Fig. 2.

Potential immune mechanisms of sex differences in mood disorders identified from pre-clinical studies of stress. There are sex differences in the populations of lymphocytes and leukocytes released from bone marrow. Females have more circulating leukocytes and lymphocytes than males. Females exhibit little or no glucocorticoid feedback on immune cell activation following stress, which may lead to a dysregulated ratio of pro-inflammatory to anti- inflammatory cytokines in the periphery. In the nucleus accumbens, Claudin-5 a tight junction protein is downregulated in patients with depression and male mice allowing increased permability of the blood brain barrier for cytokines and possibly monocytes and T cells. Within the brain, adult female rodents are reported to have more primed microglia than males, which may alter their activation by stress. In males only, stress increases spine density on medium spiny neurons in the nucleus accumbens