Evidence for the role of EPHX2 gene variants in anorexia nervosa.

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition.

A randomized controlled comparison of integrative cognitive-affective therapy (ICAT) and enhanced cognitive-behavioral therapy (CBT-E) for bulimia nervosa.

BACKGROUND: The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa (BN), integrative cognitive-affective therapy (ICAT), with an established treatment, 'enhanced' cognitive-behavioral therapy (CBT-E). METHOD: Eighty adults with symptoms of BN were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination (EDE), were assessed at baseline, at the end of treatment (EOT) and at the 4-month follow-up. Treatment outcome, measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety and self-esteem, was determined using generalized estimating equations (GEEs), logistic regression and a general linear model (intent-to-treat). RESULTS: Both treatments were associated with significant improvement in bulimic symptoms and in all measures of outcome, and no statistically significant differences were observed between the two conditions at EOT or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at EOT, 32.5% at follow-up) and CBT-E (22.5% at both EOT and follow-up) were not significantly different. CONCLUSIONS: ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for BN suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study.

Aspirin and salicylate in respiratory disease.

This article describes the natural history, pathogenesis and diagnosis of Aspirin Exacerbated Respiratory Disease. The evidence base for the role of oral aspirin and nasal L-Lysine-aspirin desensitisation is reviewed. Evidence for the role of dietary salicylic acid and its avoidance is also reviewed.

Cognitive-behavioural group therapy versus guided self-help for compulsive buying disorder: a preliminary study.

Compulsive buying (CB) is defined as extreme preoccupation with buying/shopping and frequent buying that causes substantial negative psychological, social, occupational and financial consequences. There exists preliminary evidence that group cognitive-behavioural therapy (CBT) is effective in the treatment of CB. The present pilot study made a first attempt to compare group CBT for CB with telephone-guided self-help (GSH). Fifty-six patients were allocated randomly to one of the three conditions: (1) group CBT (n = 22); (2) GSH (n = 20); and (3) a waiting list condition (n = 14). The results indicate that face-to-face group CBT is superior not only to the waiting list condition but also to GSH. Patients who received GSH tended to have more success in overcoming CB compared with the waiting list controls. Given the sample size, the results must be considered as preliminary and further research is needed to address the topic whether GSH also could be a helpful intervention in reducing CB.

Assessing the impacts of recreation on the spatial and temporal activity of mammals in an isolated alpine protected area.

The management objectives of many protected areas must meet the dual mandates of protecting biodiversity while providing recreational opportunities. It is difficult to balance these mandates because it takes considerable effort to monitor both the status of biodiversity and impacts of recreation. Using detections from 45 camera traps deployed between July 2019 and September 2021, we assessed the potential impacts of recreation on spatial and temporal activity for 8 medium- and large-bodied terrestrial mammals in an isolated alpine protected area: Cathedral Provincial Park, British Columbia, Canada. We hypothesised that some wildlife perceive a level of threat from people, such that they avoid 'risky times' or 'risky places' associated with human activity. Other species may benefit from associating with people, be it through access to anthropogenic resource subsidies or filtering of competitors/predators that are more human-averse (i.e., human shield hypothesis). Specifically, we predicted that large carnivores would show the greatest segregation from people while mesocarnivores and ungulates would associate spatially with people. We found spatial co-occurrence between ungulates and recreation, consistent with the human shield hypothesis, but did not see the predicted negative relationship between larger carnivores and humans, except for coyotes (Canis latrans). Temporally, all species other than cougars (Puma concolor) had diel activity patterns significantly different from that of recreationists, suggesting potential displacement in the temporal niche. Wolves (Canis lupus) and mountain goats (Oreamnos americanus) showed shifts in temporal activity away from people on recreation trails relative to off-trail areas, providing further evidence of potential displacement. Our results highlight the importance of monitoring spatial and temporal interactions between recreation activities and wildlife communities, in order to ensure the effectiveness of protected areas in an era of increasing human impacts.

Examining a psychosocial interactive model of binge eating and vomiting in women with bulimia nervosa and subthreshold bulimia nervosa.

The current study tested a psychosocial interactive model of perfectionism, self-efficacy, and weight/shape concern within a sample of women with clinically significant bulimic symptoms, examining how different dimensions of perfectionism operated in the model. Individuals with bulimia nervosa (full diagnostic criteria or subthreshold) completed measures of bulimic symptoms, multidimensional perfectionism, self-efficacy, and weight/shape concern. Among those who were actively binge eating (n=180), weight/shape concern was associated with binge eating frequency in the context of high perfectionism (either maladaptive or adaptive) and low self-efficacy. Among those who were actively vomiting (n=169), weight/shape concern was associated with vomiting frequency only in the context of high adaptive perfectionism and low self-efficacy. These findings provide support for the value of this psychosocial interactive model among actively binge eating and purging samples and for the importance of considering different dimensions of perfectionism in research and treatment related to bulimia nervosa.

