Trends in Neurosciences
Volume 36, Issue 2, February 2013, Pages 110-120
Journal home page for Trends in Neurosciences

Review
Special issue: neural control of appetite
Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa

https://doi.org/10.1016/j.tins.2013.01.003Get rights and content

Individuals with anorexia nervosa (AN) engage in relentless restrictive eating and often become severely emaciated. Because there are no proven treatments, AN has high rates of relapse, chronicity, and death. Those with AN tend to have childhood temperament and personality traits, such as anxiety, obsessions, and perfectionism, which may reflect neurobiological risk factors for developing AN. Restricted eating may be a means of reducing negative mood caused by skewed interactions between serotonin aversive or inhibitory and dopamine reward systems. Brain imaging studies suggest that altered eating is a consequence of dysregulated reward and/or awareness of homeostatic needs, perhaps related to enhanced executive ability to inhibit incentive motivational drives. An understanding of the neurobiology of this disorder is likely to be important for developing more effective treatments.

Introduction

Anorexia nervosa (AN) is a disorder of unknown etiology that tends to affect young women [1]. This illness is characterized by restricted eating, severe emaciation, and distorted body image, as well as high rates of chronicity, morbidity, and mortality [1]. It has a narrow range of age of onset (early adolescence), stereotypic presentation of symptoms and course, and tends to be specific to the female gender. Although often considered to be caused by psychosocial factors, recent studies have shown that genetic heritability accounts for approximately 50–80% of the risk of developing an eating disorder (ED) [2] and contributes to neurobiological factors underlying EDs [3]. A lack of understanding of the pathophysiology of these illnesses has hindered the development of effective treatments. How are individuals with AN able to consume a few hundred calories per day and maintain an extremely low weight for many years, when most people struggle to lose a few pounds? It has been controversial as to whether individuals with AN have a primary disturbance of appetite regulation or whether pathological feeding behavior is secondary to other phenomena, such as an obsessional preoccupation with body image.

Individuals with AN tend to have other puzzling symptoms and behaviors that are poorly understood, such as severe body image distortions, a lack of insight about being ill, and depriving themselves of food despite starvation (Box 1). Their disorder is egosyntonic and they often refuse or resist treatment. How are these unique behaviors encoded in neural processes? Recent studies of obesity suggest that cortico–limbic neural processes, which encode the rewarding, emotional, and cognitive aspects of food ingestion, can drive overconsumption of food, even in the presence of satiety and replete energy stores 4, 5, 6. It has been suggested that obesity and addictions share overlapping brain circuits and monoamine systems that modulate reward sensitivity, incentive motivation, conditioning (memory/learning), impulse control (behavioral inhibition), stress reactivity, and interoceptive awareness [7]. These studies have created a body of knowledge that could be used to jump-start advances towards an understanding of the neurobiology of AN. Interestingly, AN has contrasting symptoms, such as underconsumption of food (despite being emaciated) and decreased rates of alcohol and drug abuse 8, 9, which suggest differences in these neural processes compared to obesity and addiction. Although such understanding is in its infancy, we argue in this review that it is important to know how symptoms and behaviors in AN are encoded in the brain, because this is necessary to improve treatment. Because of space limitations, this review discusses selected behavioral traits in AN in relation to imaging results: first, evidence that harm avoidance (HA) is related to dopamine (DA) and serotonin (5-HT) function in AN, and second, the use of functional magnetic resonance imaging (fMRI) studies to reveal insights into the neural circuitry of gustatory sensory response, interoception, reward, and executive control.

Section snippets

Temperament and personality in AN

Although many individuals diet and seek to lose weight in our culture, relatively few develop AN. In fact, the prevalence is less than 1% of women [1]. Individuals with AN tend to have certain temperament and personality traits, which often first occur in childhood before the onset of an ED and may create a vulnerability to develop an ED. In addition to predating the disease, these traits often persist after recovery 10, 11, 12, 13, 14. The traits include anxiety, negative emotionality,

DA and 5-HT: relationship to HA

Considerable data show that AN individuals have disturbances of DA and 5-HT systems [3]. It has been proposed that 5-HT might play a role in altered satiety, impulse control, and mood, and that DA may be implicated in aberrant rewarding effects of food, motivation, or executive functions (inhibitory control, salience attribution, and decision-making). Because of space limitations, this review focuses on measures that assess 5-HT and DA levels in the brain, such as cerebrospinal fluid (CSF)

fMRI studies of appetite: relationship to food taste

fMRI imaging studies of appetitive behaviors in ED have used designs that either administer a taste of some food or present images of food to participants. The neurocircuitry of taste processing in healthy individuals is well understood 5, 7, 79. The anterior insula is the primary gustatory taste cortex and responds to tastes of food [3]. The anterior insula, as well as the anterior cingulate cortex and orbital frontal cortex, code the sensory–hedonic response to taste and innervate a broad

fMRI studies of reward and executive control

A series of fMRI studies using response to reward or executive control tasks has explored the role of ventral and dorsal corticostriatal systems in AN in comparison to control subjects to better understand the modulation of reward, emotionality, and behavioral inhibition. Control subjects show patterns of limbic striatal response that significantly distinguish positive and negative feedback [90]. By contrast, another study reported that recovered AN subjects had minimal differences to positive

Concluding remarks

Considerable evidence shows that individuals with AN have anxious, inhibited, and inflexible premorbid characteristics. It is possible that these premorbid traits are related to altered monoamine neuronal modulation, or dorsal caudate function, that predates the onset of AN. Several factors might exacerbate these vulnerabilities to cause the onset of AN in adolescence. First, puberty-related female gonadal steroids might exacerbate 5-HT and DA system dysregulation [101]. Brain changes

Acknowledgements

Our work was supported by grants from the National Institute of Mental Health (MH046001, MH042984, MH066122; MH001894 and MH092793), the Price Foundation, and the Davis/Wismer Foundation.

