Cross-Disease Comparisons - Autoantibody Convergence & Diagnostic Heterogeneity

1 Bartley & Ross 2020 — Schizophrenia: A Homecoming

Full Citation:: Bartley CM, Ross DA. Schizophrenia: A Homecoming. Biological Psychiatry. 2020;88(4):e15–e17. DOI:: 10.1016/j.biopsych.2020.06.013 PMID:: 32731925 Published:: August 2020 Study Design:: Historical review Sample Size:: N/A Key Findings::

- Traces autoantibody discovery in schizophrenia from Lehmann-Facius (1937) through Dalmau (2007) to modern unbiased phage display
- Diagnostic heterogeneity as the core barrier — Kraepelin's "dementia praecox" and Bleuler's "group of schizophrenias" parallels current ME/CFS debate
- Historical blind spots created by failure to subgroup: "many schizophrenias" hiding treatable autoantibody-defined subtypes

Conclusion:: Schizophrenia autoantibody research has returned to its origins — understanding autoantibodies as a treatable subgroup. Directly analogous to ME/CFS subgroup discovery. Limitations:: Brief perspective; no original data; limited depth. Certainty:: 0.85/1.0 Research Stream:: schizophrenia-autoantibodies

2 Casanova & Abel 2022 — Rare-to-Common Paradigm

Full Citation:: Casanova J-L, Abel L. From rare disorders of immunity to common determinants of infection: Following the mechanistic thread. Cell. 2022;185(17):3086–3103. DOI:: 10.1016/j.cell.2022.07.004 PMID:: 35985287 Published:: August 2022 Study Design:: Perspective/Review Sample Size:: N/A Key Findings::

- Rare inborn errors → common autoantibody determinants: IFN-α/β autoantibodies in ~15% critical COVID-19
- Paradigm: rare Mendelian mechanisms reveal common autoimmune pathways
- Application: rare autoimmune encephalitis → common autoantibody subgroups in idiopathic psychosis and ME/CFS

Conclusion:: The rare-to-common paradigm has heuristic value for autoantibody research across neuropsychiatric diseases including ME/CFS. Limitations:: Framework piece; not specific to schizophrenia/ME/CFS; no direct data. Certainty:: 0.85/1.0 Research Stream:: schizophrenia-autoantibodies

3 Cullen et al. 2019 — Non-neurological Autoimmune Disorders and Psychosis

Full Citation:: Cullen AE, Holmes S, Pollak TA, et al. Associations Between Non-neurological Autoimmune Disorders and Psychosis: A Meta-analysis. Biological Psychiatry. 2019;85(1):35–48. DOI:: 10.1016/j.biopsych.2018.06.016 PMID:: 30122288 Study Design:: Meta-analysis Sample Size:: 31 studies, >25 million individuals Key Findings::

- Positive overall association: OR 1.26 (95% CI 1.12–1.41, I²=88%)
- Pernicious anemia (OR 1.91), pemphigoid (OR 1.90), psoriasis (OR 1.70), celiac (OR 1.53), Graves (OR 1.33)
- Negative with RA (OR 0.65) — conserved "protective" autoimmune pattern
- Suggests convergent autoantibody mechanisms across diagnostically distinct autoimmune conditions

Conclusion:: Cross-disease autoantibody convergence is supported by elevated psychosis risk across diverse autoimmune disorders. Limitations:: Registry-based diagnoses; no antibody confirmation; cannot distinguish shared genetics from causal autoantibody mechanisms. Certainty:: 0.82/1.0 Research Stream:: schizophrenia-autoantibodies