Neurological Underpinnings of Disordered Eating
Mikayla Flanz
Eating disorders (EDs) are severe and complex psychiatric conditions characterized by maladaptive behaviors surrounding food, such as dietary restrictions, episodic binge eating, purging, body dissatisfaction, and an intense drive for a thin figure. Affecting millions worldwide, EDs are not only prevalent but are also associated with significant morbidity and mortality. Among psychiatric disorders, anorexia nervosa has one of the highest mortality rates, underscoring the critical need for better understanding and treatment. The prognosis for individuals with EDs is often poor, with many experiencing chronic symptoms and a high risk of relapse even after treatment. Despite advances in therapeutic interventions, current treatment approaches—such as cognitive-behavioral therapy, nutritional rehabilitation, and pharmacotherapy—are often limited in efficacy. Many individuals fail to achieve full recovery, and treatments that work for one individual may be ineffective for another, highlighting the need for personalized and innovative strategies. Understanding the neurobiological mechanisms underlying the onset and maintenance of EDs is vital to addressing these limitations. Research into brain chemistry, neural circuitry, and genetic predispositions could pave the way for novel treatment approaches that target the root causes of these disorders rather than merely managing symptoms. By elucidating the neurobiological basis of EDs, we can better design interventions that are not only more effective but also more enduring, ultimately improving outcomes for individuals affected by these devastating conditions.
In a cross-sectional functional brain imaging study, Frank et al. (2021) investigated the neural response to the unexpected receipt or omission of a sweet stimulus among individuals with eating disorders and healthy controls. The study hypothesized an inverse relationship between prediction error response—reflected in body mass index (BMI)—and ED behaviors when comparing under-eating with overeating. In reference to eating disorders, prediction error response measures the difference between what's expected and what actually happens via brain signaling, which is how individuals that engage with behaviors associated with bulimia nervosa and binge-eating disorder are typically of average BMI whereas those with disorders of under eating such as anorexia nervosa are of lower BMI. Overall, the conclusive results of this study suggest that eating disorder behaviors change brain reward processing, which may alter food intake control circuitry and reinforce the individual’s eating disorder behavior. Additionally, it was anticipated that effective synaptic connectivity within the energy-homeostasis and food reward-regulating circuitry would be directed from the ventral striatum to the hypothalamus within the ED sample, indicating alterations in the brain's reward processing system.
The study cohort consisted of 317 women, 197 of whom were diagnosed with anorexia nervosa, bulimia nervosa, binge eating disorder, or other specified feeding and eating disorders. These were compared to 120 healthy controls. To minimize hormonal confounding effects, healthy control participants were studied during the first 10 days of their menstrual cycle, as neuroactive peptides, including sex and gut hormones, are known to influence neurological responses (Monteleone et al., 2013). Berner et al. (2019) have demonstrated that neuroendocrine peptides, which regulate homeostasis, are often dysregulated in individuals with EDs, potentially disrupting the food reward circuitry seen in healthy controls. For example, leptin and ghrelin, hormones involved in hunger regulation, modulate dopaminergic activity in the brain, with disturbances in these pathways contributing to altered food intake control circuitry in anorexia and bulimia nervosa (Monteleone et al., 2018).
Conducted between June 2014 and November 2019, the study aimed to identify whether the hypothesized alterations in brain reward processing and response were linked specifically to the ventral striatal-hypothalamic circuitry, which is implicated in food intake regulation and reward processing. This neural circuit is critical for processing salient stimuli, such as food, and has been shown to engage dopaminergic pathways related to motivation and reward (Brown et al., 2013). When engaging with eating disorder behaviors, food acts as a natural reward in the brain’s circuitry, much like substances of abuse, and engages these reward circuits when individuals experience sensations such as hunger, desire, or the need for satiation. The study's findings underscored the role of altered dopamine-related reward processing in EDs. Neuroadaptive changes in dopamine systems appear to occur in response to extremes of food intake—where food restriction enhances dopaminergic activity, and excessive intake downregulates this circuitry. This dysregulation could be a core pathophysiological factor in eating disorders. Understanding these neural adaptations may provide insights into the biological underpinnings of ED behaviors and help provide targeted interventions and increase accessibility to precision medicine.
The results further demonstrated that behavioral traits related to EDs, such as overeating or undereating, are associated with disruptions in prediction error signaling and reward processing in the brain. These disruptions reinforce maladaptive food-related behaviors via the ventral striatal-hypothalamic circuitry. Clinically, this suggests that normalizing BMI in individuals with EDs—whether through weight gain in those with restrictive eating behaviors or weight loss in those with binge eating behaviors—could help restore healthy brain function and behavioral patterns. Overall, this study by Frank et al. (2021) provides compelling evidence that BMI modulates prediction error and food intake control circuits in the brain. These findings highlight the importance of developing treatment modules that specifically target behavioral traits linked to the dysregulation of these neural circuits, such as keystone dopaminergic systems, which may be essential for promoting long-term recovery from eating disorders.
About the Author
Mikayla Flanz (‘25) is a senior at Boston University concentrating in Health Science and Philosophy.
