Clinicians treating patients with eating disorders find the challenge great with many treatment-resistant cases.

To some extent, this is true of any clinical disorder. Outpatient treatment rolls and inpatient samples are over-represented by those failing to respond to initial interventions.

A medical example is helpful here. Endocrinologists specializing in diabetes see more complicated cases where glucose control is difficult and diabetic complications are common.

Diabetics with easy glucose control and no complications do not need to see an endocrinologists. To an endocrinologist, clinical practice seems to point to the disease as a treatment-resistant and clinically challenging disorder.

Nevertheless, treatment resistance in eating disorders is a significant issue that has been recently summarized in a nice review by Dr. Katherine Halmi.

Here are my notes from review of the Halmi manuscript using her key headings:

Core eating disorder psychopathology

• Adolescent eating disorder subjects lack insight into the seriousness of illness
• Many do not acknowledge need for treatment
• Body weight, exercise and dieting provide a distraction from other life problems
• Malnutrition in eating disorders contributes to cognitive impairment, treatment engagement problems
• Bulimia treatment resistance has been linked to greater depression, lower BMI and social adjustment problems

Psychiatric and psychological comorbidity

• U.S. National Survey found high rates of psychiatric comorbidity in eating disorders (56% in anorexia nervosa, 95% in bulimia nervosa and 79% in binge eating disorder)
• Anxiety disorders rates are elevated in eating disorders with obsessive compulsive disorder and social anxiety disorder two common conditions
• Anxiety disorders can contribute to resistance of treatment of eating disorder symptoms
• Cluster B personality disorders are elevated in bulimia nervosa and appear related to higher rates of substance dependence in this disorder
• Perfectionism is common in anorexia nervosa. Early onset and high perfectionism traits contribute to higher treatment resistance

Biological features

• Serotonin receptor and transporter function appear to influence course of illness in eating disoders
• GABA receptor genotype appears to be related to level of trait anxiety in both bulimia nervosa and anorexia nervosa
• GABA receptor abnormalities are also possibly related to treatment resistance

Treating refractory patients

• Quetiapine, olanzapine, haloperidol and duloxetine are drugs with some promise in treatment resistant anorexia nervosa
• Novel psychotherapies including CBT and the Maudsley Model  target key features of resistance in anorexia nervosa
• Treatment resistant bulimia nervosa may respond to sequential treatment strategies that include partial hospitalization, selective serotonin reuptake inhibitor (SSRI) drugs and cue exposure
• Binge eating disorder may respond to high dose SSRI therapy or topiramate in a graduated dosing schedule

This review points to the key elements for treatment of the difficult eating disorder patient.

This population needs access to specialized hospitalization units, psychopharmacology expertise and specialized psychotherapy services.

Dr. Halmi notes advances in the treatment of this population may require advances in understanding the neurobiology and neurocircuitry for the disorder.

Readers with more interest in this summary can find the free full-text manuscript by clicking on the DOI link in the citation below.

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Halmi, K. (2013). Perplexities of treatment resistence in eating disorders BMC Psychiatry, 13 (1) DOI: 10.1186/1471-244X-13-292

The recent revision of the American Psychiatric Associations Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5) altered several eating disorder diagnostic criteria.

Some have expressed concern that these revisions are overly broad and may result in over diagnosis in some clinical populations. One clinical population where this is a concern is obesity.

A research study has been recently published addressing this issue.

Jennifer Thomas and colleagues at Harvard University and Massachusetts General Hospital recruited a series of subjects from an obesity program for eating disorder diagnostic assessment.

All subjects completed an assessment for presence of an eating disorder 
diagnosis using both DSM-IV and DSM-5 criteria.

For DSM-IV eating disorder diagnoses, the research team used a validated module from a validated measure known as SCID-IV. For DSM-5 eating disorder diagnosis an early structured interview developed by the DSM-5 Eating Disorders Task Group was used.

The key findings from the study included:

• Prevalence rates for eating disorders using DSM-5 criteria did not increase compared to DSM-IV criteria
• Bulimia nervosa prevalence rates were 2% in both interviews
• Binge eating disorder prevalence rates were 9% in both interviews
• An additional 20% of the obese sample met residual eating disorder criteria in both interviews

Obese individuals with a formal eating disorder diagnosis endorsed higher rates of psychological impairment, depression and anxiety validating the impact of eating disorder comorbidity.

Assessment for the presence of eating disorders is an important part of treatment planning. Eating disorders are more prevalent in obese populations are relatively easy to diagnose.

Some studies have found poor outcomes in obese populations with severe binge eating behaviors.

Treatment of a comorbid eating disorder in obese populations may improve weight and psychological outcomes.

Readers with more interest in this research can access the free full-text manuscript by clicking on the PMID link below.

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Thomas JJ, Koh KA, Eddy KT, Hartmann AS, Murray HB, Gorman MJ, Sogg S, & Becker AE (2014). Do DSM-5 eating disorder criteria overpathologize normative eating patterns among individuals with obesity? Journal of obesity, 2014 PMID: 25057413

Binge eating is defined as the recurrent rapid consumption of high calorie meals accompanied by a feeling that eating is out of control.

Bulimia nervosa is an eating disorder characterized by binge eating paired with a purging behavior such as self-induced vomiting.

Binge eating without purging is receiving increased clinical and research attention.

Binge eating is a relative common component in elevated body mass index and obesity. Successful behavior and drug treatment for obesity often includes a significant reduction in the frequency of binge eating.

Binge eating is frequently accompanied by symptoms of gastrointestinal disorders such as gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS). However, these GI symptoms and disorders are also increased in obesity. 

These relationships have made it difficult to determine the specific effects of binge eating on GI symptoms as it is possible these effects may occur through an obesity mechanism.

Christine Peat along with colleagues from the University of North Carolina and Sweden recently published a study teasing out relationships between binge eating, BMI and GI symptoms.

This study used data from the Swedish Twin Study of Adults: Genes and Environment (STAGE). For the current study, over 23,000 twin pairs were interviewed for presence of lifetime history of binge eating, weight history and presence of gastrointestinal symptoms.

The key findings from this study included the following:

• Gastrointestinal reflux symptoms were present in 15.7% of men and 28.9% of women
• Irritable bowel syndrome (broad definition) was present in 3.7% of men and 8.1% of women
• Binge eating was linked to to higher rates of GERD and IBS
• However, when BMI was controlled binge eating was independently related to IBS but not related to GERD

The authors propose three potential mechanisms for this link between binge eating and IBS.

1. Stress may be a common factor as it is known that stress can precipitate bingeing episodes and increase IBS symptoms
2. IBS may cause dietary restriction including periods of fasting. Fasting is known to increase later risk for binge eating as the body attempts to compensate via a strong hunger mechanism
3. Binge eating of large quantities of high fat foods may directly produce IBS symptoms as the GI system responds to a feeding load

The take home message for clinicians treating IBS is that it is important to assess for the presence of binge eating. Successful reduction in the frequency of binge eating may contribute to a successful reduction in IBS symptoms. 

Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link in the citation below.

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Peat CM, Huang L, Thornton LM, Von Holle AF, Trace SE, Lichtenstein P, Pedersen NL, Overby DW, & Bulik CM (2013). Binge eating, body mass index, and gastrointestinal symptoms. Journal of psychosomatic research, 75 (5), 456-61 PMID: 24182635

There is increasing evidence for inflammation contributing to risk for a variety of psychiatric disorders.

I previously summarized research supporting use of anti-inflammatory drugs in the treatment of depression.

A recent study from Finland supports an inflammation link to the eating disorder categories.

