AMPA receptor expression is increased post-mortem samples of the anterior cingulate from subjects with major depressive disorder.
BACKGROUND
Glutamate is thought to be involved in the pathophysiology of major depressive disorder and bipolar disorder; however, the molecular changes underlying abnormal glutamatergic signalling remain poorly understood. Whilst previous studies have suggested that the NMDA receptor may be involved in the pathophysiology of mood disorders, it is unclear whether the non-NMDA receptors are also involved. Therefore, we sought to examine whether the expression of the non-NMDA, ionotropic glutamate receptors, AMPA receptor and kainate receptor, is altered in mood disorders.


METHODS
We used [3H]AMPA and [3H]kainate to measure the levels of AMPA and kainate receptor, respectively, in the anterior cingulate (BA 24) and dorsolateral prefrontal cortex (BA 46) from post-mortem CNS in 10 subjects with major depressive disorder, 10 subjects with bipolar disorder and 10 control subjects.


RESULTS
A 20.7% to 27.7% increase in [3H]AMPA binding density was seen in BA 24 (p<0.05) but not BA 46 (p>0.05) in major depressive disorder compared to control levels. [3H]AMPA binding density was not changed in bipolar disorder in either BA 24 or BA 46 (p>0.05) compared to controls. [3H]Kainate binding was not changed in either BA 24 or BA 46 in either disorder compared to controls (p>0.05).


CONCLUSIONS
Small sample sizes (n=10) were used in this study. The subjects were not drug naïve.


CONCLUSIONS
Our data suggests increased in AMPA receptor levels in the anterior cingulate are involved in the pathophysiology of major depressive disorder. This data has relevance for the development of new anti-depressant drugs targeted towards the AMPA receptors.
Rebecca L Cooper Laboratories, Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Australia. a.gibbons@mhri.edu.au
Andrew Stuart
AS
Gibbons
Lucy
L
Brooks
Elizabeth
E
Scarr
Brian
B
Dean
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000378:metabolism; D002102:Cadaver; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000378:metabolism*; D018091:Receptors, AMPA / Q000096:biosynthesis*; D017470:Receptors, Glutamate / Q000096:biosynthesis; D018092:Kainic Acid Receptors / Q000096:biosynthesis; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis
D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate