Severe depression can shrink the brain by blocking the formation of new nerve connections, a study has shown.
The effect disrupts circuits associated with mental functioning and emotion.
It could explain why people with major depressive disorder (MDD) suffer from concentration and memory loss, as well as blunted emotional responses.
Several genes involved in building synapses, the connection points between brain cells, were suppressed in people with MDD.
This was thought to contribute to shrinkage of the brain's prefrontal cortex, which is known to occur in MDD sufferers.
Researchers in the US analysed brain tissue from patients who had died after being diagnosed with MDD.
They found molecular signs of reduced activity in genes necessary for the function and structure of brain synapses.
Evidence pointed to the involvement of a single genetic "switch", or transcription factor -- a protein called GATA1.
Turning on GATA1 reduced activity of the genes and triggered the loss of brain connections.
Study leader Professor Ronald Duman said: "We wanted to test the idea that stress causes a loss of brain synapses in humans.
"We show that circuits involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated."
The research is published in the latest issue of the journal 'Nature Medicine'.
"We hope that by enhancing synaptic connections, we can develop more effective antidepressant therapies," Prof Duman said.