Eating Disorders — Anorexia and Bulimia

Eating disorders comprise a spectrum of psychiatric illnesses characterized by severe disturbances in eating behaviors and related thoughts and emotions, resulting in significant impairment of physical health and psychosocial functioning. Anorexia nervosa (AN) is characterized by severe dietary restriction and relentless pursuit of thinness, while bulimia nervosa (BN) involves recurrent binge eating followed by compensatory behaviors such as purging. These conditions have the highest mortality rate of any psychiatric disorder, with anorexia nervosa carrying a standardized mortality ratio of 5.9-6.7, substantially elevated from the general population. Prevalence of AN is approximately 0.3-1% in females and 0.1-0.3% in males during lifetime, while BN affects 1-3% of females and 0.3-0.5% of males. Recognition of eating disorders is critical for medical students and residents because patients frequently present with medical complications rather than psychiatric chief complaints, and early identification dramatically improves outcomes and reduces mortality risk.

The pathophysiology of eating disorders involves complex interactions between neurobiological, psychological, and social-cultural factors that create a self-perpetuating cycle of disordered eating behavior.

The primary regulator of appetite and satiety resides in the hypothalamus, which integrates signals from multiple neurotransmitter systems. In anorexia nervosa, malnutrition induces profound disruption of hypothalamic function through multiple mechanisms: reduced leptin secretion (the satiety hormone produced by adipose tissue) paradoxically increases hunger signals while the hypothalamus becomes desensitized to these signals; ghrelin (the orexigenic hormone from the stomach) remains elevated despite inadequate caloric intake, creating a disconnect between hunger and food consumption; and neuropeptide Y (NPY), which promotes feeding, is reduced. This creates a state where the biological imperative to eat is actively suppressed by disordered cognition. The hypothalamic-pituitary-adrenal (HPA) axis becomes dysregulated with elevated basal cortisol levels, blunted adrenocorticotropic hormone (ACTH) response to corticotropin-releasing hormone (CRH), and resistance to dexamethasone suppression—changes that persist despite weight restoration and normalize only with full psychological recovery. Additionally, thyroid hormone secretion is reduced (sick euthyroid syndrome), growth hormone secretion becomes dysregulated, gonadotropin-releasing hormone (GnRH) is suppressed (causing hypogonadism and amenorrhea), and the prolactin response to thyrotropin-releasing hormone (TRH) is blunted. In bulimia nervosa, these same axis abnormalities are present but typically less severe because the disorder does not involve the extreme caloric restriction of AN.

Dysregulation of serotonergic, noradrenergic, and dopaminergic systems is central to the pathophysiology of both AN and BN. Serotonin (5-HT) dysfunction is the most implicated: individuals with eating disorders frequently demonstrate reduced central serotonin activity, which contributes to obsessive-compulsive features (rigid food rules, ritualistic eating behaviors), perfectionism, and anxiety. The serotonin transporter (5-HTT) polymorphism has been associated with increased eating disorder susceptibility. Malnutrition further depletes tryptophan availability (the amino acid precursor to serotonin), creating a vicious cycle where undereating reduces serotonin synthesis, which paradoxically increases the compulsion to restrict (because low serotonin worsens mood and anxiety, driving further restriction as a coping mechanism). Dopamine dysfunction, particularly in the mesolimbic reward pathway, appears to reduce the hedonic response to food and increase reward sensitivity to weight loss and control behaviors—this suggests eating disorders may involve aberrant reward processing where restriction and weight loss become addictive substitutes for normal food-related reward. Norepinephrine abnormalities, including elevated plasma norepinephrine in AN, contribute to hyperarousal, anxiety, and obsessive rumination. These neurotransmitter changes partially persist after weight restoration, suggesting they may represent trait markers of vulnerability rather than purely state-dependent consequences of malnutrition.

