Peroxisomal Defects and Familial Risk for Bipolar Disorder
Condition: Bipolar Disorder; Mania
MeSH terms: Bipolar Disorder
Study type: Observational

Summary: 
      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: 
      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.
    

Observational model: Case-Crossover
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Subjects: In order to accomplish this aim, 20 healthy controls, 20 high-risk, 20 ultra-high
        risk, and 20 first-episode manic youth (ages 10-18 years old) will be recruited at a rate
        of 1 subject/group per month over the first 20 months. Subjects being recruited from the
        following IRB approved NIMH-sponsored trials: MH077138 (UC-IRB #: 07-04-10-03, BITREC
        Project 3; PI: DelBello), MH083924 (UC-IRB #: 04-09-15-03, CO-PIs DelBello/McNamara), and
        MH080973 (UC-IRB #: 08-10-30-01, PI: DelBello).
      
Biospecimen description: 
      Laboratory methods: The gas chromatography procedure used to determine red blood cell fatty
      acid composition. Briefly, total fatty acid composition will be determined. Indices of
      peroxisome function, including (1) plasma very long chain fatty acids concentrations, (2)
      plasma bile acid C27 intermediate concentrations, (3) plasma pipecolic acid concentrations,
      and (4) RBC plasmalogen concentrations, will be determined by liquid chromatography tandem
      mass spectrometry and gas chromatography. Plasma cytokine and C-Reactive Protein
      (CRP)concentrations will be determined. All blood analyses will be performed by a technician
      blinded to diagnostic group identity.