Beyond the therapeutic shackles of the monoamines: New mechanisms in bipolar disorder biology.
Multiple novel biological mechanisms putatively involved in the etiology of bipolar disorders are being explored. These include oxidative stress, altered glutamatergic neurotransmission, mitochondrial dysfunction, inflammation, cell signaling, apoptosis and impaired neurogenesis. Important clinical translational potential exists for such mechanisms to help underpin development of novel therapeutics - much needed given limitations of current therapies. These new mechanisms also help improve our understanding of how current therapeutics might exert their effects. Lithium, for example, appears to have antioxidant, immunomodulatory, signaling, anti-apoptotic and neuroprotective properties. Similar properties have been attributed to other mood stabilizers such as valproate, lamotrigine, and quetiapine. Perhaps of greatest translational value has been the recognition of such mechanisms leading to the emergence of novel therapeutics for bipolar disorders. These include the antioxidant N-acetylcysteine, the anti-inflammatory celecoxib, and ketamine - with effects on the glutamatergic system and microglial inhibition. We review these novel mechanisms and emerging therapeutics, and comment on next steps in this space.
Psychiatric Department, Hospital Beatriz Ângelo, Loures, Portugal; University of Lisbon, Faculty of Medicine, Lisbon, Portugal. Electronic address: joaodatafranco@gmail.com.
João
J
Data-Franco
Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, VIC, Australia.
Ajeet
A
Singh
Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Psychiatry Division, The Chaim Sheba Medical Center, Ramat-Gan, Israel.
Dina
D
Popovic
Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, VIC, Australia; Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia.
Melanie
M
Ashton
Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, VIC, Australia; Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia; Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia; Orygen Youth Health Research Centre, Parkville, VIC, Australia.
Michael
M
Berk
Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
Eduard
E
Vieta
University of Lisbon, Faculty of Medicine, Lisbon, Portugal.
M L
ML
Figueira
Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, VIC, Australia; Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia; Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia.
Olivia M
OM
Dean
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D015306:Biogenic Monoamines / Q000378:metabolism*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology
D000928:Antidepressive Agents; D015306:Biogenic Monoamines
Bipolar disorder; Inflammation; Minocycline; Mitochondrial dysfunction; Neurogenesis; Novel therapy; Oxidative stress