Send to

Choose Destination
See comment in PubMed Commons below
Biol Psychiatry. 2006 Jun 1;59(11):1006-20. Epub 2006 Feb 17.

Cellular plasticity cascades: targets for the development of novel therapeutics for bipolar disorder.

Author information

Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Research Program, National Institute of Mental Health, Bethesda, Maryland, USA.


For a number of patients with bipolar disorder, current pharmacotherapy is generally insufficient. Despite adequate treatment, patients continue to have recurrent mood episodes, residual symptoms, functional impairment, psychosocial disability, and significant medical and psychiatric comorbidity. Drug development for bipolar disorder may occur through one of two approaches: the first is by understanding the therapeutically relevant biochemical targets of currently effective medications. Two promising direct targets of lithium and valproate are glycogen synthase kinase-3 and histone deacetylase. The second path results from our understanding that severe mood disorders, although not classical neurodegenerative disorders, are associated with regional impairments of structural plasticity and cellular resilience. This suggests that effective treatments will need to provide both trophic and neurochemical support, which serves to enhance and maintain normal synaptic connectivity, thereby allowing the chemical signal to reinstate the optimal functioning of critical circuits necessary for normal affective functioning. For many refractory patients, drugs mimicking "traditional" strategies, which directly or indirectly alter monoaminergic levels, may be of limited benefit. Newer "plasticity enhancing" strategies that may have utility in the treatment of mood disorders include inhibitors of glutamate release, N-methyl-D-aspartate antagonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid potentiators, cyclic adenosine monophosphate phosphodiesterase inhibitors, and glucocorticoid receptor antagonists.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center