Serotonin and Dopamine Transporter Availabilities Correlate with the Loudness Dependence of Auditory Evoked Potentials in Patients with Obsessive-Compulsive Disorder

Abstract

Brain monoaminergic function is involved in the pathophysiology of psychiatric disorders. The loudness dependence (LD) of the N1/P2 component of auditory evoked potentials has been proposed as a noninvasive indicator of central serotonergic function, whereas single photon emission computed tomography (SPECT) and [ 123 I]b-CIT can be used to visualize both serotonin (SERT) and dopamine transporters (DAT). The aim of the study was to correlate LD and SPECT measures in patients with obsessive-compulsive disorder, a condition with evidence for a serotonergic dysfunction. A total of 10 subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities. The LD of the relevant subcomponents (tangential dipoles) was investigated using dipole source analysis. SPECT was performed 20-24 h after injection of a mean 140 MBq [ 123 I]b-CIT. As a measure of brain SERT and DAT availabilities, a ratio of specific to nonspecific [ 123 I]b-CIT binding for the midbrain . pons region (SERT) and the striatum (DAT) was used. The LD of the right tangential dipole correlated significantly with both SERT and DAT availabilities (Pearson's correlations: r ¼ 0.69, po0.05, and r ¼ 0.80, po0.01, respectively). The correlations remained significant after controlling for the effects of age, gender, and severity of clinical symptoms. Associations between LD and both SERT and DAT availabilities further validate the use of neurophysiological approaches as noninvasive indirect measures of neurochemical brain function and point at a hypothesized interconnection of central monoaminergic systems.

Fluvoxamine Treatment and D2 Receptors: a Pet Study on OCD Drug-Naïve Patients

“…This speculation is also in line with other preclinical and imaging findings indicating an increased dopaminergic tone in OCD striatum. In particular, (a) the administration in rodents of dopamine mimetic such as amphetamine, cocaine induces some stereotypic behaviors that resemble obsessive behaviors observed in OCD patients (Goodman et al, 1990;Grace, 2000;Pitman, 1989); (b) the increase in dopamine transporter (DAT) density reported in two out of three different SPET studies on OCD patients (Cheon et al, 2004;Kim et al, 2003;Pogarell et al, 2004).…”

Is the Loudness Dependence of the Auditory Evoked Potential a Sensitive and Selective In Vivo Marker of Central Serotonergic Function?

“…Second, the specificity of the LDAEP as a marker of serotonin neurotransmission is questionable. For example, dopamine metabolites in CSF and urine have been found to correlate with the intensity dependence of visual and auditory N1/P2 components (Von Knorring and Perris, 1981), and Juckel et al (1997) also found that the D 1 /D 2 agonist apomorphine decreased the intensity dependence in animals, and more recently, a study in patients with obsessive-compulsive disorder found a correlation between the LDAEP and striatal dopamine transporter (DAT) binding (Pogarell et al, 2004). Consequently, only a relative specificity can be expected with regard to the LDAEP and its relationship to functional aspects of the serotonergic system.…”

Examination of the effect of acute levodopa administration on the loudness dependence of auditory evoked potentials (LDAEP) in humans

“…In the studies using dopamine receptor agonists and in our trial an iatrogenic condition as a state factor is used. So far studies suggesting a dopaminergic influence on the LDAEP Kawohl et al 2008a;Pogarell et al 2004) show an association of the LDAEP with trait factors, i.e. genetic variants in dopamine pathways.…”

“…Several findings cast some doubt over its sensitivity to changes in 5-HT functioning alone (Juckel et al , 1997O'Neill et al 2006;Pogarell et al 2004;Uhl et al 2006). An association between 5-HT (SERT) and dopamine (DAT) transporter availability and the interindividual LDAEP has been found in a [123I]beta-CIT single-photon emission computed tomography (SPECT) study (Pogarell et al 2004). High availability of the transporter enzymes, indirectly suggesting reduced 5-HT and dopamine in the synaptic cleft, was correlated with an increased LDAEP in patients with obsessive-compulsive disorder.…”