Jayanthi N. Koneru, Department of Internal Medicine, Division of Cardiology and Cardiac Electrophysiology, Virginia Commonwealth University, Richmond, Virginia, USA. Christopher Kogut, Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA. Ericka L. Breden Crouse, Department of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, Inhibitors,research,lifescience,medical USA. Jules C. Hancox, School of Physiology

and Pharmacology and Cardiovascular Research Laboratories, Medical Sciences Building, University of Bristol, University Walk, Bristol BS8 1TD, UK. Antony Fernandez, Departments of Psychiatry and Virginia Commonwealth University and Mental Health Service Line, Veterans Administration Medical Center, Inhibitors,research,lifescience,medical Richmond, Virginia, USA. Ananda K. Pandurangi, Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA.

It has been over 50 years since Cade first described this simple cation’s therapeutic role in manic illness [Cade, 1949]. Since this discovery, our understanding of its mechanisms of action have developed significantly [Lenox and Hahn, 2000], although the full nature of its effects are yet to be elucidated. Lithium is primarily used in the recovery of bipolar affective disorder, with evidence supporting its role in both Inhibitors,research,lifescience,medical acute mania [Gershon and Soares,

1997; Soares and Gershon, 1998, 2000; Bowden, 2000; Poolsup et al. 2000; Shafti, 2010] and prophylactic treatment [Soares and Gershon, 1998, 2000; Burgess et al. 2001; Geddes et al. 2004, 2010]. It is also efficacious

in the treatment Inhibitors,research,lifescience,medical of unipolar depression [Coppen, 2000], particularly as augmentation therapy in severe refractory depression [Bauer et al. 2003b; Kennedy and Paykel, 2004], and bipolar depression [Lloyd et al. 2011]. In addition, it has been noted to effect aggressiveness [Jones et al. 2011], reduce suicide rates in affective disorders [Tondo and Baldessarini, 2000; Cipriani et al. Inhibitors,research,lifescience,medical 2005] and, more speculatively, has been considered as a possible therapeutic agent for treating chronic neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases [Marmol, 2008; Dudev and Lim, 2011]. Yet, despite nearly lithium’s extensive clinical applications and its ability to provide potentially lifesaving treatment to patients [Nemeroff, 2000; Jope, 2003], the exact mechanisms by which it exerts its therapeutic effects remain incompletely understood [Phiel and Klein, 2001; Gould and Manji, 2005; Haimovich et al. 2012]. Further exploration is required, to determine more fully why lithium provides effective mood stabilisation for patients and allow clearer insight into mood disorder pathophysiology. In addition, lithium’s usage is limited by its narrow therapeutic window and significant range of PI-103 research buy adverse side effects [Livingstone and Rampes, 2006; McKnight et al.