S6108 Beyond the Gut: Psychosis as an Early Manifestation of Celiac Disease

Introduction: Neuropsychiatric manifestations are a rare but recognized complication of celiac disease/gluten sensitivity, occurring in up to 22% of patients: ranging from epilepsy, cerebellar ataxia, peripheral neuropathy, schizophrenia, anxiety, attention-deficit hyperactivity disorder, to depression. The proposed pathomechanism involves cross-reactivity to neural antigens, observed in about 42% of patients. Cross-reactivity to anti-ganglioside antibodies has been documented in patients with cerebellar ataxia and peripheral neuropathy. Schizophrenia, in particular, has strong evidence in case reports where a gluten-free diet led to earlier symptom relief. Conversely, gluten reintroduction led to symptom worsening. Case Description/Methods: A 25-year-old man presented with 6 months of fatigue, 6 kg weight loss, early satiety, and intermittent nausea. He also reported persecutory delusions, visual hallucinations, disorganized thinking, and mood disturbances. Multiple psychiatric evaluations failed to yield a Diagnostic and Statistical Manual of Mental Disorders-5 diagnosis, and medications offered minimal relief. On exam, he had conjunctival pallor, muscle wasting, and a body mass index (BMI) of 17.2 kg/m². He showed food aversion, particularly to wheat. There was no family history of celiac disease or eating disorders. Labs revealed microcytic hypochromic anemia (Hb 9.0 g/dL) and albumin of 3.5 g/dL. Celiac serology was positive for anti-tTG immunoglobulin A and immunoglobulin G. Endoscopy showed scalloping and fissuring of duodenal folds. Duodenal biopsies confirmed celiac disease (Marsh III) with villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes. A strict gluten-free diet (GFD) led to marked improvement in psychiatric symptoms within 2 weeks. Delusions and hallucinations resolved entirely within a month, mood stabilized, and psychotropic medications were discontinued. Nutritional rehabilitation improved appetite, corrected anemia, and increased BMI to 21.4. The patient remains symptom-free on follow-up while continuing a GFD. Discussion: This case highlights the neuropsychiatric spectrum of celiac disease, which may precede or overshadow gastrointestinal symptoms. Gluten may trigger immune-mediated neuroinflammation or malabsorption, leading to mood disorders or psychosis. Guidelines recommend considering celiac disease in unexplained neuropsychiatric cases, especially with nutritional deficiencies. Early diagnosis prevents complications.