Neural activation of regions involved in food reward and cognitive control in young females with anorexia nervosa and atypical anorexia nervosa versus healthy controls.

Anorexia nervosa (AN) and atypical AN (AtypAN) are complex neurobiological illnesses that typically onset in adolescence with an often treatment-refractory and chronic illness trajectory. Aberrant eating behaviors in this population have been linked to abnormalities in food reward and cognitive control, but prior studies have not examined respective contributions of clinical characteristics and metabolic state. Research is needed to identify specific disruptions and inform novel intervention targets to improve outcomes. Fifty-nine females with AN (n = 34) or AtypAN (n = 25), ages 10-22 years, all ≤90% expected body weight, and 34 age-matched healthy controls (HC) completed a well-established neuroimaging food cue paradigm fasting and after a standardized meal, and we used ANCOVA models to investigate main and interaction effects of Group and Appetitive State on blood oxygenation level-dependent (BOLD) activation for the contrast of exposure to high-calorie food images minus objects. We found main effects of Group with greater BOLD activation in the dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, caudate, and putamen for AN/AtypAN versus HC groups, and in the three-group model including AN, AtypAN, and HC (sub-)groups, where differences were primarily driven by greater activation in the AtypAN subgroup versus HC group. We found a main effect of Appetitive State with increased premeal BOLD activation in the hypothalamus, amygdala, nucleus accumbens, and caudate for models that included AN/AtypAN and HC groups, and in BOLD activation in the nucleus accumbens for the model that included AN, AtypAN, and HC (sub-)groups. There were no interaction effects of Group with Appetitive State for any of the models. Our findings demonstrate robust feeding-state independent group effects reflecting greater neural activation of specific regions typically associated with reward and cognitive control processing across AN and AtypAN relative to healthy individuals in this food cue paradigm. Differential activation of specific brain regions in response to the passive viewing of high-calorie food images may underlie restrictive eating behavior in this clinical population.

Differential comorbidity profiles in avoidant/restrictive food intake disorder and anorexia nervosa: Does age play a role?

OBJECTIVE: Research comparing psychiatric comorbidities between individuals with avoidant/restrictive food intake disorder (ARFID) and anorexia nervosa (AN) is limited. ARFID often develops in childhood, whereas AN typically develops in adolescence or young adulthood. Understanding how age may impact differential psychological comorbidity profiles is important to inform etiological conceptualization, differential diagnosis, and treatment planning. We aimed to compare the lifetime frequency of psychiatric comorbidities and suicidality between females with ARFID (n = 51) and AN (n = 40), investigating the role of age as a covariate. METHOD: We used structured interviews to assess the comparative frequency of psychiatric comorbidities/suicidality. RESULTS: When age was omitted from analyses, females with ARFID had a lower frequency of depressive disorders and suicidality compared to AN. Adjusting for age, only suicidality differed between groups. DISCUSSION: This is the first study to compare comorbidities in a similar number of individuals with ARFID and AN, and a structured clinical interview to confer ARFID and comorbidities, covarying for age, and the first to compare suicidality. Although suicidality is at least three times less common in ARFID than AN, observed differences in other psychiatric comorbidities may reflect ARFID's relatively younger age of presentation compared to AN. PUBLIC SIGNIFICANCE: Our results highlight that, with the exception of suicidality, which was three times less common in ARFID than AN irrespective of age, observed differences in psychiatric comorbidities in clinical practice may reflect ARFID's younger age at clinical presentation compared to AN.

Eighteen-month Course and Outcome of Adolescent Restrictive Eating Disorders: Persistence, Crossover, and Recovery.

