weight group additionally showed higher eating disorder psychological symptom severity than the normal-weight group. The groups did not differ on mood symptoms at admission. Longitudinal results indicated that the groups showed comparable symptom improvements over treatment.DiscussionThese findings highlight the severity of higher-weight patients with bulimia nervosa. Additionally, although these patients may present with more severe symptoms, their response to an intensive treatment may be comparable to that of normal- or lower-weight groups.

BackgroundOften, patients with primary immunodeficiency diseases (PID), which are marked by the absence or loss of functional antibodies, require lifelong treatment with immunoglobulin (IG) replacement therapy administered either intravenously (intravenous immunoglobulin [IVIG]) or subcutaneously (subcutaneous immunoglobulin [SCIG]). In patients with PID, the 20% SCIG product, Ig20Gly, was shown to be efficacious and well tolerated in 2 phase 2/3 trials conducted in North America and Europe. This analysis evaluated patient satisfaction with Ig20Gly therapy and treatment preferences.MethodsThis prespecified post hoc analysis showed combined data from 2 Ig20Gly pivotal trials. Treatment satisfaction was assessed in the pre-Ig20Gly period and after ≥11 months of Ig20Gly treatment using the Life Quality Index (LQI; both studies) and the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9; North American study only). Treatment preference was assessed using a survey at the end of the European study. Median within-patient differences in LQI and TSQM-9 scores between the pre-Ig20Gly period and the end of the Ig20Gly treatment period were assessed using the Wilcoxon signed-rank test.ResultsA total of 113 patients (n = 68 [North American]; n = 45 [Europe]) with PID were included in the analysis. In the combined LQI analysis (n = 110), significant improvements were observed in the treatment interference (median ∆: + 2.8; P = 0.006) and therapy setting (median ∆: + 5.6; P

OBJECTIVE: Anorexia nervosa has the highest mortality rate of any psychiatric condition, yet the pathophysiology of this disorder and its primary symptom, extreme dietary restriction, remains poorly understood. In states of hunger relative to satiety, the rewarding value of food stimuli normally increases to promote eating, yet individuals with anorexia nervosa avoid food despite emaciation. This studys aim was to examine potential neural insensitivity to these effects of hunger in anorexia nervosa. METHODS: At two scanning sessions scheduled 24 hours apart, one after a 16-hour fast and one after a standardized meal, 26 women who were in remission from anorexia nervosa (to avoid the confounding effects of malnutrition) and 22 matched control women received tastes of sucrose solution or ionic water while functional MRI data were acquired. Within a network of interest responsible for food valuation and transforming taste signals into motivation to eat, the authors compared groups across conditions on blood-oxygen-level-dependent (BOLD) signal and task-based functional connectivity. RESULTS: Participants in the two groups had similar BOLD responses to sucrose and water tastants. A group-by-condition interaction in the ventral caudal putamen indicated that hunger had opposite effects on tastant response in the control group and the remitted anorexia nervosa group, with an increase and a decrease, respectively, in BOLD response when hungry. Hunger had a similar opposite effect on insula-to-ventral caudal putamen functional connectivity in the remitted anorexia nervosa group compared with the control group. Exploratory analyses indicated that lower caudate response to tastants when hungry was associated with higher scores on harm avoidance among participants in the remitted anorexia nervosa group. CONCLUSIONS: Reduced recruitment of neural circuitry that translates taste stimulation to motivated eating behavior when hungry may facilitate food avoidance and prolonged periods of extremely restricted food intake in anorexia nervosa.

