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.
UBC Department of Psychiatry, The University of British Columbia, UBC Hospital, 2255 Wesbrook Mall, Vancouver, BC V6T2A1, Canada. yatham@exchange.ubc.ca
Lakshmi N
LN
Yatham
Peter F
PF
Liddle
Raymond W
RW
Lam
Athanasios P
AP
Zis
A Jon
AJ
Stoessl
Vesna
V
Sossi
Michael J
MJ
Adam
Thomas J
TJ
Ruth
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