References (123)

  • W. Drevets

    Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria

    Biol. Psychiatry

    (2001)
  • W.H. Kaye

    Altered dopamine activity after recovery from restricting-type anorexia nervosa

    Neuropsychopharmacology

    (1999)
  • N. Avena et al.

    Dysregulation of brain reward systems in eating disorders: neurochemical information from animal models of binge eating, bulimia nervosa, and anorexia nervosa

    Neuropharmacology

    (2012)
  • V. Bassareo et al.

    Differential responsiveness of dopamine transmission to food-stimuli in nucleus accumbens shell/core compartments

    Neuroscience

    (1999)
  • N.D. Daw

    Opponent interactions between serotonin and dopamine

    Neural Netw.

    (2002)
  • R. Cools

    Serotoninergic regulation of emotional and behavioural control processes

    Trends Cogn. Sci.

    (2008)
  • W. Schultz

    Dopamine neurons and their role in reward mechanisms

    Curr. Opin. Neurobiol.

    (1997)
  • K. Giel

    Attentional processing of food pictures in individuals with anorexia nervosa – an eye-tracking study

    Biol. Psychiatry

    (2011)
  • S. Vocks

    Effects of gustatory stimulation on brain activity during hunger and satiety in females with restricting-type anorexia nervosa: an fMRI study

    J. Psychiatr. Res.

    (2011)
  • L. Haase

    Cortical activation in response to pure taste stimuli during the physiological states of hunger and satiety

    Neuroimage

    (2009)
  • F. Cowdrey

    Increased neural processing of rewarding and aversive food stimuli in recovered anorexia nervosa

    Biol Psychiatry

    (2011)
  • A. Simmons

    Anticipation of aversive visual stimuli is associated with increased insula activation in anxiety-prone subjects

    Biol. Psychiatry

    (2006)
  • M. Paulus et al.

    An insular view of anxiety

    Biol. Psychiatry

    (2006)
  • M. Phillips

    Neurobiology of emotion perception II: implications for major psychiatric disorders

    Biol. Psychiatry

    (2003)
  • M. Phillips

    Neurobiology of emotion perception I: the neural basis of normal emotion perception

    Biol. Psychiatry

    (2003)
  • W. Schultz

    Neural coding of basic reward terms of animal learning theory, game theory, microeconomics and behavioural ecology

    Science

    (2004)
  • American Psychiatric Association

    Diagnostic and Statistical Manual of Mental Disorders: DSM-VI-TR

    (2000)
  • C. Bulik

    Prevalence, heritability and prospective risk factors for anorexia nervosa

    Arch. Gen. Psychiatry

    (2006)
  • W. Kaye

    New insight into symptoms and neurocircuit function of anorexia nervosa

    Nat. Rev. Neurosci.

    (2009)
  • H. Berthoud

    Homeostatic and non-homeostatic pathways involved in the control of food intake and energy balance

    Obesity

    (2006)
  • E. Rolls

    Brain mechanisms underlying flavour and appetite

    Philos. Trans. R. Soc. Lond. B: Biol. Sci.

    (2006)
  • D. Small

    Central gustatory processing in humans

    Adv. Otorhinolaryngol.

    (2006)
  • N. Volkow

    Food and drug reward: overlapping circuits in human obesity and addiction

    Curr. Top. Behav. Neurosci.

    (2012)
  • A. Calero-Elvira

    Meta-analysis on drugs in people with eating disorders

    Eur. Eat. Disord. Rev.

    (2009)
  • T. Gadalla et al.

    Co-occurrence of eating disorders and alcohol use disorders in women: a meta analysis

    Arch. Womens Ment. Health

    (2007)
  • M.B. Anderluh

    Childhood obsessive–compulsive personality traits in adult women with eating disorders: defining a broader eating disorder phenotype

    Am. J. Psychiatry

    (2003)
  • W. Kaye

    Comorbidity of anxiety disorders with anorexia and bulimia nervosa

    Am. J. Psychiatry

    (2004)
  • A. Wagner

    Personality traits after recovery from eating disorders: do subtypes differ?

    Int. J. Eat. Disord.

    (2006)
  • L. Rachell et al.

    Personality and temperament

  • T. Raney

    Influence of overanxious disorder of childhood on the expression of anorexia nervosa

    Int. J. Eat. Disord.

    (2008)
  • C. Bloss

    Genetic association of recovery from eating disorders: the role of GABA receptor SNPs

    Neuropsychopharmacology

    (2011)
  • J. Steinglass

    Fear of food as a treatment target: exposure and response prevention for anorexia nervosa in an open series

    Int. J. Eat. Disord.

    (2012)
  • H. Friederich et al.

    Cognitive-behavioral flexibility in anorexia nervosa

  • K. Tchanturia

    Altered social hedonic processing in eating disorders

    Int. J. Eat. Disord.

    (2012)
  • M. Shott

    Altered implicit category learning in anorexia nervosa

    Neuropsychology

    (2012)
  • K. Fitzpatrick

    Set-shifting among adolescents with anorexia nervosa

    Int. J. Eat. Disord.

    (2012)
  • C. Cloninger

    The Temperament and Character Inventory (TCI): A Guide to its Development and Use

    (1994)
  • S. Fassino

    Temperament and character in eating disorders: ten years of studies

    Eat. Weight Disord.

    (2004)
  • K. Klump

    Personality characteristics of women before and after recovery from an eating disorder

    Psychol. Med.

    (2004)
  • G. Frank

    Heightened fear of uncertainty in anorexia and bulimia nervosa

    Int. J. Eat. Disord.

    (2012)
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