Table 1.

Literature review on serotonin quantifications using blood or blood‐derived substances from patients with autism

	Serotonin levels	Number of ASD samples	Blood or blood‐derived substances	Study outcome	References
1	Normal	6	Platelets	Endogenous 5‐HT was slightly diminished but significant increase in platelet/mL plasma; 2‐fold higher efflux of radioactive 5‐HT from ASD patient platelets, which could indicate defective 5‐HT turnover in the brain	Boullin et al18
2	Hyperserotonemia — Normal	24	Whole blood	5‐HT level and platelet count are higher in ASD, while 5‐HT level corrected for platelet count was similar between ASD and controls	Ritvo et al17
3	Hyperserotonemia	77	Whole blood	Higher 5‐HT levels in ASD while normal in mentally retarded or cognitively impaired cases. Study points to the importance of matching for age and ethnicity	McBride et al60
4	Hyposerotonemia	10	Plasma	Lower 5‐HT levels in adults with ASD and inversely correlated with Overt Aggression Scale score	Spivak et al90
5	Hyposerotonemia	17	Plasma	Lower 5‐HT levels in mothers of ASD cases supporting the hypothesis that maternal 5‐HT would be a risk factor for ASD through effects on fetal brain development	Connors et al91
6	Hyperserotonemia	53	Platelets	Higher 5‐HT levels in 32% of ASD cases and a negative correlation with their speech development	Hranilovic et al92
7	Hyperserotonemia	109	Platelets	Higher 5‐HT levels in ASD cases and this in association with common SLC6A4 and ITGB3 haplotypes, each separately but also via a significant interaction between those genetic markers	Coutinho et al93
8	Hyperserotonemia	23	Platelets	Higher 5‐HT levels in 17% of PDD cases without an elevation in intestinal permeability measured by sugar absorption	Kemperman et al94
9	Hyperserotonemia	63	Platelets	Association between high 5‐HT in ASD and common variants in genes regulating 5‐HT synthesis (TPH1) and degradation (MAOA).	Hranilović et al95
10	Hyperserotonemia	50	Serum	Higher 5‐HT and autoimmunity marker anti‐myelin‐basic protein (anti‐MBP) levels in ASD but no correction between both markers	Mostafa et al96
11	Normal	23	Plasma	Normal 5‐HT levels in plasma point out that hyperserotonemia in ASD platelets results from the platelet's handling of 5‐HT and not from their increased exposure to 5‐HT	Anderson et al97
12	Hyperserotonemia	279	Whole blood	Higher whole blood 5‐HT levels in 40%, lower plasma melatonin in 51%, and higher platelet NAS in 47% of ASD cases. This study points to a disruption of the 5‐HT/NAS/melatonin pathway in ASD	Pagan et al50
13	Hyperserotonemia	20	Plasma	Higher 5‐HT levels in ASD patients and their unaffected siblings, suggesting heritability of this trait	Bijl et al59
14	Hyperserotonemia	203	Platelets	Association between high 5‐HT in male ASD cases and common variants in MAOB gene regulating 5‐HT degradation	Chakraborti et al98
15	Hyperserotonemia	82	Whole blood	Correlation between high 5‐HT in ASD and lower gastrointestinal symptoms	Marler et al99
16	Hyperserotonemia	292	Whole blood	The largest study performed to date showing higher 5‐HT levels but only in prepubertal ASD patients (42%) and this more likely in males	Shuffrey et al100
17	Hyperserotonemia	213	Whole blood	Platelet NAS has higher heritability than hyperserotonemia and lowered melatonin in ASD	Benabou et al77
18	Hyperserotonemia	181	Whole blood	Negative correlation between maternal 5‐HT levels and cognitive abilities in ASD	Montgomery et al101
19	Hyperserotonemia	176	Platelet rich plasma	A promotor SNP in ITGB3 that results in enhanced promoter activity during megakaryocyte differentiation is associated with higher integrin β3 protein expression and higher platelet 5‐HT levels in ASD patients. ITGB3 is known to support SERT trafficking to the platelet membrane allowing enhanced 5‐HT uptake in platelets	Gabriele et al63

Abbreviations: 5‐HT, 5‐hydroxytryptamine; ASD, autism spectrum disorder; NAS, N‐acetyl serotonin; PDD, pervasive developmental disorder (part of ASD).