ORCID Profile
0000-0002-6171-0810
Current Organisation
King's College London
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Publisher: Springer Science and Business Media LLC
Date: 19-05-2020
DOI: 10.1038/S41380-020-00899-W
Abstract: Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case–control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2% OR = 1.50 95% CI: 0.58–3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs ( p 0.001). Preliminary phenotypic analyses revealed that within the CHR s le, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task ( p 0.05), and had a markedly lower IQ ( p 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up ( p 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes ( p 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and in idually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current work supports further evaluation of NMDAR autoantibodies as a possible prognostic biomarker and aetiological factor in a subset of people already meeting CHR criteria.
Publisher: Elsevier BV
Date: 2020
DOI: 10.2139/SSRN.3601761
Publisher: American Medical Association (AMA)
Date: 2021
DOI: 10.1001/JAMAPSYCHIATRY.2020.2459
Abstract: Biomarkers that are predictive of outcomes in in iduals at risk of psychosis would facilitate in idualized prognosis and stratification strategies. To investigate whether proteomic biomarkers may aid prediction of transition to psychotic disorder in the clinical high-risk (CHR) state and adolescent psychotic experiences (PEs) in the general population. This diagnostic study comprised 2 case-control studies nested within the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the Avon Longitudinal Study of Parents and Children (ALSPAC). EU-GEI is an international multisite prospective study of participants at CHR referred from local mental health services. ALSPAC is a United Kingdom–based general population birth cohort. Included were EU-GEI participants who met CHR criteria at baseline and ALSPAC participants who did not report PEs at age 12 years. Data were analyzed from September 2018 to April 2020. In EU-GEI, transition status was assessed by the Comprehensive Assessment of At-Risk Mental States or contact with clinical services. In ALSPAC, PEs at age 18 years were assessed using the Psychosis-Like Symptoms Interview. Proteomic data were obtained from mass spectrometry of baseline plasma s les in EU-GEI and plasma s les at age 12 years in ALSPAC. Support vector machine learning algorithms were used to develop predictive models. The EU-GEI subs le (133 participants at CHR (mean [SD] age, 22.6 [4.5] years 68 [51.1%] male) comprised 49 (36.8%) who developed psychosis and 84 (63.2%) who did not. A model based on baseline clinical and proteomic data demonstrated excellent performance for prediction of transition outcome (area under the receiver operating characteristic curve [AUC], 0.95 positive predictive value [PPV], 75.0% and negative predictive value [NPV], 98.6%). Functional analysis of differentially expressed proteins implicated the complement and coagulation cascade. A model based on the 10 most predictive proteins accurately predicted transition status in training (AUC, 0.99 PPV, 76.9% and NPV, 100%) and test (AUC, 0.92 PPV, 81.8% and NPV, 96.8%) data. The ALSPAC subs le (121 participants from the general population with plasma s les available at age 12 years (61 [50.4%] male) comprised 55 participants (45.5%) with PEs at age 18 years and 61 (50.4%) without PEs at age 18 years. A model using proteomic data at age 12 years predicted PEs at age 18 years, with an AUC of 0.74 (PPV, 67.8% and NPV, 75.8%). In in iduals at risk of psychosis, proteomic biomarkers may contribute to in idualized prognosis and stratification strategies. These findings implicate early dysregulation of the complement and coagulation cascade in the development of psychosis outcomes.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 02-2021
Publisher: Elsevier BV
Date: 2017
Publisher: Elsevier BV
Date: 2021
DOI: 10.2139/SSRN.3767901
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Thomas Pollak.