Angela S. Guarda

Treatment of anorexia nervosa: Insights and obstacles

Anorexia nervosa is a behavioral disorder characterized by ego-syntonic self-starvation, denial of illness and ambivalence towards treatment. Treatment refusal and drop-out rates are high and relapse is common. Treatment is best viewed as comprised of two phases, weight restoration and normalization of eating behavior followed by relapse prevention. Most patients verbalize a desire to change, however they seek treatment on their own terms, ideally with minimal or no weight gain. Successful treatment must therefore convince patients to overcome their drive to diet. Evidence-based data on treatment interventions for anorexia nervosa are scarce and methodological problems afflict the few published, controlled trials. Taken together, clinical expertise and data from correlational and controlled trials suggest that chronicity and adult status are associated with a worse prognosis. Outpatient family therapy is effective in weight-restoring the majority of adolescent patients whereas older patients, or those with severe medical or psychiatric comorbidity, often require intensive treatment on an inpatient eating disorders behavioral specialty unit. Correlational data suggest that weight-restored patients are less likely to relapse. Despite limitations of the current knowledge-base, several new areas of research hold promise in elucidating risk factors, in identifying the pathophysiology that sustains anorectic behavior, and in developing more targeted and effective treatments.

Differential brain activation in anorexia nervosa to Fat and Thin words during a Stroop task.

We measured brain activation in six anorexia nervosa patients and six healthy controls performing a novel emotional Stroop task using Fat, Thin, and Neutral words, and words made of XXXXs. Reaction times increased in the patient group in Thin and Fat conditions. In the Thin–XXXX contrast, patients showed greater activation than controls at the junction of left insula, frontal and temporal lobes and in left middle and medial frontal gyri. In the Fat–XXXX contrast, controls showed greater activation in left dorsolateral prefrontal cortex and right parietal areas. Mechanisms underlying attentional bias in anorexia nervosa likely differ under conditions of positive and negative valence. This paradigm is a promising tool to examine neural mediation of emotional response in anorexia nervosa.

Quantitation of N-acetyl-aspartyl-glutamate in microdissected rat brain nuclei and peripheral tissues: findings with a novel liquid phase radioimmunoassay

Antibodies were raised in rabbits against the neuropeptide N-acetyl-L-aspartyl-L-glutamate (NAAG) coupled to bovine serum albumin via a carbodiimide linkage. One of these rabbit antisera, which preferentially recognizes coupled NAAG-like immunoreactivity (LIR), has been previously used to immunocytochemically localize NAAG-LIR. We have now employed a second of these antisera, which preferentially recognizes free NAAG, to develop a competitive liquid phase radioimmunoassay (RIA). Using this assay, we were able to detect picomole amounts of NAAG in rat tissue extracts. The specificity of the assay revealed a 60-fold greater affinity of the antibody for NAAG over N-acetyl-aspartate (NAA) and greater than one million-fold specificity for NAAG over both aspartate and glutamate. High-pressure liquid chromatographic (HPLC) separation of tissue extracts yielded only two detectable peaks of NAAG-LIR in collected fractions and these co-chromatographed with NAAG and NAA. NAAG levels determined by this liquid phase RIA and by HPLC were essentially identical after correction for the presence of NAA crossreactivity. The antibody that preferentially recognizes coupled NAAG was used to immunocytochemically localize NAAG-LIR to the red nucleus, the facial nucleus, the dorsal raphe, and the locus coeruleus. To further confirm this localization of NAAG, these and other nuclei were microdissected and levels of NAAG were determined by liquid phase RIA. Nuclei which stained intensely were found to contain high levels of NAAG by RIA and between 60 and 100% of this NAAG-LIR co-chromatographed with NAAG. These results support our previous conclusion that NAAG is co-localized in noradrenergic, serotonergic and cholinergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Refeeding and weight restoration outcomes in anorexia nervosa: Challenging current guidelines