Obesity and addiction: can a complication of surgery help us understand the connection?

Obesity is a multifactorial, chronic disease that has proven difficult to treat. An increased understanding of aetiological mechanisms is critical to the development of more effective obesity prevention and treatment strategies. A growing body of empirical evidence has demonstrated parallels between obesity, overeating and substance abuse, including shared behavioural, psychological and neurophysiological factors implicated in the excessive intake of both food and substances of abuse. Several different lines of research have recently emerged that hold the potential to shed light on the connection between obesity, food reward and addiction, with studies examining changes in alcohol use/misuse after weight loss surgery providing a particularly interesting perspective on these interrelationships. However, these lines of investigation have proceeded in relative isolation, and relevant research findings have yet to be integrated in a synthesized, comprehensive manner. To provide an opportunity to achieve such a synthesis, a scientific symposium was convened at the Radcliffe Institute in Cambridge, Massachusetts. Invited participants were researchers working in diverse domains related to the intersection between obesity and addiction. Extensive discussion was generated suggesting novel research directions. In this article, we summarize and synthesize the symposium participants' ongoing research in this area, incorporating additional relevant research holding potential clues regarding the connections between obesity, weight loss surgery and addiction.

Development and validation of a low-cost microsurgery Ear Trainer for low-resource settings.

OBJECTIVE: Chronic suppurative otitis media is a neglected condition affecting up to 330 million people worldwide, with the burden of the disease in impoverished countries. The need for non-governmental organisations to hardwire training into their programmes has been highlighted. An ear surgery simulator appropriate for training in resource-poor settings was developed, and its effectiveness in facilitating the acquisition of headlight and microsurgical skills necessary to safely perform procedures via the ear canal was investigated. METHODS: Face validity was assessed via questionnaires. Six tasks were developed: a headlight foreign body removal task, and microscope tasks of foreign body removal, ventilation tube insertion, tympanomeatal flap raising, myringoplasty and middle-ear manipulation. Participants with varying ENT experience were video-recorded performing each task and scored by a blinded expert observer to assess construct validity. RESULTS: Face validity results confirmed that our Ear Trainer was a realistic representation of the ear. Construct validity results showed a statistically significant trend, with experts performing the best and those with limited experience performing better than novices. CONCLUSION: This study validates our Ear Trainer as a useful training tool for assessing headlight and microsurgical skills required to perform otological procedures.

Long-term outcome of bulimia nervosa.

BACKGROUND: Since bulimia nervosa's introduction to the psychiatric nomenclature in 1979, data concerning long-term outcome have been largely unavailable. METHODS: Women with the diagnosis of bulimia nervosa between 1981 and 1987 who participated in 1 of 2 studies were located and invited to participate in follow-up assessments. RESULTS: More than 80% of the women from these studies participated in follow-up assessments and the results represent findings for 173 women. More than 10 years following presentation (mean+/-SD length of follow-up, 11.5+/-1.9 years), 11% of this sample met full criteria for bulimia nervosa, and 0.6% met full criteria for anorexia nervosa. An additional 18.5% met criteria for eating disorder not otherwise specified, and 69.90% of this sample were either in full or in partial remission. For predictive factors, only the duration of the disorder at presentation and history of substance use problems demonstrated prognostic significance. Baseline treatment condition was not associated with remission of disordered eating symptoms by the follow-up assessment. CONCLUSIONS: The findings suggest that the number of women who continue to meet full criteria for bulimia nervosa declines as the duration of follow-up increases; approximately 30%, however, continued to engage in recurrent binge eating or purging behaviors (incidence rate, 0.026 cases per person-years). A history of substance use problems and a longer duration of the disorder at presentation predicted worse outcome.

A comparison study of antidepressants and structured intensive group psychotherapy in the treatment of bulimia nervosa.

Previous research on the treatment of outpatients with bulimia nervosa has focused on two treatment strategies: (1) drug therapy, primarily using tricyclic antidepressants, and (2) psychotherapy, often employing behavioral and cognitive behavioral techniques. We report here the short-term treatment outcome of a 12-week comparison trial of bulimic outpatients who were randomly assigned to one of four treatment cells: (1) imipramine hydrochloride treatment, (2) placebo treatment, (3) imipramine treatment combined with intensive group psychotherapy, and (4) placebo treatment combined with intensive group psychotherapy. All three active treatment cells resulted in significant reductions in target-eating behaviors and in a significant improvement in mood relative to placebo treatment. However, the results also suggested that the amount of improvement obtained with the intensive group psychotherapy component was superior to that obtained with antidepressant treatment alone. The addition of antidepressant treatment to the intensive group psychotherapy component did not significantly improve outcome over intensive group psychotherapy combined with placebo treatment in terms of eating behavior, but did result in more improvement in the symptoms of depression and anxiety.

