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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

Avoidant/restrictive food intake disorder (ARFID) occurs across the weight spectrum, however research addressing the coexistesnce of ARFID with overweight/obesity (OV/OB) is lacking. We aimed to establish co-occurrence of OV/OB and ARFID and to characterize divergent neurobiological features of ARFID by weight.Youth with full/subthreshold ARFID (12 with healthy weight [HW], 11 with OV/OB) underwent fasting brain fMRI scan while viewing food/non-food images (M age = 16.92 years, 65% female, 87% white). We compared groups on BOLD response to high-calorie foods (HCF) (vs. objects) in food cue processing regions of interest. Following fMRI scanning, we evaluated subjective hunger pre- vs. post-meal. We used a mediation model to explore the association between BMI, brain activation, and hunger.Participants with ARFID and OV/OB demonstrated significant hyperactivation in response to HCF (vs. objects) in the orbitofrontal cortex (OFC) and anterior insula compared with HW participants with ARFID. Mediation analysis yielded a significant indirect effect of group (HW vs. OV/OB) on hunger via OFC activation (effect = 18.39, SE = 11.27, 95% CI [-45.09, -3.00]), suggesting that OFC activation mediates differences in hunger between ARFID participants with HW and OV/OB.Compared to youth with ARFID and HW, those with OV/OB demonstrate hyperactivation of brain areas critical for the reward value of food cues. Postprandial changes in subjective hunger depend on BMI and are mediated by OFC activation to food cues. Whether these neurobiological differences contribute to selective hyperphagia in ARFID presenting with OV/OB and represent potential treatment targets is an important area for future investigation.

Background: Obesity is a major public health concern with an estimated two thirds of the population being overweight or obese. Women have a higher rate of obesity than men (40% vs. 35%), twice the rate of class 3 obesity (10% vs. 5% with BMI>40), and greater increases in obesity prevalence from 2005-2014. While emerging evidence highlights the role of food motivation circuitry in eating behavior and obesity risk, sex-specific neurobiological mechanisms have not been well defined in this population but are important to guide individual treatment strategies. Using a well-established food motivation functional magnetic resonance (fMRI) paradigm, we ran a preliminary set of analyses to investigate whether sex modulates the brain response to visual presentations of food items. We hypothesized that in a fasted state, women would demonstrate greater blood-oxygen-level-dependent (BOLD) activation in response to food images in reward-related brain regions compared to men. Methods: Twenty-nine adults with obesity (16 female, age (mean±SD): 31.2±4.9 years, and BMI=36.5±4.1 kg/m2) completed fMRI imaging in a 3T scanner while viewing images of food (high-calorie vs. low-calorie), non-food items, and fixation stimuli following a 10-hour overnight fast. Functional MRI data were analyzed using SPM12. Regions of interest included the nucleus accumbens (NAcc), amygdala, caudate, anterior insula (aINS), hypothalamus, putamen, orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), dorsal anterior cingulate cortex (dACC), and supplementary motor area (SMA). Statistical significance of p Results: Women with obesity exhibited greater activation than men in response to food (vs. non-food) stimuli in NAcc (t=2.44, p[uncorrected]=0.011), caudate (t=2.9, p[uncorrected]=0.004), DLPFC (t=3.32, p[uncorrected]=0.001), and dACC (t=3.17, p[uncorrected]=0.002) in a fasted state. There were no regions in which men exhibited greater activation than women. Conclusion: Our preliminary results show that during a fasting state, women with obesity (vs. men) show greater activation in brain regions processing reward (NAcc) and control over behavior (DLPFC, dACC) in response to food (vs. non-food) stimuli. Future studies with larger sample sizes are needed to investigate the link between the highlighted sex differences in neural responses to food in the context of obesity and eating behavior and weight to further inform whether men and women would benefit from different approaches in the treatment of obesity.

