Effect of electroconvulsive therapy on brain 5-HT(2) receptors in major depression.
BACKGROUND
Brain serotonin(2) (5-hydroxytryptamine(2); 5-HT(2)) receptors were considered potential targets for therapeutic efficacy of electroconvulsive therapy (ECT), but pre-clinical studies showed that electroconvulsive shock up-regulates 5-HT(2) receptors in contrast to antidepressant medications, which down-regulate brain 5-HT(2) receptors. Positron emission tomography (PET) studies in individuals with depression confirmed that antidepressant medications reduce brain 5-HT(2) receptors, but the effects of ECT on these receptors in individuals with depression are unknown.


OBJECTIVE
To determine if a course of ECT alters brain 5-HT(2) receptors in individuals with depression and whether such changes correlate with improvement in symptoms.


METHODS
Fifteen people with major depression, refractory to antidepressant therapy and referred for a course of ECT, had an [18F]setoperone scan during baseline drug-free washout period and another after a course of ECT. We assessed changes in brain 5-HT(2) receptors with ECT and their relationship to therapeutic outcome.


RESULTS
Widespread reduction in brain 5-HT(2) receptors was observed in all cortical areas with changes slightly more prominent in the right hemisphere. There was a trend for correlation between reduction in brain 5-HT(2) receptors in right parahippocampal gyrus, right lingual gyrus and right medial frontal gyrus, and improvement in depressive symptoms.


CONCLUSIONS
Unlike in rodents, and similar to antidepressants, ECT reduces brain 5-HT(2) receptors in individuals with depression. The ability of ECT to further down-regulate brain 5-HT(2) receptors in antidepressant non-responsive individuals may explain its efficacy in those people with antidepressant refractory depression.
Yatham
Lakshmi N
LN
UBC Department of Psychiatry, The University of British Columbia, UBC Hospital, 2255 Wesbrook Mall, Vancouver, BC V6T2A1, Canada. yatham@exchange.ubc.ca
Liddle
Peter F
PF
Lam
Raymond W
RW
Zis
Athanasios P
AP
Stoessl
A Jon
AJ
Sossi
Vesna
V
Adam
Michael J
MJ
Ruth
Thomas J
TJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D001931:Brain Mapping; D003287:Contrast Media; D003865:Major Depressive Disorder / Q000628:therapy*; D015536:Down-Regulation; D004565:Electroconvulsive Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D016896:Treatment Outcome; D055815:Young Adult
D003287:Contrast Media; D011744:Pyrimidinones; D044348:Receptors, Serotonin, 5-HT2; C045359:setoperone