Neuropsychopharmacology Reviews
Neuropsychopharmacology (2008) 33, 110–133; doi:10.1038/sj.npp.1301575; published online 3 October 2007
Neuropsychopharmacology (2008) 33, 110–133; doi:10.1038/sj.npp.1301575; published online 3 October 2007
Cellular Plasticity Cascades in the Pathophysiology and Treatment of Bipolar Disorder
1Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, NIH, Bethesda, MD, USA
2Department of Medicine (Hematology-Oncology), University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Correspondence: Dr HK Manji, Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, Porter Neuroscience Research Center, Building 35, Room 1C-917, 35 Convent Drive, Bethesda, MD 20892, USA. Tel: +1 301 496 9802; Fax: +1 301 480 0123; E-mail: manjih@mail.nih.gov
3Dr Schloesser and Dr Huang share first authorship.
Received 16 July 2007; Revised 1 August 2007; Accepted 14 August 2007; Published online 3 October 2007.
Abstract
Bipolar disorder (BPD) is characterized by recurrent episodes of disturbed affect including mania and depression as well as changes in psychovegetative function, cognitive performance, and general health. A growing body of data suggests that BPD arises from abnormalities in synaptic and neuronal plasticity cascades, leading to aberrant information processing in critical synapses and circuits. Thus, these illnesses can best be conceptualized as genetically influenced disorders of synapses and circuits rather than simply as deficits or excesses in individual neurotransmitters. In addition, commonly used mood-stabilizing drugs that are effective in treating BPD have been shown to target intracellular signaling pathways that control synaptic plasticity and cellular resilience. In this article we draw on clinical, preclinical, neuroimaging, and post-mortem data to discuss the neurobiology of BPD within a conceptual framework while highlighting the role of neuroplasticity in the pathophysiology and treatment of this disorder.
Keywords:
bipolar disorder, neuroplasticity, intracellular signaling cascades, lithium, valproic acid, mood stabilizer
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