The brains of people with recurrent depression have a significantly smaller hippocampus than healthy individuals, researchers said.
The study is the largest international research to compare brain volumes in people with and without major depression, they said.
It highlights the need to identify and treat depression effectively when it first occurs, particularly among teenagers and young adults.
Using magnetic resonance imaged (MRI) brain scans, and clinical data from 1,728 people with major depression and 7,199 healthy individuals, the study combined 15 datasets from Europe, the US and Australia.
It is a serious clinical mood disorder in which feelings of sadness, frustration, loss, or anger interfere with a person's everyday life for weeks, months or years at a time.
The key finding was largely explained by subjects with recurrent depression. People with recurrent depression represented 65 per cent of study subjects with major depression, researchers said.
People with an early age of onset of major depression (before the age of 21 years) also had a smaller hippocampus than healthy individuals, consistent with the notion that many of these young people go on to have recurrent disorders.
"These findings shed new light on brain structures and possible mechanisms responsible for depression," said Associate Professor Jim Lagopoulos of the University of Sydney's Brain and Mind Research Institute.
"This large study confirms the need to treat first episodes of depression effectively, particularly in teenagers and young adults, to prevent the brain changes that accompany recurrent depression," said Co-Director of the Brain and Mind Research Institute, Professor Ian Hickie.
The study was published in the journal Molecular Psychiatry.
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