Peripheral Immune System in Individuals With Schizophrenia

The investigators are seeking healthy volunteers and people with schizophrenia or schizoaffective disorder for a clinical study of the immune system in psychotic disorders. This is an observational study, to understand the ways in which the immune system may be contributing to the disease process.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Schizo Affective Disorder; Schizophreniform Disorders
• Intervention / Treatment: Diagnostic test: SCID (Standardized Clinical Interview for DSM-V); Diagnostic test: PSS (Perceived Stress Score); Diagnostic test: Urine Toxicology Screen; Diagnostic test: Vitals; Diagnostic test: Blood Work; Diagnostic test: COVID Screening; Diagnostic test: Positive and Negative Syndrome Scale (PANSS); Diagnostic test: PQ-B

Detailed Description

Genetic studies have linked the number of copies coding for C4 protein to risk for schizophrenia. Studies examining the amount of mRNA, the molecules that point to how much C4 protein is likely being made, found more C4 mRNA in the brains from individuals with schizophrenia. Studies in mice have suggested that expressing more C4 protein in the brain, specifically the A-type of C4, can result in abnormalities in behavior. However, researchers have also found that pathways that involve this protein in the blood to be abnormal in individuals even before they develop schizophrenia and hypothesize these abnormalities change the blood brain barrier. In this work, the researchers are hoping to understand the ways in which C4 protein is abnormal in the peripheral blood and how this may be contributing to the disease process in hopes of finding new ways of helping individuals with schizophrenia and possibly other mental health disorders. A major goal of this study is to collect blood tissue for ongoing translational study of pathophysiological mechanisms of schizophrenia.

Interested participants will be asked a series of questions about their medical and mental health history, be able to provide informed consent, undergo a urine toxicology screen and be willing to provide a blood sample.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Diane E Wakeham, PhD; Phone Number: 650-736-5243; Email: wakeham@stanford.edu
• Study Contact Backup: Name: Study Coordinator; Phone Number: 650-736-5243

Study Locations

• United States
  • California
    • Stanford, California, United States, 94704
      • Recruiting
      • Stanford University School of Medicine
      • Contact: Diane E Wakeham, PhD; Phone Number: 650-736-5243; Email: wakeham@stanford.edu
      • Contact: Study Coordinator; Phone Number: 650-736-5243
      • Principal Investigator: Jong Yoon, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Patients seen at local outpatient clinics for schizophrenia, local community residents, and volunteers on clinical study database.

Description

Inclusion Criteria for Subjects with schizophrenia and schizoaffective disorders:

• Schizophrenia or schizoaffective disorder diagnosis verified by interview
• Diagnosis or initiation of antipsychotic medication was within last 5 years

Inclusion Criteria for Healthy Controls:

• No known diagnosis of schizophrenia or schizoaffective disorder
• No history of depression, anxiety, bipolar disorder, PTSD, agoraphobia, panic disorder, or generalized anxiety disorder
• Negative assessment for psychotic symptoms on day of interview

Exclusion Criteria (for both groups):

• Participants have a history of bleeding disorders or are taking blood thinners.
• Participants have a history of epilepsy, known genetic disorders
• Immunocompromised state (eg., receiving immunosuppressive therapy, transplant).
• History of brain-related disease (eg., stroke)
• Any uncontrolled medical disorder such as cancer.
• History of substance abuse or positive urine toxicology screen (including test for marijuana) on the day of the blood draw