OBJECTIVE: In adults, low-weight restrictive eating disorders, including anorexia nervosa (AN), are marked by chronicity and diagnostic crossover from restricting to binge-eating/purging. Less is known about the naturalistic course of these eating disorders in adolescents, particularly atypical AN (atyp-AN) and avoidant/restrictive food intake disorder (ARFID). To inform nosology of low-weight restrictive eating disorders in adolescents, we examined outcomes including persistence, crossover, and recovery in an 18-month observational study. METHOD: We assessed 82 women (ages 10-23 years) with low-weight eating disorders including AN (n = 40; 29 restricting, 11 binge-eating/purging), atyp-AN (n = 26; 19 restricting, seven binge-eating/purging), and ARFID (n = 16) at baseline, nine months (9 M; 75% retention), and 18 months (18 M; 73% retention) via semi-structured interviews. First-order Markov modeling was used to determine diagnostic persistence, crossover, and recovery occurring at 9 M or 18 M. RESULTS: Among all diagnoses, the likelihood of remaining stable within a given diagnosis was greater than that of transitioning, with the greatest probability among ARFID (0.84) and AN-R (0.62). Persistence of BP and atypical presentations at follow-up periods was less stable (AN-BP probability 0.40; atyp-AN-R probability 0.48; atyp-AN-BP probability, 0.50). Crossover from binge-eating/purging to restricting occurred 72% of the time; crossover from restricting to binge-eating/purging occurred 23% of the time. The likelihood of stable recovery (e.g., recovery at both 9 M and 18 M) was between 0.00 and 0.36. CONCLUSION: Across groups, intake diagnosis persisted in about two-thirds, and recovery was infrequent, underscoring the urgent need for innovative treatment approaches to these illnesses. Frequent crossover between AN and atyp-AN supports continuity between typical and atypical presentations, whereas no crossover to ARFID supports its distinction.

Meta-analysis of structural MRI studies in anorexia nervosa and the role of recovery: a systematic review protocol.

BACKGROUND: Anorexia nervosa (AN) is associated with structural brain abnormalities. Studies have reported less cerebral tissue and more cerebrospinal fluid (CSF) in individuals with AN relative to healthy controls, although findings are variable and inconsistent due to variations in sample size, age, and disease state (e.g., active AN, weight-recovered AN). Further, it remains unclear if structural brain abnormalities observed in AN are a consequence of specific brain pathologies or malnutrition, as very few longitudinal neuroimaging studies in AN have been completed. METHODS: To overcome this issue, this comprehensive meta-analysis will combine region-of-interest (ROI) and voxel-based morphometry (VBM) approaches to understand how regional and global structural brain abnormalities differ among individuals with AN and healthy controls (HCs). Additionally, we aim to understand how clinical characteristics and physiological changes during the course of illness, including acute illness vs. weight recovery, may moderate these structural abnormalities. We will create an online database of studies that have investigated structural brain abnormalities in AN. Data will be reviewed independently by two members of our team using MEDLINE databases, Web of Science, PsycINFO, EMBASE, and CINAHL. We will conduct ROI and VBM meta-analysis using seed-based d mapping in AN and HCs. We will include all studies that include structural neuroimaging of individuals with AN (both acute and weight-recovered) and HCs between January 1997 and 2020. DISCUSSION: This systematic review will assess the effects of AN compared to HC on brain structure. Futhermore, it will explore the role of acute AN and weight-recovered AN on brain structure. Findings will help researchers and clinicians to better understand the course of illness in AN and the nature of recovery, in terms of weight, malnutrition, and the state of the brain. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020180921.

Cognitive-behavioral therapy for adults with avoidant/restrictive food intake disorder.

There are currently no evidence-based treatments for adults with avoidant/restrictive food intake disorder (ARFID). The purpose of this study was to evaluate the acceptability, feasibility, and proof-of-concept of cognitive-behavioral therapy for ARFID (CBT-AR) for adults. Males and females (ages 18-55 years) were offered 20-30 outpatient sessions of CBT-AR delivered by one of five therapists. Of 18 eligible adults offered CBT-AR, 15 chose to participate and 14 completed treatment. All patients endorsed high ratings of treatment credibility and expected improvement after the first session, and 93% of completers provided high ratings of satisfaction at the conclusion of treatment. Therapists rated the majority (80%) of patients as "much improved" or "very much improved." Based on intent-to-treat analyses, ARFID severity on the Pica, ARFID, and Rumination Disorder Interview (PARDI) showed a large and significant decrease from pre- to post-treatment; and patients incorporated a mean of 18.0 novel foods. The underweight subgroup (n = 4) gained an average of 11.38 pounds, showing a large and significant increase in mean BMI from the underweight to the normal-weight range. At post-treatment, 47% of patients no longer met criteria for ARFID. To our knowledge, this is the first prospective treatment study of ARFID in adults. The findings of this study provide preliminary evidence of feasibility, acceptability, and proof-of-concept of CBT-AR for heterogeneous presentations of ARFID in adults. Randomized controlled trials are needed to confirm these findings. ClinicalTrials.gov Identifier: NCT02963220.