A Longitudinal Natural History Study of Immune Biomarkers in Neuropsychiatric Illness

Study Description: This study aims to identify and characterize biomarkers in biospecimens collected during clinical care or research encounters, which are not required for clinical or research testing. These "surplus" biospecimens consist of: (1) residual tissue, blood, or CSF remaining after clinical testing is complete; (2) additional blood collected for research purposes at the time of clinical biospecimen collection; (3) residual tissue, blood or CSF collected as part of a human research study; or (4) additional blood collected solely for this research protocol at the same time as biospecimen collection for a separate research protocol from which research blood are already being collected. Additionally, (5) blood will be collected longitudinally from a subset of enrolled participants. Biospecimen categories 1 - 4 do not require an additional venipuncture, whereas 5 does require an additional venipuncture. The biospecimen collection events will occur: (1) at the National Institutes of Health (NIH), (2) at medical centers and academic research institutions, and (3) at commercial phlebotomy facilities in the United States and its affiliated territories. Research activities utilizing the collected biospecimens will occur (1) at the NIH or, after de-identification, in (2) collaborating research laboratories or (3) commercial service facilities. It is anticipated that such studies will yield molecular correlates of and biomarkers for diverse neuropsychiatric illnesses. Objectives: The primary objective of this study is to identify immune factors that improve the diagnosis and classification of individuals with suspected immune-associated neuropsychiatric disorders. The secondary objective is to correlate these immune factors with endotypes and endophenotypes of diverse neuropsychiatric disorders. Endpoints: Primary Endpoints: * Identification of autoantibodies that are recurrently detected and statistically enriched (presence vs absence) in prespecified neuropsychiatric diagnostic or phenotypic subgroups compared with control participants, using twosided Fisher's Exact tests, with adjustment for multiple comparisons as appropriate. * Identification of biomarker signatures that reliably classify psychotic subgroups as distinct from controls. Secondary Endpoints: -Derivation and characterization, when feasible, of research grade human monoclonal autoantibodies from biospecimens of participants with candidate or recurrent autoantibody responses, for use in in vitro and ex vivo mechanistic studies.