OBJECTIVE:Anorexia nervosa has the highest mortality rate of any psychiatric condition, yet the pathophysiology of this disorder and its primary symptom, extreme dietary restriction, remains poorly understood. In states of hunger relative to satiety, the rewarding value of food stimuli normally increases to promote eating, yet individuals with anorexia nervosa avoid food despite emaciation. This study's aim was to examine potential neural insensitivity to these effects of hunger in anorexia nervosa. METHODS:At two scanning sessions scheduled 24 hours apart, one after a 16-hour fast and one after a standardized meal, 26 women who were in remission from anorexia nervosa (to avoid the confounding effects of malnutrition) and 22 matched control women received tastes of sucrose solution or ionic water while functional MRI data were acquired. Within a network of interest responsible for food valuation and transforming taste signals into motivation to eat, the authors compared groups across conditions on blood-oxygen-level-dependent (BOLD) signal and task-based functional connectivity. RESULTS:Participants in the two groups had similar BOLD responses to sucrose and water tastants. A group-by-condition interaction in the ventral caudal putamen indicated that hunger had opposite effects on tastant response in the control group and the remitted anorexia nervosa group, with an increase and a decrease, respectively, in BOLD response when hungry. Hunger had a similar opposite effect on insula-to-ventral caudal putamen functional connectivity in the remitted anorexia nervosa group compared with the control group. Exploratory analyses indicated that lower caudate response to tastants when hungry was associated with higher scores on harm avoidance among participants in the remitted anorexia nervosa group. CONCLUSIONS:Reduced recruitment of neural circuitry that translates taste stimulation to motivated eating behavior when hungry may facilitate food avoidance and prolonged periods of extremely restricted food intake in anorexia nervosa.

Interoceptive awareness (IA), or the awareness of internal body states, is known to be impaired in individuals with eating disorders (EDs); however, little is understood about how IA and ED symptoms are connected. Network analysis is a statistical approach useful for examining how symptoms interrelate and how comorbidities may be maintained. The present study used network analysis to (1) test central symptoms within an IA-ED network, (2) identify symptoms that may bridge the association between IA and ED symptoms, and (3) explore whether central and bridge symptoms predict ED remission at discharge from intensive treatment. A regularized partial correlation network was estimated in a sample of 428 adolescent (n = 187) and adult (n = 241) ED patients in a partial hospital program. IA was assessed using items from the Multidimensional Assessment of Interoceptive Awareness, and ED symptoms were assessed using items from the Eating Disorder Examination-Questionnaire. Central symptoms within the network were strong desire to lose weight, feeling guilty, and listening for information from the body about emotional state. The most central symptom bridging IA and ED symptoms was (not) feeling safe in one's body. Of the central symptoms, greater desire to lose weight predicted lower likelihood of remission at treatment discharge. Bridge symptoms did not significantly predict remission. Body mistrust may be a mechanism by which associations between IA and EDs are maintained. Findings suggest targeting central and bridge symptoms may be helpful to improve IA and ED symptoms. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Emotion regulation deficits are associated with eating disorder (ED) symptoms, regardless of eating disorder diagnosis. Thus, recent treatment approaches for EDs, such as dialectical behavior therapy (DBT), have focused on teaching patients skills to better regulate emotions. The present study examined changes in emotion regulation among adult patients with EDs during DBT-oriented partial hospital treatment, and at follow-up (M[SD] = 309.58[144.59] days from discharge). Exploratory analyses examined associations between changes in emotion regulation and ED symptoms. Patients with anorexia nervosa, restricting (AN-R, n = 77), and binge-eating/purging subtype (AN-BP, n = 46), or bulimia nervosa (BN, n = 118) completed the Difficulties in Emotion Regulation Scale (DERS) at admission, discharge, and follow-up. Patients with BN demonstrated significant improvements across all facets of emotion dysregulation from admission to discharge and maintained improvements at follow-up. Although patients with AN-BP demonstrated statistically significant improvements on overall emotion regulation, impulsivity, and acceptance, awareness, and clarity of emotions, from admission to discharge, these improvements were not significant at follow-up. Patients with AN-R demonstrated statistically significant improvements on overall emotion dysregulation from treatment admission to discharge. Changes in emotion regulation were moderately correlated with changes in ED symptoms over time. Results support different trajectories of emotion regulation symptom change in DBT-oriented partial hospital treatment across ED diagnoses, with patients with BN demonstrating the most consistent significant improvements.

