Biomarkers/Biotypes, Course of Early Psychosis and Specialty Services (BICEPS)

The Biomarkers/Biotypes, Course of Early Psychosis and Specialty Services (BICEPS) study aims to understand the early stages of psychotic disorders like Schizophrenia, Schizoaffective Disorder, and Bipolar I Disorder. It involves gathering mental health information, brain scans (MRI), eye movement patterns (Eye-Tracking), and brain electrical waves (EEG) data from individuals who have experienced these disorders in recent years. Participants will be involved for about a year, with four visits over this period. Screening procedures, lasting approximately 3 hours, include tests for drug use, a pregnancy test for eligible women, clinical interviews about feelings and experiences, psychiatric and family history interviews, and a medical history review. Research procedures for eligible participants include DNA collection, a neuropsychological test battery, EEG, eye-tracking, and MRI. These procedures will help researchers understand brain function, genetics, and cognitive abilities related to psychotic disorders. Follow-up visits at 1-month, 6-month, and 12-month intervals involve modified clinical interviews and repeating neuropsychological tests to track changes over time. Participants may opt to provide DNA samples for genetic analysis, undergo various cognitive tests, EEG to record brain waves, eye-tracking to monitor eye movements, and MRI scans to visualize brain structure. Follow-up visits at regular intervals will help researchers track changes in symptoms and cognitive function. This study provides comprehensive insight into the onset and progression of psychotic disorders and offers valuable information for patients, families, and healthcare providers involved in managing these conditions. Our goal is to better understand whether a combination of biological markers and different types of people (BT1, BT2, BT3) can help us predict how well individuals with early psychosis respond to specialized care. We expect that those in BT3 will have the best outcomes, BT2 will have intermediate outcomes, and BT1 will have the poorest outcomes. Even though BT1 and BT2 might start with similar cognitive issues, their biology might lead to different responses to treatment. This research can help us understand which treatments work best for different people with early psychosis.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Schizoaffective Disorder; Delusional Disorder; Bipolar 1 Disorder; Psychosis Not Otherwise Specified; Early Psychosis

Detailed Description

This proposal seeks to characterize the early course of psychotic disorders and to identify clinical and biological predictors of outcome. The large sample (=320) required will necessitate a multi-site study. All B-SNIP sites have coordinated specialty services for early course psychosis and have harmonized study procedures for uniform data collection. Each site will recruit 1/5 of the participants; The project will be managed by an all-site steering committee meeting weekly. Boston will be the coordinating site.

The outcome of early course psychosis (EP) is heterogeneous, ranging from early full recovery to treatment resistance and functional decline from the onset of illness. The ability to predict individual level outcomes would be highly valuable for treatment planning and for tailoring the duration and intensity of psychosocial and pharmacological interventions. Clinical features related to early psychosis onset are poor predictors of remission and recovery. At the same time, the field has not yet established the clinical utility of promising findings from decades of biomarker development/neuroscience research, especially in EP patients for whom empirically guided treatment planning may have the greatest impact. For example, neurocognitive, electroencephalographic (EEG) and imaging biomarkers early in the illness may predict outcome, but used individually, their prognostic value is limited. Multivariate approaches to clinical and neurobiological features may offer better value for outcome prediction.

Toward this goal, we will leverage the biomarker (EEG, eye movement testing, and neurocognition) based categorization of a cross-diagnostic sample of psychosis (biotypes) developed, replicated and validated by our Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) consortium. We have shown that Biotype-1, characterized by impaired cognition and decreased sensorimotor responses to salient stimuli is associated with the most severe impairments in functioning. Biotype-2 have the same level of cognitive impairment as Biotype-1 but increased sensorimotor reactivity. Biotype-3 cases are relatively normal on these measures and have the least impairments. These subgroups are not synonymous with DSM diagnosis and are not captured by any individual variable. We do not know if this categorization is predictive of symptomatic and functional outcome, given the cross-sectional design of B-SNIP. We will use the B-SNIP battery with EP participants in the context of Coordinated Specialty Care (CSC) treatment programs for EP available at established B-SNIP sites. Our overall goal is to identify biomarkers/Biotypes that predict clinical and functional outcome to CSC in EP. This success could guide targeted interventions in CSC programs. For those unlikely to have a successful CSC outcome, other targeted interventions could be developed and implemented. We have active EP Clinics in the consortium; each will enter about16 patients/year, 80/year overall, providing 320 EP (schizophrenia, schizoaffective disorder, psychotic bipolar disorder and schizophreniform disorder participants with approximately 240 completer cases, assuming 25% attrition) enrolled during the first 4 years of the proposed funding period. All EP cases will be tested with B-SNIP biomarker assessments at baseline, and the clinical and cognition assessments will be repeated at 1, 6, and 12 months. We will use an adapted version of the B-SNIP biomarker battery (called ADEPT) which can be implemented in under-resourced, community settings.

