The Nutrition Society Paper of the Month for May is from Nutrition Research Reviews and is entitled ‘The progression of coeliac disease: its neurological and psychiatric implications‘, by Giovanna Campagna, Mirko Pesce, Raffaella Tatangelo, Alessia Rizzuto, Irene La Fratta, Alfredo Grilli

Coeliac Disease (CD) was recently presented by The European Society for Pediatric Gastroenterology, Hepatology and Nutrition, describing it as “… an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals and characterized by a variable of gluten-dependent manifestations, CD-specific antibodies, HLA-DQ2 or HLA-DQ8 haplotypes, and enteropathy” [1]. This broader view of the disease seen as an inflammatory disease is supported by clinical observations of extra-intestinal manifestations such as dermatologic, hepatic, osteologic, endocrine and neurological signs [2].

Untreated CD patients are characterized by more neurological symptoms. Cerebellar ataxia is one of the first symptoms, and one of the most frequently recognized neurological disturbances in CD [3]. It could be followed by other neurological complications, such as epilepsy [4], and peripheral neuropathy that has been evidenced in up to 50% of cases [5]. Nevertheless, adult patients suffering from CD, reported milder to severe forms of cognitive impairment [6]. The milder form is known as ‘brain fog’ which is characterized by the difficulty in concentrating, problems with attentiveness, short-term memory lapses, difficulties in word-finding, temporary loss in mental acuity as well as confusion and/or disorientation [7].

The association of CD with psychiatric disorders has also been identified for a long time. Psychiatric symptoms have been reported as common complications in many patients suffering from CD, though the effects of a diet on one’s mood and psychiatric symptoms remain largely unknown [8]. Psychiatric symptoms usually presented include depressive symptoms, apathy, excessive anxiety, irritability [9], eating disorders [10], attention deficit/hyperactivity disorder [11] and autism [12] as well as sleep disorders that are inversely related to the Quality Of Life [13].

It is still not fully explained how the pathogenic mechanism of CD affects the patient’s mental health, but one hypothesis suggests that it is due to the serotonin imbalance or due to the opioid neuro-transmission caused by gluten and gluten metabolites which effect the Central Nervous System (CNS) [14]. Given that the gastrointestinal tract is connected to the CNS, this means that the communication involves neural pathways as well as immune and endocrine mechanisms. The intestinal barrier prevents toxins, pathogens and antigens in altering the various neuro-active compounds [15].

The existence of a rich gut-to-brain communication increases the possibility that intestinal barrier alterations could take part in the pathophysiology of CNS disorders and therefore determine the neuropsychiatric symptoms [16].

To date, the only treatment for CD with complete remission of the symptoms is a lifetime diet with the total elimination of gluten. Even the ingestion of small amounts of gluten could cause major disruptions, therefore adherence to a gluten-free regimen is effective in the treatment of depression, anxiety and neurological complications associated with CD. While some of these symptoms could improve with a GFD, our advice is to diagnose CD as early as possible, given that delays in the diagnosis could cause severe implications in the nervous system. The importance of an early diagnosis is fundamental and the only treatment available is a GFD to be followed for a lifetime.

The full paper, ‘The progression of coeliac disease: its neurological and psychiatric implications‘ is freely available on Cambridge Core.

Nutrition Society Paper of the Month
Each month a paper is selected by one of the Editors of the five Nutrition Society Publications (British Journal of Nutrition, Public Health Nutrition, Nutrition Research Reviews, Proceedings of the Nutrition Society and Journal of Nutritional Science).

Take a look at at the entire Nutrition Society Paper of the Month collection

1. Husby S et al. (2012) European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. Celiac position statement for pediatric celiac disease. J Pediatr Gastroenterol Nutr 54, 136-160.
2. Uygur-Bayramicli O & Melih Özel A (2011) Celiac Disease Is Associated with Neurological Syndromes. Dig Dis Sci 56, 1587–1588.
3. Fasano A (2003) Celiac disease: How to handle a clinical chameleon. New England Journal of Medicine 348, 2568–2570.
4. Ludvigsson JF et al. (2012) Increased risk of epilepsy in biopsy-verified celiac disease: A population-based cohort study. Neurology 78, 1401–1407.
5. Parisi P et al. (2015) Role of the gluten-free diet on neurological-EEG findings and sleep disordered breathing in children with celiac disease. Seizure 25, 181–183.
6. Lurie Y, Landau DA, Pfeffer J et al. (2008) Celiac disease diagnosed in the elderly. J Clin Gastroenterol 42, 59–61.
7. Theoharides C et al. (2015) Brain “fog,” inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin. Frontiers in Neuroscience 9, 1–11.
8. Cicarelli G, Della Rocca G, Amboni M et al. (2003) Clinical and neurological abnormalities in adult celiac disease. Neurol Sci 24, 311–317.
9. Bushara KO (2005) Neurologic Presentation of Celiac Disease. Gastroenterology 128, S92–S97.
10. Karwautz A, Wagner G, Berger G et al. (2008) Eating pathology in adolescents with celiac disease. Psychosomatics 49, 399–406.
11. Niederhofer H, Pittschieler K (2006) A preliminary investigation of ADHD symptoms in persons with celiac disease. J Atten Disord 10, 200–204.
12. Barcia G, Posar A, Santucci M, Parmeggiani A (2008) Autism and coeliac disease. J Autism Dev Disord 38, 407–408.
13. Zingone F et al. (2010) The quality of sleep in patients with coeliac disease. Aliment Pharmacol Ther 32, 1031–1036.
14. Kukla U (2015) Mental disorders in digestive system diseases – internist’s and psychiatrist’s insight. Pol Merkur Lekarski 38, 245-249.
15. González-Arancibia C (2016) What goes around comes around: novel pharmacological targets in the gut–brain axis. Ther Adv Gastroenterol 9, 339–353.
16. Julio-Pieper M et al (2014) Intestinal barrier dysfunction and central nervous system disorders – a controversial association. Aliment Pharmacol Ther 40, 1187–1201.