Literature DB >> 22711881

Mitochondrial modulators for bipolar disorder: a pathophysiologically informed paradigm for new drug development.

Andrew A Nierenberg1, Christine Kansky, Brian P Brennan, Richard C Shelton, Roy Perlis, Dan V Iosifescu.   

Abstract

OBJECTIVES: Bipolar patients frequently relapse within 12 months of their previous mood episode, even in the context of adequate treatment, suggesting that better continuation and maintenance treatments are needed. Based on recent research of the pathophysiology of bipolar disorder, we review the evidence for mitochondrial dysregulation and selected mitochondrial modulators (MM) as potential treatments.
METHODS: We reviewed the literature about mitochondrial dysfunction and potential MMs worthy of study that could improve the course of bipolar disorder, reduce subsyndromal symptoms, and prevent subsequent mood episodes.
RESULTS: MM treatment targets mitochondrial dysfunction, oxidative stress, altered brain energy metabolism and the dysregulation of multiple mitochondrial genes in patients with bipolar disorder. Several tolerable and readily available candidates include N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q(10) (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin. The specific metabolic pathways by which these MMs may improve the symptoms of bipolar disorder are discussed and combinations of selected MMs could be of interest as well.
CONCLUSIONS: Convergent data implicate mitochondrial dysfunction as an important component of the pathophysiology of bipolar disorder. Clinical trials of individual MMs as well as combinations are warranted.

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Year:  2012        PMID: 22711881     DOI: 10.1177/0004867412449303

Source DB:  PubMed          Journal:  Aust N Z J Psychiatry        ISSN: 0004-8674            Impact factor:   5.744


  31 in total

1.  Mitochondrial modulators improve lipid composition and attenuate memory deficits in experimental model of Huntington's disease.

Authors:  Arpit Mehrotra; Abhilasha Sood; Rajat Sandhir
Journal:  Mol Cell Biochem       Date:  2015-09-15       Impact factor: 3.396

Review 2.  Multiple levels of impaired neural plasticity and cellular resilience in bipolar disorder: developing treatments using an integrated translational approach.

Authors:  Rodrigo Machado-Vieira; Marcio G Soeiro-De-Souza; Erica M Richards; Antonio L Teixeira; Carlos A Zarate
Journal:  World J Biol Psychiatry       Date:  2013-09-02       Impact factor: 4.132

Review 3.  Role of immune-inflammatory and oxidative and nitrosative stress pathways in the etiology of depression: therapeutic implications.

Authors:  George Anderson; Michael Berk; Olivia Dean; Steven Moylan; Michael Maes
Journal:  CNS Drugs       Date:  2014-01       Impact factor: 5.749

Review 4.  A mitochondrial bioenergetic basis of depression.

Authors:  N Jennifer Klinedinst; William T Regenold
Journal:  J Bioenerg Biomembr       Date:  2014-09-28       Impact factor: 2.945

5.  Tissue Type-Specific Bioenergetic Abnormalities in Adults with Major Depression.

Authors:  David G Harper; J Eric Jensen; Caitlin Ravichandran; Roy H Perlis; Maurizio Fava; Perry F Renshaw; Dan V Iosifescu
Journal:  Neuropsychopharmacology       Date:  2016-09-02       Impact factor: 7.853

Review 6.  Targeting Mitochondrial Dysfunction for Bipolar Disorder.

Authors:  Maya Kuperberg; Sophie L A Greenebaum; Andrew A Nierenberg
Journal:  Curr Top Behav Neurosci       Date:  2021

Review 7.  Intracellular Signaling Cascades in Bipolar Disorder.

Authors:  Gregory H Jones; Carola Rong; Aisha S Shariq; Abhinav Mishra; Rodrigo Machado-Vieira
Journal:  Curr Top Behav Neurosci       Date:  2021

8.  Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder.

Authors:  Joanne H Huang; Shaunna S Berkovitch; Jonathan Iaconelli; Bradley Watmuff; Hyoungjun Park; Shrikanta Chattopadhyay; Donna McPhie; Dost Öngür; Bruce M Cohen; Clary B Clish; Rakesh Karmacharya
Journal:  Mol Neuropsychiatry       Date:  2016-06-24

Review 9.  Coenzyme Q10 depletion in medical and neuropsychiatric disorders: potential repercussions and therapeutic implications.

Authors:  Gerwyn Morris; George Anderson; Michael Berk; Michael Maes
Journal:  Mol Neurobiol       Date:  2013-06-13       Impact factor: 5.590

10.  Treatment of mitochondrial disorders.

Authors:  Sreenivas Avula; Sumit Parikh; Scott Demarest; Jonathan Kurz; Andrea Gropman
Journal:  Curr Treat Options Neurol       Date:  2014-06       Impact factor: 3.598

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