Intranasal oxytocin attenuates attentional bias for eating and fat shape stimuli in patients with anorexia nervosa

doi:10.1016/j.psyneuen.2014.02.019

Psychoneuroendocrinology

Volume 44, June 2014, Pages 133-142

https://doi.org/10.1016/j.psyneuen.2014.02.019 Get rights and content

Summary

We examined the impact of oxytocin on attentional processes for eating, shape, and weight stimuli in patients with anorexia nervosa (AN). A double-blind, placebo-controlled within-subject crossover design was used. Intranasal oxytocin or placebo followed by a visual probe detection task with food, weight, and shape images was administered to 64 female subjects: 31 patients with AN and 33 control students. The AN group showed significant reductions in the attentional biases toward eating-related stimuli (p = 0.030, d = 0.516) and toward negative shape stimuli (p = 0.015, d = 0.498) under the influence of intranasal oxytocin. The effect of oxytocin was correlated with autistic spectrum traits in the AN group. Oxytocin had no effect on the amount of juice consumed in either group. The results of this study suggest that oxytocin attenuates the attentional vigilance to eating and fat shape stimuli in patients with AN. Further studies using oxytocin as a form of intervention for patients with AN are needed.

Section snippets

Participants

Sixty-four women (31 patients with AN and 33 healthy university students) between the age of 16 and 45 took part in this double-blind, placebo-controlled, cross-over study. The first participant entered the study on August 16, 2012, and the last participant was examined on November 30, 2013. The patients with AN were recruited from the Eating Disorders Clinic of Seoul Paik Hospital, Seoul, South Korea. As the study aimed to examine broadly whether oxytocin might be of benefit in the short term,

Demographic and group characteristics

The demographic and group characteristics of the participants are presented in Table 1. The AN and HC groups were similar in age and intelligence, but significantly different in body mass index and all four subscales of the EDE-Q. The AN group also scored higher in the BDI, the STAI, and the Social Skill and Communication subscales of AQ compared to the HC group. The mean EDE interview scores for the AN were 5.07 ± 6.04 for the Restraint subscale, 3.73 ± 4.41 for the Eating Concern subscale, 4.35 ±

Discussion

The aim of this study was to examine whether oxytocin has an impact on attentional processes to food, fatness and eating behavior in patients with AN. Our first hypothesis of increased attentional bias to food in patients with AN was not proved, because although the mean attentional bias was increased, the large variance meant that this did not reach the level of significance (ES = 0.192). In our second hypothesis, there was a tendency for the AN group to be more vigilant to the negative (fat)

Role of funding source

The funders had no role on the study design, the collection, analysis, and interpretation of the data, nor in writing the manuscript or the decision on where to submit the manuscript for publication.

Conflict of interest

All authors report no biomedical financial interests or potential conflicts of interest.

Acknowledgements

We thank Professor Roz Shafran for offering the photos. This study was supported under the framework of the international cooperation program managed by the National Research Foundation of Korea (2011-0030914) and the Basic Science Research Program through the National Research Foundation of Korea, which is funded by the Ministry of Education (MOE) (NRF-2011-0024415) to Youl-Ri Kim. Janet Treasure is part funded by the National Institute for Health Research (NIHR) Mental Health Biomedical