Cognitive dysfunction predicts poorer emotion recognition in bariatric surgery candidates.

OBJECTIVE: Deficits in traditional cognitive domains (e.g. executive function and memory) are common in persons with severe obesity, but it is unclear if this pattern of dysfunction extends to social cognition. The present study examined whether cognitive impairment was associated with poorer emotion recognition in bariatric surgery candidates. METHODS: One hundred sixteen bariatric surgery candidates (mean age = 43.62 ± 11.03; 81% female) completed the computerized Integneuro test battery as part of a larger study visit. In addition to assessing traditional cognitive domains, the Integneuro also includes an emotion recognition measure. This task presents 48 faces (eight different individuals depicting neutral, happiness, fear, sadness, anger and disgust), and participants must choose the correct verbal label from six expression options. Number of correct responses and average reaction time for correct responses served as primary dependent variables. RESULTS: Stepwise multiple regression analyses revealed that older age, more maze errors, and history of hypertension predicted less accuracy in emotion recognition (adjusted R2 = .22, F[3, 111] = 11.86, p < .001) and that slower switching of attention-digits, worse long-delay recall, and older age predicted speed of responses (adjusted R2 = .26, F[3, 111] = 13.00, p < .001). DISCUSSION: Results show that cognitive dysfunction is associated with poorer performance on a computerized test of emotion recognition, consistent with those in persons with a range of psychiatric and neurological disorders. Additional work is needed to clarify the mechanisms and functional impact of these impairments, especially in relation to weight loss following bariatric surgery.

Metabolic and endocrine investigations in women of normal weight with the bulimia syndrome.

Bulimia is a disorder characterized by episodes of binge-eating. Patients with this problem consume large amounts of food when binge-eating and, subsequently, to avoid weight gain, usually self-induce vomiting or induce diarrhea with laxatives. Metabolic and endocrine investigations in six bulimic subjects of normal weight are reported. Normal fasting plasma glucose concentrations and glucose tolerance were present in all. Five subjects had normal serum T4 and T3 concentrations. Only one subject had depressed serum T4 and T3 concentrations and this subject had a normal serum TSH level. Menstrual irregularities were present in all patients and, in three, were associated with modestly elevated serum prolactin levels. In four subjects there was an abnormal increase in serum growth hormone following TRH administration and in three, growth hormone failed to suppress normally after oral glucose. Two subjects were found to have a hypokalimic metabolic alkalosis, presumably due to vomiting. Urinary 17-OH steroid excretion and urinary concentrating ability were normal or nearly so in all subjects.

High-dose naltrexone therapy and dietary counseling for obesity.

There is considerable evidence that antagonism of the endogenous opioids will suppress food intake in a variety of animal species. The authors report a double-blind, placebo-controlled trial of the long-acting, orally active narcotic antagonist naltrexone in the promotion of weight loss in obese male subjects who were also undergoing dietary counseling for weight reduction. Subjects received medication (naltrexone, 300 mg/day or placebo) for 8 weeks following an initial 2-week single-blind placebo phase. The results failed to demonstrate an advantage for the active drug. However, the naltrexone was associated with hepatotoxicity when used at this dosage in this population.

Naloxone but not CCK-8 may attenuate binge-eating behavior in patients with the bulimia syndrome.

We undertook a study to see if putative anorectic agents could attenuate binge eating episodes in bulimic patients. Bolus intravenous administration, followed by continuous intravenous infusion of naloxone, resulted in a significant decrease in the amount of food consumed during binge-eating episodes, whereas bolus followed by continuous intravenous infusion of CCK-8 failed to significantly suppress binge eating behavior. These results suggest that the endogenous opioid system is involved in the maintenance of binge eating behavior in patients with bulimia.

Effect of naltrexone on mood and cognitive functioning among overweight men.

The effects of naltrexone on both mood and cognition were examined in overweight male subjects. Subjects were randomly prescribed, in a double-blind fashion, either placebo or naltrexone for 8 weeks. The results of the study showed that a chronic administration of a high dose of naltrexone (300 mg/day) does not significantly change mood or cognitive functioning among overweight adult men.

Bone mineral density and anorexia nervosa in women.

