Anorexia nervosa (AN) is a serious psychiatric disorder characterized by restrictive eating, an intense fear of gaining weight, and a distorted perception of body shape. While behavioral symptoms are often viewed as purely psychological, AN involves significant alterations to the brain’s structure, function, and chemistry. The illness involves complex neurological components that drive and maintain the disorder. Understanding how chronic malnutrition physically and functionally rewires the central nervous system is fundamental to developing effective treatment strategies. This exploration details the profound changes the brain undergoes during acute AN and its potential for healing during recovery.
Structural Changes in the Brain
Chronic starvation associated with acute AN leads to observable anatomical changes in the brain, largely a consequence of severe malnutrition. Neuroimaging studies consistently reveal a global reduction in brain volume in acutely ill patients compared to healthy individuals. This reduction affects both the gray matter (GM), which contains neuron cell bodies, and the white matter (WM), composed of myelinated nerve fibers that connect brain regions.
The loss of gray matter volume is widespread, spanning across the frontal, temporal, and parietal lobes, as well as the cerebellum. The frontal lobes, involved in executive functions like decision-making, and the temporal lobes, linked to emotional processing, show significant atrophy. This volume loss is often accompanied by an increase in the size of the cerebral ventricles, known as ventricular enlargement.
The reduced brain volume is often described as pseudoatrophy, suggesting changes relate to the loss of tissue components like fat and water rather than permanent cell death. White matter integrity is also compromised, reducing the efficiency of communication pathways between brain areas. These structural alterations, driven by a lack of essential nutrients, set the stage for the functional changes observed in the disorder.
Altered Functional Circuits
The structural changes translate into distinct alterations in how the brain processes information, particularly in circuits governing reward, control, and internal awareness. The reward system, which typically motivates behavior, shows a disconnect in individuals with AN. When presented with food stimuli, the brain’s reward pathways, such as the ventral striatum, often display a hyporesponsive state.
Paradoxically, the reward circuitry may become hyperresponsive to non-food related rewards, such as the feeling of accomplishment from restriction or excessive physical activity. This shift reinforces the compulsive, restrictive behaviors that define the illness. Furthermore, the brain’s prediction error response—a dopamine-related signal reflecting surprise at receiving an unexpected reward—is higher in acutely ill patients.
A defining functional change is the over-activity observed in brain regions responsible for cognitive control and inhibition, such as the lateral prefrontal cortex. This hyperactivity provides a mechanism for the compulsive nature of the disorder, allowing powerful inhibition of the drive to eat despite extreme hunger. Functional connectivity studies suggest a “top-down” control mechanism, where higher-order cognitive areas override normal signals from subcortical appetite centers like the hypothalamus.
The circuit responsible for interoception, the sense of the internal physiological state, is profoundly affected. The insula, a region involved in sensing hunger, fullness, and emotional states, shows volume alterations that may impair the accurate recognition of internal body signals. This disruption means individuals may struggle to identify true hunger or satiety cues, contributing to the persistent misinterpretation of their body’s needs.
The Neurochemical Landscape
The functional disruptions in AN are underpinned by a dysregulated neurochemical environment involving key neurotransmitters and peripheral hormones. Serotonin (5-HT), which regulates mood, anxiety, and appetite, has been extensively studied, with abnormalities potentially predating the illness. Starvation may temporarily decrease serotonin activity, which can reduce anxiety in vulnerable individuals, providing a reinforcing, calming effect for the restrictive behavior.
When re-feeding begins, serotonin levels can increase or “spike,” which may paradoxically trigger intense anxiety and emotional distress. This spike contributes to the difficulty of weight restoration, as the body’s return to a healthy state is experienced as psychologically aversive. Altered serotonin activity, including receptor sensitivity, may persist even after long-term recovery, indicating an enduring vulnerability to anxiety and perfectionism.
Dopamine, a neurotransmitter associated with motivation, pleasure, and reward, also shows dysregulation. Altered dopamine signaling is linked to the compulsive behaviors and the modified reward response seen in AN. Hypotheses suggest that altered processing of dopamine may contribute to temperament traits often associated with the disorder, such as harm avoidance and high anxiety.
Peripheral appetite hormones that communicate with the brain’s hypothalamic centers are dramatically affected by starvation. Ghrelin, the primary hunger-stimulating hormone, is found at significantly increased levels in acutely ill patients, reflecting the body’s attempt to signal the need for energy. Conversely, Leptin, the hormone released by fat cells to signal satiety, is drastically decreased due to the lack of adipose tissue. This creates a powerful, yet overridden, biological state of intense hunger and low satiety signaling, which cognitive control circuits suppress.
Brain Response to Nutritional Recovery
Many of the brain changes observed in acute AN are not permanent and show a significant capacity for reversal with nutritional rehabilitation. The structural changes, including reductions in gray and white matter volume, are largely considered state-dependent, meaning they are a direct consequence of the malnourished state. With sustained weight gain and restoration of normal nutritional status, the brain’s volume often increases, and ventricular enlargement recedes.
Studies tracking patients over time show that the volume of both gray and white matter can approach normalization within months to a few years following successful weight restoration. This demonstrates the remarkable neuroplasticity of the brain, particularly in younger patients. While structural healing is often robust, functional and neurochemical normalization can take longer and may not be entirely complete.
Underlying vulnerabilities related to circuitry function, such as altered serotonin activity, may persist for years, suggesting they are a trait or scar of the illness. Weight restoration is a necessary and foundational first step for neurological healing. However, it must be followed by targeted psychological interventions to address the lingering functional and chemical dysregulation. Sustained nutritional recovery provides the resources the brain needs to repair and stabilize its complex systems.