Sex Differences in Response to Stress: Relation to Depressive Phenotypes

I have been studying sex differences in response to stress since 1997. Females show different patterns of neural and behavioural responses to stress than males. I 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 stressBarha 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 development of depressive-like symptoms. Meanwhile testosterone can alleviate some depressive endophenotypes after chronic unpredictable stressWainwright et al in press H&B. Work by Steve Wainwright suggests that PSA-NCAM is required for antidepressant efficacy Wainwright et al in press, NPP 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.