Trends in Neurosciences
ReviewSpecial issue: neural control of appetiteNothing tastes as good as skinny feels: the neurobiology of anorexia nervosa
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.
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