Sex Differences in Response to Stress: Relation to Depressive Phenotypes

Dr. Galea has been studying sex differences in response to stress since 1997.

Females show different patterns of neural and behavioural responses to stress than males. Liisa performed the first study to examine sex differences in the effects of stress on hippocampal neurogenesis in which males showed an acute stress-induced suppression in cell proliferation, but females did not (Falconer and Galea, 2003). Chronic high corticosterone (CORT) suppressed neurogenesis in the ventral, but not dorsal, hippocampus in females but both regions in males (Brummelte & Galea, 2010) while chronic stress resulted in differential hippocampal dendritic remodeling in the male and female rat (Galea et al., 1997). Adult females, but not males, exposed to stress during adolescence had reduced hippocampal neurogenesis and higher basal CORT levels (Barha et al., 2010).

These studies show that stress differentially alters hippocampal plasticity in males and females. Female meadow voles exhibit more “depressive-like” behaviours than males (Galea et al., 2001) and females, but not males, have enhanced working memory after acute stress (Barha et al., 2007), indicating that there are differential behavioural responses to stress between the sexes. Furthermore, castration in males (Wainwright et al., 2011) and withdrawal from a hormone stimulated pregnancy (Green & Galea, 2008; Green et al., 2009) was associated with the development of depressive-like symptoms. Meanwhile, testosterone can alleviate some depressive endophenotypes after chronic unpredictable stress (Wainwright et al., 2016). Work by Steve Wainwright suggests that PSA-NCAM is required for antidepressant efficacy (Wainwright et al., 2015) and grad student Rand Mahmoud found that ovariectomy increased expression of a depressive phenotype including activation of microglia (Mahmoud et al., under revision). We found that antidepressants increased the density of immature neurons in adult depressed women only (Epp et al., 2013). We also found that the density of p21-ir cells (cell cycle arrest protein) was increased in older, but not younger, depressed patients (Epp et al., 2013).