OBJECTIVE Cohort study from February 2003 through May 2011 to determine weight restoration and refeeding complication outcomes for patients with anorexia nervosa (AN) treated in an integrated inpatient-partial hospital eating disorder program designed to produce rapid weight gain and weight restoration in the majority. METHOD Consecutive admissions (females and males, adolescents and adults; N = 361 patients, 461 admissions) at least 1.8 kg below target weight with AN or subthreshold variants were included. Main outcome measures were rates of hypophosphatemia, transfer to medicine, or death; rates of weight gain and percent achieving weight restoration. RESULTS Hypophosphatemia was present in 7.9% of cases at admission and in 18.5% at some point during treatment. Hypophosphatemia was mild to moderate. Lower admission body mass index (BMI), but not rate of weight gain, predicted hypophosphatemia [OR = 0.65; p < .00001 (95% CI 0.57-0.76)]. Five patients (1.1%) were transferred to medicine or surgery, none because of refeeding. There were no deaths. Mean inpatient weight gain was 1.98 kg/week; mean partial hospital weight gain was 1.36 kg/week. By program discharge, 71.8% of adults reached a BMI of 19, 58.5% a BMI of 20. For adolescents, 80.4% came within 2 kg of their target weight; 76.1% came within 1 kg. DISCUSSION Refeeding patients with AN using a hospital-based, behavioral protocol may be accomplished safely and more rapidly than generally recognized, weight restoring most patients by discharge. Helpful elements may include the programs integrated, step-down structure; multidisciplinary team approach emphasizing group therapy to effect behavior change; and close medical monitoring for those with BMI < 15.

Cigarette smoking and its relationship to other substance use among eating disordered inpatients.

Objective: The present study examines prevalence rates of tobacco, caffeine, alcohol and other substance use and abuse among eating disordered inpatients and compares smokers (regular vs occasional vs non-smokers) and eating disorder (ED) subtypes [anorexia nervosa (AN) vs bulimia nervosa (BN); restrictors vs purgers] on substance use behaviors, family history, depressive symptoms and impulsivity. Method: Participants were 100 ED inpatients who completed assessment upon treatment entry. Results: A high incidence of regular cigarette smoking (29%) and occasional smoking (13%) was detected and associations were found with caffeine abuse, alcohol and marijuana use, family history and depression. BNs were more likely to smoke occasionally and use alcohol than ANs, while Purgers demonstrated higher caffeine and alcohol use than Restrictors. Discussion: Comprehensive assessment and intervention for smoking, caffeine and other substance use among ED patients is clearly indicated.

Dietary conditions and highly palatable food access alter rat cannabinoid receptor expression and binding density.

Endogenous cannabinoid signaling, mediated predominately by CB1 receptor activation, is involved in food intake control and body weight regulation. Despite advances in determining the role of the CB1 receptor in obesity, its involvement in the driven nature of eating pathologies has received little attention. The present study examined CB1 receptor alterations as a consequence of dietary-induced binge eating in female Sprague Dawley rats. Four control groups were used to control for calorie restriction and highly palatable food variables characterizing this behavioral model. All groups were kept on their respective feeding schedules for 6-weeks and were given a uniform 33% calorie restriction (~22 h food deprivation) prior to sacrifice. Our findings indicate that regional CB1 mRNA and density were influenced by dietary conditions, but were not specific to the dietary-induced binge eating paradigm used. An increase of approximately 50% (compared with naive controls) in CB1 receptor mRNA levels in the nucleus of the solitary tract as measured by in situ hybridization was found in animals receiving continuous access to a highly palatable food (i.e., vegetable shortening with 10% sucrose). This group also had a significant increase in body weight and adiposity. An approximate 20% reduction in CB1 mRNA was observed in the cingulate cortex (areas 1 and 2) in animals exposed to an intermittent schedule of feeding, compared with groups that had ad libitum feeding schedules (i.e., continuous access and naive controls). Receptor density as measured by [(3)H]CP55,940 autoradiography, was reduced by approximately 30% in the nucleus accumbens shell region in groups receiving repeated access to the highly palatable food. Taken together, these findings indicate that dietary conditions can differentially influence CB1 receptors in forebrain and hindbrain regions.

A systematic review of approaches to refeeding in patients with anorexia nervosa.

OBJECTIVE Given the importance of weight restoration for recovery in patients with anorexia nervosa (AN), we examined approaches to refeeding in adolescents and adults across treatment settings. METHODS Systematic review of PubMed, PsycINFO, Scopus, and Clinical Trials databases (1960-2015) using terms refeeding, weight restoration, hypophosphatemia, anorexia nervosa, anorexia, and anorexic. RESULTS Of 948 screened abstracts, 27 met these inclusion criteria: participants had AN; reproducible refeeding approach; weight gain, hypophosphatemia or cognitive/behavioral outcomes. Twenty-six studies (96%) were observational/prospective or retrospective and performed in hospital. Twelve studies published since 2010 examined approaches starting with higher calories than currently recommended (≥1400 kcal/d). The evidence supports 8 conclusions: 1) In mildly and moderately malnourished patients, lower calorie refeeding is too conservative; 2) Both meal-based approaches or combined nasogastric+meals can administer higher calories; 3) Higher calorie refeeding has not been associated with increased risk for the refeeding syndrome under close medical monitoring with electrolyte correction; 4) In severely malnourished inpatients, there is insufficient evidence to change the current standard of care; 5) Parenteral nutrition is not recommended; 6) Nutrient compositions within recommended ranges are appropriate; 7) More research is needed in non-hospital settings; 8) The long-term impact of different approaches is unknown; DISCUSSION Findings support higher calorie approaches to refeeding in mildly and moderately malnourished patients under close medical monitoring, however the safety, long-term outcomes, and feasibility outside of hospital have not been established. Further research is also needed on refeeding approaches in severely malnourished patients, methods of delivery, nutrient compositions and treatment settings.

