Event-related potentials and monoamines in autistic children on a clinical trial of fenfluramine
Introduction: As autistic persons have problems with selecting and encoding meaningful stimuli and multi-centre studies (Ritvo et al., 1983, 1986) had reported mild behavioural improvements following treatment with fenfluramine, event-related potential (ERP) stages of information processing were studied in childhood autism as part of a double blind crossover study of the efficacy of dl fenfluramine. Methods: Acceptable recordings were derived from midline and 4 lateral sites on the scalp of 7 from 14 young persons with autism who understood the task (6 male, 1 female 5.8-17.7 years-of-age). A three-tone oddball paradigm was presented in a passive and active-task form (72% at 1 kHz, 14% at 0.5 kHz and 14% at 2.0 kHz) under placebo and drug conditions (where each condition lasted 5 months). Eleven patients provided blood and urine samples for monoamine analyses in both conditions. Results: a) With fenfluramine treatment blood serotonin decreased and urinary catecholamine levels fell (25-45%, but dopamine utilization (HVA/DA) increased 2-4-fold. b) Under fenfluramine autistic subjects responded non-significantly faster, with fewer errors of omission and improved /decreased beta criterion (signal detection). [IQ measures increased 7.5 points.] c) N1 amplitudes (Fz) decreased and latencies increased in the fenfluramine condition. Early negativity (especially on the right) correlated inversely with HVA/DA actvivity. Subtraction of the ERPs in nontarget from target conditions showed that the Negative difference (Nd) increased during fenfluramine treatment. d) P3 amplitudes (especially after the deviants) increased with fenfluramine treatment. But in the difference waveform (active-minus-passive condition) the P3 amplitude was halved. The distribution of the P3 component moved rostrally with treatment. Conclusions: N1 and P3 components of the ERP were responsive to fenfluramine treament. Treatment appears to have mildly improved early stimulus processing at stages represented by the early negative components, but to have mildly impaired processing at the P3-stage. The N1 / Nd - related improvement seems to be related to increased dopamine activity (cf. neuroleptic-like properties of racemate fenfluramine).