Twin studies demonstrate heritability of approximately 56% for AN and 62% for BN, indicating substantial genetic contribution. Multiple candidate genes have been identified through genome-wide association studies (GWAS), including genes involved in: appetite regulation (FTO, BDNF), metabolism (MTIF2), and psychiatric comorbidity (COMT, involved in dopamine metabolism). However, no single gene is deterministic; rather, eating disorders appear polygenic with multiple common variants each contributing small effect sizes. Epigenetic modifications (DNA methylation and histone acetylation) affecting genes involved in stress response and reward processing have been identified in individuals with eating disorders, and these modifications may be influenced by early adversity and environmental stressors. The critical insight is that genetic vulnerability likely predisposes to certain temperament traits (perfectionism, harm avoidance, obsessionality) that increase susceptibility when combined with environmental triggers such as dieting, social pressure regarding appearance, or specific life stressors.

Neuroimaging studies reveal significant structural and functional abnormalities in eating disorders: reduced grey matter volume in the anterior cingulate cortex (involved in decision-making and error detection), dorsolateral prefrontal cortex (DLPFC, involved in inhibitory control and rational decision-making), insula (involved in interoception and body awareness), and temporal regions. These structural changes are partially reversible with weight restoration but may persist in chronic cases. Functional abnormalities include hyperactivity in the anterior insula during viewing of food or body images (heightened interoceptive awareness and anxiety), abnormal activation patterns in the amygdala (enhanced emotional reactivity), and reduced connectivity in circuits underlying impulse control. White matter integrity is reduced, particularly in tracts connecting prefrontal regions to limbic structures, compromising the ability to use rational thought to override emotional impulses toward restriction or binge eating.

A core feature of eating disorders involves marked distortion in the perception of body size and shape despite objective evidence to the contrary. The insula, which processes interoceptive information (signals from internal organs), shows both structural abnormalities and abnormal activation patterns in response to body-related stimuli. This suggests that individuals with eating disorders have fundamentally altered perception of their body state—they may literally perceive themselves as larger than reality. Additionally, the posterior insula, which integrates visceral sensations with emotional responses, may be dysregulated, leading to inappropriate emotional reactions to hunger or fullness cues. This interoceptive dysfunction is thought to contribute to the profound body image distortion and the inability to accurately perceive satiety signals.

Severe caloric restriction and malnutrition induce compensatory metabolic adaptations that paradoxically reinforce the disorder: resting metabolic rate decreases by 20-30% in an attempt to conserve energy; protein catabolism increases as the body breaks down muscle tissue for gluconeogenesis; fat stores become preferentially mobilized; and thermoregulation is impaired. These changes create a state where the body becomes increasingly efficient at surviving on minimal calories, allowing individuals to continue restricting without immediate acute collapse. Specific nutrient deficiencies further perpetuate dysfunction: phosphate depletion impairs ATP synthesis and cellular energy; potassium depletion increases cardiac arrhythmia risk and neural dysfunction; zinc depletion worsens taste perception (creating a vicious cycle where food becomes less palatable, promoting further restriction); and iron depletion causes fatigue that paradoxically may be attributed to being "weak" and therefore requiring more exercise. Glucose metabolism is impaired, with reduced hepatic glucose production and altered pancreatic beta-cell function, predisposing to hypoglycemia.

Family history is one of the strongest risk factors for eating disorders: first-degree relatives of individuals with AN have a 10-12 times increased risk of developing AN themselves, and a 5-fold increased risk of developing BN. Twin studies demonstrate that genetic factors account for the majority of heritable variance in eating disorder susceptibility. Importantly, genetic vulnerability typically manifests as temperament traits (perfectionism, harm avoidance, constraint, reduced impulsivity in AN; impulsivity and behavioral disinhibition in BN) rather than as a specific drive to restrict calories. These traits only develop into clinical eating disorders when combined with environmental triggers.

