Biomarkers in First Episode Schizophrenia

Completed

Conditions: Schizophrenia
Schizophreniform Disorder
Schizoaffective Disorder, Depressed Type

Registration Number: NCT02033382

Lead Sponsor: NYU Langone Health

Brief Summary: 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

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 165

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Salivary Cortisol Levels	Baseline	Compare biomarkers for stress (salivary cortisol) in medication-naïve schizophrenia/schizophreniform subjects and matched healthy controls to identify illness-related factors.
Biomarkers	Baseline	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.
Change in Salivary Cortisol Levels	Baseline and week 8	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.

Secondary Outcome Measures

Name	Time	Method
Left Hippocampal Volumetric Integrity (HVI)	Baseline	Compare hippocampal volume in medication-naïve schizophrenia/schizophreniform subjects and healthy controls and examine whether biomarkers predict differences between groups in baseline hippocampal volume.
Annualized Change in Left Hippocampal Volume Integrity	Baseline, week 8	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.
Cognitive Performance	Baseline, week 8	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.