Endophenotypes and Biomarkers in Eating Disorders: Genetic Underpinnings, Personality Traits, Vulnerabilities – Part 2

This post continues the discussion of the chapter on eating disorders by Carolina Lopez, Marion Roberts, and Janet Treasure from The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes (2009). Part 1 focused on neurotransmitter biomarkers, and this second part will focus on the neuropsychological biomarkers.

NEUROPSYCHOLOGICAL BIOMARKERS

Attentional biases

Attentional bias is the tendency for individuals to attend to or be distracted by emotionally relevant stimuli over neutral stimuli. Attentional biases have been observed in several studies:

• Current AN and BN individuals showed bias towards food, body-related stimuli.
• Past AN but not past BN showed bias towards body shape concerns.
• Both current and “long-term recovered” AN showed “abnormally higher activation in the medial prefrontal and anterior cingulate cortices in response to food stimuli using fMRI [brain imaging]” (232)

These biases can be minimal but annoying: waiting in line at the pharmacy, staring into space and finding your focus automatically pulled to the magazine headlines promising diet tips or drop a dress size in a week! even if those topics would not normally interest you. Or they might have a more intrusive effect on your daily functioning, such as sitting in a seminar and not being able to concentrate on a word being said because you’re hyper-aware of someone eating a bag of Doritos two rows away. Or not being able to remember what you did at work last Tuesday, but being able to recall in perfect detail every single meal you ate and its calorie/macronutrient breakdown (emotional salience impacts our ability to encode events in our memory, too.)

A study also found evidence in AN of an attentional bias on social cognition tasks, compared to healthy controls:

• “[I]n the acute illness state, women with AN have an attentional bias to social stimuli using the E-Stroop (Emotional Stroop) paradigm, where those with higher levels of depressive symptoms also display a bias to angry over neutral faces.”
• “Additionally, women with acute AN appear to be impaired in visual and verbal recognition of emotions.” (234)

This bias might begin to explain some of the thoughts and behavior seen in some people with active EDs: sensitivity to criticism, experiencing negative evaluation or judgement from others where it may not actually exist, hyperawareness of how others might perceive them. However, the study did not examine women in recovery, so it remains to be seen whether this attentional bias and impaired emotion processing persists after the acute illness state. (See Emotion Recognition and Regulation in Anorexia Nervosa for more information)

Set-shifting

Set-shifting is one of the main aspects of executive functioning and refers to the ability to be flexible with one’s mindset in adapting to new task demands or changes in situations. (232)

• “People with ED were found to perform generally poorer than the healthy controls in measures of set-shifting” 
  A meta-analysis found evidence of set-shifting difficulty in people with current eating disorders “across diagnostic groups and illness state”, though the degree of impairment varied depending on the sample and measurements used in the individual studies.
• As one might expect, “Women recovered from AN also demonstrate impairment in set-shifting ability but with reduced effect sizes.”
• “First-degree relatives of women with ED have also been found to have poor set-shifting. Specifically, sisters of women with AN took longer to shift set [on various tasks] and showed significantly greater perceptual rigidity.” Another study examining sister pairs (one sister with AN or BN/one healthy sister) found that the healthy sisters  exhibited more difficulty set-shifting compared to controls.

The last is particularly intriguing. As previously mentioned, the problem with identifying potential biomarkers is that we can’t predict who will develop an ED and assess them before the disorder manifests, so it can be difficult to ascertain whether they are present pre-ED, or due to changes in the brain during the illness, some of which may persist into recovery/remission. Thus similar findings in first-degree relatives (parents, siblings, children) can provide some support for their being preexisting traits with a possible genetic link – though the authors caution that more studies with larger samples are needed.

I have always had difficulty set-shifting, exemplified by my childhood behavior: Whenever my mother would take me and my younger sister to the playground, I would go straight to the swings and stay there swinging until the last possible moment, while my sister raced from slide to sandbox to seesaw as if it was her duty to cover every single piece of equipment with her fingerprints before our time was up. As an adult, I hate being interrupted at a task – once I get settled, nothing irritates me more than, say, becoming hungry or having to use the restroom, thus necessitating that I switch focus to address those needs, then switch again. In terms of my eating disorder, I discovered that “transitional periods” like leaving class to get on the subway to come home were some of the times when I was most vulnerable to behaviors like bingeing/purging: I was already easily distracted and stressed. (I find it helps to have some kind of positive distraction to focus on during these times – doing the NYTimes crossword app on my iPod is my latest obsession.)

