Peroxisomal Defects and Familial Risk for Bipolar Disorder

Study Overview
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Brief Summary
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The purpose of this study is to screen for peroxisome defects in child and adolescent offspring of Bipolar Disorder I (BD-I) parents at different stages of risk for transitioning to mania and following the onset of mania. Prediction 1: Youth with an elevated risk for developing BD-I and first-episode manic patients will exhibit graded deficits in measures of peroxisomal function compared with healthy controls. Prediction 2: Indices of peroxisomal function will be correlated with Red Blood Cells Docosahexaenoic acid (DHA) composition. Prediction 3: Graded deficits in measures of peroxisomal function will be inversely correlated with manic and depression symptom severity scores.

Detailed Description
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Overall Study Design: This study entails collecting fasting venous blood (20 ml) from, and administering the 'omega-3 questionnaire' to, subjects being recruited from ongoing National Institute of Mental Health (NIMH)-sponsored trials within the Department of Psychiatry, University of Cincinnati College of Medicine. Specifically, blood will be collected from 20 healthy controls (i.e., no personal or family history of any Axis I mood disorder according to the Diagnostic and Statistical Manual of Mental Disorders-IV [DSM-IV]) and 20 asymptomatic high-risk (i.e., have a biological parent with BD-I) adolescents (aged 10-18 years old) recruited for study MH077138 (UC-IRB #: 07-04-10-03, BITREC Project 3; PI: DelBello), 20 ultra-high risk (i.e., have a biological parent with BD-I and a Major Depressive Disorder (MDD) diagnosis) recruited for study MH083924 (UC-IRB #: 04-09-15-03, CO-Principal Investigators DelBello/McNamara), and 20 adolescents who are admitted for their first hospitalization and who have a diagnosis of BD-I recruited for study MH080973 (UC-IRB #: 08-10-30-01, Principal Investigator: DelBello). Blood will then be processed, and de-identified tubes sent to the Kennedy Krieger Institute, Peroxisomal Diseases Section, to determine the following measures of peroxisomal function: (1) plasma very long chain fatty acids (C24:0 & C26:0) concentrations, (2) plasma bile acid C27 intermediate (dehydrocrepenynic acid {DHCA},tetrahydrocannabinolic acid {THCA})concentrations, (3) plasma pipecolic acid concentrations, and (4) Red Blood Cell (RBC) plasmalogen concentrations. Additionally, RBC fatty acid composition will be determined by gas chromatography, and platelet function and plasma inflammatory markers assayed using commercially available kits according to manufacturer's instructions.

Official Title
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Peroxisomal Defects and Familial Risk for Bipolar Disorder

Conditions
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Bipolar Disorder, Mania

Participation Criteria
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Eligibility Criteria
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Subject characteristics: All subjects will be 10-18 year old males and females. Up to 80 patients will be enrolled in this study. Subjects will be screened according to previously approved individual study criteria (UC-IRB #: 07-04-10-03; 04-09-15-03; 08-10-30-01). Inclusion Criteria: 10 -18 year old males & females Based on currently enrolled study. Exclusion Criteria: Based on currently enrolled study.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Health Controls<br> | |
| Bipolar Patients with High-Risk of Mania<br> | |
| Bipolar Patients with Ultra-High Risk<br> | |
| First Manic Episode Bipolar Youth<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Youth with an elevated risk for developing BD-I and first-episode manic patients will exhibit graded deficits in measures of peroxisomal function compared with healthy controls. | Prediction 1: Youth with an elevated risk for developing BD-I and first-episode manic patients will exhibit graded deficits in measures of peroxisomal function compared with healthy controls. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| peroxisomal function will be inversely correlated with manic and depression symptom severity scores. | Prediction 3: Graded deficits in measures of peroxisomal function will be inversely correlated with manic and depression symptom severity scores. | 1 day | 
| Indices of peroxisomal function will be correlated with RBC DHA composition. | Prediction 2: Indices of peroxisomal function will be correlated with RBC DHA composition. | 1 day |