2026 ECNP Congress

PS03-3236

Immunological differences between first-episode psychosis with and without circulating auto-antibodies: preliminary findings from the PHLAMES study

Alessandro Pigoni — M. Rocchetti, G. Delvecchio, A. Mandrini, A. Ferro, A. Callari, S. Scaranzin, C. Morandi, T. Bovo, M. Bellani, M. Gastaldi, P. Brambilla · Fondazione IRCCS Ca’ Granda- Ospedale Maggiore Policlinico- Milan- Italy, Department of Neurosciences and Mental Health, Milano, Italy

2026 ECNP Congress

Introduction

The recent years witnessed an increase in the knowledge and awareness regarding autoimmune encephalitis (AE). These autoimmune entities present often with mixed psychiatric and neurologic features and in up to 4% of the cases the presentation is purely psychiatric.

AE are characterized by autoimmune Neuronal Surface Autoantibodies (NSAbs), that can be found in the Cerebro Spinal Fluid and are pathognomonic. The diagnosis can be made only through the discovery of such NSAbs in the Cerebro Spinal Fluid, but symptoms and signs of possible and probable diagnosis have been described [1].

However, NSAbs can be found also in peripheral blood in various percentages of patients, even without the clinical syndrome of AE. The role of these antibodies in psychiatric patients is not yet known.

On these bases, first episode psychosis (FEP) patients were recruited in the PHLAMES study with the double aim of evaluating for signs and symptoms of AE in a psychiatric setting and assessing the role of circulating NSAbs in psychiatric patients.

Aims

The objective of the present study is to assess for differences in immunological markers between FEP with and without circulating NSAbs.

Methods

162 patients with FEP were recruited as part of the PHLAMES Study, in three different sites (Milano, Pavia, Verona). Clinical and sociodemographic characteristics were obtained at baseline. All the subjects underwent blood exams to test for circulating serum antibodies against brain structures (for a total of 13 different antibodies, including NMDAR, GAD, LGI1, CASPR2, GABA-R, AMPAR). Similarly they were tested for mRNA expression of 11 immunological genes, able to distinguish different subtypes of psychotic patients based on previous literature [2].

Gene expression levels were compared between groups defined by nabs_siero across 11 genes. Differences between groups were assessed using two-sample t-test allowing for unequal variances.

For each gene, the magnitude of the difference in expression between groups was quantified using the log fold change (logFC), calculated as the difference between mean log-transformed expression values in the two groups (group 1 - group 0). Positive logFC values indicate higher expression in the nabs-positive group, while negative values indicate higher expression in the nabs-negative group.

Results

Of the 162 patients, 22 showed circulating autoantibodies against brain structures (NSAbs-POS-FEP), while the remaining part of the subjects did not (NSAbs-NEG-FEP).

No significant differences were observed between groups in age (p = 0.59), body mass index (p = 0.67), or sex distribution (p = 0.70), indicating comparable baseline characteristics between groups.

The only gene the showed a significant difference between the 2 groups was PTX3 (p = 0,02), which was more expressed in the NSAbs-NEG-FEP

Conclusions

One single gene was significantly different in our sample, namely PTX3. Interestingly, this protein, part of the pentraxins family, has been involved in in the regulation of immune responses, tissue remodeling and oncosuppressive processes [3]. Its role in psychosis is not clear yet, and future studies should confirm this aspect.

References

  1. Pollack, et al., Lancet Psychiatry, 2020. doi: 10.1016/S2215-0366(19)30290-1
  2. Enrico, et al., Mol Psychiatry, 2023. doi: https://doi.org/10.1038/s41380-022-01911-1
  3. Chiari, et al., Front Endocrinol, 2023. doi: 10.3389/fendo.2023.1146017.