Lipid peroxidation biomarkers in adolescents with or at high-risk for bipolar disorder

Gustavo Scola, Robert K. McNamara, Paul E. Croarkin, Jarrod M. Leffler, Kathryn R. Cullen, Jennifer R. Geske, Joanna M. Biernacka, Mark A. Frye, Melissa P. Delbello, Ana C. Andreazza

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22 Scopus citations

Abstract

Background Prior work suggests that adult bipolar disorder (BD) is associated with increased oxidative stress and inflammation. This exploratory study examined markers of lipid and protein oxidation and inflammation in adolescents with and at varying risk for BD type I (BD-I). Methods Blood was obtained from four groups of adolescents (9-20 years of age): (1) healthy comparison subjects with no personal or family history of psychiatric disorders (n=13), (2) subjects with no psychiatric diagnosis and at least one parent with BD-I ('high-risk', n=15), (3) subjects with at least one parent with BD-I and a diagnosis of depressive disorder not-otherwise-specified ('ultra-high-risk', n=20), and (4) first-episode patients exhibiting mixed or manic symptoms that received a diagnosis of BD-I (n=16). Plasma levels of lipid peroxidation (LPH, 4-HNE, 8-ISO), protein carbonyl, and inflammation (IL-1α-β, IL-6, IL-10, IFNγ, TNFα) were assessed using analysis of variance and covariance models. Results LPH was lower in adolescents with fully syndromal BD than controls, while LPH levels in the at-risk groups were between healthy controls and fully syndromal BD. Post-hoc analysis showed a non-significant increase in the (4-HNE+8-ISO)/LPH ratio suggesting a potential conversion of LPH into late-stage markers of lipid peroxidation. There were no significant differences among protein carbonyl content and inflammatory markers. Conclusions In adolescents, fully syndromal BD is associated with significant reductions in LPH levels, and LPH levels decrease along the spectrum of risk for BD-I. Quantifying lipid peroxidation in longitudinal studies may help clarify the role of LPH in BD risk progression.

Original languageEnglish (US)
Pages (from-to)176-183
Number of pages8
JournalJournal of Affective Disorders
Volume192
DOIs
StatePublished - Mar 1 2016

Bibliographical note

Funding Information:
This study was funded by the Marriott Foundation and Mayo Clinic Center for Individualized Medicine . Dr. Scola is supported by the CAMH Foundation (Grant no. 1000109). Dr. Croarkin is supported by NIMH under Award number K23MH100266 . Dr. DelBello and Dr. McNamara are supported by NIH/NIMH R34 MH081206 and Dr. DelBello is also supported by NIMH R01 MH080973 .

Funding Information:
This study was funded by the Marriott Foundation and Mayo Clinic Center for Individualized Medicine to supported patient collection data and statistical analysis. Dr. Scola is supported by the CAMH Foundation, which provided source of funding for his salary. Dr. Croarkin is supported by NIMH under Award number K23MH100266, which supported patient collection data. Dr. DelBello and Dr. McNamara are supported by NIH/NIMH R34 MH081206 and Dr. DelBello is also supported by NIMH R01 MH080973, which supported patient collection data. Dr. Andreazza is supported by Ontario Mental Health Foundation ( OMHF 498567 ), CIHR ( MOP-133439 ) and Ontario Ministry of Research and Innovation ( ERA-14-10-022 ), which supported biochemical analysis of this study.

Funding Information:
All authors have approved the final article. Dr. Scola has no disclosures. Dr. McNamara has received research support from Martek Biosciences Inc, the Inflammation Research Foundation, Ortho-McNeil Janssen, AstraZeneca, Eli Lilly, NARSAD, NIMH, NIDDK, and NIA.Dr. Croarkin has received grant support from Pfizer Inc, the National Institute of Mental Health (NIMH) (K23MH100266), the Brain and Behavior Research Foundation, and the Mayo Foundation. He has received in-kind support for equipment and supplies from Neuronetics Inc and AssureRx Health Inc. Drs. Leffler and Cullen, and Ms Geske have no disclosures. Dr. Biernacka has received research funding as a principal investigator from the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism in the National Institutes of Health at the US Department of Health and Human Services; as a co-investigator from the National Institute of Mental Health and the National Institute of General Medical Sciences in the National Institutes of Health at the US Department of Health and Human Services; and as a co-principal investigator from the Marriott Foundation for the Mayo Clinic Bipolar Disorder Biobank. Dr. Frye has received grant support from AssureRx Health Inc, Myriad, Pfizer Inc, NIMH (R01 MH079261), the National Institute on Alcohol Abuse and Alcoholism (P20AA017830) in the National Institutes of Health at the US Department of Health and Human Services, and the Mayo Foundation. He has been a consultant to Janssen Global Services LLC, Mitsubishi Tanabe Pharma Corp, Myriad Genetics Inc, Sunovion Pharmaceuticals Inc, and Teva Pharmaceutical Industries Ltd. He has received continuing medical education/travel/presentation support from CME Outfitters LLC and Sunovion Pharmaceuticals Inc. Dr. DelBello has received grant support from AstraZeneca, Eli Lilly, Martek, Johnson & Johnson, Shire, Ortho-McNeil Janssen, Pfizer, Bristol Myers Squibb, Repligen, Somerset, Sumitomo, Thrasher Foundation, GlaxoSmithKline, NARSAD, and NIMH, NIDA, NIAAA, and has served as a consultant for GlaxoSmithKline, Eli Lilly, France Foundation, Kappa Clinical, Pfizer, Medical Communications Media, Shering-Plough, and Merck. Dr. Andreazza is funded by Canadian Institute of Health Research, Ontario Mental Health Foundation and Ministry of Research and Innovation of Canada.

Funding Information:
This study was funded by the Marriott Foundation and Mayo Clinic Center for Individualized Medicine. Dr. Scola is supported by the CAMH Foundation (Grant no. 1000109). Dr. Croarkin is supported by NIMH under Award number K23MH100266. Dr. DelBello and Dr. McNamara are supported by NIH/NIMH R34 MH081206 and Dr. DelBello is also supported by NIMH R01 MH080973.

Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Adolescent bipolar disorder
  • At-risk adolescents
  • Lipid peroxidation
  • Oxidative stress markers

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