Event-related potentials and monoamines in autistic children on a clinical trial of fenfluramine.
In a double blind, crossover study of the response of autistic subjects to fenfluramine, event-related potentials (ERPs) were recorded from 7 subjects on an attention-demanding auditory choice reaction time task (ACRT). ACRT, IQ and biochemical measures were taken after 5 months placebo and 5 months fenfluramine treatment. After fenfluramine treatment blood serotonin levels fell, urinary catecholamine levels fell and the HVA/DA ratio rose. IQ and ACRT performance improved. On the ACRT subjects were asked to press a button to a rare target (500 Hz, P = 0.14) and to ignore higher pitched rare (2,000 Hz, P = 0.14) and frequent non-targets (1,000 Hz). After fenfluramine treatment N1 latencies increased. The scalp distribution of ERP maxima changes slightly with treatment. P3 maxima elicited by rare non-targets were recorded more rostrally after fenfluramine treatment. After rare non-targets N1 amplitudes at Fz decreased but P3 amplitudes at Pz increased. Early negativity after the rare non-target (particularly on the right side) was negatively correlated with the HVA/DA ratio. Subtraction of the P3 component elicited in a passive condition where no response was required from the active condition showed that P3 positivity to targets was halved with treatment. (In contrast Nd increased on fenfluramine treatment). Overall, N1 and P3 components showed greatest responsiveness to rare non-targets on fenfluramine. N1 but not P3 changes may represent slight improvement of attention-related function with treatment. Small changes in ERP latency and distribution, associated with the neuroleptic action of fenfluramine may be partly responsible for a mild improvement of IQ and ACRT performance on medication.
Department of Physiology, Flinders Medical Centre, Bedford Park, Australia.
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RD
Oades
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Stern
M K
MK
Walker
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Clark
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Kapoor
D000293:Adolescent; D001288:Attention / Q000187:drug effects; D001321:Autistic Disorder / Q000188:drug therapy / Q000503:physiopathology*; D015306:Biogenic Monoamines / Q000378:metabolism*; D002648:Child; D004311:Double-Blind Method; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D005277:Fenfluramine / Q000627:therapeutic use*; D006719:Homovanillic Acid / Q000652:urine; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D009483:Neuropsychological Tests; D016032:Randomized Controlled Trials as Topic; D011930:Reaction Time / Q000187:drug effects
D015306:Biogenic Monoamines; D005277:Fenfluramine; D006719:Homovanillic Acid