Table 1.

Phenotypes of STS-deficient individuals and associated biological mechanisms

Experimental group	Associated phenotypes	Possible underlying biological mechanism(s)
Women heterozygous for genetic deletions including STS	Increased risk of developmental and (postpartum) mood disorders	Decreased volume of basal ganglia structures (putamen, globus pallidum, nucleus accumbens)
	Increased self-reported irritability, psychological distress, manic symptoms, and tiredness/low energy
	Altered sleeping patterns/weight change
	Rare cases with paranoid schizophrenia
Male mice with genetic deletions including Sts, or with STS enzyme acutely inhibited	Inattention	Increased serotonin (5-HT) levels in the striatum and hippocampus; increased Htr2c (serotonin 5-HT 2c receptor) expression in the hippocampus
		Increased hippocampal acetylcholine release
	Increased levels of anxiety-like behaviour, aggression, and perseveration
		Imbalance between sulfated and free steroids (notably increased dehydroepiandrosterone sulfate (DHEAS) and decreased DHEA)
	Effects on learning and memory
	Enhanced response inhibition
Postpartum female mice with STS enzyme acutely inhibited	Decreased acoustic startle response; alleviated by antipsychotic administration	Increased whole-brain expression of Ccn2, Ccn3, Adcy8, Arhgdig, Cyp2g1, Stoml3, and genes involved in olfactory signalling
	Altered exploration of aversive environment
Postpartum female pigs	Infanticidal behaviour together with anxiety/restlessness in < 10% individuals	Quantitative trait loci overlapping Sts and Htr2c; increased Ccn2 and Htr2c (long variant) expression in the hypothalamus/brain