The Role of Dysmyelination in Cognitive Impairment of Psychotic Spectrum Disorders

This is a single center study that uses both between-group comparisons and correlational analyses to establish biomarkers of dysmyelination and cognitive impairment in Psychotic Spectrum Disorders using imaging and neuropsychological assays.The study will provide non-invasive biomarkers of cognitive dysfunction in Psychotic Spectrum Disorder.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Bipolar Disorder
• Intervention / Treatment: Diagnostic test: Cognitive Function Assessments

• Study Type: Observational
• Enrollment (Actual): 139

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study will include patients with a diagnosis of Schizophrenia or Bipolar Disorder with Psychotic features, their unaffected siblings, and comparison healthy subjects.

Description

Inclusion Criteria:

Patients:

• current DSM-5-defined diagnosis of a schizophrenia or bipolar disorder. A best estimate diagnostic approach will be utilized in which information from the Diagnostic Interview for Genetic Studies (DIGS) is supplemented by information from family informants, psychiatrists, and medical records to generate a diagnosis as needed
• no alcohol or substance abuse during the last 6 month
• no current substance-induced psychotic disorder or a psychotic disorder due to a general medical condition determined by DSM-5 criteria
• ages 18 to 30 years old;
• any race
• competent and willing to sign informed consent
• within 5 years from the disease onset.

Siblings:

• have the same biological parents as their PSD sibling
• any race
• no current or past history of psychotropic medication usage
• no alcohol or substance abuse during the last 6 months
• competent and willing to sign informed consent;
• ages 18 to 30 years old.

Healthy controls:

• matched for age to PSD patients
• no current or past history of psychotropic medication usage
• no prodromal symptoms and no family history of PSD
• no alcohol or substance abuse during the last 6 months
• competent and willing to sign informed consent.
• all attempts will be made to recruit controls with similar parental SES as patients. However, given that PSD are both a neurodevelopmental and familial disorder, exact matching for educational level or IQ may neither be possible nor desirable.

have the same biological parents as their PSD sibling

• any race
• no current or past history of psychotropic medication usage
• no alcohol or substance abuse during the last 6 months
• competent and willing to sign informed consent;
• ages 18 to 30 years old.

Exclusion Criteria:

• a serious neurological or endocrine disorder or any medical condition or treatment known to affect the brain, 2) organic brain disorder, mental retardation, or significant medical illness;
• significant risk of suicidal or homicidal behavior;
• must not have met DSM-5 criteria for current alcohol or drug dependence in the last 6 months;
• contraindications to MRI scanning (i.e., metal implants, pacemakers, pregnancy, etc.);
• documented loss of consciousness (LOC) for longer than 30 minutes or LOC with any neurological sequelae.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Diagnosis of Schizophrenia	Diagnostic test: Cognitive Function Assessments; The NIMH-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) is a consensus battery that is considered state-of-the art in the evaluation of cognitive skills for schizophrenia research.(Burton et al., 2013, Harvey, 2014) The complete cognitive battery takes about one hour to administer, and is comprised of 10 subtests measuring seven essential domains of function, with very good reliability and validity.(Nuechterlein 2008, August et al., 2012) The MATRICS subtests have been incorporated into the cognitive battery described below, with supplementary subtests included where indicated within each domain.
Diagnosis of Bipolar Disorder	Diagnostic test: Cognitive Function Assessments; The NIMH-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) is a consensus battery that is considered state-of-the art in the evaluation of cognitive skills for schizophrenia research.(Burton et al., 2013, Harvey, 2014) The complete cognitive battery takes about one hour to administer, and is comprised of 10 subtests measuring seven essential domains of function, with very good reliability and validity.(Nuechterlein 2008, August et al., 2012) The MATRICS subtests have been incorporated into the cognitive battery described below, with supplementary subtests included where indicated within each domain.
Unaffected siblings of the SZ groups	Diagnostic test: Cognitive Function Assessments; The NIMH-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) is a consensus battery that is considered state-of-the art in the evaluation of cognitive skills for schizophrenia research.(Burton et al., 2013, Harvey, 2014) The complete cognitive battery takes about one hour to administer, and is comprised of 10 subtests measuring seven essential domains of function, with very good reliability and validity.(Nuechterlein 2008, August et al., 2012) The MATRICS subtests have been incorporated into the cognitive battery described below, with supplementary subtests included where indicated within each domain.
Unaffected siblings of the BP group	Diagnostic test: Cognitive Function Assessments; The NIMH-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) is a consensus battery that is considered state-of-the art in the evaluation of cognitive skills for schizophrenia research.(Burton et al., 2013, Harvey, 2014) The complete cognitive battery takes about one hour to administer, and is comprised of 10 subtests measuring seven essential domains of function, with very good reliability and validity.(Nuechterlein 2008, August et al., 2012) The MATRICS subtests have been incorporated into the cognitive battery described below, with supplementary subtests included where indicated within each domain.
Healthy control (HC) comparison group	Diagnostic test: Cognitive Function Assessments; The NIMH-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) is a consensus battery that is considered state-of-the art in the evaluation of cognitive skills for schizophrenia research.(Burton et al., 2013, Harvey, 2014) The complete cognitive battery takes about one hour to administer, and is comprised of 10 subtests measuring seven essential domains of function, with very good reliability and validity.(Nuechterlein 2008, August et al., 2012) The MATRICS subtests have been incorporated into the cognitive battery described below, with supplementary subtests included where indicated within each domain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DKI(metrics RDextra, faxon, and ADextra) Metrics	To compare DKI metrics (faxon, RDextra, and ADextra) in patients with SZ or BP, their unaffected siblings (SIB), and healthy comparison control (HC) subjects	6 Years
Magnetic Resonance Spectroscopy will be employed to obtain quantitative metrics of choline (Cho)	Choline Concentration (1H-MRS)	1 Hour

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Mariana Lazar, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 5, 2016
• Primary Completion (ACTUAL): March 1, 2022
• Study Completion (ACTUAL): March 1, 2022

Study Registration Dates

• First Submitted: May 23, 2017
• First Submitted That Met QC Criteria: May 23, 2017
• First Posted (ACTUAL): May 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Psychotic Spectrum Disorders
• Additional Relevant MeSH Terms: Pathologic Processes; Neurocognitive Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Cognition Disorders; Bipolar and Related Disorders; Schizophrenia; Disease; Psychotic Disorders; Mental Disorders; Cognitive Dysfunction; Bipolar Disorder
• Other Study ID Numbers: 15-00754

Drug and device information, study documents

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