PSYCHOTIC MANIFESTATIONS IN PRIMARY SJÖGREN’S SYNDROME: CLINICAL CHARACTERISTICS AND PATHOPHYSIOLOGICAL INSIGHTS
Abstract
Psychotic manifestations in primary Sjögren’s syndrome (SS) represent a rare but clinically meaningful complication of the disease. The aim of this paper was to analyze the clinical characteristics, potential pathophysiological mechanisms, therapeutic approaches, and outcomes of psychotic symptoms in patients with SS.
A narrative review of the available literature was conducted, with particular focus on case reports and small case series describing psychosis in the context of SS.
Psychotic manifestations in SS may arise from central nervous system involvement, immune-inflammatory mechanisms, cytokine dysregulation, and neurotransmitter alterations, as well as from corticosteroid therapy. Pro-inflammatory cytokines, particularly interleukin-6, have been linked to dopaminergic dysfunction and the emergence of positive psychotic symptoms. Corticosteroids may induce psychotic episodes depending on dose and duration of treatment. Chronic somatic symptoms, including ocular and oral dryness, pain, and fatigue, may be vulnerable to delusional misinterpretation. In several reported cases, psychotic symptoms improved following immunosuppressive therapy, supporting a potential immune-mediated subtype of psychosis in this population.
Psychosis in primary Sjögren’s syndrome likely has a multifactorial etiology. Early recognition of a possible autoimmune basis is essential, as treatment strategies may require immunomodulatory therapy in addition to standard psychiatric management.
References
André F, Böckle BC. Sjögren's syndrome. J Dtsch Dermatol Ges. 2022;20(7):980-1002. doi:10.1111/ddg.14823
Bombardieri M, Argyropoulou OD, Ferro F, Coleby R, Pontarini E, Governato G, et al. One year in review 2020: pathogenesis of primary Sjögren’s syndrome. Clin Exp Rheumatol. 2020;38Suppl 126:3-15.
Wong JK, Nortley R, Andrews T, D'Cruz D. Psychiatric manifestations of primary Sjögren's syndrome: a case report and literature review. BMJ Case Rep. 2014;2014:bcr2012008038. doi:10.1136/bcr-2012-008038
El-Ouakhoumi A, Joulal H, Yousfi J, Benjilali L, Zahlane M, Essaadouni L. Refractory depressive disorder as the first manifestation of adolescent Sjögren's syndrome, successfully treated with rituximab. Eur J Case Rep Intern Med. 2024;11(7):004621. doi:10.12890/2024_004621
Wang N, Jin Y, Lu S, Li G, Li Y, He J. Central nervous symptoms as the prominent manifestation of Sjögren's disease: a case report. BMC Neurol. 2026;26(1):97. doi:10.1186/s12883-026-04630-0
Morreale M, Marchione P, Giacomini P, Pontecorvo S, Marianetti M, Vento C, et al. Neurological involvement in primary Sjögren syndrome: a focus on central nervous system. PLoS One. 2014;9(1):e84605. doi:10.1371/journal.pone.0084605
Kilciksiz CM, Keefe R, Benoit J, Öngür D, Torous J. Verbal memory measurement towards digital perspectives in first-episode psychosis: a review. Schizophr Res Cogn. 2020 ;21:100177. doi: 10.1016/j.scog.2020.100177.
Perzyńska-Mazan J, Maślińska M, Gasik R. Neurological manifestations of primary Sjögren's syndrome. Reumatologia. 2018;56(2):99-105. doi: 10.5114/reum.2018.75521.
Skorić J, Pavković B. Infectious mononucleosis and autoimmune hepatitis. Sanamed. 2021;16(1):91-4. doi: 10.24125/sanamed.v16i1.502.
Barsottini OGP, Moraes MPM, Fraiman PHA, Marussi VHR, Souza AWS, Braga Neto P, et al. Sjogren's syndrome: a neurological perspective. ArqNeuropsiquiatr. 2023;81(12):1077-83. doi:10.1055/s-0043-1777105.
Peschard-Franco M, Piña-Rosales E, García-Santos A. A 56-year-old woman with initial severe electrolyte imbalance who developed altered mental status, psychosis and catatonia. Neurohospitalist. 2025;16(1):19418744251364125. doi:10.1177/19418744251364125.
van Leeuwen N, Bossema ER, Van Middendorp H, Kruize AA, Bootsma H, Bijlsma JW, et al. Dealing with emotions when the ability to cry is hampered: emotion processing and regulation in patients with primary Sjögren's syndrome. Clin Exp Rheumatol. 2012;30(4):492-8.
