Possible Contribution of Multiple Sclerosis Pathology to Treatment-Resistant Schizophrenia: A Case Study

Neuropsychopharmacol Rep. 2026 Sep;46(3):e70158. doi: 10.1002/npr2.70158.

ABSTRACT

Multiple sclerosis (MS) can present with neurological and psychiatric symptoms that may overlap with those of schizophrenia, making differentiation difficult particularly because their typical onset ages are similar. We present the case of a woman in her 50s who developed persecutory delusions and a subjective sense of being under surveillance in Year X-31 and was diagnosed with schizophrenia. Despite the long-term antipsychotic treatment, the patient’s symptoms persisted and worsened. In Year X-1, brain magnetic resonance imaging revealed multiple white matter lesions, and then cerebrospinal fluid analysis revealed oligoclonal bands, leading to a diagnosis of MS. Treatment with ofatumumab was initiated. Owing to persistent psychiatric symptoms, clozapine was administered, which showed partial effectiveness. This case highlights the clinical overlap between schizophrenia and MS and suggests that comorbid MS pathology may be clinically relevant in the context of treatment resistance and cognitive impairment. Similarities in symptoms and disease course raise the possibility that a subset of patients with schizophrenia may share pathophysiological features with MS. In addition, postmortem studies, including our previous and current observations, provide hypothesis-generating support for partially overlapping MS-like changes in some patients with schizophrenia. Clinicians should consider the possibility of comorbid MS in patients with treatment-resistant schizophrenia, particularly when atypical clinical or neurological features are present.

PMID:42559701 | DOI:10.1002/npr2.70158