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Anorexia nervosa (AN) is an eating disorder (ED) with high mortality rates and limited response to existing treatments, prompting the need to identify effective agents and adjuncts. There is evidence for an emerging role for the neuropeptide oxytocin (OT) in the pathophysiology of AN, with studies showing a perturbed oxytocinergic system in patients with AN. Preliminary evidence has demonstrated that intranasal OT (IN-OT) can produce anxiolytic effects in AN, as well as reducing concern about eating, and dysfunctional attentional biases related to the disorder. IN-OT is a non-invasive treatment option for AN that requires investigation as an adjunct to nutritional rehabilitation.
This multi-site study (Trial Registration:ACTRN1261000897460) sought to replicate and extend a previous randomised placebo-controlled pilot trial of repeated dose IN-OT in patients with AN hospitalised for nutritional rehabilitation. Patients with AN (N=61) received daily IN-OT (18 IU twice per day) or placebo for four weeks, whilst undergoing inpatient hospital treatment. Outcome measures included ED psychopathology (primary) as measured by the Eating Disorder Examination (EDE) and Body Mass Index (BMI; secondary). Participants were assessed pre- and post-treatment, and at six months following the intervention. The effects of the first and last doses of IN-OT on responses (anxiety ratings and salivary cortisol) to a high-energy snack were also examined.
Sixty-one female inpatients (M_age=24.36,SD=7.87) with an average BMI of 16.24 (range: 11.43–18.55), were recruited into the study. No significant differences were found between placebo and OT groups at any of the time points on the outcomes of interest, but significant improvements in almost all psychological parameters in both groups were evident over time. IN-OT did not significantly reduce anxiety nor salivary cortisol in response to a high-calorie snack.
This is the largest randomised placebo-controlled trial of repeated dose intranasal OT in people with AN, during refeeding. The therapeutically promising findings of the pilot study were not replicated. Limitations and reasons for the non-replication included relatively large variance, baseline psychopathology scores being higher in this patient group, potential ceiling effects in BMI and ED psychopathology as well as differing comorbidities.
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Previous research has shown that patients with anorexia nervosa (AN) show an attentional bias to food. However, due to different conceptualizations of attentional bias and the use of various paradigms, results are inconclusive and more precise insights into the exact nature of this attentional bias are needed. Therefore, an eye-tracking paradigm with food (low and high caloric) and non-food (objects) pictures was used to investigate biases in AN patients (n = 25) compared to healthy controls (n = 22). Several indices of visual attention were examined, both during free (initial orientation, fixation frequency, fixation time) and explicitly instructed (engagement, disengagement) viewing. Our results during the free viewing phase indicated that AN patients (as compared to healthy matched controls) looked less frequently and spent less time fixating on food stimuli, compared to the comparison group. No differences between both groups (n = 47) in initial orientation could be observed. Interestingly, during the instructed viewing phase, no differences between the patient and the comparison group were observed in engagement or disengagement to food stimuli. These results suggest an (initial) attentional avoidance of food in AN patients when closely investigating spontaneous attentional processes, while this could not be observed during gaze behaviour when receiving clear instructions. Hence, future research should look into how attentional bias during spontaneous gaze patterns could serve as a potential marker of AN, and how targeting this bias could be applied in treatment interventions.
Oxytocin and eating disorders: Knowledge gaps and future directions
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Eating disorders continue to be a major public health issue and important cause of morbidity and premature mortality, particularly for young people. Yet in a concerning dialectic, this occurs in the context of an epidemic of obesity which, with its medical complications, constitutes another vexing public health challenge. While it is not an eating disorder per se obesity is often comorbid with eating disorders. Effective treatment for both eating disorders and obesity has proven to be elusive and in the search for novel therapeutic interventions, the prosocial, anxiolytic, brain plasticity and metabolic effects of oxytocin (OT) have been examined from this perspective. The availability of intranasal oxytocin (IN-OT) has led to a number of interventional treatment studies in anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), their atypical and subclinical forms and in medical and psychiatric conditions co-occurring or comorbid with these, obesity with BED would be included here. The aim of this mini review is to collate recent findings on OT as a novel therapeutic intervention in eating disorders and obesity and to identify and address some of the knowledge gaps in the use of IN-OT. The wider clinical perspective utilised here might better address some of the gaps and identify future directions of research. Clearly much remains to be done for OT to fulfil its therapeutic promise in eating disorders. OT might yet be of therapeutic promise and will be appreciated where treatment advances have been hard to come by and prevention challenging for these disorders.
Eating Disorders (Anorexia Nervosa and Bulimia Nervosa, Binge Eating Disorder)
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Eating disorders are severe psychiatric disorders with complex bio-psycho-social underpinnings. Research has made progress understanding contributing genetic and neurobiological factors to eating disorder illness development and maintenance. However, we need to continue developing models for targeted pharmacological interventions in eating disorders. This article reviews the available literature on psychopharmacological trials to treat anorexia nervosa, bulimia nervosa and binge eating disorder. No medication has been approved for anorexia nervosa, while the serotonin reuptake inhibitor fluoxetine has United States Food and Drug Administration (FDA) approval for treatment of bulimia nervosa, and the stimulant prodrug lisdexamfetamine for treatment of binge eating disorder. The chapter provides a neuroscience based practical approach to prescribing medication for eating disorders and perspectives for future studies.
Intranasal oxytocin reduces attentional bias to food stimuli
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Citation Excerpt :
Future studies should explore whether a snack consumed before an attentional bias task, alters participant responses to food cues, either by way of a priming effect or via an effect of elevated glucose on attention. Methodological differences between the Kim, Kim, et al. (2014) study and the present experiment may have contributed to the lack of attentional bias modification by oxytocin in normal eaters in the Kim group that was demonstrated in this experiment. Increased attention in the dot-probe paradigm within the anorexic cohort may be, at least partly, due to increased threat processing, as has been demonstrated in individuals with anxiety disorders towards, for example, spiders (Öhman & Soares, 1994).
Attentional biases to food-related stimuli have been demonstrated in response to hunger as well as during restrained eating. Such biases are often associated with obesity, but healthy-weight individuals who do not self-report hunger have also demonstrated attentional biases to stimuli signalling food using laboratory-based cognitive tasks. Levels of the anorectic neuropeptide oxytocin are elevated by food intake and, when administered intranasally, oxytocin inhibits food intake in the laboratory. To investigate whether oxytocin can affect appetite via an action on attentional processes, 40 adults (29 women; mean age 24.0 years old) self-administered 24 IU of oxytocin or placebo intranasally. Forty minutes after administration, participants ate a small snack to maintain alertness and ameliorate deprivation-induced hunger before starting a computerized dot-probe attentional bias task that presented 180 trials of paired visual stimuli comprising neutral, food, social and/or romantic images (500 ms presentation time). Reaction times to probe stimuli that appeared after the offset of the visual images indicated a significant attentional bias to food pictures after placebo; this effect was significantly attenuated by oxytocin, p < .001. The effect of oxytocin on attentional bias to the food pictures was not altered by the type of stimulus paired with the food image, and was independent of BMI, age, sex, self-rated eating behaviour, and self-reported parental bonding; however, the effect was modulated by self-reported food cravings and trait stress. The findings support and extend previous work which has suggested that oxytocin can counteract attentional biases to food-related stimuli in a sample with anorexia by demonstrating the same effect for the first time in a cohort who do not have an eating disorder.

