2026 American Academy of Neurology Autoimmune Abstract Website

Objective:

To determine whether immunomodulation improves the symptoms of patients with likely autoimmune schizophrenic psychosis.

Background:

A consensus exists that schizophrenia is not a single disease, but the final pathway of a variety of still unknown neurobiological derangements. Many patients might have an autoimmune etiology, as suggested by several lines of evidence. First, schizophrenia typically begins in adolescence or early adulthood and courses with remissions and exacerbations. Second, it shares age of onset and psychiatric symptoms with a disorder caused by autoantibodies against the NMDA receptor, known to be downregulated in schizophrenia. Third, several of the leading risk genes associated with schizophrenia in genome-wide association studies code for proteins critical for immunity.

Design/Methods:

A sample of 40 patients ages 18-35 with normal academic performance before age 15 but with schizophrenia defined by the MINI test is being randomized to either ocrelizumab (two infusions of 300 mg IV) or placebo. The outcome is being recorded with the PANSS and cognitive testing multiple times over a period of 18 months.

Results:

In an interim, blinded analysis of 18 patients (age 25.5 ± 4.1 years, 8 women) in both treatment arms who had a 3 month follow up after the second ocrelizumab infusion, results are as follows:

Variable	Baseline Mean	12-Week Mean	Mean Change	% Change
PANSS Positive	19.9	11.9	−7.9	−39.9%
PANSS Negative	19.5	15.0	−4.5	−23.2%
Antipsychotic Dose (mg CPZeq)	381.4	354.5	−26.9	−7.1%
Quality of Life (RQL)	42.8	51.2	+8.4	+19.7%

Conclusions:

The 39.9% reduction in PANSS Positive scores in the overall sample exceeds the conventional 20% benchmark for significant clinical improvement, while the 23.2% reduction in PANSS Negative scores also meets the threshold for meaningful change. The modest 7% decrease in antipsychotic dose suggests improvement was not driven by higher dosing. Quality of life improved by nearly 20%, aligning with functional recovery.