title: Multiple levels of impaired neural plasticity and cellular resilience in bipolar disorder: developing treatments using an integrated translational approach.
abstract: OBJECTIVE
  This paper reviews the neurobiology of bipolar disorder (BD), particularly findings associated with impaired cellular resilience and plasticity.
  
  
  METHODS
  PubMed/Medline articles and book chapters published over the last 20 years were identified using the following keyword combinations: BD, calcium, cytokines, endoplasmic reticulum (ER), genetics, glucocorticoids, glutamate, imaging, ketamine, lithium, mania, mitochondria, neuroplasticity, neuroprotection, neurotrophic, oxidative stress, plasticity, resilience, and valproate.
  
  
  RESULTS
  BD is associated with impaired cellular resilience and synaptic dysfunction at multiple levels, associated with impaired cellular resilience and plasticity. These findings were partially prevented or even reversed with the use of mood stabilizers, but longitudinal studies associated with clinical outcome remain scarce.
  
  
  CONCLUSIONS
  Evidence consistently suggests that BD involves impaired neural plasticity and cellular resilience at multiple levels. This includes the genetic and intra- and intercellular signalling levels, their impact on brain structure and function, as well as the final translation into behaviour/cognitive changes. Future studies are expected to adopt integrated translational approaches using a variety of methods (e.g., microarray approaches, neuroimaging, genetics, electrophysiology, and the new generation of -omics techniques). These studies will likely focus on more precise diagnoses and a personalized medicine paradigm in order to develop better treatments for those who need them most.
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, NIH , Bethesda, MD , USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
authors.forename: Marcio G
authors.initials: MG
authors.lastname: Soeiro-De-Souza
authors.forename: Erica M
authors.initials: EM
authors.lastname: Richards
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Teixeira
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
mesh_terms: D000818:Animals; D001714:Bipolar Disorder / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D057170:Translational Research, Biomedical