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Impairments in social interaction and communication, in combination with restricted, repetitive behaviors and interests, define the neurodevelopmental diagnosis of autism spectrum disorder (ASD). The biological underpinnings of ASD are not well known, but the hypothesis of serotonin (5-HT) involvement in the neurodevelopment of ASD is one of the longest standing. Reuptake through the 5-HT transporter (5-HTT) is the main pathway decreasing extracellular 5-HT in the brain and a marker for the 5-HT system, but in vivo investigations of the 5-HTT and the 5-HT system in ASD are scarce and so far inconclusive. To quantify possible alterations in the 5-HT system in ASD, we used positron emission tomography and the radioligand [ 11 C]MADAM to measure 5-HTT availability in the brain of 15 adults with ASD and 15 controls. Moreover, we examined correlations between regional 5-HTT availability and behavioral phenotype assessments regarding ASD core symptoms. In the ASD group, we found significantly lower 5-HTT availability in total gray matter, brainstem, and 9 of 18 examined subregions of gray matter. In addition, several correlations between regional 5-HTT availability and social cognitive test performance were found. The results confirm the hypothesis that 5-HTT availability is lower in the brain of adult individuals with ASD, and are consistent with the theory of 5-HT involvement in ASD neurodevelopment. The findings endorse the central role of 5-HT in the physiology of ASD, and confirm the need for a continued investigation of the 5-HT system in order to disentangle the biology of ASD.

Serotonin transporter availability in adults with autism—a positron emission tomography study