Auditory Evoked Potential Modifications according to Clinical and Biochemical Responsiveness to Fenfluramine Treatment in Children with Autistic Behavior

Abstract

Evoked potentials to auditory stimulations varying in intensity were studied in 13 children with autistic behavior treated with fenfluramine. Modifications of both amplitude and single-trial potential variability were considered according to the clinical and biochemical responsiveness to this drug. Six children (responders) were clinically improved by the treatment. Electrophysiological data were affected according to the clinical and biochemical responsiveness to fenfluramine: the auditory evoked potential amplitude increased, and the single-trial potential variability decreased at each intensity level only in responders whose dopaminergic metabolism was significantly modified by fenfluramine treatment. No modification was found in nonresponders. Both biochemical and electrophysiological results argued for an amphetamine-like action of fenfluramine in those autistic children whose attention deficits are associated with motor disturbances including hyperactivity.

Auditory Evoked Potentials Reflect Serotonergic Neuronal Activity—A Study in Behaving Cats Administered Drugs Acting on 5-HT1A Autoreceptors in the Dorsal Raphe Nucleus

“…Although the extrapolation of the present results in cats to humans must be made cautiously, and the specificity might be limited, some evidence suggests that the intensity dependence of AEP is of clinical value in assessing central serotonergic function. For example, several studies have revealed that patients with low serotonergic activity, indicated by a strong intensity dependence before treatment, respond more favorably to drugs that increase serotonergic neurotransmission, such as fluoxetine (Paige et al 1994), fluvoxamine (Hegerl and Juckel 1993), fenfluramine (Bruneau et al 1989), paroxetine , or lithium (Hegerl and Juckel 1993) than patients with normal or high serotonergic activity, as indicated by a weak intensity dependence of AEP. Regarding the fact that brain serotonin cannot be measured directly and that no valid biochemical indicator of the central serotonergic function is available, the finding of a close relationship between the intensity dependence recorded from the primary auditory cortex and central serotonergic activity is of great clinical interest.…”

Intensity Dependence of Auditory Evoked N1/P2 Component and Personality

“…1991] and to the clinical response to serotonin agonists like lithium [Hegerl et al. 1987, 170 Hegerl/Karnauchow/Herrmann/ Muller-Oerlinghausen 1992: Hegerl, 1992] and fenfluramine [Bruneau et al, 1989], Furhtermore. reduced serotonergic function seems to be related to 'action-oriented' personality traits like 'impulsivity'.…”

High Intensity Dependence of Auditory Evoked Dipole Source Activity Indicates Decreased Serotonergic Activity in Abstinent Ecstasy (MDMA) Users

“…The auditory evoked N1/P2 component and, particularly, its tangential dipole source activity increased strongly with higher stimulus intensities in persons with personality traits thought to be associated with diminished serotonergic activity such as high novelty or sensation seeking (Zuckerman 1990;Juckel et al 1994; Hegerl et al 1995a,b). Finally, a high intensity dependence of the auditory evoked N1/P2 component predicted good clinical response to such serotonergic drugs as fenfluramine and lithium in clinical populations (Bruneau et al 1989;Hegerl et al 1987Hegerl et al , 1992.…”

“…The auditory evoked N1/P2 component and, particularly, its tangential dipole source activity increased strongly with higher stimulus intensities in persons with personality traits thought to be associated with diminished serotonergic activity such as high novelty or sensation seeking (Zuckerman 1990;Juckel et al 1994; Hegerl et al 1995a,b). Finally, a high intensity dependence of the auditory evoked N1/P2 component predicted good clinical response to such serotonergic drugs as fenfluramine and lithium in clinical populations (Bruneau et al 1989;Hegerl et al 1987Hegerl et al , 1992.According to studies of dipole source analysis (Scherg 1991;Scherg et al 1989), the tangentially oriented dipole of the N1/P2 component of AEP represents mainly the activity of the primary auditory cortex; whereas, the radially oriented dipole represents the activity of the secondary auditory cortex in the more lateral part of the temporal lobe . Although serotonergic fibers from the raphe nuclei project to virtually every brain area, the highest rate of serotonergic innervation has been found in the primary sensory cortex; whereas, serotonergic innervation in the secondary sensory areas is clearly lower (Azmitia and Gannon 1986;Campbell et al 1987;Lewis et al 1987;Morrison and Foote 1986;Takeuchi and Sano 1983).…”