Abstract
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 [11C]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.
Highlights
These authors contributed : Jacqueline Borg, Johan Lundberg
The controls were matched to the subjects with autism spectrum disorder (ASD), and the groups did not differ on sex, age, or intelligence quotient (IQ) level; a significantly higher educational level was seen in the control group
We confirm our primary hypothesis that 5-HT transporter (5-HTT) availability is significantly lower in total gray matter of adults with ASD compared with control subjects
Summary
ParticipantsThe study was approved by the Regional Ethics Committee in Stockholm County and the Radiation Safety Committee of the Karolinska University Hospital. Participants with ASD had community diagnoses of ASD (ICD-10 or DSM-IV) from specialized units for neurodevelopmental assessments and according to clinical guidelines of Region Stockholm [38], corroborated by the usage of standardized measures, such as the Autism Quotient, Autism Spectrum Diagnostic Interview, and the Ritvo Autism Asperger Diagnostic Scale. They were assessed using the Autism Diagnostic Observation Schedule-2, module 4. To allow for paired statistical analysis of PET data, each participant with ASD was matched to a control subject based on sex and age (±3 years). Participants in this study are identical to those described as the Stockholm sample in the previously published article by Horder et al [41]
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