Despite the important role the choroid plexus (CP) plays in brain homeostasis, it is largely unexplored in psychiatry. The CP consists of a network of capillaries enclosed by a single layer of ...epithelial cells joined together by tight junctions to form the blood-CSF barrier. The blood-CSF barrier is an active barrier, secreting CSF and transferring metabolites from CSF to blood bidirectionally, and thus, playing a crucial role in communicating inflammatory reactions from the periphery to the central nervous system. Integrity of the CP is crucial for maintaining CSF ion homeostasis and blood-CSF barrier permeability. Enlargement of CP may reflect greater neuroinflammation, as abnormal function of the CP requires greater passage of peripheral inflammation markers to dampen neuroinflammation. The current study explores the role of the choroid plexus in restrictive eating disorders, severe psychiatric disorders in which disruptions in appetite and motivation are hypothesized to be maintained by neuroinflammation. Adolescents and young adults with anorexia nervosa (N= 59) and age-matched healthy controls (N=39) completed 3T MRI scans which were parcellated with Freesurfer, as well as hand-drawn masking of the lateral choroid plexus by a neuroanatomist, to capture CP enlargement in cases and controls. To confirm that enlargement was driven truly by the CP, we ran a series of linear models accounting to total lateral ventricles, total gray matter, and lateral ventricles + total gray matter. We also compared freesurfer CP volumes to hand-draw models and discuss challenges of CP imaging. In all models, the left CP was significantly lager in eating disorders, compared to controls (all p< 0.001). Correlations with targeted-proteomics of peripheral inflammation markers will be incorporated in future analyses. In addition, we will discuss and incorporate on-going collection of CSF in cases, to discuss central and peripheral inflammation relationships with CP enlargement.
ABSTRACT Objective Avoidant/restrictive food intake disorder (ARFID) is common among populations with nutrition‐related medical conditions. Less is known about the medical comorbidity/complication ...frequencies in youth with ARFID. We evaluated the medical comorbidities and metabolic/nutritional markers among female and male youth with full/subthreshold ARFID across the weight spectrum compared with healthy controls (HC). Method In youth with full/subthreshold ARFID ( n = 100; 49% female) and HC ( n = 58; 78% female), we assessed self‐reported medical comorbidities via clinician interview and explored abnormalities in metabolic (lipid panel and high‐sensitive C‐reactive protein hs‐CRP) and nutritional (25OH vitamin D, vitamin B12, and folate) markers. Results Youth with ARFID, compared with HC, were over 10 times as likely to have self‐reported gastrointestinal conditions (37% vs. 3%; OR = 21.2; 95% CI = 6.2–112.1) and over two times as likely to have self‐reported immune‐mediated conditions (42% vs. 24%; OR = 2.3; 95% CI = 1.1–4.9). ARFID, compared with HC, had a four to five times higher frequency of elevated triglycerides (28% vs. 12%; OR = 4.0; 95% CI = 1.7–10.5) and hs‐CRP (17% vs. 4%; OR = 5.0; 95% CI = 1.4–27.0) levels. Discussion Self‐reported gastrointestinal and certain immune comorbidities were common in ARFID, suggestive of possible bidirectional risk/maintenance factors. Elevated cardiovascular risk markers in ARFID may be a consequence of limited dietary variety marked by high carbohydrate and sugar intake.
Atypical anorexia nervosa (AAN) in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), is characterized by meeting all criteria for anorexia nervosa (AN) except for weight ...being within or above the “normal” range despite significant weight loss. The current definition is plagued by several problems, resulting in widely heterogeneous operationalizations in research and clinical practice. As such, the poorly defined diagnosis of AAN negatively impacts affected individuals and frustrates research attempts to better understand the syndrome. We consider conceptual flaws in the AAN description and contend that the undefined weight range and nature of weight loss renders these two factors functionally inapplicable in research and practice. They also represent a departure from the originally intended use of the AAN category, i.e., arresting a negative weight trajectory likely to result in AN, making the target population, and the application of the label, unclear. We propose revised criteria and a new name, restrictive eating disorder (RED), intended to reduce stigma and encompass a wide but better-defined range of presentations. The RED criteria focus on clinically significant restrictive behavior that disrupts normal living (i.e., impairment), and cognitive symptoms of overevaluation, disturbed experience, and lack of recognition of illness seriousness. We believe that RED may enable more appropriate clinical application, but also inspire coordinated research toward a more valid psychiatric nosology in the eating disorders field.
