title: Biomarkers in mood disorders research: developing new and improved therapeutics.
abstract: BACKGROUND
  Recently, surrogate neurobiological biomarkers that correlate with target engagement and therapeutic response have been developed and tested in early phase studies of mood disorders.
  
  
  OBJECTIVE
  The identification of biomarkers could help develop personalized psychiatric treatments that may impact public health.
  
  
  METHODS
  These biomarkers, which are associated with clinical response post-treatment, can be directly validated using multimodal approaches including genetic tools, proteomics/metabolomics, peripheral measures, neuroimaging, biostatistical predictors, and clinical predictors.
  
  
  RESULTS
  To date, early phase biomarker studies have sought to identify measures that can serve as "biosignatures", or biological patterns of clinical response. These studies have also sought to identify clinical predictors and surrogate outcomes associated with pathophysiological domains consistently described in the National Institute of Mental Health's (NIMH) new Research Domain Criteria (RDoC). Using the N-methyl-D-aspartate (NMDA) antagonist ketamine as an example, we identified changes in several domains (clinical, cognitive, and neurophysiological) that predicted ketamine's rapid and sustained antidepressant effects in individuals with treatment-resistant major depressive disorder (MDD) or bipolar depression.
  
  
  CONCLUSIONS
  These approaches may ultimately provide clues into the neurobiology of psychiatric disorders and may have enormous impact Backon the development of novel therapeutics.
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Niciu
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Mathews
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
authors.forename: Dawn F
authors.initials: DF
authors.lastname: Ionescu
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Richards
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
authors.forename: Maura L
authors.initials: ML
authors.lastname: Furey
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
authors.forename: Peixiong
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
authors.forename: Allison C
authors.initials: AC
authors.lastname: Nugent
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
authors.forename: Ioline D
authors.initials: ID
authors.lastname: Henter
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
keywords: Biomarker; anxiety; bipolar disorder; depression; drug development