Alessitimia e pathway immunoendocrino nel lupus eritematoso sistemico e nell'artrite reumatoide [Alexithymia and immunoendocrine parameters in patients affected by systemic lupus erythematosus and rheumatoid arthritis]. Reumatismo. 2008;60(1):50-6. doi:10.4081/reumatismo.2008.50. [Article in Italian]
Ozdemir E, Xiao Z, Griffiths H, MacBeth A. Alexithymia in schizophrenia and psychosis vulnerability: a systematic review and meta-analysis. J Clin Psychol. 2025;81(6):410-24. doi:10.1002/jclp.23788.
van der Velde J, Swart M, van Rijn S, van der Meer L, Wunderink L, Wiersma D, et al. Cognitive alexithymia is associated with the degree of risk for psychosis. PLoS One. 2015;10(6):e0124803. doi:10.1371/journal.pone.0124803.
de Oliveira FR, Fantucci MZ, Adriano L, Valim V, Cunha TM, Louzada-Junior P, et al. Neurological and inflammatory manifestations in Sjögren's syndrome: the role of the kynurenine metabolic pathway. Int J Mol Sci. 2018;19(12):3953. doi:10.3390/ijms19123953.
de Oliveira FR, Appenzeller S, Pasoto SG, Fernandes MLMS, Lemos Lopes ML, de Magalhães Souza Fialho SC, et al. Recommendations on neurologic, cognitive, and psychiatric manifestations in patients with Sjögren's disease by the Brazilian Society of Rheumatology. Adv Rheumatol. 2025;65(1):7. doi:10.1186/s42358-025-00438-7
Catalán A, Aymerich C, Rodríguez-Sánchez JM, Pedruzo B, Salazar de Pablo G, Gil P, et al. Peripheral inflammation and neurocognitive functioning in early psychosis: specific associations of TNF-α and IL-6 with social cognition. Eur Psychiatry. 2025;68(1):e95. doi:10.1192/j.eurpsy.2025.10063.
Speers LJ, Bilkey DK. Inflammation in schizophrenia: the role of disordered oscillatory mechanisms. Cells. 2025;14(9):650. doi:10.3390/cells14090650.
Gostoli S, Carrozzino D, Raimondi G, Subach R, Gigante G, Rafanelli C. Corticosteroid-induced manic and/or psychotic symptoms: a systematic review. Front Pharmacol. 2025;16:1628765. doi:10.3389/fphar.2025.1628765.
El Kodsi S, Elouadoudi J, Denani M, Alfa MA, Laffinti MA. Severe corticosteroid-induced mania with psychotic features in an HIV-positive patient: a case report. Cureus. 2025;17(12):e99486. doi:10.7759/cureus.99486.
Sofía-Avendaño-Lopez S, Rodríguez-Marín AJ, Lara-Castillo M, Agresott-Carrillo J, Lara-Cortés LE, Sánchez-Almanzar JF, et al. Molecular, pathophysiological, and clinical aspects of corticosteroid-induced neuropsychiatric effects: from bench to bedside. Biomedicines. 2024;12(9):2131. doi:10.3390/biomedicines12092131.
Cerullo MA. Corticosteroid-induced mania: prepare for the unpredictable. Curr Psychiatr. 2006;5:43-50.
Bachu AK, Davis V, Abdulrahim M, Harbaugh L, Prasad S, Kotapati VP, et al. Corticosteroid-induced psychosis: a report of three cases. Cureus. 2023;15(5):e39221. doi:10.7759/cureus.39221.
Nasereddin L, Alnajjar O, Bashar H, Abuarab SF, Al-Adwan R, Chellappan DK, et al. Corticosteroid-induced psychiatric disorders: mechanisms, outcomes, and clinical implications. Diseases. 2024;12(12):300. doi:10.3390/diseases12120300.
Canessa-Muñoz S, Yelmo-Cruz S, Hamilton-Lopez A, Baez-Marrero C. Corticosteroid-induced psychosis: a report of two cases and review of the literature. Cureus. 2025;17(3):e81515. doi:10.7759/cureus.81515.
National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Committee on Selected Immune Disorders and Disability. Selected immune disorders and disability. Washington (DC): National Academies Press; 2022.
Tashbayev B, Rusthen S, Young A, Herlofson BB, Hove LH, Singh PB, et al. Interdisciplinary, comprehensive oral and ocular evaluation of patients with primary Sjögren’s syndrome. Sci Rep. 2017;7(1):10761. doi:10.1038/s41598-017-10809-w.
Ngo DYJ, Thomson WM, Nolan A, Ferguson S. The lived experience of Sjögren’s syndrome. BMC Oral Health. 2016;16:7. doi:10.1186/s12903-016-0165-4.
Pienkos E, Giersch A, Hansen M, Humpston C, McCarthy-Jones S, Mishara A, et al. Hallucinations beyond voices: a conceptual review of the phenomenology of altered perception in psychosis. Schizophr Bull. 2019;45(Suppl 1):S67-77. doi:10.1093/schbul/sby057.
Reeves RR, Torres RA. Exacerbation of psychosis by misinterpretation of physical symptoms. South Med J. 2003;96(7):702-4. doi:10.1097/01.SMJ.0000078686.34109.11.
Lin CE. One patient with Sjogren’s syndrome presenting schizophrenia-like symptoms. Neuropsychiatr Dis Treat. 2016;12:661-666. doi:10.2147/NDT.S97753.
Hammett EK, Fernandez-Carbonell C, Crayne C, Boneparth A, Cron RQ, Radhakrishna SM. Adolescent Sjogren’s syndrome presenting as psychosis: a case series. Pediatr Rheumatol Online J. 2020;18(1):15. doi:10.1186/s12969-020-0412-8.
PT S, Jacob JA, Modi U, George D. Primary Sjogren's syndrome presenting as acute psychosis with catatonic symptoms. Indian J Psychiatry. 2022;64(Suppl 3):S687-8. doi:10.4103/0019-5545.342028.
Rosado SN, Silveira V, Reis AI, Gordinho A, Noronha C. Catatonia and psychosis as manifestations of primary Sjögren’s syndrome. Eur J Case Rep Intern Med. 2018;5(6):000855. doi:10.12890/2018_000855.
Inagaki T, Kudo K, Kurimoto N, Aoki T, Kuriyama K. A case of prolonged catatonia caused by Sjögren’s syndrome. Case Rep Immunol. 2020;2020:8881503. doi:10.1155/2020/8881503.
Mardale DA, Opriș-Belinski D, Bojincă V, Bojincă M, Mazilu D, Păsăran E, et al. The physical and psychosocial impact of fatigue among patients with Sjögren’s syndrome: a systematic review. J Clin Med. 2023;13(6):1537. doi:10.3390/jcm13061537.
Sampogna G, Di Vincenzo M, Giuliani L, Menculini G, Mancuso E, Arsenio E, et al. A systematic review on the effectiveness of antipsychotic drugs on the quality of life of patients with schizophrenia. Brain Sci. 2023;13(11):1577. doi:10.3390/brainsci13111577.
Lazović B, Blažić I, Zlatković-Švenda M, Zugić V. Severe pneumonia caused by antipsychotic drugs – what does not suit, the patient or the drug? Sanamed. 2018;13(3):307-10. doi: 10.24125/sanamed.v13i3.257.
Mohamed AA, Almulhim AS, Alnijadi AA, Abd Aziz Fb, Alajmi KK, Al-Mudhaffar AA, et al. Evaluation of prescription patterns of antipsychotics in schizophrenia patients: a single-center prospective study. J Clin Med. 2025;14(9):2941. doi:10.3390/jcm14092941.
Vallianatou K. Antipsychotics. Medicine (Baltimore). 2024;52(9):573-6. doi:10.1016/j.mpmed.2024.06.016.
Inić T, Stanković Stevanović N, Čuturić B, Cvjetković Bošnjak M, MešiBosić V. Psychotic presentation as a first clinical manifestation of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis – case report. MD-Medical Data. 2025;17(3):179–183.
Copyright (c) 2026 Sanamed

This work is licensed under a Creative Commons Attribution 4.0 International License.
Journal Sanamed is published under an Open Access license. All its content is available free of charge. Users can read, download, copy, distribute, print, search the full text of articles, as well as establish HTML links to them, without having to seek the consent of the author or publisher.
The right to use content without consent does not release the users from the obligation to give the credit to the journal and its content in a manner described under CC BY.