•DSM-5 Atypical AN is poorly defined and illogically dependent on AN criteria.•As a central problem, AN requires low weight, but Atypical AN prohibits it.•We propose “Restrictive Eating Disorder” (RED) to solve these problems.•RED avoids the invalidating “atypical” and is more well-defined.•Research should investigate the validity and clinical utility of RED criteria.
Heterogeneity, frequent diagnostic fluctuation across presentations, and global concerns
with the absence of effective treatments all encourage science that moves the field toward individualized
or ...precision medicine in eating disorders. We review recent advances in psychiatric genetics
focusing on genome-wide association studies (GWAS) in eating disorders. Given that the only eating
disorder to be the subject of GWAS to date is anorexia nervosa, we review anorexia GWAS and
enumerate the prospects and challenges of a genomics-driven approach towards personalized intervention
in eating disorders.
The role of craving in binge eating characteristic of bulimia nervosa (BN) is inconclusive. A network of regions associated with cue reactivity to food and substances has been identified, comprised ...of the amygdala, orbitofrontal cortex, insula, and striatum. The goal of this study was to examine individual differences in BOLD response in this appetitive network as moderators of the relationship between craving and binging in the natural environment in women with BN. Women with BN (N = 16) completed a baseline measure of craving and a fMRI scan, where they viewed neutral cues and food cues. After each run, craving for food was assessed. Participants then completed an ecological momentary assessment six times a day via smart phone and recorded binge eating and craving. Participants exhibited significantly increased BOLD response in the left amygdala in response to food cues compared to neutral cues. However, individual differences in BOLD response were not correlated with self-report craving throughout the scan. The relationship between craving and binging in everyday life was moderated by individual differences in activation in the caudate, insula, and amygdala. Women with greater activation in these regions demonstrated significant increases in craving prior to binge eating. Those who did not exhibit increases in activation did not exhibit increases in craving prior to binge eating in the natural environment. Craving may not underlie binge eating for all individuals with BN. However, these results indicate that neural response to food cues may affect individual differences in the daily experience of craving and binge eating.
Introduction
Objective binge eating and problematic alcohol use often co-occur and are common behaviors in emerging adults. Both behaviors are thought to be driven by affect regulation processes. ...Objective binge eating often occurs in the context of increasing or acute negative affect, and often occurs in solitude. Alcohol use in emerging adults can also be associated with negative affect regulation. However, in contrast to objective binge eating, a large body of research indicates that there are positively valenced pathways to alcohol use in this age group. Emerging adults often drink socially, to enhance enjoyment, and in the context of positive mood. We propose that one pathway to objective binge eating in this developmental period is through alcohol use itself, such that emerging adults who consume alcohol and who are more likely to act impulsively in the context of positive emotion (i.e., have high levels of positive urgency) may be more likely to binge eat following drinking.
Methods
We collected data using ecological momentary assessment in 106 undergraduates on positive and negative affect, motives for drinking and eating, and alcohol use and objective binge eating, in addition to baseline questionnaires of impulsivity.
Results
There were no significant changes in affect prior to drinking in this sample. Alcohol use at one time point significantly increased odds of objective binge eating at a later time point in the same day. Individual differences in positive urgency, the tendency to act rashly while experiencing positive affect, were also associated with increased odds of objective binge eating that occurred after alcohol use. Individual differences in negative urgency, the tendency to act rashly after experiencing negative affect, did not have a main effect on objective binge episodes, but did interact with alcohol use to increase the odds of objective binge eating following drinking. The vast majority of drinking episodes prior to objective binge eating were social drinking episodes, and participants most commonly endorsed "to have fun" as a reason for drinking.
Discussion
Results suggest that alcohol consumption may increase risk for objective binge eating in emerging adults.
