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Case Report

Late-Onset Psychotic Symptoms Associated With Vitamin B12 Deficiency in a Patient With Celiac Disease

Tomás Teodoro, MD, MSca,b,c,d,*

Published: May 23, 2023

Prim Care Companion CNS Disord 2023;25(3):22cr03405

To cite: Teodoro T. Late-onset psychotic symptoms associated with vitamin B12 deficiency in a patient with celiac disease. Prim Care Companion CNS Disord. 2023;25(3):22cr03405.
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© 2023 Physicians Postgraduate Press, Inc.

aEarly Intervention and First Episode Psychosis Unit, Department of Psychiatry, Centro Hospitalar Psiquiátrico de Lisboa, Lisbon, Portugal
bAdult ADHD and Neurodevelopmental Disorders Outpatient Service, Centro Hospitalar Psiquiátrico de Lisboa, Lisbon, Portugal
cPsychiatry Emergency Department, Hospital São José, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
dCHRC—Comprehensive Health Research Centre, NOVA University Lisbon, Lisbon, Portugal
*Corresponding author: Tomás Teodoro, Department of Psychiatry, Centro Hospitalar Psiquiátrico de Lisboa, Avenida do Brasil 53, 1749-002 Lisbon, Portugal (

Nutritional psychiatry is an emerging field, ranging from dietary strategies to the study of gut microbiota and immune dysregulation and their impact on prevention and treatment of psychiatric disorders.1,2 Cobalamin (vitamin B12) deficiency has been consistently associated with several neuropsychiatric symptoms including seizures, peripheral neuropathy, depression, dementia, and psychosis.3,4 Schizophrenia-like symptoms may present due to other conditions.5–8 Here, a case of chronic hallucinatory psychosis associated with cobalamin deficiency and celiac disease is presented.

Case Report

A 75-year-old woman was admitted to an acute inpatient unit after presenting with auditory hallucinations, persecutory delusions, thought broadcasting, and insomnia. She described several voices commenting on her actions and occasionally insulting her as well as thought echo. She attributed these voices to neighbors and started believing they were conspiring against her and accessing her thoughts. At presentation, timing of symptom onset was unclear but was estimated to have resulted in functional impairment at least 1 month before presentation. The physical and neurologic examination was unremarkable, and there was no recent history of sensory or motor abnormalities. Her Mini-Mental State Examination (MMSE)9 score was 30/30. Laboratory investigations detected mild anemia (hemoglobin: 11.6 mg/dL) and cobalamin deficiency (< 125 pg/mL) but were unremarkable for other causes of psychosis (including brain computed tomography, infectious serologies, and thyroid function).

Clinical records revealed that she first developed psychotic symptoms at age 68 years, with 2 previous admissions since then and discharge diagnoses of delusional disorder and schizoaffective disorder (ICD-10). During her previous admissions, no mood symptoms were described, and the MMSE scores and neuropsychological assessment were within normal limits. Investigations did not include vitamin levels. Since her first admission, she was on monotherapy with risperidone 4 mg/d with partial remission but with periods of poor adherence. Until her first admission for psychosis, she had past psychiatric history of recurrent depressive disorder (ICD-10) with 2 previous mild-moderate depressive episodes but no admissions or psychotic symptoms. Data regarding past antidepressant pharmacologic treatment were unavailable. She had not undergone antipsychotic psychopharmacologic treatment until her first psychiatric admission to the best of our knowledge. Past general medical history included celiac disease diagnosed at age 50 years, and she had been on a gluten-free diet since then. There was no family history of psychiatric disorders.

During this admission, she was treated with a D2 antagonist (olanzapine titrated to 15 mg/d) and intramuscular cyanocobalamin. After starting olanzapine and cobalamin replacement, she had a good clinical response with full remission of delusions in 5 days. Although auditory hallucinations persisted for another week, there was a marked decrease in volume and frequency of these phenomena, with the patient quickly developing insight. She was discharged with her psychotic symptoms in full remission and with good insight. She remained symptom free at several follow-up assessments with her community mental health team and maintained normal cobalamin levels as monitored by her primary care team.


The patient’s presentation is consistent with the historical syndromes of systematized paraphrenia and the French concept of chronic hallucinatory psychosis.10,11 In current classification systems (DSM-5 and ICD-11), these concepts have been incorporated in schizophrenia and the controversial category of schizoaffective disorder.12 Secondary psychotic syndromes are part of the differential diagnosis of any condition presenting as schizophrenia-like psychosis.13 The definite diagnosis of secondary psychosis (organic psychoses) has always been problematic in part due to the challenges in establishing causality and the lack of pathognomonic symptoms.14 Several non-neurologic autoimmune and gastrointestinal conditions, in particular celiac disease, have shown a positive association with psychosis.15,16 Although the patient presented here adhered to the recommended dietary restrictions, it has been reported that deficiencies of cobalamin may persist with a gluten-free diet.17–19 Several vitamin deficiencies have been linked to psychosis.20–24 Cobalamin deficiency, albeit rarely, has also been associated with isolated psychotic symptoms either in absence of or preceding hematologic abnormalities.25–28 Whether there is a direct causal relationship between nutritional deficits and psychosis, or these are epiphenomena with modulatory effects on their complex pathophysiology, clinicians need to be aware of their relevance and include a nutritional assessment as part of the diagnostic workup of new-onset psychotic symptoms at any age.

Published online: May 23, 2023.
Relevant financial relationships: None.
Funding/support: None.
Patient consent: Consent was received from the patient to publish the case report, and information has been de-identified to protect anonymity.
ORCID: Tomás Teodoro:

Volume: 25

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