Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa
Trends in Neurosciences
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
... nin aversive or inhibitory and dopamine reward systems. Brain imaging studies suggest 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. Understanding the neurobiology of this disorder is likely to be important for developing more effective treatments. approximately 50-80% of the risk of developing an eating disorder (ED) 2 and contributes to neurobiological factors underlying ED. 3 A lack of understanding of the pathophysiology of these illnesses has hindered 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, as well as depriving themselves of food despite starvation (Box 1). Their disorder is ego-syntonic 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. 4-6 It has been suggested 7 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. These studies have created a body of knowledge that could be used to "jumpstart" advances towards understanding the neurobiology of AN. Interestingly, AN has contrasting symptoms, such as the under-consumption 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. While 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 will discuss 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. Temperament and personality in AN While 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. 10-14 These traits include anxiety, negative emotionality, perfectionism, inflexibility, HA, and obsessive behaviors (particularly with order, exactness, and symmetry). This personality and behavioral profile may constitute an intermediate phenotype between genes and vulnerability to AN. A brief overview of some of these behaviors is given below. Anxiety AN is associated with high anxiety that is premorbid to the illness 11 and persists after weight restoration. This suggests an underlying anxious trait that is independent of nutritional status. 13 Comorbid anxiety disorders occur significantly more frequently in AN individuals than in controls, with lifetime prevalence rates of up to 50%. 15 The presence of childhood anxiety disorders predicts more severe ED symptoms, such as lower body mass index (BMI) and more psychopathology 15, 16 and elevated anxiety is associated with poor outcome. 17 Kaye et al.