Hippocampal atrophy has been noted in patients with major depression, but the cause had not been established.

Dr Angela Lee and colleagues from Stanford University in the US suggested that overt hippocampal neuron death could cause the loss of volume, most likely due to excessive exposure to glucocorticoids. To test this theory they reviewed current knowledge about how hippocampal neurons die during insults.

According to research, about half of all cases of major depression involve some variant of hypercortisolism.

Furthermore, prolonged elevations of glucocorticoids have shown pronounced adverse effects on the hippocampus, both directly and by increasing the neurotoxicity of various hippocampal insults.

Two candidate mechanisms for damage identified include the inhibition of glucose transport by glucocorticoid and the elevation of free cytosolic calcium concentrations.

Recently, there has also been interest in the additional role played by the calcium-dependent generation of oxygen radicals, which is thought to be exacerbated by glucocorticoids.

A number of primate studies indicate that prenatal glucocorticoid exposure causes loss of hippocampal neurons that persists into adolescence and adult exposure to severe and fatal social stress has been associated with selective loss of hippocampal neurons.

However, there is no current evidence that there is hippocampal neuron loss during depression.

Dr Lee and colleagues concluded that glucocorticoids might play a role in any putative hippocampal neuron loss.

“This possibility is made more pressing by the fact that the subtypes of depression most associated with atrophy tend towards the highest rates of hypercortisolism,” they said.

Reference: Lee et al, Bipolar Disorders 2002;4:117-128
© Health Media Ltd 2002