The Role of Dysmyelination in Cognitive Impairment of Psychotic Spectrum Disorders

Study Overview
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Brief Summary
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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.

Official Title
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The Role of Dysmyelination in Cognitive Impairment of Psychotic Spectrum Disorders

Conditions
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Schizophrenia, Bipolar Disorder

Intervention / Treatment
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* Diagnostic Test: Cognitive Function Assessments


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Diagnosis of Schizophrenia<br> | Diagnostic Test: Cognitive Function Assessments<br>* 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.<br>|
| Diagnosis of Bipolar Disorder<br> | Diagnostic Test: Cognitive Function Assessments<br>* 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.<br>|
| Unaffected siblings of the SZ groups<br> | Diagnostic Test: Cognitive Function Assessments<br>* 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.<br>|
| Unaffected siblings of the BP group<br> | Diagnostic Test: Cognitive Function Assessments<br>* 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.<br>|
| Healthy control (HC) comparison group<br> | Diagnostic Test: Cognitive Function Assessments<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psychotic Spectrum Disorders