Anorexia Nervosa (AN) is a severe psychiatric disorder characterized by restrictive eating, intense fear of gaining weight, and a distorted body image. Psychosis involves a break from reality, often manifesting as hallucinations or delusions. Clinical observation suggests a connection between these seemingly different disorders. The profound state of starvation in AN may directly trigger psychotic symptoms, pointing toward shared underlying biology. Understanding this relationship requires examining the physical consequences of malnutrition, the dysregulation of brain chemistry, and potential shared genetic predispositions.
The Clinical Co-occurrence of Anorexia and Psychosis
AN and chronic conditions like schizophrenia frequently co-occur in the clinical setting. Studies show that between 3% and 10% of patients with an eating disorder may also meet the criteria for a primary psychotic disorder. Additionally, 10% to 15% of individuals with an eating disorder experience transient psychotic episodes.
Primary psychotic disorders are persistent and rooted in long-term neurological factors. Secondary psychosis, however, is temporary and a direct consequence of a medical or metabolic disturbance. In the context of AN, psychosis is often secondary, meaning the psychotic symptoms—such as auditory hallucinations or paranoia—emerge during periods of severe malnutrition. These transient symptoms usually resolve completely once the patient achieves nutritional rehabilitation, strongly suggesting a cause-and-effect link mediated by the physical state of starvation.
Starvation’s Immediate Impact on Brain Structure and Metabolism
The physiological stress of severe malnutrition directly impacts central nervous system function. The brain relies almost exclusively on glucose for fuel, and chronic glucose deprivation, a hallmark of AN, impairs the activity of brain regions responsible for higher-level cognitive function, particularly the frontal lobes. This metabolic disruption can rapidly lead to cognitive distortions that resemble psychotic features.
Imaging studies reveal a phenomenon known as “starved brain,” characterized by a reduction in both gray and white matter volume, which is often reversible with weight restoration. Gray matter loss, which contains the majority of the brain’s neuron cell bodies, is particularly observed in areas like the precuneus, a region involved in self-processing and self-reflection. The resulting changes in brain size and function can manifest behaviorally as poor concentration, impaired memory, and a rigid, fear-driven mindset.
Severe restriction in AN frequently causes significant electrolyte imbalances, such as dangerously low levels of potassium (hypokalemia) or sodium (hyponatremia). Neuronal signaling relies on the careful movement of these charged ions across cell membranes to fire electrical impulses. When electrolyte concentrations are severely disrupted, this delicate electrical communication breaks down, which can trigger acute delirium, seizures, and transient psychotic symptoms.
Shared Neurotransmitter Dysregulation Pathways
Both AN and primary psychotic disorders share pathways of chemical messenger dysregulation, suggesting a common biological vulnerability. The dopaminergic system, which regulates motivation, reward, and movement, is implicated in both conditions. In psychosis, dopamine overactivity in certain brain pathways is associated with positive symptoms like delusions and hallucinations.
A similar pattern of altered dopamine activity is observed in AN patients, especially in the early stages of the disorder. This hyperactivity may contribute to the characteristic drive and energy seen in severely underweight individuals, or it may reinforce restrictive behavior by altering the brain’s perception of reward. Chronic malnutrition alters the brain’s chemical environment, changing the production, uptake, and sensitivity of dopamine receptors.
The serotonergic system, which influences mood, impulse control, and sensory processing, is also disrupted in AN and psychosis. Prolonged dietary restriction reduces the availability of tryptophan, an amino acid precursor necessary for serotonin synthesis. The resulting drop in serotonin activity is linked to dysphoric mood, increased anxiety, and obsessive thinking patterns common in AN. This neurochemical instability, compounded by dopamine dysregulation, can lead to the emergence of psychotic symptoms.
Genetic and Inflammatory Vulnerabilities
Shared genetic risk factors support the overlap between AN and psychosis. Large-scale genome-wide association studies have identified a considerable polygenic overlap, meaning that many of the same genes that increase the risk for schizophrenia also increase the risk for AN. The shared genetic component is substantial, estimated to be over 60% between AN and schizophrenia.
These shared genetic loci often involve genes highly expressed in brain regions like the hippocampus and the orbitofrontal cortex, which are involved in memory, emotion regulation, and decision-making. This suggests a true shared biological basis for the two conditions. This genetic vulnerability may predispose an individual to developing either AN or psychosis, or both, depending on environmental and physiological stressors.
Neuroinflammation is also a systemic factor linking the two disorders. Chronic starvation in AN acts as a severe physical stressor, leading to an increase in pro-inflammatory markers, or cytokines, circulating throughout the body. These cytokines, such as Interleukin-1 beta (IL-1β) and Tumor Necrosis Factor-alpha (TNF-α), cross the blood-brain barrier and disrupt neurotransmission. Elevated inflammatory markers are also a consistent finding in individuals experiencing a first episode of psychosis.