An international team of scientists has analyzed the brain scans of thousands of people and concluded that a structure important to memory, the hippocampus, is smaller in people with recurrent major depression than it is in people without the disorder. The size difference is most pronounced in those who first experienced depression at a young age.

Previous studies have reported structural changes to the brain linked with major depression, including reduction in the size of the hippocampus. However, it was unclear whether these changes might be affected by factors such as how often a patient had experienced depressive episodes or whether they had taken antidepressant medications.

The new study, reported June 30th in the journal Molecular Psychiatry, is the largest structural analysis to date of the brains of patients with major depression. Scientists pooled data from several previous studies, so they could analyze MRI scans of nearly 9,000 people, including 1,728 people with major depression.

The team was led by Lianne Schmaal, Ph.D. and Dick Veltman, M.D., Ph.D., heads of the ENIGMA MDD Working Group at the Vrije Universiteit Medical Centre, and included NARSAD 2003 Distinguished Investigator Philip Cowen, M.D., at the University of Oxford; as well as past NARSAD Young Investigator Glenda MacQueen, M.D., Ph.D., at the University of Calgary; and past NARSAD Independent Investigators Andrew McIntosh, M.D., at the University of Edinburgh and Jim Lagopoulos, Ph.D., at the University of Sydney.

The scientists measured the size of nine different brain structures, searching for any significant differences between healthy people and those with major depression. One clear difference emerged: patients with recurrent major depressive disorder had significantly smaller hippocampi than healthy individuals. (The human brain has two hippocampi, one on each side of the brain.) This was true whether or not patients had taken antidepressant medications.

The reduction in hippocampus size was even greater among people whose major depression began before the age of 21. On the other hand, those whose brain scans were taken during their first depressive episode showed no significant structural differences from healthy people. This suggests that it usually takes several episodes before a reduction in hippocampus size can be noted.  

Further studies are needed to determine whether depression directly causes the hippocampus to shrink. Alternatively, the scientists say, having abnormally small hippocampi might put people at greater risk for developing major depression.

Read the paper.