Background: Avoidant/Restrictive Food Intake Disorder (ARFID) is a recent diagnosis incorporated into the DSM-5 to provide diagnostic specificity to individuals who may have avoidant/restrictive eating behavior unrelated to body image/weight concerns and display three core profiles: insufficient intake/low interest in feeding, fear of aversive consequences related to food intake (e.g., choking) and avoidance based on sensory characteristics of food. Various studies have shown a higher preponderance of male patients in ARFID compared to other eating disorder groups. To elucidate potential sex differences in the neurobiology of ARFID, we examined food motivation pathways by assessing levels of key appetite regulating hormones, anorexigenic peptide YY (PYY) and orexigenic ghrelin, and fMRI activation of relevant brain circuitry in females compared to males with ARFID. Based on prior fMRI studies in healthy controls, we hypothesized that in a fasted state, females (vs. males) would demonstrate greater blood-oxygen-level-dependent (BOLD) activation in response to high-calorie food (vs. non-food) images in the orbitofrontal cortex (OFC) and the right lateral prefrontal cortex (LPFC), while males (vs. females) would demonstrate greater activation in the right hippocampus. Methods: Seventy-five adolescents and young adults with ARFID and sub-threshold ARFID (43 female) were studied after a 10-hour overnight fast. PYY and ghrelin levels were assessed in a subset of 62 individuals (31 female). All participants completed fMRI imaging in a 3T scanner while viewing images of foods, non-food items, and fixation stimuli. Functional MRI data were analyzed using SPM12. A priori regions of interest included the right lateral prefrontal cortex (LPFC), right hippocampus and orbitofrontal cortex (OFC). Secondary exploratory whole-brain analysis was also performed. Statistical significance is reported at the p Results: Females and males did not differ in age ((mean±SD): 16.1±3.7 years) or BMI (19.9±5.4 kg/m2). There were no statistically significant differences between females and males in PYY (p=0.10) or ghrelin (p=0.47) levels. Furthermore, analysis of fMRI data yielded no significant differences between females and males with ARFID in a priori regions of interest (OFC: p(FWE-corr)>0.50; R LPFC: no suprathreshold clusters, or R hippocampus: p(FWE-corr)=0.25 and 0.33) or in the secondary whole-brain analysis (cluster p(FWE-corr)=0.304). Conclusion: This is the first study to investigate sex differences in the neurobiology of ARFID, an important line of research to advance treatment approaches. We found no sex-specific neurobiological differences in adolescents and young adults with ARFID. Future studies with larger sample sizes are needed to further investigate potential sex differences across the different ARFID profiles.

Objective: Avoidant/restrictive food intake disorder (ARFID) occurs across the weight spectrum, however research addressing the coexistence of ARFID with overweight/obesity (OV/OB) is lacking. We aimed to establish co-occurrence of OV/OB and ARFID and to characterize divergent neurobiological features of ARFID by weight. Method: Youth with full/subthreshold ARFID (11 with healthy weight [HW], 12 with OV/OB) underwent fasting brain fMRI scan while viewing food/non-food images (M age = 16.92 years, 65% female, 87% white). We compared groups on BOLD response to high-calorie foods (HCF) (vs. objects) in food cue processing regions of interest. Following fMRI scanning, we evaluated subjective hunger pre- vs. post-meal. We used a mediation model to explore the association between BMI, brain activation and hunger. Results: Participants with ARFID and OV/OB demonstrated significant hyperactivation in response to HCF (vs. objects) in the orbitofrontal cortex (OFC) and anterior insula compared with HW subjects with ARFID. Mediation analysis yielded a significant indirect effect of group (HW vs. OV/OB) on hunger via OFC activation (effect=18.39, SE=11.27, 95% CI [-45.09, -3.00]), suggesting that OFC activation mediates differences in hunger between ARFID participants with HW and OV/OB. Conclusions: Compared to youth with ARFID and HW, those with OV/OB demonstrate hyperactivation of brain areas critical for reward value of food cues. Postprandial changes in subjective hunger depend on BMI and are mediated by OFC activation to food cues. Whether these neurobiological differences contribute to selective hyperphagia in ARFID presenting with OV/OB and represent potential treatment targets is an important area for future investigation.