Evidence briefing

Organic causes of first-episode psychosis

Written by a language model from the cited research, from 4 full texts and the abstracts of the other 8. No human author wrote or checked this text. Not peer reviewed.

Generated 21 August 2026 · 12 sources cited, 2020–2026 · Full text read for 4 of 12 sources · Not peer reviewed

Subjectorganic causes for psychosis

QuestionWhat identifiable medical, neurological, autoimmune, endocrine and infectious conditions can produce psychotic symptoms, particularly at first episode, and how often are they found.

AnswerOrganic causes appear to be identified in a minority of first-episode psychosis presentations. Estimates include 5.6 percent in a review focused on ages 15 to 30 years and approximately 14 percent when toxic aetiologies are counted. A meta-analysis estimated clinically relevant magnetic resonance imaging abnormalities in 5.9 percent of first-episode patients, whereas a young-adult cohort reported management-changing findings in 1.2 percent of scans. Reviews list dozens of mostly rare neurological, autoimmune, endocrine, genetic and infectious aetiologies. Case reports document conditions such as anti-NMDA receptor encephalitis, thyroid disease, Wilson disease and neurosyphilis that may prove treatable after initial attribution to primary psychosis. International guidelines appear inconsistent on routine investigation. Evidence comes from reviews, one imaging meta-analysis, a retrospective cohort and cases; no controlled comparison of screening protocols exists.

Keywords first-episode psychosis; organic psychosis; autoimmune encephalitis; anti-nmda receptor encephalitis; neuroimaging; secondary psychosis; thyroid disease; wilson disease

What the evidence shows

Every figure in this review was located in the material read for the cited sources — their abstracts, and the open-access full text where one was retrieved.

A systematic review of 569 articles identified ninety possible aetiologies or groups of aetiologies that can cause first-episode psychosis in people aged 15 to 30 years and reported an organic origin in 5.6% of first-episode psychosis.¹
A scoping review listed 84 physical health disorders that may present with psychosis, most of them rare and typically accompanied by neurological or systemic features, while a review of 25 guidelines found marked heterogeneity in recommended investigations beyond metabolic screening.²
A random-effects meta-analysis of 12 magnetic resonance imaging studies (1613 patients with first-episode psychosis) estimated that 26.4% had any intracranial radiological abnormality and 5.9% (95% CI 3.2%–9.0%) had a clinically relevant abnormality, a number needed to assess of 18.³
In a 10-year retrospective cohort of 812 patients aged 18–40 years admitted with first-episode psychosis, 421 (51.8%) underwent MRI; 20.0% of scans showed radiological abnormalities, but findings were reported to change diagnosis or treatment in only 5 patients (1.2%).⁴
A narrative review described autoantibody-associated autoimmune encephalitides, including anti-NMDA-R encephalitis, as putative secondary schizophreniform psychoses that typically begin with acute polymorphic psychotic symptoms and later seizures, movement disorders or reduced consciousness, and outlined stepwise antibody testing.⁵
A clinical article reported that an organic or toxic etiology is identified in approximately 14% of first-episode psychosis cases and outlined a proposed protocol using laboratory alterations and clinical red flags for urgent neurological referral.⁶
Two case reports described anti-NMDAR encephalitis apparently presenting as first-episode psychosis. A 26-year-old woman progressed to coma with an ovarian teratoma, antibodies confirmed after immunotherapy and resection.⁷ A 25-year-old man developed cognitive deficits, dyskinesia, seizures and an extreme delta brush electroencephalogram, with cerebrospinal fluid antibodies confirmed after empirical immunotherapy.⁸
Case reports have identified other apparently treatable organic causes after an initial psychiatric label. These included severe hypothyroidism with anti-TPO antibodies in a 39-year-old man previously treated for schizophrenia⁹ and Graves disease presenting with psychosis in a 47-year-old woman whose symptoms resolved after thyroid normalisation.¹⁰ They also included Wilson disease in an 18-year-old man after abnormal copper studies¹¹ and neurosyphilis in a 67-year-old woman whose late-onset psychosis had been attributed to schizophrenia.¹²

Methods

Search strategy. Candidate records were retrieved on 21 August 2026 from Semantic Scholar Graph API, OpenAlex and Europe PMC, using the search strings ‘organic psychosis etiology’; ‘psychotic disorder due to another medical condition’; ‘secondary psychosis neurological causes’; ‘anti-NMDA receptor encephalitis psychosis’. Records without a retrievable abstract were discarded, leaving 40 for screening. Each remaining record was assessed for how directly it addresses organic causes for psychosis and labelled direct, related or background; 12 were cited here and are listed in Table 1.

Evidence handling. Titles and abstracts were read for every record, and the open-access full texts of 5 sources were retrieved from their open-access copies and read alongside them (4 of which are cited here and marked in Table 1); claims resting on the remaining sources draw on no data beyond an abstract. Decimals, percentages, effect estimates and quantities carrying a clinical unit were then checked automatically, each against the sources its own sentence cites, within exactly the material shown to the model — the abstracts plus those full-text excerpts. A figure that could not be located, or that appears only in a source other than the one cited, is flagged under Limitations.

Generation. Search planning, source curation and drafting were performed by a large language model (x-ai/grok-4.6). Source retrieval, relevance tabulation, citation numbering, Table 1, Fig. 1 and the statistical check are deterministic and were not model-generated.

