Effects of lamotrigine on hippocampal activation in corticosteroid-treated patients.
BACKGROUND
An extensive animal literature suggests that stress or excessive corticosteroid exposure is associated with changes in hippocampal function and memory. These findings are pertinent to psychiatric disorders with elevated cortisol, Cushing's disease and the millions of patients receiving prescription corticosteroids. In animals, agents that decrease glutamate release attenuate the effects of corticosteroids on the hippocampus. Minimal data are available on preventing or reversing the effects of corticosteroids on the human hippocampus. We previously reported improvement in memory in corticosteroid-treated patients given lamotrigine. In this report, we examined the impact of lamotrigine on task-related hippocampal activation in patients taking prescription corticosteroids.


METHODS
A total of 28 outpatients taking long-term oral prednisone for medical conditions, such as renal transplant rejection, were randomized to lamotrigine or placebo for 24 weeks. Hippocampal activation in response to a visual memory task was assessed with blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI).


RESULTS
Consistent with a reduction in glutamate release, the right posterior hippocampus showed a significant decrease in task-related activation in the lamotrigine group as compared to the placebo group.


CONCLUSIONS
The modest sample size and an assessment period of only 24 weeks are study limitations.


CONCLUSIONS
Between-group differences in hippocampal activation were observed. The results suggest that an agent that modulates glutamate may modify the effects of long-term corticosteroid exposure on the human hippocampus.
Brown
E Sherwood
ES
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8849, United States. Sherwood.Brown@UTSouthwestern.edu
Zaidel
Liam
L
Allen
Greg
G
McColl
Roderick
R
Vazquez
Miguel
M
Ringe
Wendy K
WK
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D004292:Dominance, Cerebral / Q000187:drug effects; D004311:Double-Blind Method; D017352:Echo-Planar Imaging; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006084:Graft Rejection / Q000188:drug therapy* / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016030:Kidney Transplantation / Q000523:psychology*; D000077213:Lamotrigine; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D010100:Oxygen / Q000097:blood*; D010364:Pattern Recognition, Visual / Q000187:drug effects; D011241:Prednisone / Q000009:adverse effects* / Q000627:therapeutic use; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D000927:Anticonvulsants; D014227:Triazines; D018698:Glutamic Acid; D010100:Oxygen; D000077213:Lamotrigine; D011241:Prednisone