The key elements of the design of this study included:

• Subjects: 2342 subjects admitted for treatment in the Eating Disorders Unit at the central hospital in Finland. Four controls were identified for each case matched by age, gender and place of residence
• Identification of presence for autoimmune diseases: Cases and controls were examined for the presence of one of 30 autoimmune diagnoses in their Hospital Discharge Register
• Statistical analysis: Period and lifetime rates for autoimmune disorders were compared between eating disorder cases and control using logistic regression modeling with calculation of odds ratios and 95% confidence intervals.

Here are the important findings from the study:

• Eating disorders subjects had a 5.6% rate for presence of any autoimmune disease compared to only 2.8% of controls (Odds ratio 2.13, 95% confidence interval 1.71-2.65)
• Rates for autoimmune disorders were increased across all eating disorder diagnostic categories including anorexia nervosa, bulimia nervosa and binge eating disorder
• Within autoimmune disease subtypes, endocrinological and gastroenterological diseases were statistically increased in eating disorders
• Type I diabetes and Crohn's disease were individual autoimmune disorders found at higher rates in eating disorders

The authors note there are several methods that could explain the association between autoimmunity and eating disorder risk. Higher rates of autoantibodies against peptides that control appetite and stress response could contribute to eating disorder risk.

Additionally, the authors note disturbed eating may contribute to disturbance of the microbiome of the gut. Gut microbiome is a known regulator of autoimmunity and a contributor to allergies and type I diabetes risk.

The authors noted additional specific autoimmune disorders may be increased in eating disorders but due to small sample size their study may have not found a statistical association.

Systemic lupus erythematosis rates were increased in the eating disorder group but this was one of the individual disorders that failed to reach statistical significance.

The take home message for clinicians treating eating disorder patients is to be vigilant for the presence of autoimmune medical disorders in this population. Accurate and early detection of autoimmune disorders in those with eating disorders may contribute to improved medical outcomes.

Readers with more interest can access the free full text manuscript by clicking on the PMID link below.

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Raevuori A, Haukka J, Vaarala O, Suvisaari JM, Gissler M, Grainger M, Linna MS, & Suokas JT (2014). The increased risk for autoimmune diseases in patients with eating disorders. PloS one, 9 (8) PMID: 25147950

In November I will be looking at some research research in eating disorders.

On my first look at some of important research these five studies stood out for more review.

I will be posting more on several of these studies in the next few weeks.

You can click on the manuscript title to go to the abstract.  All studies have free full-text manuscripts that can be access through the abstract link.

The Neuropsychology of Starvation
One of the key problems in studying anorexia nervosa is the isolation of psychological effects from the effects of starvation on the brain. In this study, 60 healthy female subjects were studied after 18 hours of starvation and again when satiated. Short-term starvation was linked to changes in set-shifting and central coherence.

Resting State Connectivity in Anorexia Nervosa
In this study, 35 subjects with anorexia nervosa were studied using resting state functional magnetic resonance imaging. The study found increased connectivity between the angular gyrus and the fronto-parietal brain ciruit. Additionally, anterior insula connectivity was linked to deficits in interoceptive awareness.

Neuropsychology of Body Perception in Anorexia Nervosa
Patients with anorexia nervosa commonly display impaired perception of body shape and size. They often feel "fat" with body part size misperception. This manuscript reviews studies of nonvisual multisensory neuropsychological performance in anorexia nervosa. The review found support for deficits in tactile and proprioreceptive function in patients with anorexia nervosa.

Body Fat Distribution in Anorexia Nervosa
This literature review examined studies of body fat distribution before and during weight loss and with weight restoration. The authors found key differences between body fat distribution patterns in adolescents with anorexia nervosa compared to adult women with anorexia. The authors note body fat loss and re-accumulation may be an important metabolic and nutritional component of anorexia nervosa treatment.

Anorexia Nervosa Treatment Outcome After Urgent Hospitalization
This study examined the effect of several variables on outcome following urgent inpatient hospitalizations. Several psychological variables failed to contribute to poor outcome. However, lower BMI at admission was linked to several poor outcome measures.

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