Biomarkers/Biotypes, Course of Early Psychosis and Specialty Services

Recruiting

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

• Registration Number: NCT06740383
• Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary

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.

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 Timeline

• Study Start: 2023-01-01
• Study First Submitted: 2024-12-13
• Study First Submitted QC: 2024-12-13
• Study First Posted: 2024-12-18
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-21
• Last Update Posted: 2025-05-25
• Primary Completion: 2027-06-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 320

Inclusion Criteria

• Males and females, all races and ethnicities
• 18-35 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 3 years

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 3o min, history of stroke, AIDS, etc.)
• Comorbid DSM-5 diagnosis of alcohol or substance use disorders in prior 3 months (cases with cannabis use not meeting criteria for cannabis use disorder will be allowed).

MRI-Specific Exclusion Criteria:

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Treatment Response	From enrollment at baseline to end of study at 1 year	\>30% reduction in Positive and Negative Syndrome Scale (PANSS) score
Symptomatic Remission	From enrollment at baseline to end of study at 1 year	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
Functional Remission	From enrollment at baseline to end of study at 1 year	Score ≥ 7 on Global Functioning Role and Social Scales
Relapse	From enrollment at baseline to end of study at 1 year	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.

Trial Locations

Locations (6)

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

University of Georgia; 🇺🇸 Athens, Georgia, United States

University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

McLean Hospital; 🇺🇸 Belmont, Massachusetts, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States