Figure 2.

Proposed model of sex-specific major depressive disorder (MDD) mechanism involving dendritic spines and microglia. Male control subjects have more dendritic spines and fewer activated microglia than male subjects with MDD, but female control subjects have fewer dendritic spines and more activated microglia than female subjects with MDD. MDD effects appear to be opposite in male and female subjects, converging on a similar MDD phenotype across sexes. Successful treatment would push male and female subjects back to their sex-specific baselines, which would require opposite effects on microglia. Further, it is possible that a successful treatment in one sex might push the other sex further from their sex-specific baseline, which could be detrimental. Pyramidal cells are in pink. Ramified microglia are in yellow, reactive/ameboid microglia are in red, and intermediate microglia are in orange.