Perfectionism, defined as setting excessively high standards and engaging in harsh self-criticism for failure, is one of the strongest psychological correlates of eating disorder development and is elevated premorbidly (present before illness onset). Obsessive-compulsive traits and rumination perpetuate the disorder through rigid food rules and obsessive calorie counting. Negative urgency (the tendency to engage in rash behaviors when experiencing negative emotions) and low self-directedness predispose particularly to BN with its episodic loss of control during binges. Anxiety disorders, particularly obsessive-compulsive disorder, often predate eating disorder onset. Depression, though often concurrent with eating disorders, may be partially secondary to the neurobiological effects of malnutrition and weight loss (which trigger dopaminergic dysregulation). Emotion dysregulation—the difficulty in identifying and managing emotions—is a core feature of bulimia nervosa in particular, with binges often serving as maladaptive emotion regulation strategies.

Although not present in all individuals with eating disorders, childhood trauma (physical or sexual abuse) is reported in approximately 30% of individuals with eating disorders, substantially higher than general population rates. Trauma may interact with genetic vulnerability to increase eating disorder risk through multiple mechanisms: altered HPA axis responsiveness; disrupted trust in bodily sensations (particularly relevant in sexual abuse); and maladaptive emotion regulation strategies. Additionally, parental criticism regarding appearance and weight, parental modeling of restrictive eating or body dissatisfaction, and perfectionist family cultures create environmental vulnerability.

Western societies' idealization of thinness (particularly for females) and emphasis on physical appearance create powerful environmental pressures. Social media exposure, thin-ideal internalization, and comparison with peer appearances have emerged as significant risk factors, particularly in adolescent females. The prevalence of dieting in childhood predicts later eating disorder development. Participation in appearance-focused (modeling, dance, gymnastics) or weight-sensitive (wrestling, rowing, distance running) activities substantially elevates risk. Peer groups with shared appearance concerns amplify risk through social contagion effects. Notably, while sociocultural factors are important, they are not sufficient for eating disorder development—populations exposed to identical thin-ideal pressures show substantial variation in who develops eating disorders, highlighting the importance of genetic and individual vulnerability.

Type 1 diabetes mellitus increases eating disorder risk, particularly eating disorders with "diabulimia" (intentional insulin restriction to control weight). Hyperthyroidism, inflammatory bowel disease, and celiac disease may be complicated by eating disorder development. Medications including topiramate (which causes weight loss), stimulants (which suppress appetite), and certain selective serotonin reuptake inhibitors (SSRIs) may trigger or exacerbate eating pathology in vulnerable individuals.

While approximately 90% of individuals with AN and 85% of those with BN are female, males with eating disorders represent an underdiagnosed population with potentially worse outcomes due to delayed recognition. The mean age of onset for AN is 16-17 years (peak onset in late adolescence), while BN typically onset is 18-21 years. Developmental vulnerability in adolescence relates to: pubertal weight and body changes; identity formation; and peer socialization around appearance. Males with eating disorders often present with muscularity-focused variants (termed "muscle dysmorphia" or reverse anorexia) characterized by excessive exercise, steroid use, and preoccupation with insufficient muscle mass.

The defining behavioral feature is severe dietary restriction leading to a body mass index (BMI) substantially below expected for age, sex, and height. In adults, AN is diagnosed when BMI falls below 17.5 kg/m² (approximately 85% of expected body weight), though the threshold is adjusted for children and adolescents using growth charts. Patients restrict calories through various mechanisms: eliminating entire food groups (particularly fats and carbohydrates), eating only "safe foods" (often limited to vegetables and diet products), and rigid rules about meal timing and food preparation. The restriction is often accompanied by excessive exercise that seems inconsistent with the patient's caloric intake and physical state—a hallmark finding that should raise suspicion. Importantly, patients frequently underestimate their degree of restriction and deny its severity, and they may openly acknowledge the harmfulness of their behavior while remaining unable to modify it, reflecting the ego-syntonic nature of the illness.

The subjective experience involves intense fear of weight gain that persists despite objectively low weight, and profound body image disturbance where patients perceive themselves as overweight despite frank emaciation. This perceptual distortion is not merely a belief but appears to reflect altered sensory processing of body-related stimuli. Preoccupation with food, weight, and body shape becomes all-consuming, with patients spending hours contemplating meals, planning restriction, exercising, and weighing themselves multiple times daily. The disease becomes a form of identity and pseudo-achievement—patients derive a profound sense of control and accomplishment from successful restriction, and weight loss becomes equated with success and self-worth.

