In recent years, coeliac disease has increasingly been recognised not merely as a simple enteropathy, but as a systemic, immune-mediated condition capable of affecting organs and systems far beyond the gut. Among its extraintestinal manifestations, neurological and psychiatric symptoms represent a field that is as significant as it is still under-recognised in clinical practice. A recent narrative review published in Frontiers in Pediatrics proposes viewing coeliac disease as a genuine model of autoimmunity involving the gut-brain axis, examining the spectrum of neuropsychiatric manifestations, the pathophysiological mechanisms underpinning them, and the response to a gluten-free diet (1). In this article, we analyse the key points of the review to assist clinicians in recognising and managing these presentations, with a focus on the differences between paediatric and adult patients.

Neuropsychiatric manifestations may appear at the onset of the disease or during its course, and in some cases represent the sole clinical sign at diagnosis.

It is estimated that around one fifth of coeliac patients develop neurological manifestations such as:

• Peripheral neuropathy: reported in up to 39% of patients with coeliac disease. It may precede, or occur without, gastrointestinal symptoms and typically presents with loss of sensation and distal, symmetrical paraesthesia
• Gluten-induced ataxia: an immune-mediated condition affecting the cerebellum, typically presenting with progressive gait ataxia, slurred speech (dysarthria) and abnormal eye movements.
• Epilepsy: some evidence points towards an increased risk of epilepsy in young coeliac patients (2).
• Headache, memory problems, attention difficulties and sleep disturbances.

On the psychiatric front, a meta-analysis of 37 studies documents an increased risk in coeliac patients of autism spectrum disorders, ADHD, anxiety, eating disorders and depression (3) . The latter is particularly significant: the prevalence of major depressive disorder in coeliac patients is markedly higher than in control groups (31% vs 7%), with symptoms often preceding diagnosis.

The review (1) summarises various mechanisms through which exposure to gluten can lead to neurological damage or a psychiatric disorder:

A gluten-free diet (GFD) remains the cornerstone of treatment, including for neuropsychiatric manifestations, but the response varies and depends on the type of manifestation and the timeliness of intervention. Indeed, according to the literature, psychiatric symptoms tend to improve after just three months on the diet, and ADHD in children within six months. In the case of gluten-induced ataxia, early diagnosis and dietary intervention can halt progression before permanent anatomical damage occurs, whilst peripheral neuropathy has a less predictable response.

Depression, on the other hand, is more persistent and may require dedicated psychological support. One finding is particularly relevant for follow-up: persistent serological positivity (due to non-adherence to the diet) is a key risk factor for cerebellar atrophy, confirming the importance of strict adherence and regular monitoring.

In practical terms, the review proposes specific guidelines for different specialists (1):

1. For the gastroenterologist: routinely assess neurological and psychiatric symptoms, correct micronutrient deficiencies and refer early to a specialist in the event of persistent symptoms despite a GFD.
2. For the neuropsychiatrist: suspect coeliac disease in atypical or treatment-resistant forms of depression, anxiety, ADHD, ASD or schizophrenia, and monitor psychiatric symptoms that affect adherence and quality of life.
3. For the neurologist: consider coeliac disease in cases of ataxia, neuropathies, epilepsy (with occipital calcifications), headaches or cognitive decline of unknown origin, and test for coeliac serology in refractory neurological cases.

The review in Frontiers in Pediatrics reinforces the view of coeliac disease as a systemic condition with a broad spectrum of extraintestinal manifestations, ranging from mild cognitive impairments to severe neurological and psychiatric presentations.

For clinicians, the message is clear: we must remain highly vigilant regarding atypical presentations of coeliac disease and establish a multidisciplinary approach that integrates gastroenterology, neurology, psychiatry and nutrition.

Early diagnosis, a strict and well-balanced gluten-free diet, and constant clinical and serological monitoring remain the key tools for preventing neurological damage and improving patients’ quality of life, in both children and adults.