Evaluation of cerebellar serotonin synthesis capacity using alpha[¹¹C]methyl-L-tryptophan (AMT) PET scan in children with autism spectrum disorder

Objectives Serotonin plays an important role in brain development, and links between serotonin and autism spectrum disorder (ASD), as well as cerebellum and ASD, have been long suggested. The purpose of the present study was to assess developmental changes of cerebellar serotonin synthesis capacity in children with ASD with alpha[¹¹C]methyl-L-tryptophan (AMT) PET scan.

Methods Children with ASD (N=34, mean age-6.1 years; 24 males) were divided into high (HF-ASD) and low functioning groups (LF-ASD) and compared to typically developing children (N=10; mean age-7.6 years; 5 males). The unidirectional uptake rate constant (K-Cplx) of AMT was calculated for cerebellum. The interaction of age with K-Cplx was fitted with a linear function for each group, and a Z-test was applied to determine the differences between groups.

Results Developmental changes of cerebellar serotonin synthesis showed the same slope in HF-ASD and controls, but the HF-ASD showed lower K-Cplx values (0.0068+0.0019 vs. 0.0083+0.0025 ml/gm/min). In contrast, the slope was lower in the LF-ASD group (p=0.04). K-Cplx values at young ages were similar in both ASD groups, but decreased more slowly with age in the LF-ASD group, such that K-Cplx was higher for the LF-ASD group compared to both HF-ASD and control groups at older ages.

Conclusions The developmental trajectory of cerebellar serotonin synthesis in ASD is different than that seen in typically developing children. Differences in changes in serotonin synthesis with age between children with high or low functioning ASD suggest a role for serotonin in cognitive development in ASD