Sex bias in the serotonin transporter knockout model: Implications for neuropsychiatric disorder research

Serotonergic signalling is implicated in the aetiology of many neuropsychiatric disorders. The serotonin reuptake transporter (SERT) is an important regulator of synaptic serotonin, being an important pharmacological target with genetic variants implicated with risk of developing neuropsychiatric disorders. Animal models have played an important role in understanding the genetic risk and role of SERT function in brain development having highlighted sex differences in incidence, presentation, and treatment efficacy, however, sex bias due to unequal representation of sexes in research remains a significant issue. While more studies are addressing sex as a biological variable this is not reflected in studies using SERT knockout models as the proportion including sex comparisons has declined since 2000. This bias needs to be addressed if research findings from animal studies are to have translation relevance to human conditions.

Automated summary

Serotonergic signaling is important in neuropsychiatric disorders, with SERT playing a crucial role. Animal models have highlighted sex differences in SERT function and brain development, but there is a bias in representation of sexes.