OBJECTIVE: A review of reports of reduced bone mineral density in women with anorexia nervosa was undertaken in order to profile specific risk factors, which could then be used as the basis for suggestions for future research and treatment. METHOD: Thirteen research studies and four case studies of reduced bone mineral density and fractures in women with anorexia nervosa were reviewed. The relationships between bone mineral density and amenorrhea, estrogen, calcium intake, physical activity, parathyroid hormone, alkaline phosphatase, 1,25-dihydroxyvitamin D, cortisol, and growth hormone were examined in the reports of these studies and other reports of altered physiology during anorexia nervosa. RESULTS: The average spinal, radial, and femoral bone mineral density in anorexic women was significantly lower than it was in normal control subjects. Concurrent with the low intake of nutrients by individuals with anorexia nervosa, low body weight, early onset and long duration of amenorrhea, low calcium intake, reduced physical activity, and hypercortisolism appeared more likely to contribute to decreased bone mineral density than did other abnormal aspects of the disorder. CONCLUSIONS: Future research needs to address how such factors as amenorrhea and hypercortisolism affect bone mineral density in anorexia nervosa. Since no controlled trials of estrogen replacement or calcium supplementation in anorexia nervosa have been reported, the proper treatment for decreased bone mineral density is not known. However, the most obviously important intervention is to encourage medical stabilization and weight gain.

Case report of bulimia associated with increased intracranial pressure.

A patient whose symptoms suggested bulimia was found to have increased intracranial pressure. Following insertion of a ventriculo-peritoneal shunt, the bulimic symptoms resolved. The relationship between increased CSF pressure and bulimic symptoms is discussed.

Antipsychotic drug therapy and sexual dysfunction in men.

The authors review the literature on male sexual dysfunction associated with antipsychotic drug treatment. Erectile and ejaculatory disturbances have been most frequently reported. Changes in libido have also been reported, but the effects of these drugs on sexual drive have apparently not been systematically studied. Fortunately, most types of sexual dysfunction associated with antipsychotic drugs appear to be medically benign and reversible with drug discontinuation. An exception is priapism, which necessitates prompt urological consultation and may require surgical intervention.

Outcome in bulimia nervosa.

OBJECTIVE: The authors sought to synthesize existing data on outcome for individuals diagnosed with bulimia nervosa in order to better understand long-term outcome and prognostic factors. METHOD: They reviewed 88 studies that conducted follow-up assessments with bulimic subjects at least 6 months after presentation. Findings are summarized for the areas of mortality, recovery, relapse, crossover, and prognostic variables. RESULTS: The crude mortality rate due to all causes of death for subjects with bulimia nervosa in these studies was 0.3% (seven deaths among 2,194 subjects); however, ascertainment rates and follow-up periods were small and likely to produce underestimation. Five to 10 years following presentation, approximately 50% of women initially diagnosed with bulimia nervosa had fully recovered from their disorder, while nearly 20% continued to meet full criteria for bulimia nervosa. Approximately 30% of women experienced relapse into bulimic symptoms, and risk of relapse appeared to decline 4 years after presentation. Few prognostic factors have been consistently identified, but personality traits, such as impulsivity, may contribute to poorer outcome. In addition, participation in a treatment outcome study was associated with improved outcome for follow-up periods less than 5 years. CONCLUSIONS: Treatment interventions may speed eventual recovery but do not appear to alter outcome more than 5 years following presentation. Long-term outcome for women diagnosed with bulimia nervosa remains unclear. However, this disorder may be chronic for at least a subset of women.

Characteristics of 60 adult chronic hair pullers.

OBJECTIVE: This study was constructed to detail the demographic and phenomenological features of chronic hair pullers as well as to assess psychiatric comorbidity in a sizable study group. METHOD: Subjects were drawn from an outpatient population of chronic hair pullers who had been referred to a trichotillomania clinic or had responded to a newspaper advertisement announcing a treatment study of adults who pull out their hair. Sixty adult chronic hair pullers completed a semistructured interview that focused on their hair-pulling behavior and demographic characteristics and that incorporated screening questions for DSM-III-R axis I disorders. The data were tabulated to derive a comprehensive picture of this group. RESULTS: The typical subject was a 34-year-old woman who had pulled hair from two or more sites for 21 years. All subjects described either tension before or relief/gratification after pulling hair from the primary site, but 17% (N = 10) failed to describe both of these characteristics and thus failed to fulfill the DMS-III-R criteria for trichotillomania. Forty-nine subjects (82%) qualified for past or current axis I diagnoses other than trichotillomania. Several characteristics of the study group suggested phenomenological differences between obsessive-compulsive disorder and trichotillomania. CONCLUSIONS: Adult trichotillomania is a chronic disorder, frequently involving multiple hair sites, and is associated with high rates of psychiatric comorbidity. Its relation to obsessive-compulsive disorder requires further clarification. The tension-reduction requirement in DSM-III-R for the diagnosis of trichotillomania may be overly restrictive.