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Neuroplasticity and cellular resilience in mood disorders
H K Manji1, G J Moore, G Rajkowska
1Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, USA. manjih@intra.nimh.nih.gov
Molecular Psychiatry
|December 29, 2000
Summary
Mood disorders may involve structural brain changes and impaired neuroplasticity, challenging traditional good prognosis views. Early, aggressive treatment with neurotrophic agents is proposed for better long-term outcomes in these conditions.
Area of Science:
- Neuroscience
- Psychiatry
- Cell Biology
Background:
- Mood disorders traditionally viewed as having good prognosis.
- Emerging data indicates less favorable long-term outcomes for many patients.
- Structural brain changes, including reduced CNS volume and neuronal/glial numbers, are increasingly evident.
Purpose of the Study:
- To explore the pathophysiology of mood disorders.
- To investigate optimal long-term treatment strategies.
- To propose a reconceptualization of mood disorder treatment based on neuroplasticity and cellular resilience.
Main Methods:
- Review of morphometric studies on brain structure in mood disorders.
- Analysis of clinical and preclinical studies on mood stabilizers and antidepressants.
- Investigation of molecular and cellular targets related to neuroplasticity and cell survival pathways.
Main Results:
- Evidence of significant regional reductions in CNS volume and neuronal/glial elements.
- Identification of molecular pathways (CREB, BDNF, bcl-2, MAP kinases) regulated by current treatments.
- Potential for lithium, valproate, and antidepressants to exert neurotrophic effects.
Conclusions:
- Impaired neuroplasticity and cellular resilience may underlie mood disorder pathophysiology.
- Optimal long-term treatment may require early, aggressive use of neurotrophic/neuroprotective agents.
- Novel treatments targeting cell survival pathways could enhance neuroplasticity and improve long-term outcomes.