Current rodent models of anorexia nervosa (AN) often have accelerated weight loss that often do not allow for investigation of physiological ramifications of prolonged low weight status ...characteristic of AN. The purpose of this project was to refine a rodent model of AN to extend the duration of low weight status and allow for investigation of recovery. Eight‐week‐old female Sprague Dawley rats underwent 50%–60% food restriction for 30 days. Rats were group‐housed except during feeding, where AN rats were individually housed and given up to 2 h to consume food. Control (CON) rats were allowed to consume food ad libitum. To simulate recovery, a separate cohort of animals underwent the same food restriction protocol for 30 days, then rats (AN‐R) were allowed to consume food ad libitum to facilitate weight recovery for an additional 30 days. AN‐R rats were compared to age matched controls (CON‐R). AN rats lost ~15% bodyweight and were ~30% lighter than CON. Compared to CON, AN rats had ~35% lower fat content, ~18% lower bone mineral density, ~22% smaller plantaris muscle mass and ~52% smaller ovaries. Upon reintroduction of food, AN‐R rats achieved comparable bodyweights to CON‐R rats after ~10 days. However, after 30 days of recovery, AN‐R rats still had ~14% lower bone mineral density and ~11% smaller plantaris mass and ~21% smaller ovaries. This refinement of rodent AN results in physiological side effects of AN without reaching excessive weight loss requiring euthanasia. Moreover, some physiological consequences of simulated AN are not resolved with weight restoration.
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.
Recent research suggests that individuals with eating disorders (EDs) report elevated anhedonia, or loss of pleasure. Although individuals with avoidant/restrictive food intake disorder (ARFID) often ...express that they do not look forward to eating, it is unclear whether they experience lower pleasure than those without EDs. Thus, identifying whether individuals with ARFID experience anhedonia may yield important insights that inform clinical conceptualization and treatment.
A sample of 71 participants ages 10-23 with full and subthreshold ARFID and 33 healthy controls (HCs) completed the Pica, ARFID, and Rumination Disorder Interview, a diagnostic interview to assess ARFID profile severity (lack of interest in food, sensory sensitivity, fear of aversive consequences) and the Temporal Experience of Pleasure Scale (TEPS), a self-report measure of consummatory and anticipatory pleasure. Statistical analyses were performed using the full TEPS and also the TEPS with food-related items removed.
The ARFID group reported significantly lower anticipatory and consummatory pleasure compared to HCs, but these differences were no longer significant after controlling for depression, nor after removing food items from the TEPS. Within the ARFID sample, greater ARFID severity was associated with lower anticipatory pleasure across analyses, and greater endorsement of the lack of interest in food profile was related to lower anticipatory pleasure. ARFID severity was also associated with lower consummatory pleasure using the full TEPS, but this relationship was no longer significant with food items removed.
These results provide initial evidence for lower pleasure before potentially pleasurable events in individuals with more severe ARFID, particularly those with the lack of interest phenotype. Our findings also suggest that depression is likely to contribute low pleasure in this population. Future research should seek to further characterize how dimensions of pleasure relate to the maintenance and treatment of ARFID symptoms.
The Pica, ARFID, and Rumination Disorder Interview (PARDI) is a structured interview that can be used to determine diagnosis, presenting characteristics, and severity across three disorders, ...including avoidant/restrictive food intake disorder (ARFID). The purpose of this study was to evaluate the psychometric properties of a questionnaire focused specifically on ARFID (PARDI-AR-Q), which has the potential to provide related information with less participant burden.
Adolescents and adults (n = 71, ages 14-40 years) with ARFID (n = 42) and healthy control participants (HC, n = 29) completed the PARDI-AR-Q and other measures. A subset of the ARFID group (n = 27) also completed the PARDI interview.
An exploratory factor analysis of proposed subscale items identified three factors corresponding to the ARFID phenotypes of avoidance based on the sensory characteristics of food, lack of interest in eating or food, and concern about aversive consequences of eating. Further analyses supported the internal consistency and convergent validity of the PARDI-AR-Q subscales, and subscale ratings on the questionnaire showed large and significant correlations (all p-values < 0.001; r's ranging from 0.48 to 0.77) with the corresponding subscales on the interview. The ARFID group scored significantly higher than HC on all subscales. Furthermore, 90% of the ARFID group scored positive on the PARDI-AR-Q diagnostic algorithm while 93% of the HC scored negative.
Though replication in larger and more diverse samples is needed, findings provide early support for the validity of the PARDI-AR-Q as a self-report measure for possible ARFID in clinical or research settings.
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