Elsevier

Psychiatry Research

Volume 158, Issue 1, 28 February 2008, Pages 79-82
Psychiatry Research

Brief report
Loudness dependence of the auditory evoked N1/P2 component as an indicator of serotonergic dysfunction in patients with schizophrenia — A replication study

https://doi.org/10.1016/j.psychres.2007.08.013Get rights and content

Abstract

Serotonergic dysfunction appears to be involved in the pathogenesis of schizophrenia. The loudness dependence of auditory evoked potentials (LDAEP) has been suggested to be a valid indicator of the brain serotonin system's activity in humans. Patients with schizophrenia showed weaker LDAEP, indicating high serotonergic activity, in comparison to healthy controls. Thus, we were able again to demonstrate electrophysiological evidence for an upregulated serotonergic system in schizophrenia.

Introduction

The most dominant neurochemical hypothesis of schizophrenia is the dopamine hypothesis, which originated from the relationship between the efficacy of the classical neuroleptics and their affinity for dopamine receptors (Seeman et al., 1976). Besides that, other neurotransmitter systems appear to contribute to the pathophysiology of schizophrenia as well. Serotonergic neurotransmission is of growing scientific interest in schizophrenia research particularly due to the role of serotonergic mechanisms in the therapeutic effects of atypical neuroleptics (Meltzer, 1999). Furthemore, postmortem studies, cerebrospinal fluid studies of 5-hydroxyindoleacetic acid, genetic studies and neuroima-ging findings show an increased serotonergic neurotransmission in schizophrenia (Sawa and Snyder, 2002).

Until recently, there has been a lack of valid indicators of central serotonergic activity. Peripheral serotonergic measurements only indirectly reflect serotonergic brain function, without reflecting short-term changes in this system (Hegerl and Juckel, 1993). The loudness dependence of auditory evoked potentials (LDAEP) has been proposed as a valid indicator for the serotonergic system. The LDAEP is a measure of auditory cortex activity that reflects the increase or decrease of the auditory evoked N1/P2 component with increasing tone loudness. Previous studies on animals as well as on psychiatric patients found an inverse association between this parameter and serotonergic activity (Hegerl and Juckel, 1993, Juckel et al., 1999, Nathan et al., 2006), although there are also conflicting results (Hensch et al., 2006, Uhl et al., 2006). A weak LDAEP indicates high serotonergic activity and vice versa. In line with the hypothesis of an increased serotonergic tone in schizophrenia, a previous study reported a decreased LDAEP in unmedicated patients with schizophrenia compared with healthy volunteers (Juckel et al., 2003). In the present study, the LDAEP was investigated again to replicate the previously reported abnormalities in schizophrenic patients compared with healthy subjects as well as to explore whether or not a decreased LDAEP can also be found in medicated patients, indicating that enhanced serotonergic neurotransmission could be a trait characteristic and the weak LDAEP a marker for serotonergic activity.

Section snippets

Methods

Subjects comprised 36 male patients with schizophrenia (all medicated: 11 with only typical neuroleptics, 19 with only atypical neuroleptics, and 6 with both) and 36 age-matched healthy volunteers. Table 1 presents the demographic and clinical data. The patients were inpatients and outpatients from the Psychiatric Hospital of the Ludwig-Maximilians—University in Munich. Healthy controls were selected from the general population of Munich. The study was carried out in accordance with the

Results

The LDAEP of the left tangential dipole was significantly lower in schizophrenic (0.09 ± 0.17 μV/10 dB) than in healthy subjects (0.16 ± 0.13 μV/10 dB) (P < 0.05; Fig. 1). No significant difference was found for the LDAEP of the right hemisphere (0.13 ± 0.25 μV/10 dB vs. 0.15 ± 0.15 μV/10 dB, n.s.). The LDAEP of radial dipoles did not differ between schizophrenic patients and healthy controls (left: 0.13 ± 0.14 μV/10 dB vs. 0.12 ± 0.11 μV/10 dB, n.s; right: 0.11 ± 0.15 μV/10 dB vs. 0.09 ± 0.12 μV/10 dB, n.s).

Discussion

In accordance with our previous study, patients with schizophrenia showed significantly weaker LDAEP of the primary, but not of the secondary, auditory cortex (tangential dipole) than healthy controls (Juckel et al., 2003). According to the hypothesis of an inverse relationship between LDAEP and central serotonergic activity, patients with schizophrenia showed an increased level of serotonergic activity. This finding is consistent with other findings regarding the role of an enhanced

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