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Individuals with primary psychotic disorders; Participants who have received any of the following diagnoses: schizophrenia, schizoaffective disorder, or schizophreniform disorder. Participants will have urine toxicology screen, vitals recorded, and blood drawn in a single visit.	Diagnostic test: SCID (Standardized Clinical Interview for DSM-V); The Structured Clinical Interview for DSM-5 (SCID-5) is a semistructured interview guide for a clinician or trained mental health professional to diagnose major mental illnesses.; Diagnostic test: PSS (Perceived Stress Score); The Perceived Stress Scale (PSS) is the most widely used psychological instrument for measuring the perception of stress. It is a measure of the degree to which situations in one's life are appraised as stressful. Items were designed to tap how unpredictable, uncontrollable, and overloaded respondents find their lives. Demographic information will also be collected.; Diagnostic test: Urine Toxicology Screen; Participants will be asked to provide a urine sample. Evidence of active substance abuse (marijuana, opioids, other non-prescription drugs) by the urine toxicology screen will disqualify participants from the study.; Diagnostic test: Vitals; Height and weight will be measured in order to calculate BMI.; Diagnostic test: Blood Work; A venipuncture will be performed for the purpose of collecting blood tissue for study.; Diagnostic test: COVID Screening; Questionnaire to assess risk of transmission of COVID-19.; Diagnostic test: Positive and Negative Syndrome Scale (PANSS); Instrument that is completed by clinical interviewer to measure symptom severity in individuals with psychotic disorders.
Healthy Controls; Healthy participants who do not have any exclusion criteria will undergo an assessment to confirm absence of psychiatric disorder. Participants will have urine toxicology screen, vitals recorded, and blood drawn in a single visit.	Diagnostic test: SCID (Standardized Clinical Interview for DSM-V); The Structured Clinical Interview for DSM-5 (SCID-5) is a semistructured interview guide for a clinician or trained mental health professional to diagnose major mental illnesses.; Diagnostic test: PSS (Perceived Stress Score); The Perceived Stress Scale (PSS) is the most widely used psychological instrument for measuring the perception of stress. It is a measure of the degree to which situations in one's life are appraised as stressful. Items were designed to tap how unpredictable, uncontrollable, and overloaded respondents find their lives. Demographic information will also be collected.; Diagnostic test: Urine Toxicology Screen; Participants will be asked to provide a urine sample. Evidence of active substance abuse (marijuana, opioids, other non-prescription drugs) by the urine toxicology screen will disqualify participants from the study.; Diagnostic test: Vitals; Height and weight will be measured in order to calculate BMI.; Diagnostic test: Blood Work; A venipuncture will be performed for the purpose of collecting blood tissue for study.; Diagnostic test: COVID Screening; Questionnaire to assess risk of transmission of COVID-19.; Diagnostic test: PQ-B; The Prodromal Questionnaire - Brief Version (PQ-B) is a self-report measure designed to identify people who may be experiencing psychotic symptoms when they do not have a schizophrenia diagnosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group comparison of C4 protein in immune cells	Measure the concentration of complement 4 protein in immune cells.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Mass Index and its relationship to C4 protein concentration	The relationship between body mass index, calculated from the measured height and weight of participants, and the primary outcome (C4 protein concentration) will be determined.	Day 1
C4 Gene Copy Number	Determine the C4 Gene Copy Number its relationship to C4 protein concentration in immune cells.	Day 1
C4 Activation	Measure activity of C4 protein and its relationship to the primary outcome.	Day 1
Relationship to symptom presentation	Explore the relationship between clinical severity scores (PANSS) and the primary outcome.	Day 1
Relationship to stress	Explore the relationship between perceived stress (PSS) and the primary outcome.	Day 1

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Jong Yoon, MD, Professor of Psychiatry and Behavior Sciences

Publications and helpful links

General Publications

• Kalinowski A, Liliental J, Anker LA, Linkovski O, Culbertson C, Hall JN, Pattni R, Sabatti C, Noordsy D, Hallmayer JF, Mellins ED, Ballon JS, O'Hara R, Levinson DF, Urban AE. Increased activation product of complement 4 protein in plasma of individuals with schizophrenia. Transl Psychiatry. 2021 Sep 22;11(1):486. doi: 10.1038/s41398-021-01583-5.

Helpful Links

• Laskaris, et.al. Schizophr Res . 2019 Feb;204:30-37.
• Mongan, et. al. Jama Psychiatry 2021;78(1):77-90
• Yilmaz, et. al. Nat Neurosci . 2021 Feb;24(2):214-224.
• Sekar, at al. Nature . 2016 Feb 11;530(7589):177-83.
• Radhakrishnan, et al. Mol Psychiatry . 2021 Jun 16.
• Onwordi, et. al. Transl Psychiatry . 2021 Jul 17;11(1):393.
• Onwordi, et. al. Nat Commun . 2020 Jan 14;11(1):246.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: October 26, 2021
• First Submitted That Met QC Criteria: October 26, 2021
• First Posted (Actual): November 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: psychosis; psychiatry; complement immune system
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mood Disorders
• Other Study ID Numbers: 58926

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No