The hippocampus, an area of the brain responsible for memory and emotion, shrinks in people with recurrent and poorly treated depression, a global study has found.

The findings highlighted the importance of treating depression early, particularly in teenagers and young adults, the study concluded.

Fifteen research institutes around the world, including from the US, Europe and Australia, collaborated to combine the results of their existing, smaller studies comparing the hippocampuses of depressed and healthy people.

This allowed them to examine the brain magnetic resonance imaging data of 8,927 people, 1,728 of whom had major depression and the rest of whom were healthy.

The researchers found 65% of the depressed study participants had recurrent depression and it was these people who had a smaller hippocampus, which is near the centre of the brain and is involved with long-term memory, forming new memories, and connecting emotions to those memories.

The findings of the largest international study to compare brain volumes in people with and without major depression were published in the medical journal Molecular Psychiatry.

The University of Sydney’s brain and mind research institute led the Australian arm of the study. Its co-director, Professor Ian Hickie, said those people in the study experiencing their first depressive episode had a normal hippocampus size.

“But the more episodes of depression a person had, the greater the reduction in hippocampus size,” he said.

“So recurrent or persistent depression does more harm to the hippocampus the more you leave it untreated. This largely settles the question of what comes first: the smaller hippocampus or the depression? The damage to the brain comes from recurrent illness.”

Hickie, who is also a national mental health commissioner, said it meant identifying and treating depression effectively when it first occurred was vital to prevent this damage, particularly among teenagers and young adults.

But there was good evidence that with treatment, the damage was reversible, he said.

“Other studies have demonstrated reversibility, and the hippocampus is one of the unique areas of the brain that rapidly generates new connections between cells, and what are lost here are connections between cells rather than the cells themselves,” Hickie said.

“Treating depression effectively does not just mean medicines. If you are unemployed, for example, and then sit in a room doing nothing as a result, this can shrink the hippocampus. So social interventions are just as important, and treatments such as fish oils are also thought to be neuro-protective.”

There was some evidence that the hippocampus was larger in those patients taking antidepressants, Hickie said, indicating these medications could have a protective effect.

“There is a lot of nonsense said about antidepressants that constantly perpetuates the evils of them, but there is a good bit of evidence that they have a protective effect,” he said.

“But that doesn’t mean they are the only treatment. There are, in fact, a broad range of treatments that should be explored, and in young people psychotherapy would often be explored as the first line of treatment, not medicines.”

A co-author of the study, Associate Professor Jim Lagopoulos, said the findings provided new insight on brain structures and possible mechanisms responsible for depression.

It also indicated the findings that were possible through collaboration.

“Despite intensive research aimed at identifying brain structures linked to depression in recent decades, our understanding of what causes depression is still rudimentary,” he said.

“One reason for this has been the lack of sufficiently large studies, variability in the disease and treatments provided, and the complex interactions between clinical characteristics and brain structure.”