Regulation of signal transduction pathways and gene expression by mood stabilizers and antidepressants.
OBJECTIVE
To determine whether the currently available evidence supports the hypothesis that antidepressants and mood stabilizers may bring about some of their long-term therapeutic effects by regulating signal transduction pathways and gene expression in the central nervous system.


METHODS
To address this question, we reviewed the evidence showing that chronic administration of antidepressants and mood stabilizers involves alterations in signaling pathways and gene expression in the central nervous system.


RESULTS
A large body of data has shown that lithium and valproate exert effects on the protein kinase C signaling pathway and the activator protein 1 family of transcription factors; in contrast, antidepressants affect the cyclic adenosine monophosphate pathway and may bring about their therapeutic effects by modulating cyclic adenosine monophosphate-regulated gene expression in the central nervous system.


CONCLUSIONS
Given the key roles of these signaling cascades in the amplification and integration of signals in the central nervous system, the findings have clear implications not only for research into the etiology and pathophysiology of the severe mood disorders but also for the development of novel and innovative treatment strategies.
Chen
G
G
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Hasanat
K A
KA
Bebchuk
J M
JM
Moore
G J
GJ
Glitz
D
D
Manji
H K
HK
D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018692:Antimanic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008094:Lithium / Q000494:pharmacology; D019964:Mood Disorders / Q000188:drug therapy* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011953:Receptors, Cyclic AMP / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology
D000928:Antidepressive Agents; D018692:Antimanic Agents; D011953:Receptors, Cyclic AMP; D018808:Transcription Factor AP-1; D014635:Valproic Acid; D008094:Lithium; D011493:Protein Kinase C; D019204:GTP-Binding Proteins