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Intranasal oxytocin attenuates attentional bias for eating and fat shape stimuli in patients with anorexia nervosa

Summary

Section snippets

Participants

Demographic and group characteristics

Discussion

Role of funding source

Conflict of interest

Acknowledgements

Appetite

Clin. Psychol. Rev.

Appetite

Metabolism

Clin. Psychol. Rev.

Biol. Psychiatry

Appetite

Pers. Ind. Dif.

Psychoneuroendocrinology

Behav. Res. Ther.

Appetite

Neurosci. Biobehav. Rev.

Psychoneuroendocrinology

Biol. Psychiatry

Appetite

Appetite

The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample

Psychopharmacology (Berl)

A review of attention biases in women with eating disorders

Cogn. Emot.

Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy

Transl. Psychiatry

Threat-related attentional bias in anxious and nonanxious individuals: a meta-analytic study

Psychol. Bull.

Do girls with anorexia nervosa have elevated autistic traits?

Mol. Autism

The Autism-Spectrum Quotient (AQ): evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians

J. Autism Dev. Disord.

An inventory for measuring depression

Arch. Gen. Psychiatry

Attentional bias for emotional faces in generalized anxiety disorder

Br. J. Clin. Psychol.

Mealtime support in anorexia nervosa: a within-subject comparison study of a novel vodcast intervention

Psychother. Psychosom.

A power primer

Psychol. Bull.

Toward the future of psychiatric diagnosis: the seven pillars of RDoC

BMC Med.

CSF oxytocin in anorexia nervosa and bulimia nervosa: clinical and pathophysiologic considerations

Am. J. Psychiatry

Assessment of eating disorders—Interview or self-report questionnaire

Int. J. Eat. Disord.

The Eating Disorder Examination