Anorexia nervosa (AN) is a severe mental illness characterized by an intense fear of gaining weight, a distorted body image, and extremely restricted eating. While psychological and social factors contribute to its onset, research highlights the biological mechanisms that underpin its development and persistence. Understanding these biological underpinnings, known as pathophysiology, reveals how the body’s systems are altered and contribute to the disorder’s persistence. This article focuses on these biological aspects, exploring how genetic predispositions, brain alterations, hormonal imbalances, and the gut microbiome play roles in the manifestation of AN.
Genetic and Epigenetic Factors
Individual susceptibility to anorexia nervosa is influenced by genetic predispositions; inherited traits increase the likelihood of developing it. Studies on twins show substantial heritability for AN, with estimates suggesting genetic factors account for approximately 50-70% of the risk. Researchers are investigating gene variations related to metabolic processes, brain function, and personality traits often associated with AN, such as perfectionism or anxiety.
These genetic influences do not mean AN is predetermined, but rather that certain biological vulnerabilities are present. Beyond the direct DNA sequence, epigenetics offers another layer of understanding. Epigenetic mechanisms involve modifications to gene expression that do not alter the underlying DNA sequence, but can turn genes “on” or “off.” Environmental factors, such as early life stress or nutritional deficiencies, can induce these epigenetic changes, potentially influencing an individual’s risk for AN or its severity.
Neurobiological Alterations
The brain undergoes significant structural and functional changes in individuals with anorexia nervosa, impacting perceptions and behaviors. Brain regions involved in reward processing, such as the striatum, show altered activity, potentially explaining why food loses its rewarding properties. This can contribute to the sustained avoidance of eating, despite severe hunger. Furthermore, areas associated with decision-making and cognitive control, like the prefrontal cortex, may exhibit hyperactivity, leading to rigid thinking and an inability to deviate from strict eating rules.
Changes in emotion regulation circuits, including the amygdala, can intensify anxiety around food and weight, making it difficult to challenge restrictive behaviors. Interoception, the sense of the body’s internal state like hunger or fullness, is also often impaired, leading to a disconnect from physiological cues. Neurotransmitter systems, the brain’s chemical messengers, are also dysregulated. Dopamine, involved in reward and motivation, and serotonin, which regulates mood and appetite, show altered levels and receptor sensitivity. This contributes to AN’s characteristic symptoms: distorted body image, intense fear of weight gain, and persistent restrictive eating.
Hormonal and Metabolic Dysregulation
Prolonged starvation and malnutrition in anorexia nervosa lead to significant hormonal imbalances throughout the body. Leptin, a satiety hormone produced by fat cells, becomes severely depleted due to low body fat, yet individuals with AN often do not report increased hunger. Conversely, ghrelin, a hormone that stimulates appetite, may be elevated, but its hunger-promoting effects appear blunted in severe caloric restriction. This complex interplay disrupts normal hunger and satiety signals.
Thyroid hormones, which regulate metabolism and energy expenditure, are significantly suppressed, leading to a slowed metabolic rate as the body tries to conserve energy. Cortisol, a stress hormone, is often elevated, reflecting the chronic physiological stress of starvation and contributing to bone demineralization and other systemic effects. Sex hormones, such as estrogen in females, are also severely reduced, leading to amenorrhea (loss of menstruation) and long-term implications for bone density and reproductive health. The body undergoes metabolic adaptations, shifting from using glucose as a primary energy source to breaking down fat and eventually muscle protein for fuel. This dysregulation not only perpetuates the illness but also has serious health consequences.
Gut-Brain Axis and Immune System
Emerging research highlights the intricate connection between the gut and the brain, known as the gut-brain axis, in anorexia nervosa pathophysiology. The gut microbiota, microorganisms in the digestive tract, can influence brain function, mood, and appetite through various pathways, including producing neurotransmitters and modulating immune responses. In individuals with AN, the composition and diversity of gut bacteria are often significantly altered, a condition known as dysbiosis. This imbalance might contribute to gastrointestinal symptoms common in AN, such as bloating and constipation, and potentially influence mood and anxiety levels.
It is being investigated whether this dysbiosis is a consequence of severe malnutrition or if it actively contributes to the development and perpetuation of AN symptoms. The immune system also plays a role in this complex picture. Chronic malnutrition can suppress immune function, making individuals more susceptible to infections. However, there is also evidence of low-grade inflammation in some individuals with AN, which could be linked to altered gut permeability or other metabolic stressors. This interplay between the gut microbiome, immune system, and brain function represents a promising area for future research into AN’s biological mechanisms.