4.6 Stress, depression and neurogenesis in the hippocampus

Duman et al. (1997, 1999) suggested that the development of depression was likely to involve processes that affected plasticity in the brain. Plasticity essentially means remodeling. Several brain areas including the prefrontal cortex and hippocampus are likely to be affected, but Duman and his colleagues focused their research on the hippocampus for a number of reasons. First, it had been discovered in the 1990s that, unusually for a structure in the adult human brain, the hippocampus continues to exhibit neurogenesis, making it a good candidate for the study of any changes in neurogenesis associated with depression or antidepressant treatment.

Second, there is evidence to suggest that neurogenesis in the hippocampus is highly susceptible to the effects of stress: especially when severe or prolonged, stress can inhibit neurogenesis and accelerate cell loss in the hippocampus. This effect appears to be due in large part to the effects of hormones such as cortisol (a glucocorticoid) that are overproduced by the adrenal gland during situations of chronic stress (Activity 6).

Third, as we also considered there is evidence that stress and stressful events are important in triggering clinical depression (Kendler et al., 1999), and that depression in humans is associated with hyperactivity of the stress system.

Putting these pieces of the jigsaw together, current thinking is that stress, via the effects of glucocorticoid hormones, leads to a decline in hippocampal function (through some combination of decline in hippocampal neurogenesis and increase in hippocampal atrophy), and that hippocampal dysfunction is linked to some of the symptoms of depression.