Pediatric loss of control eating syndrome: Association with attention‐deficit/hyperactivity disorder and impulsivity

OBJECTIVE Despite data linking Attention-deficit/Hyperactivity Disorder (ADHD) and adult binge eating, there are limited data in children with loss of control (LOC) eating. We examined inhibitory control in children with LOC eating syndrome (LOC-ES) and its association with ADHD. METHOD 79 children (8-14 years) over the fifth weight percentile were recruited, irrespective of LOC eating or ADHD status. The Eating Disorder Examination for Children and the Standard Pediatric Eating Episode Interview assessed LOC-ES. ADHD diagnosis was determined by the Schedule for Affective Disorders and Schizophrenia for children and Conners-3 (Parent Report) DSM-IV Scales of Inattention and/or Hyperactivity (T score > 65). The Go/No-Go (GNG) Task and the Behavior Regulation Inventory of Executive Function (BRIEF) assessed impulse control. RESULTS Odds of LOC-ES were increased 12 times for children with ADHD (adjusted odds ratio [aOR] = 12.68, 95% confidence interval [CI] = 3.11, 51.64, p < 0.001), after adjusting for BMI z scores and relevant covariates. Children had 1.17 times higher odds of reporting LOC-ES with every 5% increase in GNG Commission Rate (aOR = 1.17, CI = 1.01, 1.36, p < 0.05) and 1.25 times higher odds of reporting LOC-ES with every 5 unit T-score increase in BRIEF Inhibit Scale (aOR = 1.25, CI = 1.04, 1.50, p < 0.05). DISCUSSION Children with ADHD had significantly greater odds of LOC-ES compared to children without ADHD. Children with LOC-ES had significantly greater impulse control deficits on performance-based neuropsychological assessments and on parent reports than children without LOC-ES. These findings suggest a need to investigate possible shared mechanisms such as impulse control deficits, among children with LOC-ES and ADHD.

The Eating Disorder Recovery Self-Efficacy Questionnaire (EDRSQ): change with treatment and prediction of outcome.

The purpose of this study was to examine the predictive validity of the Eating Disorder Recovery Self-Efficacy Questionnaire (EDRSQ), an empirically-derived self-report instrument that assesses confidence to eat without engaging in eating disordered behavior or experiencing undue emotional distress (Normative Eating Self-Efficacy) and confidence to maintain a realistic body image that is not dominated by pursuit of thinness (Body Image Self-Efficacy). Participants were 104 female inpatients with anorexia nervosa (AN), subthreshold AN, or underweight bulimia nervosa who were treated at a specialized eating disorder clinic and completed the EDRSQ and Eating Disorder Inventory-2 (EDI-2) Drive for Thinness (DT) and Body Dissatisfaction (BD) subscales upon admission. A subset of patients completed the EDRSQ (n=81) and EDI-2 subscales (n=70) following inpatient treatment. Self-efficacy increased significantly during treatment. EDRSQ scores at admission were inversely related to length of hospital stay and posttreatment DT and BD subscales and positively related to partial hospital weight gain rate. The EDRSQ significantly predicted length of hospital stay and posttreatment BD above and beyond clinical indicators and eating disorder psychopathology at inpatient admission. Findings support the validity of the EDRSQ and suggest it is a useful predictor of short-term hospital treatment outcome in underweight eating disorder patients.

Validation and predictive utility of the Sociocultural Attitudes Toward Appearance Questionnaire for Eating Disorders (SATAQ-ED): Internalization of sociocultural ideals predicts weight gain

A widely used measure of societal influences on body image and eating disturbances--the Sociocultural Attitudes Toward Appearance Questionnaire (SATAQ) was validated in women with eating disorders. The original SATAQ and measures of convergence and divergence were administered to 165 eating disordered inpatients. Factor analyses were conducted to determine the underlying structure of the SATAQ. Convergent validity, diagnostic category norms and the predictive utility of the revised SATAQ were examined. Factor analyses indicated three factors: Internalization, Awareness, and Success. Internalization significantly predicted treatment success after controlling for admission BMI and drive for thinness. The revised SATAQ-ED measures multiple aspects of societal influence, predicts short-term outcome, and can be a useful tool for evaluating potential outcome and treatment efficacy.