Literature review sheet covering recent developments in the understanding of the psychoneuroimmunologic aspects of schizophrenia pathogenesis, diagnostic approach, and antibody-specific iatrologic tailoring. I created this sheet as a handout for a brief talk given to a group of psychiatrists, psychiatry residents, and medical students at East Central Regional Hospital in Augusta, GA, USA on Wednesday, September 18, 2019.

1. PSRY 5000 Jackson David Reynolds, BS, AS, AA 9/18/2019
Antibodies & Theranostics in Schizophrenia
Key Takeaways
‣ Anti-N-methyl-D-aspartate-type glutamate receptor
(anti-NMDAR) encephalitis can sometimes present w/
marked psychotic sx (e.g., Brain on Fire by Susannah
Calahan).
‣ Schizophrenic pts w/anti-NMDAR Abs have ↑ sx
severity than anti-NMDAR Ab -ve schizophrenic pts,
despite -ve test for encephalitis.
‣ In schizophrenics, there are at least 20 autoAbs
present at ↑ freq. than in gen. pop., incl., ANA, anti-
cardiolipin, anti-NMDAR, & anti-5HT receptor.
‣ (Doesn’t necessarily mean that any/all are directly
implicated, per se, but is quite suggestive.)
‣ Chicken or egg? (Hopefully egg.)
‣ Two basic approaches to establishing
relationships b/w Ab molecular markers &
psychopathologies (Fig. 1).
‣ Prognostic Abs & Potential Theranostic TX’s:
‣ Prognostic: In pts w/an est. dx of schizophrenia,
severity of dz course (non-suicidality vs. active
suicidality & suicide attempts) +ly correlated w/titer
of Abs to toxoplasma & CMV!
‣ Theranostic (Dx for Tailored TX):
‣ Schizophrenics +ve for anti-NMDAR Abs may
have a primarily glutaminergic (rather than
dopaminergic) pathology, ∴ GLU-modulating RX
may demonstrate ↑ efficacy in sx-reduction in
these pts. (Anti-NMDAR Ab +ve pts were also
found to have ↑ adverse RXNs to F/SGAs (incl.
rhabdomyolysis, NMS-like sx, & EPS)!)
‣ Marked correlation b/t serum & intrathecal IgG
response to bovine milk casein seen in pts w/
first-episode schizophrenia, but not in CTRLs, ∴
pre-screening for diet-engendered Ab responses
may provide an avenue for prophylaxis of
psychotic break via selective dietary abstinence.
Additional Articles of Interest:
• Hanly, et al, Autoantibodies as biomarkers for the prediction of
neuropsychiatric events in systemic lupus erythematosus, Annals of
the Rheumatic Diseases, 2011;70:1726-1732.
• Suvisaari, et al, Is It Possible to Predict the Future in First-Episode
Psychosis? Front Psychiatry, 2018;9:580.
• Pathmanandavel, et al, Autoantibodies and the Immune Hypothesis
in Psychotic Brain Diseases: Challenges and Perspectives, Clinical
and Developmental Immunology, 2013; Article ID 257184.
• Mirzakhanian, et al, Biomarkers in psychosis: An approach to early
identification and individualized treatment, Biomarkers in Medicine,
2014;8(1), 51-57.
• Severance, et al, IgG dynamics of dietary antigens point to
cerebrospinal fluid barrier or flow dysfunction in first-episode
schizophrenia, Brain, Behavior, and Immunity, 2015;44:148-158.
From: Antibodies in the Diagnosis, Prognosis, and Prediction of Psychotic Disorders, 2019, by Pollak, et al
(& other papers)
Fig. 1: Top-Down vs. Bottom-Up Approaches to Linking Specific
Markers w/Specific Psychiatric Conditions (Pollak, et al, 2019)