[123I] ADAM brainstem binding correlates with the loudness dependence of auditory evoked potentials

Abstract

The in vivo assessment of brain serotonergic function might be of clinical relevance in neuropsychiatry. The loudness dependence of auditory evoked potentials (LD) has been proposed as an indirect indicator of cortical serotonergic activity, whereas single photon emission computed tomography (SPECT) and [123I]ADAM allow the selective assessment of brain serotonin transporters (SERT). The aim of this study was to investigate LD and SERT availability as independent variables of the brain serotonergic system in healthy volunteers. Fifteen (six male, nine female) subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities; the LD was analyzed using dipole source analysis. SPECT was performed four hours after injection of 137 +/- 11.4 MBq [123I]ADAM. As a measure of SERT availability specific ADAM brainstem binding was used. LD correlated significantly with SERT availability (Pearson's correlations: rho = -0.57, p < 0.05). The correlations remained significant after controlling for the effects of age or gender (partial correlations: rho = -0.60, p < 0.05) but were pronounced in the female group (rho = -0.83, p < 0.01). Associations between LD and SERT availability contribute to the understanding of the central serotonergic system and further validate the use of neurophysiological approaches as indirect measures of neurochemical brain activity.

Loudness dependence of auditory evoked potentials (LDAEP) correlates with the availability of dopamine transporters and serotonin transporters in healthy volunteers—a two isotopes SPECT study

“…Elevated levels of transporter availability could be associated with monoamine deficit, because the elevation reflects an increased capacity of presynaptic monoamine reuptake or because it is the consequence of an elevated number of available binding sites due to decreased competition by lower endogenous monoamine levels (Meyer et al 2004;Meyer 2007). Another viewpoint could be that low monoamine transporter availability could reflect a low monoamine tone, which could lead to a downregulation of the presynaptic reuptake sites of endogenous monoamine (Malison et al 1998;Pogarell et al 2007b;Yang et al 2007).…”

“…High LD may not be interpreted absolutely as 5-HT deficiency. Pogarell et al (2004Pogarell et al ( , 2007b used [ 123 I] ADAM and β-CIT as radioligands in SPECT analysis to study the associations between LDAEP and presynaptic monoamine transporter availability (SERT and DAT). Compared with Pogarell's study, our study had three main differences in methodology.…”

“…Two isotopes ([ 99m Tc] TRODAT and [ 123 I] ADAM) were used to approximate the availability of DAT and SERT. It is found that the SERT and DAT availability are influenced by age and sex (Hesse et al 2003;Pirker et al 2000;Pogarell et al 2007b;Staley et al 1994). Significant association between LD and the availability of both monoamine transports after controlling the demographic effects were hypothesized.…”

Brainstem Raphe Alterations Depicted by Transcranial Sonography Do Not Result in Serotonergic Functional Impairment

“…The loudness dependence of auditory evoked potentials (LDAEP), indicating an amplitude change of the evoked N1/P2 component in response to different auditory stimulus intensities, has been proposed as a valid indirect indicator of serotonergic activity . Evidence for a strong LDAEP reflecting low central serotonergic activity and vice versa was shown in experimental studies with animals and humans . In depressed patients, the LDAEP was identified as a predictor of treatment response, especially to selective serotonin reuptake inhibitor (SSRI) antidepressants …”