An examination of acute changes in serotonergic neurotransmission using the loudness dependence measure of auditory cortex evoked activity: effects of citalopram, escitalopram and sertraline.
OBJECTIVE
The underlying effect of serotonergic neurotransmission has been implicated in several psychiatric disorders. The inability to routinely and non-invasively determine the integrity of the serotonergic system in vivo has limited our understanding of disorders with a putative serotonergic abnormality. The loudness dependence of the auditory evoked potential (LDAEP) has been proposed as a reliable measure of central serotonin function in humans. While animal studies suggest that the LDAEP is sensitive to changes in central serotonin neurotransmission, evidence in humans has been indirect and inconsistent. The aim of this study was to assess the sensitivity of the LDAEP to acute augmentation in central serotonergic neurotransmission in humans.


METHODS
The study used a double-blind, placebo-controlled cross-over design, in which healthy subjects were tested under four acute treatment conditions, with pharmacologically equivalent single doses of placebo, escitalopram (10 mg), citalopram (20 mg) and sertraline (50 mg) to examine the direct effect of acute enhancement of synaptic serotonin on the LDAEP. Furthermore, the outcome of the serotonergic modulatory effects on the LDAEP was also examined using two methods (dipole source analysis (DSA) vs. scalp analysis).


RESULTS
Escitalopram, citalopram and sertraline had no effects on the LDAEP and were independent of the analysis method used.


CONCLUSIONS
These findings question the sensitivity of the LDAEP to acute changes in serotonin neurotransmission and its validity as a reliable measure of central serotonin function in humans.
Guille
Valérie
V
Biological Psychiatry Research Unit, Brain Sciences Institute, Swinburne University of Technology, Melbourne, VIC, Australia.
Croft
Rodney J
RJ
O'Neill
Barry V
BV
Illic
Susan
S
Phan
K Luan
KL
Nathan
Pradeep J
PJ
D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects; D001303:Auditory Cortex / Q000187:drug effects* / Q000502:physiology; D001519:Behavior / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005072:Evoked Potentials, Auditory; D006801:Humans; D008297:Male; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology; D009435:Synaptic Transmission
D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline