Amygdala cyclic adenosine monophosphate response element binding protein phosphorylation in patients with mood disorders: effects of diagnosis, suicide, and drug treatment.
BACKGROUND
Signal transduction abnormalities have been identified in patients with bipolar (BD) and major depressive (MDD) disorders and are targets for lithium and antidepressant drugs. A key downstream target for signal transduction pathways is the transcription factor cyclic adenosine monophosphate (cAMP) response element binding protein (CREB). Therefore, we measured the levels of phosphorylated CREB (pCREB) in the amygdala, a region critical to emotional processing and important in the pathophysiology of both BD and MDD.


METHODS
Human postmortem amygdala sections were generously provided by the Stanley Foundation Neuropathology Consortium. Samples consisted of subjects with MDD, BD, schizophrenia (SCZ), and nonpsychiatric-nonneurologic comparison subjects (n = 15 per group). Levels of pCREB were measured by immunohistochemistry, relative to total cell number.


RESULTS
There were no differences between diagnostic groups--control subjects and subjects with BD, MDD, or SCZ--but increased numbers of pCREB stained cells were found in several amygdalar nuclei in subjects who had died by suicide. In contrast, patients treated with lithium at the time of death had significantly lower pCREB levels in the same region.


CONCLUSIONS
These results suggest that CREB activity may be an important factor in the neurobiology of suicide and the well-documented antisuicidal effect of lithium.
Young
L Trevor
LT
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Bezchlibnyk
Yarema B
YB
Chen
Biao
B
Wang
Jun-Feng
JF
MacQueen
Glenda M
GM
D000328:Adult; D000367:Age Factors; D000368:Aged; D000679:Amygdala / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D002452:Cell Count / Q000379:methods; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008094:Lithium / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013194:Staining and Labeling / Q000379:methods; D013405:Suicide / Q000706:statistics & numerical data
D017362:Cyclic AMP Response Element-Binding Protein; D008094:Lithium