References
In a cross-sectional functional brain imaging study, Frank et al. (2021) investigated the neural response to the unexpected receipt or omission of a sweet stimulus among individuals with eating disorders and healthy controls. The study hypothesized an inverse relationship between prediction error response—reflected in body mass index (BMI)—and ED behaviors when comparing under-eating with overeating. In reference to eating disorders, prediction error response measures the difference between what's expected and what actually happens via brain signaling, which is how individuals that engage with behaviors associated with bulimia nervosa and binge-eating disorder are typically of average BMI whereas those with disorders of under eating such as anorexia nervosa are of lower BMI. Overall, the conclusive results of this study suggest that eating disorder behaviors change brain reward processing, which may alter food intake control circuitry and reinforce the individual’s eating disorder behavior. Additionally, it was anticipated that effective synaptic connectivity within the energy-homeostasis and food reward-regulating circuitry would be directed from the ventral striatum to the hypothalamus within the ED sample, indicating alterations in the brain's reward processing system.
The study cohort consisted of 317 women, 197 of whom were diagnosed with anorexia nervosa, bulimia nervosa, binge eating disorder, or other specified feeding and eating disorders. These were compared to 120 healthy controls. To minimize hormonal confounding effects, healthy control participants were studied during the first 10 days of their menstrual cycle, as neuroactive peptides, including sex and gut hormones, are known to influence neurological responses (Monteleone et al., 2013). Berner et al. (2019) have demonstrated that neuroendocrine peptides, which regulate homeostasis, are often dysregulated in individuals with EDs, potentially disrupting the food reward circuitry seen in healthy controls. For example, leptin and ghrelin, hormones involved in hunger regulation, modulate dopaminergic activity in the brain, with disturbances in these pathways contributing to altered food intake control circuitry in anorexia and bulimia nervosa (Monteleone et al., 2018).
Conducted between June 2014 and November 2019, the study aimed to identify whether the hypothesized alterations in brain reward processing and response were linked specifically to the ventral striatal-hypothalamic circuitry, which is implicated in food intake regulation and reward processing. This neural circuit is critical for processing salient stimuli, such as food, and has been shown to engage dopaminergic pathways related to motivation and reward (Brown et al., 2013). When engaging with eating disorder behaviors, food acts as a natural reward in the brain’s circuitry, much like substances of abuse, and engages these reward circuits when individuals experience sensations such as hunger, desire, or the need for satiation. The study's findings underscored the role of altered dopamine-related reward processing in EDs. Neuroadaptive changes in dopamine systems appear to occur in response to extremes of food intake—where food restriction enhances dopaminergic activity, and excessive intake downregulates this circuitry. This dysregulation could be a core pathophysiological factor in eating disorders. Understanding these neural adaptations may provide insights into the biological underpinnings of ED behaviors and help provide targeted interventions and increase accessibility to precision medicine.
The results further demonstrated that behavioral traits related to EDs, such as overeating or undereating, are associated with disruptions in prediction error signaling and reward processing in the brain. These disruptions reinforce maladaptive food-related behaviors via the ventral striatal-hypothalamic circuitry. Clinically, this suggests that normalizing BMI in individuals with EDs—whether through weight gain in those with restrictive eating behaviors or weight loss in those with binge eating behaviors—could help restore healthy brain function and behavioral patterns. Overall, this study by Frank et al. (2021) provides compelling evidence that BMI modulates prediction error and food intake control circuits in the brain. These findings highlight the importance of developing treatment modules that specifically target behavioral traits linked to the dysregulation of these neural circuits, such as keystone dopaminergic systems, which may be essential for promoting long-term recovery from eating disorders.
About the Author
Mikayla Flanz (‘25) is a senior at Boston University concentrating in Health Science and Philosophy.
References
- Berner, L. A., Brown, T. A., Lavender, J. M., Lopez, E., Wierenga, C. E., & Kaye, W. H. (2019). Neuroendocrinology of reward in anorexia nervosa and bulimia nervosa: Beyond leptin and ghrelin. Molecular and Cellular Endocrinology, 497(110320), 110320. https://doi.org/10.1016/j.mce.2018.10.018
- Brown, L. (2013). ClinicalKey. Journal of the Medical Library Association: JMLA, 101(4), 342–343. https://doi.org/10.3163/1536-5050.101.4.023
- Frank, G. K. W., Shott, M. E., Stoddard, J., Swindle, S., & Pryor, T. L. (2021). Association of brain reward response with body mass index and ventral striatal-hypothalamic circuitry among young women with eating disorders. JAMA Psychiatry (Chicago, Ill.), 78(10), 1123–1133. https://doi.org/10.1001/jamapsychiatry.2021.1580
- Monteleone, A. M., Castellini, G., Volpe, U., Ricca, V., Lelli, L., Monteleone, P., & Maj, M. (2018). Neuroendocrinology and brain imaging of reward in eating disorders: A possible key to the treatment of anorexia nervosa and bulimia nervosa. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 80, 132–142. https://doi.org/10.1016/j.pnpbp.2017.02.020
- Monteleone, P., & Maj, M. (2013). Dysfunctions of leptin, ghrelin, BDNF, and endocannabinoids in eating disorders: Beyond the homeostatic control of food intake. Psych neuroendocrinology, 38(3), 312–330. https://doi.org/10.1016/j.psyneuen.2012.10.021