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Evidence that Illness-Compatible Cues Are Rewarding in Women Recovered from Anorexia Nervosa: A Study of the Effects of Dopamine Depletion on Eye-Blink Startle Responses.

ABSTRACT: In anorexia nervosa (AN), motivational salience is attributed to illness-compatible cues (e.g., underweight and active female bodies) and this is hypothesised to involve dopaminergic reward circuitry. We investigated the effects of reducing dopamine (DA) transmission on the motivational processing of AN-compatible cues in women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15). This involved the acute phenylalanine and tyrosine depletion (APTD) procedure and a startle eye-blink modulation (SEM) task. In a balanced amino acid state, AN REC showed an increased appetitive response (decreased startle potentiation) to illness-compatible cues (underweight and active female body pictures (relative to neutral and non-active cues, respectively)). The HC had an aversive response (increased startle potentiation) to the same illness-compatible stimuli (relative to neutral cues). Importantly, these effects, which may be taken to resemble symptoms observed in the acute stage of illness and healthy behaviour respectively, were not present when DA was depleted. Thus, AN REC implicitly appraised underweight and exercise cues as more rewarding than did HC and the process may, in part, be DA-dependent. It is proposed that the positive motivational salience attributed to cues of emaciation and physical activity is, in part, mediated by dopaminergic reward processes and this contributes to illness pathology. These observations are consistent with the proposal that, in AN, aberrant reward-based learning contributes to the development of habituation of AN-compatible behaviours.

SUBMITTER: O'Hara CB

PROVIDER: S-EPMC5072564 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Evidence that Illness-Compatible Cues Are Rewarding in Women Recovered from Anorexia Nervosa: A Study of the Effects of Dopamine Depletion on Eye-Blink Startle Responses.

O'Hara Caitlin B CB Keyes Alexandra A Renwick Bethany B Giel Katrin E KE Campbell Iain C IC Schmidt Ulrike U

PloS one 20161020 10

In anorexia nervosa (AN), motivational salience is attributed to illness-compatible cues (e.g., underweight and active female bodies) and this is hypothesised to involve dopaminergic reward circuitry. We investigated the effects of reducing dopamine (DA) transmission on the motivational processing of AN-compatible cues in women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15). This involved the acute phenylalanine and tyrosine depletion (APTD) procedure and a startle eye-blin ...[more]

PMID: 27764214

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Project description:Anorexia nervosa (AN) is a severe mental disorder characterized by food restriction and weight loss. This study aimed to test the model posed by Brooks et al. (2012a,b) that women suffering from chronic AN show decreased food-cue processing activity in brain regions associated with energy balance and food reward (bottom-up; BU) and increased activity in brain regions associated with cognitive control (top-down; TD) when compared with long-term recovered AN (REC) and healthy controls (HC). Three groups of women, 15 AN (mean illness duration 7.8?±?4.1 years), 14 REC (mean duration of recovery 4.7?±?2.7?years) and 15 HC viewed alternating blocks of food and non-food images preceded by a short instruction during functional magnetic resonance imaging (fMRI), after fasting overnight. Functional region of interests (fROIs) were defined in BU (e.g., striatum, hippocampus, amygdala, hypothalamus, and cerebellum), TD (e.g., medial and lateral prefrontal cortex, and anterior cingulate), the insula, and visual processing areas (VPA). Food-cue processing activation was extracted from all fROIs and compared between the groups. In addition, functional connectivity between the fROIs was examined by modular partitioning of the correlation matrix of all fROIs. We could not confirm the hypothesis that BU areas are activated to a lesser extent in AN upon visual processing of food images. Among the BU areas the caudate showed higher activation in both patient groups compared to HC. In accordance with Brooks et al.'s model, we did find evidence for increased TD control in AN and REC. The functional connectivity analysis yielded two clusters in HC and REC, but three clusters in AN. In HC, fROIs across BU, TD, and VPA areas clustered; in AN, one cluster span across BU, TD, and insula; one across BU, TD, and VPA areas; and one was confined to the VPA network. In REC, BU, TD, and VPA or VPA and insula clustered. In conclusion, despite weight recovery, neural processing of food cues is also altered in recovered AN patients.

Project description:BackgroundAnorexia nervosa is a complex psychiatric illness that includes severe low body weight with cognitive distortions and altered eating behaviors. Brain structures, including cortical thicknesses in many regions, are reduced in underweight patients who are acutely ill with anorexia nervosa. However, few studies have examined adult outpatients in the process of recovering from anorexia nervosa. Evaluating neurobiological problems at different physiological stages of anorexia nervosa may facilitate our understanding of the recovery process.MethodsMagnetic resonance imaging (MRI) images from 37 partially weight-restored women with anorexia nervosa (pwAN), 32 women with a history of anorexia nervosa maintaining weight restoration (wrAN), and 41 healthy control women were analyzed using FreeSurfer. Group differences in brain structure, including cortical thickness, areas, and volumes, were compared using a series of factorial f-tests, including age as a covariate, and correcting for multiple comparisons with the False Discovery Rate method.ResultsThe pwAN and wrAN cohorts differed from each other in body mass index, eating disorder symptoms, and social problem solving orientations, but not depression or self-esteem. Relative to the HC cohort, eight cortical thicknesses were thinner for the pwAN cohort; these regions were predominately right-sided and in the cingulate and frontal lobe. One of these regions, the right pars orbitalis, was also thinner for the wrAN cohort. One region, the right parahippocampal gyrus, was thicker in the pwAN cohort. One volume, the right cerebellar white matter, was reduced in the pwAN cohort. There were no differences in global white matter, gray matter, or subcortical volumes across the cohorts.ConclusionsMany regional structural differences were observed in the pwAN cohort with minimal differences in the wrAN cohort. These data support a treatment focus on achieving and sustaining full weight restoration to mitigate possible neurobiological sequela of AN. In addition, the regions showing cortical thinning are similar to structural changes reported elsewhere for suicide attempts, anxiety disorders, and autistic spectrum disorder. Understanding how brain structure and function are related to clinical symptoms expressed during the course of recovering from AN is needed.

Dataset Information

Evidence that Illness-Compatible Cues Are Rewarding in Women Recovered from Anorexia Nervosa: A Study of the Effects of Dopamine Depletion on Eye-Blink Startle Responses.

Publications

Evidence that Illness-Compatible Cues Are Rewarding in Women Recovered from Anorexia Nervosa: A Study of the Effects of Dopamine Depletion on Eye-Blink Startle Responses.

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