Dopaminergic dysfunction has been implicated in autism. 1 Dopamine modulates motor activity, attentional skills, social behaviour, and perception of the outside world, all of which are abnormal in autism. Plasma and urine concentrations of homovanillic acid, a dopamine metabolite, have been reported abnormal in those with the condition. Dopaminereceptor antagonists are the only drugs with consistent clinical efficacy in controlled trials in autism. Normal individuals, but not those with Asperger syndrome (a variant of autism), activate the medial prefrontal cortex during a task that relies upon the ability to attribute mental states to others. 2 This task targets the “theory of mind” which may be central to the social impairment observed in autism. We used positron emission tomographic scanning (PET) to measure accumulation of fluorine-18-labelled fluorodopa (FDOPA) in the head of the caudate nucleus, putamen, midbrain area (substantia nigra and ventral tegmentum), lateral and medial anterior prefrontal regions, and occipital cortex in 14 medication-free autistic children (by DSM-IIIR)(age 13 [SD 2· 4] years, eight boys, six girls; IQ 74· 0 [23· 1], range 46–123) and ten healthy children (age 14 [2· 0] years; seven boys, three girls; IQ 112· 3 [6· 7], range 103–126). Quantification of the positron-emitting FDOPA tracer as the ratio of specific (regions rich in dopamine terminals) to non-specific (occipital cortex, a region poor in dopamine terminals) gives an estimate of localised presynaptic dopaminergic activity. 3 The FDOPA signal was recorded 90 min after tracer injection for 30 min. 11 of the 14 autistic children were sedated with propofol immediately before scanning was begun. This approach allowed for accurate scanning while avoiding any possible effect of propofol on FDOPA uptake. The groups did not differ in age, sexual maturation, gender, handedness, or socioeconomic status.

The regional FDOPA ratio was reduced by 39% in the anterior medial prefrontal cortex in the autistic group compared to the control group (t= 2· 6; df= 1· 22; p= 0· 016, student’s t test), but there were no other differences in regional FDOPA ratios between groups (table). Also, regional FDOPA ratios were unrelated to IQ; the anterior medial prefrontal FDOPA ratios of the autistic children with high IQs (IQ higher than 80) were all lower than the lowest value of the FDOPA ratios in the controls. Dopamine is important in prefrontal function, 4 and this dopaminergic deficit may contribute to the cognitive impairment seen in autism). These findings do not exclude other abnormalities as potential contributors to the syndrome of autism, 5 but FDOPA PET studies could help subtype autistic patients for genetic studies and for treatment protocols which target dopaminergic function.