Serotonin dynamics in and around the central nervous system: Is autism solvable without fundamental insights?

•Autism has been associated with developmental alterations in 5-HT signaling.•Further progress may require new approaches in fundamental neuroscience.•5-HT is a multipurpose signaling molecule in the mammalian body.•Serotonergic varicosities and blood platelets may be functionally linked.

Altered serotonin (5-hydroxytryptamine, 5-HT) signaling has been implicated in some developmental abnormalities of autism spectrum disorder (ASD). However, the presumed role of 5-HT in ASD raises new questions in fundamental neuroscience. Specifically, it is not clear if the current piecemeal approach to 5-HT signaling in the mammalian body is effective and whether new conceptual approaches may be required. This review briefly discusses 5-HT production and circulation in the central nervous system and outside of it, especially with regard to ASD, and proposes a more encompassing approach that questions the utility of the “neurotransmitter” concept. It then introduces the idea of a generalized 5-HT packet that may offer insights into possible links between serotonergic varicosities and blood platelets. These approaches have theoretical significance, but they are also well positioned to advance our understanding of some long-standing problems in autism research.