The physical examination reflects the profound metabolic consequences of malnutrition. Vital sign abnormalities include significant bradycardia (resting heart rate often 35-50 bpm even in young patients, reflecting parasympathetic predominance), orthostatic hypotension and postural tachycardia, and hypothermia (core body temperature may be 35-36°C). These findings reflect both compensatory metabolic adaptation and loss of thermoregulatory capacity.

Integumentary findings include: fine body hair (lanugo) on the face, arms, and trunk (the body's adaptation to reduce heat loss in the setting of reduced subcutaneous fat); dry, brittle skin and nails; calluses on the dorsal hands and knuckles (Russell's sign, from contact with teeth during purging, though not present in all individuals who purge); and hair loss (telogen effluvium from protein depletion and micronutrient deficiency).

Skeletal examination reveals severe muscle wasting with prominent bony prominences—ribs, vertebral spinous processes, iliac crests, and shoulders become visibly prominent, and the examiner's hands may meet in the middle of the back when assessing for thoracic kyphosis. Bone density is dramatically reduced (osteoporosis or osteopenia present in 50-80% of individuals with AN), predisposing to fractures with minimal trauma; furthermore, young patients with AN paradoxically show accelerated bone loss, and the bone loss may not fully recover even after weight restoration and menstrual function normalization, representing a critical long-term consequence.

Cardiac examination may reveal a midsystolic click if mitral valve prolapse is present (common in eating disorders), diminished heart sounds from reduced cardiac mass, and cardiac arrhythmias including supraventricular ectopy.

Extremity examination shows evidence of volume depletion—reduced skin turgor, sunken eyes and cheeks, and in severe cases, dependent edema (paradoxically present in some individuals despite severe malnutrition, likely due to hypoalbuminemia and venous insufficiency).

Neurological examination may reveal cognitive slowing, difficulty with concentration, and in severe cases, signs of thiamine deficiency (Wernicke encephalopathy with ophthalmoplegia, ataxia, and confusion) though this is uncommon.

Amenorrhea (cessation of menses for ≥3 consecutive months) is a cardinal feature, though it has been removed from the formal diagnostic criteria in DSM-5 as patients may maintain menses through oral contraceptive use or may remain amenorrheic after weight restoration due to other factors. Amenorrhea develops through multiple mechanisms: suppression of GnRH pulsatility by reduced leptin and elevated cortisol; reduced estrogen production by depleted adipose tissue; and direct effects of malnutrition on ovarian function. The amenorrhea reflects reproductive shutdown in the setting of insufficient energy availability—the body's priority is survival, not reproduction. In adolescent girls, menarche may be delayed or menstruation may never establish despite otherwise typical pubertal progression. Males with AN experience reduced testosterone, erectile dysfunction, and reduced fertility.

Unlike AN, individuals with BN maintain body weight within the normal range (BMI typically 18.5-24.9 kg/m²), though some may be overweight. The defining feature is recurrent binge eating episodes (at

Diagnosis is clinical — there is no confirmatory laboratory test. Testing serves to exclude mimics and to grade medical instability.

Step 1 — decide inpatient vs outpatient (medical stabilization first): Per the APA 2023 eating disorders guideline and Society for Adolescent Health and Medicine criteria, hospitalize for bradycardia (heart rate roughly in the 40s or below, or lower in adolescents), hypotension, orthostatic instability, hypothermia, arrhythmia or marked QT prolongation, electrolyte derangement, hypoglycemia, severe/rapid weight loss, or failure of outpatient care. Correct potassium, magnesium, and phosphate before and during feeding, and give thiamine before carbohydrate loading.

Step 2 — nutritional rehabilitation is the definitive therapy for anorexia nervosa. Weight restoration reverses most endocrine, cognitive, and marrow abnormalities. Advance calories with daily electrolyte monitoring for refeeding syndrome; cardiac monitoring for the severely malnourished.