Central coherence

Central coherence is the ability to integrate many disparate pieces of information from the environment into an organized, meaningful whole. Weak central coherence has been found to be present in people with autism-spectrum disorders, as well as their first-degree relatives, and in obsessive-compulsive personality disorder. Individuals with this cognitive style tend to “get hung up on details” and have trouble “seeing the forest for the trees.”

In eating disorders, a meta-analysis of previous studies found that:

• Those with current AN and BN performed better on the detail-oriented tasks on standard assessments, but worse on tasks that required global processing (or construction of a single object from many pieces of information), compared to controls.
• Women recovered from AN showed similar results – though their performance on most tasks was better than was seen in current AN/BN.
• “…like their AN sisters, 30 healthy sisters of those with AN displayed a more detail focussed processing style… Likewise, 20 healthy sisters of BN patients displayed weak coherence on these tasks compared to healthy controls” (233)

Again, the authors caution that this evidence of differences in central coherence is not yet sufficient to fulfill criteria for a full endophenotype.

Anxiety

Many (though not all) people with EDs frequently feel quite anxious, and often one major purpose that behaviors such as bingeing, purging, restriction or exercising serve is to reduce these overwhelming feelings of anxiety.

• “High levels of anxiety have been found in both AN and BN… 
• …and seem to persist in recovery although with reduced effect sizes” – i.e., the anxiety may lessen somewhat with recovery.
• In first-degree relatives of people with AN, “higher rates of lifetime anxiety disorders such as generalised anxiety, obsessive-compulsive disorder, separation anxiety, social phobia, and panic disorder have also been found… which suggest a possible heritability for anxiety and fear propensity.” (234)

So what does this all mean?

As Lopez et al. write,

The search for potential biomarkers and endophenotypes in ED has revealed a number of features that are present in the acute state of the illness that also persist after recovery, suggesting specific vulnerabilities in the development and maintenance of these disorders. This evidence can be of use to inform treatment strategies that may reduce the duration of the illness and improve outcome.

These treatment strategies involve targeting certain vulnerabilities, such as using Cognitive Remediation Therapy techniques in order to improve set-shifting and central coherence, building ability to think flexibly and integrate details into “the bigger picture.”

Motivational interviewing is a technique in which patient and clinician engage in a negotiative process in order to increase readiness to change, “using ambivalence about change in the “how” of thinking to produce an enhanced meta-cognitive ability. Patients are encouraged to reflect on their own cognitive functioning and to undertake behavioural experiments to adjust their response when their natural tendency may not be advantageous to them.” Motivational interviewing can also be used to address the “emotional disturbances [that] have been highlighted as a core target in the treatment of ED due to the key role in the maintenance of these disorders.” 

However, these new components of treatment require further testing in randomized clinical trials and in larger samples in order to determine whether a) the components elicit behavioral or cognitive change, and b) whether those changes mediate outcome (i.e., make a difference in level of symptoms and thought distortions.) Janet Treasure has done considerable work in this area, focusing on Motivational Interviewing as a potential component of eating disorder treatment for adults and those with chronic EDs.

The authors conclude,

Eating Disorders have a complex etiology and a clear picture of what makes people vulnerable to develop these disorders is as yet unknown. It is hoped that a better understanding of the causal and maintaining factors may translate into more sophisticated and successful treatments and a reduced stigma for the sufferers.

… It is hoped that such a deeper understanding of ED based on biomarkers and the search for endophenotypes will improve awareness, early intervention and make for better prognosis in the long term.

A final thought: It is important to note that endophenotypes and biomarkers are population concepts – not all individuals will have all of the traits described, and it’s certainly possible that there may be some individuals for whom none of these seem to apply.

Does knowledge of these concepts (endophenotypes and biomarkers) impact your understanding of eating disorders?

What do you think about treatment interventions based on addressing specific vulnerabilities like these (or others)?

References

Carolina Lopez, Marion Roberts, & Janet Treasure (2009). Biomarkers and Endophenotypes in Eating Disorders The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes, 227-237 DOI: 10.1007/978-1-4020-9464-4_16