Given the high rates of comorbidity between eating disorders (EDs) and substance use disorders (SUDs), it is important to develop effective treatment approaches for individuals with both an ED and SUD (ED-SUD). To date, there is limited information guiding the concurrent treatment of these disorders. To build on existing research, the present study compared adult patients with ED-SUD (n = 36) to patients with ED-only (n = 62) in terms of demographics, psychiatric comorbidity, and self-reported eating disorder and related psychopathology. Results indicated that ED-SUD patients had a higher number of psychiatric comorbidities, were more likely to be prescribed mood stabilizers, and were more sensitive to reward. They also reported greater difficulty with emotion regulation, including more difficulty engaging in goal-directed activity, higher impulsivity, and more limited access to emotion regulation strategies. These differences highlight the importance of targeting emotion dysregulation for ED-SUD, and provide evidence for the importance of integrated, transdiagnostic treatment to simultaneously address the SUD, ED, and other psychiatric comorbidities. Implications for tailoring treatment are discussed with a focus on Dialectical Behavior Therapy (DBT).

ObjectiveModels of anorexia nervosa (AN) posit that set-shifting deficits may contribute to behavioral inflexibility and extreme dietary restriction. Findings from neurocognitive studies of set-shifting in AN have been somewhat mixed, perhaps due to the use of tasks that cannot distinguish shifting from other processes (i.e., learning). To more precisely characterize cognitive flexibility and selectively assess this process independent of rule learning and feedback sensitivity, we examined task-switching ability in AN.MethodWomen ill with AN, subthreshold AN or atypical AN (IAN; n = 40), women remitted from AN (RAN; n = 24), and age-matched healthy control women (n = 42) completed a computerized cued color-shape task-switching paradigm. Groups were compared on mix costs (reflecting global cognitive control) and switch costs (reflecting transient cognitive control).ResultsAlthough mix costs were equivalent across groups, switch costs were more pronounced in the IAN group, as indicated by a group-by-trial type interaction for reaction times on stay and switch trials.DiscussionFindings indicate that IAN, but not RAN, have difficulty flexibly switching between cognitive task sets, and suggest that prior findings of set-shifting deficits in AN may reflect difficulty with cognitive flexibility independent of learning deficits. As such, task-switching may represent a promising adjunctive treatment target.

Bulimia nervosa (BN) is characterized by dysregulated intake of food, which may indicate homeostatic imbalance. Critically important for homeostatic regulation is interoception, or the sensing and processing of body-relevant information. A well-documented link between avoidance of unpleasant body sensations and BN symptoms suggests that aversive interoceptive experiences may be particularly relevant to BN pathophysiology. This study examined whether individuals with a history of BN show aberrant neural processing of aversive interoceptive stimuli. Using a cued inspiratory breathing load paradigm, we compared women remitted from BN (RBN; n = 24; to reduce the confounding effects of active bulimic symptoms) and control women (CW; n = 25). During breathing load anticipation, the RBN group, relative to CW, showed increased activation in mid-insula, superior frontal gyrus, putamen, dorsal anterior cingulate, posterior cingulate, and amygdala. However, over the course of the aversive experience, neural activation in RBN relative to CW showed an aberrant decline in most of these regions. Exploratory analyses indicated that greater activation during breathing load anticipation was associated with past bulimic symptom severity and the duration of symptom remission. An exaggerated anticipatory response and an abnormally decreasing response during aversive homeostatic perturbations may promote hallmark bulimic behaviors-binge eating, dietary restriction, and purging. Our findings support a role for homeostatic instability in BN, and these altered patterns of brain activation may serve as novel targets for pharmacological, neuromodulatory, and behavioral interventions.

Interoception, or the sensing and integration of bodily state signals, has been implicated in anorexia nervosa (AN), given that the hallmark symptoms involve food restriction and body image disturbance. Here we focus on brain response to the anticipation and experience of affective interoceptive stimuli. Women remitted from AN (RAN; N = 18) and healthy comparison women (CW; N = 26) underwent a pleasant affective touch paradigm consisting of gentle strokes with a soft brush administered to the forearm or palm during functional neuroimaging. RAN had a lower brain response relative to CW during anticipation of touch, but a greater response when experiencing touch in the right ventral mid-insula. In RAN, this reduced anticipatory response was associated with higher levels of harm avoidance. Exploratory analyses in RAN also suggested that lower response during touch anticipation was associated with greater body dissatisfaction and higher perceived touch intensity ratings. This reduced responsivity to the anticipation of pleasant affective interoceptive stimuli in association with higher harm avoidance, along with an elevated response to the experience of touch, suggests an impaired ability in AN to predict and interpret incoming physiological stimuli. Impaired interoception may thus impact one's sense of self, thereby supporting observations of disturbed body image and avoidance of affective and social stimuli. Therapeutic approaches that help AN to better anticipate and interpret salient affective stimuli or improve tolerance of interoceptive experiences may be an important addition to current interventions.