Evidence assessment

Of the 12 sources cited, 12 address the review question directly, 0 are related and 0 provide background only; they were published in 2020–2026. The composition of the evidence base is shown in Fig. 1.

Limitations. This synthesis was prepared from the open-access full texts of 4 cited sources and the abstracts of the remaining 8. Where only an abstract was available, effect estimates, methodological detail, and the limitations that authors report only in a full text were unavailable, so the strength of those studies could not be appraised here.

Table 1 | Characteristics of the cited evidence. Design is inferred from each record's title, journal and index metadata and is left blank where it could not be inferred; no quality appraisal was performed. Relevance is the curation label for how directly each source addresses the review question. Read records whether the model saw the source's open-access full text or its abstract only.

Ref.	Study	Year	Source	Design	Relevance	Read
1	Tesnières et al.	2026	L'Encephale	—	Direct	Abstract
2	Warren et al.	2026	The Australian and New Zealand journal of psychiatry	—	Direct	Full text
3	Blackman et al.	2023	JAMA Psychiatry	—	Direct	Abstract
4	Khorsandian et al.	2026	BMC psychiatry	Observational	Direct	Full text
5	Endres et al.	2020	European Archives of Psychiatry and Clinical Neuroscience	—	Direct	Abstract
6	Salamoni et al.	2026	Revue medicale suisse	—	Direct	Abstract
7	Ko et al.	2025	Cureus	—	Direct	Abstract
8	Mourad et al.	2025	Case reports in psychiatry	Observational	Direct	Abstract
9	Tahir et al.	2026	Malaysian family physician : the official journal of the Academy of Family Physicians of Malaysia	—	Direct	Full text
10	Ahmad & Man	2026	Cureus	Observational	Direct	Full text
11	Sowell & Gracious	2025	HCA healthcare journal of medicine	Observational	Direct	Abstract
12	Nutile	2021	American Journal of Psychiatry Residents Journal	—	Direct	Abstract

Glossary

first-episode psychosis: The first clinical presentation of psychotic symptoms, which may reflect a primary psychiatric disorder or an identifiable organic disease.
autoimmune encephalitis: Brain inflammation driven by autoantibodies against neuronal antigens, which can begin with psychiatric symptoms that mimic primary psychosis.
clinically relevant neuroradiological abnormality: An intracranial imaging finding that leads to a change in diagnosis or treatment.
anti-NMDA receptor encephalitis: An autoimmune encephalitis associated with antibodies against the NMDA receptor, often presenting with acute psychosis, seizures and autonomic instability.

References

Tesnières, C., Meunier, S. & Dollfus, S. [Organic causes of first episode psychosis: Review of the literature]. L'Encephale (2026).
Warren, N. et al. Initial physical health assessment for psychosis in Australia and New Zealand: 2026 recommendations. The Australian and New Zealand journal of psychiatry (2026).
Blackman, G. et al. Prevalence of Neuroradiological Abnormalities in First-Episode Psychosis. JAMA Psychiatry (2023). Cited by 43
Khorsandian, M. C. et al. Neuroradiological abnormalities in individuals with first-episode psychosis - a retrospective cohort study. BMC psychiatry (2026).
Endres, D. et al. Autoimmune encephalitis as a differential diagnosis of schizophreniform psychosis: clinical symptomatology, pathophysiology, diagnostic approach, and therapeutic considerations. European Archives of Psychiatry and Clinical Neuroscience (2020). Cited by 108
Salamoni, J. et al. [Organic etiology in first-episode psychosis: when should it be considered ?]. Revue medicale suisse (2026).
Ko, T. et al. From Psychosis to Coma: Diagnostic Pitfalls and Therapeutic Challenges in Anti-N-Methyl-D-Aspartate Receptor (Anti-NMDAR) Encephalitis Associated With Ovarian Teratoma. Cureus (2025). Cited by 1
Mourad, M. et al. Autoimmune Psychosis Exists: Early Diagnosis of an Anti-NMDA Receptor Autoimmune Encephalitis Presenting as First-Episode Psychosis in a 25-Year-Old Male-A Case Report. Case reports in psychiatry (2025).
Tahir, S., Idris, N. S. & Zainudin, A. M. Psychosis with untreated hypothyroidism: How a generalist made a difference. Malaysian family physician : the official journal of the Academy of Family Physicians of Malaysia (2026).
Ahmad, K. A. & Man, M. C. Organic Psychosis Secondary to Untreated Graves' Disease: A Case Report. Cureus (2026).
Sowell, L. C. & Gracious, B. L. Wilson's Disease Psychosis in a Young Man With Autism Spectrum Disorder: A Case Report and Focus on Management. HCA healthcare journal of medicine (2025).
Nutile, L. Neurosyphilis With Psychosis as the Primary Presentation. American Journal of Psychiatry Residents Journal (2021). Cited by 6

Additional information

Data availability. No new data were generated. All evidence cited is published and openly indexed; 12 of the 12 cited records resolve through the links in the reference list.

Author contributions. Search planning, source curation and drafting were carried out by an automated pipeline (articlegen, x-ai/grok-4.6). No human author wrote or verified the text before publication of this draft.

Competing interests. None declared.

Peer review. This article has not been peer reviewed and is not a publication of record.