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Lithium as a Mood Lithium as a Mood Stabiliser in the Stabiliser in the Treatment of Bipolar Treatment of Bipolar Disorder Disorder
| Content Provider | Semantic Scholar |
|---|---|
| Author | Manji, Husseini K. Moore, Gregory J. Chen, Guang |
| Abstract | New research is dramatically altering our understanding dramatically altering our understanding of the molecular mechanisms underlying of the molecular mechanisms underlying neuronal communication. neuronal communication. Aim Aim To elucidate the molecular To elucidate the molecular mechanisms underlying the therapeutic mechanisms underlying the therapeutic effects of mood stabilisers. effects of mood stabilisers. Method Method Results from integrated Results from integrated clinical and laboratory studies are clinical and laboratory studies are reviewed. reviewed. Results Results Chronic administration of Chronic administration of lithium and valproate produced a striking lithium and valproate produced a striking reduction in protein kinase C (PKC) reduction in protein kinase C (PKC) isozymes in rat frontal cortex and isozymes in rat frontal cortex and hippocampus.In a small study, tamoxifen hippocampus.In a small study, tamoxifen (also a PKC inhibitor) had marked (also a PKC inhibitor) had marked antimanic efficacy.Both lithium and antimanic efficacy.Both lithium and valproate regulate the DNA binding valproate regulate the DNA binding activity of the activator protein1family activity of the activator protein1family of transcription factors.Using mRNA of transcription factors.Using mRNA differential display, it was also shown that differential display, it was also shown that chronic administration of lithium and chronic administration of lithium and valproate modulates expression of several valproate modulates expression of several genes. An exciting finding is that of a genes. An exciting finding is that of a robust elevation in the levels of the robust elevation in the levels of the cytoprotective protein, bcl-2. cytoprotective protein, bcl-2. Conclusions Conclusions The results suggestthat The results suggestthat regulation of signalling pathways may play regulation of signalling pathways may play a major part in the long-term actions of a major part in the long-term actions of mood stabilisers. Additionally, mood mood stabilisers. Additionally, mood stabilisers may exert underappreciated stabilisers may exert underappreciated neuroprotective effects. neuroprotective effects. Despite well-established genetic diatheses Despite well-established genetic diatheses and extensive research, the biochemical and extensive research, the biochemical abnormalities underlying the predisposi-abnormalities underlying the predisposition to and the pathophysiology of bi-tion to and the pathophysiology of bi-polar disorder have yet to be clearly polar disorder have yet to be clearly established. Early biological explanations established. Early biological explanations of bipolar disorder implicated neurotrans-of bipolar disorder implicated neurotrans-mitters, in particular the biogenic amines. mitters, in particular the biogenic amines. However, advances in our understanding However, advances in our understanding of the cellular mechanisms underlying of the cellular mechanisms underlying neuronal communication have … |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://bjp.rcpsych.org/content/bjprcpsych/178/41/s107.full.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