BackgroundThe neural mechanisms of anorexia nervosa (AN), a severe and chronic psychiatric illness, are still poorly understood. Altered body state processing, or interoception, has been documented in AN, and disturbances in aversive interoception may contribute to distorted body perception, extreme dietary restriction, and anxiety. As prior data implicate a potential mismatch between interoceptive expectation and experience in AN, we examined whether AN is associated with altered brain activation before, during, and after an unpleasant interoceptive state change.MethodsAdult women remitted from AN (RAN; n = 17) and healthy control women (CW; n = 25) underwent functional magnetic resonance imaging during an inspiratory breathing load paradigm.ResultsDuring stimulus anticipation, the RAN group, relative to CW, showed reduced activation in right mid-insula. In contrast, during the aversive breathing load, the RAN group showed increased activation compared with CW in striatum and cingulate and prefrontal cortices (PFC). The RAN group also showed increased activation in PFC, bilateral insula, striatum, and amygdala after stimulus offset. Time course analyses indicated that RAN responses in interoceptive processing regions during breathing load increased more steeply than those of CW. Exploratory analyses revealed that hyperactivation after breathing load was associated with markers of past AN severity.ConclusionsAnticipatory deactivation with a subsequent exaggerated brain response during and after an aversive body state may contribute to difficulty predicting and adapting to internal state fluctuation. Because eating changes our interoceptive state, restriction may be one method of avoiding aversive, unpredictable internal change in AN.

Altered interoceptive awareness (IA) has been implicated in the pathophysiology of eating disorders; however, few comprehensive self-report measures of IA exist in eating disorders. The present study sought to validate the Multidimensional Assessment of Interoceptive Awareness (MAIA), originally developed to assess IA in individuals practicing mind-body therapies, in an eating disorder sample. Adult and adolescent patients (n = 376) completed assessments upon admission to a partial hospital programme. Analyses examined the factor structure of the MAIA, scale means, scale-scale correlations, internal consistency and construct validity. Analyses also examined associations between MAIA subscales and eating disorder symptoms. Results supported the original eight-factor structure of the MAIA. Internal consistency was acceptable, and the scales converged with associated measures. Importantly, Not Distracting, Self-regulation, Body Listening and Trusting were most strongly associated with eating disorder symptoms. Results support use of the MAIA among eating disorders and provide further support for the relevance of IA in eating disorders. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Individuals with bulimia nervosa (BN) engage in episodes of binge eating, marked by loss of control and eating despite fullness. Does altered reward and metabolic state contribute to BN pathophysiology? Normally, hunger increases (and satiety decreases) reward salience to regulate eating. We investigated whether BN is associated with an abnormal response in a neural circuit involved in translating taste signals into motivated behavior, when hungry and fed. Twenty-six women remitted from BN (RBN) and 22 control women (CW) were administered water and sucrose during 2 counterbalanced fMRI visits, following a 16-hr fast or a standardized breakfast. Significant Group × Condition interactions were found in the left putamen, insula, and amygdala. Post hoc analyses revealed CW were significantly more responsive to taste stimuli when hungry versus fed in the left putamen and amygdala. In contrast, RBN response did not differ between conditions. Further, RBN had greater activation in the left amygdala compared with CW when fed. Findings suggest that RBN neural response to rewarding stimuli may not be modulated by metabolic state. Data raise the possibility that disinhibited eating in BN could result from a failure to devalue food reward when fed, resulting in an exaggerated response. (PsycINFO Database Record

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41% of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation.