Biomarkers in First Episode Schizophrenia

This study will identify and evaluate relevant biomarkers and structural brain imaging for understanding potential biological illness related mechanisms in medication-naïve subjects with early psychosis before and after initiation of antipsychotic medication

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizophreniform Disorder; Schizoaffective Disorder, Depressed Type

Detailed Description

It is currently unknown whether deterioration early in the course of psychotic illness represents medication toxicity or the natural course of the illness. The study will help clarify this issue in observing 70 schizophrenic patients before and after they are prescribed an antipsychotic via standard of care.

In addition, schizophrenia is a heterogeneous disorder and a putative brain-derived neurotrophic factor (BDNF) deficit, while possibly a common pathway, may not fully capture the biological diversity-the supplemental biomarkers will allow us to perform a more comprehensive assessment of factors contributing to clinical course. Taken together analysis of these biomarkers in relation to clinical course and in relation to healthy subjects will inform us about biological mechanisms contributing to illness onset, effects of antipsychotic medication on these mechanisms, and the predictive value of the biomarkers for clinical course. This information will provide the foundation for future early intervention trials targeting biological mechanisms utilizing a personalized medicine approach.

The baseline visit for 70 schizophrenic patients and 70 healthy age and gender matched controls consists of structural and functional MRI in addition to a blood draw for biomarkers including BDNF, inflammation markers, DNA, oxidative stress, and folate status and additionally a salivary cortisol sample collection. Biomarkers and imaging will be repeated after 8 weeks of antipsychotic treatment in patients.

• Study Type: Observational
• Enrollment (Actual): 165

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • Bellevue Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects will be 70 patients, ages 15-40, with first episode schizophrenia or schizophreniform disorder with onset before age 35 who are medication naive and do not meet criteria for major depression or significant suicidal ideation or substance abuse (except nicotine) and 70 age and gender matched healthy controls. Subjects will be recruited by physicians in the Bellevue Hospital emergency room, outpatient clinic and on the Bellevue psychiatric inpatient units as well as through the inpatient / outpatient services at Shanghai Mental Health Center .

Potential subjects will be identified by clinicians and asked whether they would like to speak to a researcher. Healthy subjects will be recruited through advertising by using a flyer.

Description

Inclusion Criteria:

1. Male or female
2. Ages 15-40 years
3. Schizophrenia, any subtype or Schizophreniform disorder
4. Sufficient proficiency in English or Spanish to complete assessments (US)

Exclusion Criteria:

1. Major depression by the Diagnostic and Statistical Manual of Mental Disorders IV criteria
2. Calgary Depression Scale for Schizophrenia (CDSS) score of 7 or greater.
3. Clinical Global Assessment of Severity of Suicidality of 3 (moderate) or greater.
4. Serious suicide attempt within three years
5. Treatment with an antipsychotic or antidepressant within the last six months
6. Active alcohol or other substance abuse or dependence within one month
7. Unstable medical illness

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy Controls; Age and gender matched healthy controls
Patients; Participants diagnosed with Schizophrenia, schizophreniform disorder, or schizoaffective disorder, depressed type that are naive to anti-psychotic treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	Compare biomarkers for inflammation, BDNF, oxidative stress, glucocorticoids and folate/methylation status in medication-naïve schizophrenia/schizophreniform subjects and matched healthy controls to identify illness-related factors.	Baseline
Salivary Cortisol Levels	Compare biomarkers at baseline and after 8 weeks of risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects to identify treatment-related factors. Since Blood and Saliva was only collected from First Episode participants (FEP) at week 8 (not from healthy controls) these results only report the baseline and week 8 biomarker levels for FEP participants who completed week 8.	Baseline and week 8
Salivary Cortisol Levels	Compare biomarkers for stress (salivary cortisol) in medication-naïve schizophrenia/schizophreniform subjects and matched healthy controls to identify illness-related factors.	Baseline
Change in Salivary Cortisol Levels	Compare salivary cortisol at baseline and after 8 weeks of risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects to identify treatment-related factors. Since Blood and Saliva was only collected from First Episode participants (FEP) at week 8 (not from healthy controls) these results only report the baseline and week 8 biomarker levels for FEP participants who completed week 8.	Baseline and week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Hippocampal Volumetric Integrity (HVI)	Compare hippocampal volume in medication-naïve schizophrenia/schizophreniform subjects and healthy controls and examine whether biomarkers predict differences between groups in baseline hippocampal volume.	Baseline
Cognitive Performance	Compare cognitive performance on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) in medication- naïve schizophrenia/schizophreniform subjects and healthy controls and examine whether biomarkers predict differences between groups in baseline cognitive performance. The composite score on the MCCB is calculated by the software using all tests administered. The composite score is a t-score assuming the mean score (50%) is the normative performance of the general population. The composite score ranges from 0-100 with a standard deviation of 10. A score greater than 50 implies a score better than the average population norm and a score less than 50 indicates performance worse than the general population norm. For schizophrenia subjects who complete 8 weeks of antipsychotic treatment, week 8 MATRICS testing results will be used to minimize the effect of psychosis on cognitive performance.	Baseline, week 8
Annualized Change in Left Hippocampal Volume Integrity	Compare hippocampal volume in medication-naïve schizophrenia/schizophreniform subjects before and after 8 weeks treatment with antipsychotic to assess evidence for early neurotoxicity. This outcome measure reports annualized rate of change in Left Hippocampal Volume Integrity (LHVI) because a few participants had a delay in their week 8 visit.	Baseline, week 8

Collaborators and Investigators

• Sponsor: NYU Langone Health

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: January 7, 2014
• First Submitted That Met QC Criteria: January 9, 2014
• First Posted (Estimate): January 10, 2014

Study Record Updates

• Last Update Posted (Actual): January 14, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Disease; Psychotic Disorders
• Other Study ID Numbers: 12-02903