Multiomic Diagnostics in Youth With Psychosis

Rady Children's Institute for Genomic Medicine seeks to understand the genomes and immune systems in 15 children and adolescents who are admitted to Rady Children's Hospital Child and Adolescent Psychiatry Service with psychotic symptoms or schizophrenia. Cutting-edge genome and protein sequencing technology will be used to better understand how immunological and genetic assessments may improve our ability to identify the cause of psychosis and impact care. The investigator also hopes to identify new genetic and/or autoimmune causes of psychosis that may inform new treatment for future patients.

Schizophrenia is a severe mental illness that often starts in late adolescence or early adulthood where individuals experience changes in how they perceive and interact with the world around them (psychosis). These extreme changes in how one perceives and interacts with the world can cause great distress and have a very negative impact on one's life. In most cases, the cause of schizophrenia or psychosis is unknown. However, in a small subset of people who develop schizophrenia or psychosis, their own immune system creates antibodies that attack the brain, which leads to psychosis (autoimmune psychosis). In another subset of patients, there are specific genetic changes that serve as major risk factors for developing psychosis. Identifying autoimmune and genetic factors associated with psychosis with psychosis can inform diagnosis, treatment and prognosis. However, it is still currently unknown how frequently these autoimmune and genetic factors are present in adolescents presenting to the hospital with their first psychotic episode and whether testing for them impacts care. The investigator proposes a deep analysis of both genomes and immune systems of 15 children and adolescents who are admitted to Rady Children's Hospital Child and Adolescent Psychiatry Service with new psychotic symptoms or schizophrenia. The investigator plans to use cutting-edge genome and protein sequencing technology to better understand how immunological and genetic assessments may improve our ability to identify the cause of psychosis and impact care. The investigator also hopes to identify new genetic and/or autoimmune causes of psychosis that may inform new treatments for future patients.

These participants will be subject to whole genome sequencing and Phage ImmunoPrecipiation sequencing (PhIP-Seq) to identify genetic changes and novel antibodies associated with psychosis.

Whole Proteome programmable phage display immunoprecipitation sequencing will be used to diagnose known and novel autoantibodies.

Diagnostic rate of brain reactive autoantibodies via genomic and whole human proteome programmable phage display immunoprecipitation sequencing (PhIP-Seq)

Inclusion Criteria: Individual in whom one of the following criteria is met: Child/adolescent admitted to the Rady Children's CAPS with symptoms of first break psychosis OR Biological parents of child/adolescent enrolled in this study for the purposes of reflex testing. Family members are eligible for participation in this study if they are presumed genetically related to a patient participant. Exclusion Criteria: Child/Adolescent patients who do not meet any of the inclusion criteria, or those who: Already received any prior whole genome sequencing or exome sequencing. Unable to approach the family or patient for enrollment. Unable to obtain informed consent. Family members are ineligible for participation in this study if: They are known to not be genetically related to the child/adolescent patient participant They are a member of a protected research population