Chronic modulation of serotonergic neurotransmission with sertraline attenuates the loudness dependence of the auditory evoked potential in healthy participants

Rationale The loudness dependence of the auditory evoked potential (LDAEP) has been reported to be an effective non-invasive measure of central serotonergic neurotransmission. However, acute manipulations of the serotonergic system in humans and animals have yielded inconsistent findings. Objectives In this study, we examined the chronic effect of serotonergic manipulation using the selective serotonin reuptake inhibitor, sertraline, on the LDAEP. In addition, we examined the influence of 5-HTTLPR genotype and individual differences in plasma drug concentrations on the LDAEP. Methods The study utilised a double-blind, placebocontrolled, between-group design in which 40 (24 female) healthy adults (M age=22.0 years, SE=0.7) were tested following placebo or sertraline for an average of 24 days. The LDAEP was assessed 6 h post-final dose, and changes in the slope of amplitude of the N1/P2 across intensities (60, 70, 80, 90, 100 dB) were examined at Cz. Results The sertraline group had a significantly smaller LDAEP than the placebo group [F(1,38)=5.97, p=0.02]. Drug plasma levels did not correlate with the LDAEP in the sertraline group, and there was no influence of 5-HTTLPR genotype. Conclusions We show for the first time that chronically modulating serotonin neurotransmission alters the LDAEP in healthy adults, consistent with extant literature indicating a moderating role of serotonin on this neurophysiological biomarker. The findings from this study together with previous studies suggest that the LDAEP may be a more sensitive marker of long-term or chronic rather than acute changes in the serotonin system.