Serotonin’s fundamental role in early social development: Socio-affective communication through ultrasonic vocalizations, maternal affiliation, and the bidirectional nature of mother-infant interactions

Serotonin (also known as 5-hydroxytryptamine, 5-HT) is a conserved neurotransmitter implicated in modulating social behavior across mammals, yet its specific contribution to early social development during infancy remains poorly understood. This is largely due to ethical and methodological constraints in human studies. Genetic animal models with constitutive deficiency of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme for 5-HT synthesis in the brain, provide a unique opportunity to investigate how central 5-HT shapes social behavior during infancy. In this review, we synthesized findings from Tph2- deficient mice, rats, and non-human primates to highlight the role of central 5-HT in early socio-affective communication, maternal affiliation, and mother-infant interactions. Across rodent species, lack of central 5-HT is consistently associated with profound impairments in socio-affective communication through ultrasonic vocalizations (USV), which show limited sensitivity to oxytocin (OXT) system activation and early social enrichment through communal nesting (CN). In contrast, deficits in maternal affiliation appear partially amenable to modulation by OXT signaling or CN, suggesting the engagement of other neurotransmitter pathways. This view is further supported by evidence from non-human primates, in which OXT administration similarly reverses impaired maternal affiliation associated with 5-HT deficiency. Collectively, these findings support a model in which central 5-HT functions as a fundamental modulator of early social development, particularly socio-affective communication, with downstream consequences for mother-infant interactions, growth, and early social development. This framework provides a foundation for future studies aimed at identifying critical developmental windows and elucidating interactions between the 5-HT system and early social environments in shaping social development. • Brain serotonin is essential for early communication and maternal affiliation. • Affiliation but not communication deficits can be rescued by communal nesting. • Affiliation but not communication deficits can be rescued by oxytocin activation. • Early communication and maternal affiliation possibly rely on distinct mechanisms.