Sex differences in human brain networks in normal and psychiatric populations from the perspective of small-world properties

Females and males are known to be different in the prevalences of multiple psychiatric disorders, while the underlying neural mechanisms are unclear. Based on non-invasive neuroimaging techniques and graph theory, many researchers have tried to use a small-world network model to elucidate sex differences in the brain. This manuscript aims to compile the related research findings from the past few years and summarize the sex differences in human brain networks in both normal and psychiatric populations from the perspective of small-world properties. We reviewed published reports examining altered small-world properties in both the functional and structural brain networks between males and females. Based on four patterns of altered small-world properties proposed: randomization, regularization, stronger small-worldization, and weaker small-worldization, we found that current results point to a significant trend toward more regularization in normal females and more randomization in normal males in functional brain networks. On the other hand, there seems to be no consensus to date on the sex differences in small-world properties of the structural brain networks in normal populations. Nevertheless, we noticed that the sample sizes in many published studies are small, and future studies with larger samples are warranted to obtain more reliable results. Moreover, the number of related studies conducted in psychiatric populations is still limited and more investigations might be needed. We anticipate that these conclusions will contribute to a deeper understanding of the sex differences in the brain, which may be also valuable for developing new methods in the treatment of psychiatric disorders.