Substantial evidence against sex differences in bed nucleus of the stria terminalis volume in the human brain

The bed nucleus of the stria terminalis (BNST) is a sexually dimorphic basal forebrain region is a claim prevalent across rodent and human neuroscience research, arising from the observation that it is substantially larger in male versus female brains. Despite the pervasiveness of this claim, which may have implications for understanding sex differences in anxiety and substance use disorders, inspection of prior literature reveals a complex and nuanced picture. Research on volumetric human BNST sex differences comes from a handful of mostly small-scale post-mortem studies and two MRI studies, between them reporting no, moderate, or very large differences. This indicates the need for a more detailed systematic investigation. Addressing this, we developed a novel 3T T1-weighted (T1w) manual segmentation protocol for the BNST, which was applied to sub-millimetre resolution T1w structural MRI data in 170 young human adults. Using a Bayesian modelling approach, taking into account existing data and accounting for total brain volume, age, and sibship, we find substantial evidence favouring no sex difference in total BNST volume. We recommend that researchers exercise caution when reporting evidence of BNST sexual dimorphism, particularly when translating findings from rodent models in which the BNST may play a different, olfaction-focused, role.