The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa

O’Hara, Caitlin B; Keyes, Alexandra; Renwick, Bethany; Leyton, Marco; Campbell, Iain C.; Schmidt, Ulrike

doi:10.1371/journal.pone.0145894

Cited by 30 publications

(19 citation statements)

References 66 publications

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“…Individuals with AN demonstrate elevated skin conductance, decreased eye blink startle, and increased electroencephalogram late positive potential in response to underweight stimuli (Clarke, Ramoz, Fladung, & Gorwood, ; Horndasch et al, ; O'Hara et al, ), indicating greater salience and PA responding. This altered dopaminergic functioning and reward response is corroborated by a study showing increased eye blink startle in response to thinness images following dopamine depletion (O'Hara et al, ).…”

Section: Current Evidencementioning

confidence: 68%

The posited effect of positive affect in anorexia nervosa: Advocating for a forgotten piece of a puzzling disease

Coniglio

Christensen

Haynos

et al. 2019

Intl J Eating Disorders

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Anorexia nervosa (AN) is a complex and life‐threatening eating disorder. Current models of AN onset and maintenance have largely focused on the role of negative affect, while fewer models have described the role of positive affect (PA). Given that these theoretical models have informed current treatment approaches, and that treatment remains minimally effective for adults with AN, we advocate that targeting PA is one avenue for advancing maintenance models and by extension, treatment. We specifically propose that AN may arise and be chronically and pervasively maintained as a function of dysregulated PA in response to weight loss and weight loss behaviors (e.g., restriction, excessive exercise), to a degree that is not accounted for in existing models of AN. We present evidence from multiple domains, including biological, behavioral, and self‐report, supporting the hypothesis that PA dysregulation in AN contributes to the maintenance of the disorder. We conclude with several specific avenues for treatment development research as well as a call for future work elucidating the biological correlates of PA.

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Section: Current Evidencementioning

confidence: 68%

The posited effect of positive affect in anorexia nervosa: Advocating for a forgotten piece of a puzzling disease

Coniglio

Christensen

Haynos

et al. 2019

Intl J Eating Disorders

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“…In accord with this hypothesis, a recent study showed that decreasing DA (via APTD) did not reduce motivation to exercise in AN REC, but did so in HC. This suggests that drive to exercise develops into a behaviour that is independent of DA-mediated reward processes and may become dependent on corticostriatal neurocircuitry that regulates automated, habit-like behaviours [ 63 ]. Therefore, in the present study, diminished reflexive startle response to underweight and exercise cues in AN REC during BAL (but not during APTD) suggests that, unlike HC, these individuals reflexively appraise such cues as more rewarding and that this is partly DA-dependent.…”

Section: Discussionmentioning

confidence: 99%

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’Hara¹,

Keyes²,

Renwick³

et al. 2016

PLoS ONE

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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.

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“…Dysfunction of the neural network involved in reward, punishment, and motivational processes is also described in ED patients [40,53]. Several studies have shown that dopamine system disturbance contributes to the development and maintenance of AN and other EDs [54,55].…”

Section: Neurobiological Regulationmentioning

confidence: 99%

An Evolutionary Genetic Perspective of Eating Disorders

Mayhew

Pigeyre

Couturier³

et al. 2017

Neuroendocrinology

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Eating disorders (ED) including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) affect up to 5% of the population in Western countries. Risk factors for developing an ED include personality traits, family environment, gender, age, ethnicity, and culture. Despite being moderately to highly heritable with estimates ranging from 28 to 83%, no genetic risk factors have been conclusively identified. Our objective was to explore evolutionary theories of EDs to provide a new perspective on research into novel biological mechanisms and genetic causes of EDs. We developed a framework that explains the possible interactions between genetic risk and cultural influences in the development of ED. The framework includes three genetic predisposition categories (people with mainly AN restrictive gene variants, people with mainly BED variants, and people with gene variants predisposing to both diseases) and a binary variable of either the presence or absence of pressure to be thin. We propose novel theories to explain the overlapping characteristics of the subtypes of AN (binge/purge and restrictive), BN, and BED. For instance, mutations/structural gene variants in the same gene causing opposite effects or mutations in nearby genes resulting in partial disequilibrium for the genes causing AN (restrictive) and BED may explain the overlap of phenotypes seen in AN (binge/purge).

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The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa

Cited by 30 publications

References 66 publications

The posited effect of positive affect in anorexia nervosa: Advocating for a forgotten piece of a puzzling disease

The posited effect of positive affect in anorexia nervosa: Advocating for a forgotten piece of a puzzling disease

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

An Evolutionary Genetic Perspective of Eating Disorders

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