Research report
Acute tryptophan depletion attenuates auditory event related potentials in bipolar disorder: a preliminary study

https://doi.org/10.1016/S0165-0327(00)00382-7Get rights and content

Abstract

Background: 5-HT modulates electroencephalographic (EEG) activity, which is abnormal in bipolar disorder and EEG abnormalities persist in euthymic bipolar patients. The EEG may therefore be a sensitive marker of 5-HT function in bipolar disorder. We examined the effects of acute tryptophan depletion (ATD) on EEG activity in bipolar patients. Methods: Fourteen patients with DSM IV Bipolar 1 disorder participated in a within-subject, double-blind, placebo-controlled, random-order crossover study. Following ATD quantitative power spectrum brain mapping and measurement of auditory evoked potentials were carried out. Results: ATD produced a significant fall in the amplitude of N1P2 and P300 components of the auditory evoked potential, but no significant changes in the power spectrum. There was an 83% reduction in plasma tryptophan after the depleting but not the control drink. Limitations: The effect of ATD on brain 5-HT levels was not directly measured. The number of patients is relatively small. The control condition may alter these electrophysiological measures. Conclusions: ATD attenuates auditory evoked potentials in bipolar disorder with the distribution of this effect being towards the front of the brain. These changes are not related to any change in mood. This is a potential trait marker of bipolar disorder, however there needs to be further exploration of this paradigm in controls and other patient groups.

Introduction

The neurotransmitter serotonin (5-Hydroxytryptamine, 5-HT) is implicated in the pathophysiology of mood disorders and the mechanism of action of the mood stabiliser lithium (Cowen et al., 1991, Cowen, 1996). Serotonin modulates brain electrophysiological (EEG) activity (Dijk et al., 1989, Seifritz et al., 1996) and the EEG is abnormal in mood disorders (Ashton et al., 1988, Muir et al., 1991, Gangadhar et al., 1993, Souza et al., 1995). These abnormalities partially normalise following treatment of mood disorders with drugs that alter serotonergic activity. However, some EEG abnormalities have been shown to persist in euthymic patients with unipolar (Dahabra et al., 1998) and bipolar depression (El Badri et al., 1997). EEG activity may therefore be a sensitive marker of vulnerability to mood disorders and also an indicator of neurotransmitter function. Acute tryptophan depletion (ATD) lowers central serotonergic availability and has been widely used to study brain 5-HT function in clinical populations (Reilly et al., 1997). To examine the role of serotonin in EEG measures, we acutely tryptophan depleted euthymic bipolar patients symptomatically stable on lithium.

Section snippets

Methods

Patient characteristics are shown in Table 1. Fourteen patients (aged 22 to 62, 9 males) with DSM IV Bipolar I affective disorder were recruited from outpatient clinics in the Newcastle area. All had been euthymic for at least 3 months and were receiving lithium in therapeutic doses. Two of the patients were receiving single low dose typical neuroleptic medication (one a single dose of droperidol 10 mg at night and the other a single dose of chlorpromazine 100 mg at night) in addition to

Biochemical measurements

The depleting drink was well tolerated and none of the subjects complained of adverse effects. Patient characteristics are detailed in Table 1. Mood ratings were not affected (Hughes et al., 2000a, Hughes et al., 2000b). The results for the biochemical measures are shown in Table 2. There was a significant effect of depleting drink compared to control drink on both free and total tryptophan concentration, with 83% depletion of free tryptophan (paired t-test, P=0.016) and 84% depletion of total

Discussion

These data show that ATD produces significant changes in auditory evoked potentials in bipolar patients. Amplitudes of the N1P2 and P300 components of the auditory evoked potential are reduced after depletion, especially in frontal and central areas. These effects occurred in the absence of any shifts in mood or any adverse effects of the experimental procedure. The patients studied were a carefully selected sample, who had bipolar I disorder without any concurrent axis I diagnosis or

Acknowledgements

We thank the Theodore and Vada Stanley Foundation for their support of this study.

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