SIGNIFICANCE AND BACKGROUND FOR THE STUDY Schizophrenia and related psychoses cause enormous suffering for affected individual and their families and caregivers. They have a lifetime prevalence of around 3%, and cost ~ $155 billion per year in direct healthcare and indirect societal costs in the USA [5]. Relapse and poor response to treatment contribute to a significant illness burden due to high rates of hospitalization and poor social and occupational functioning. About 20% of early course psychosis (EP) cases relapse in year 1, and about 40% by year 2 [6]. Mortality is increased four-fold in EP compared to the general population [7]. EP outcomes are highly variable [8] with multiple trajectories, i.e. episodic vs persistent, initial remission vs treatment resistance [9-11]. Given this heterogeneity, actionable outcome predictors are needed to reliably individualize care for EP [12].

• Study Type: Observational
• Enrollment (Estimated): 320

Contacts and Locations

• Study Contact: Name: Matcheri S. Keshavan, MD; Phone Number: 617-754-1256; Email: mkeshava@bidmc.harvard.edu
• Study Contact Backup: Name: Brendan Stiltner, BA; Email: bstiltne@bidmc.harvard.edu

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Recruiting
      • Hartford Hospital
      • Contact: Godfrey Pearlson, MA, MBBS; Phone Number: 860.545.7757; Email: Godfrey.Pearlson@HHChealth.org
      • Principal Investigator: Godfrey Pearlson, MA, MBBS
  • Georgia
    • Athens, Georgia, United States, 30602
      • Recruiting
      • University of Georgia
      • Contact: Brett Clementz, PhD; Phone Number: 706-542-2174; Email: clementz@uga.edu
      • Principal Investigator: Brett Clementz, PhD
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
      • Contact: Sarah K. Keedy, PhD; Phone Number: 773-834-7178; Email: skeedy@bsd.uchicago.edu
      • Contact: Elliot S. Gershon, MD; Email: egershon@bsd.uchicago.edu
      • Principal Investigator: Sarah S. Keedy, PhD
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • Recruiting
      • McLean Hospital
      • Contact: Kathryn E. Lewandowski, PhD; Phone Number: 617-855-2886; Email: klewanowski@mclean.harvard.edu
      • Principal Investigator: Kathryn E Lewandowski, PhD
    • Boston, Massachusetts, United States, 02215-5400
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Matcheri S. Keshavan, MD; Phone Number: 617-754-1256; Email: mkeshava@bidmc.harvard.edu
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
      • Contact: Carol Tamminga, MD; Phone Number: 214-404-2284; Email: carol.tamminga@UTSouthwestern.edu
      • Principal Investigator: Carol Tamminga, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants are recruited from 5 different sites across the United States including Boston, Dallas, Hartford, Chicago, and Georgia. The target population for this study includes individuals who meet DSM-5 criteria for a psychotic disorder (i.e., schizophrenia, schizophreniform, schizoaffective disorder, bipolar I disorder or major depression with psychotic features, delusional disorder, or psychosis N.O.S.). Participants will be between 18 and 40 years of age, males and females, of all races and ethnicities who are experiencing early course psychosis.

Description

Inclusion Criteria:

• Males and females, all races and ethnicities
• 18-40 y/o
• Meet DSM-5 criteria for a psychotic disorder, i.e. schizophrenia, schizophreniform, schizoaffective disorder, or bipolar I disorder or major depression with psychotic features, delusional disorder or psychosis N.O.S.
• Able to read, speak, and understand English
• Able and willing to provide written informed consent, and willing to commit to the study protocol
• Illness duration from psychosis onset less than or equal to 4 years
• At baseline only: receiving both psychopharmacology and psychotherapy

Exclusion Criteria:

• Estimated premorbid intellectual ability <70 (WRAT-4, Word Reading subtest, age-corrected standardized score)
• Neurological or medical disorder that may affect brain function (seizure disorder, traumatic brain injury with a loss of consciousness greater than or equal to 30 min, history of stroke, AIDS, etc.)
• Psychoses secondary to substance use i.e., Comorbid DSM-5 diagnosis of alcohol or substance use disorders that may explain the diagnosis of psychotic disorders (individuals with cannabis use disorders unrelated to psychosis onset will be allowed. Participants encouraged to abstain from substances for 24 hours prior to lab visits)

MRI-Specific Exclusion Criteria:

• Pregnant women
• Presence of ferromagnetic objects in body
• Weight or body size exceeding scanner capacity (>300 lbs)
• Claustrophobia

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Individuals with Early Psychosis enrolled in Coordinated Specialty Care Clinics; In this naturalistic longitudinal study, we administer the B-SNIP biomarker batter to individuals with Early Psychosis (EP) in EP clinics with Coordinated Specialty Care treatment programs to characterize outcome trajectories and biotypes. EP individuals of both sexes, age 18-40 will be included after they meet study criteria and provide informed consent. Individuals with psychosis duration < 4 years will be included. Individuals in this cohort of EP are diagnosed with Schizophrenia, Schizoaffective Disorder, Schizophreniform, Bipolar I Disorder with psychotic features, Delusional Disorder, Major Depressive Disorder with psychotic features, and Psychosis Not Otherwise Specified.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Response	>30% reduction in Positive and Negative Syndrome Scale (PANSS) score	From enrollment at baseline to end of study at 1 year
Symptomatic Remission	Score of ≤ 3 on 8 core on the Positive and Negative Syndrome Scale (PANSS) items (P1, P2, P3, 1, N4, N6, N7, G5, and G9) for at least one month	From enrollment at baseline to end of study at 1 year
Functional Remission	Score ≥ 7 on Global Functioning Role and Social Scales	From enrollment at baseline to end of study at 1 year
Relapse	1) Positive and Negative Syndrome Scale (PANSS) score of ≥ 4 for a psychosis item (P1, P2, P3, and P6) and ≥ 25% increase on the total PANSS score or ≥ 10 points and 2) an increased level of care, i.e. hospitalization, ER visits, etc.	From enrollment at baseline to end of study at 1 year

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: National Institute of Mental Health (NIMH); Yale University; University of Chicago; University of Texas Southwestern Medical Center; University of Georgia; Hartford Hospital; Mclean Hospital
• Investigators: Principal Investigator: Matcheri S. Keshavan, MD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: December 13, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): December 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: schizophrenia; schizoaffective disorder; psychosis; bipolar disorder; Biomarkers; major depression; schizophreniform; delusional disorder; Biotypes; coordinated specialty care
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Mood Disorders; Depressive Disorder; Schizophrenia; Psychotic Disorders; Bipolar Disorder; Depressive Disorder, Major; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia, Paranoid
• Other Study ID Numbers: 2022P000622; R01MH127174-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study team includes a dedicated staff member, Noora Al-Musawe, who is responsible for data preparation and sharing. Since the beginning of the study and during the reporting period, we have been adherent with the data sharing plan and guidelines. The study has been registered in NIH/NIMH Data Archive (NDA) (Study#: C4330). Data Submission Agreement is in place. The data will be uploaded to NDA during regular data sharing cycles.
• IPD Sharing Time Frame: January 1st 2023 until June 30th 2028, one year after study completion
• IPD Sharing Access Criteria: The study has been registered in NIH/NIMH Data Archive (NDA) (Study#: C4330). Data Submission Agreement is in place. The data will be uploaded to NDA during regular data sharing cycles.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No