New evidence from animal studies has linked post-natal depression in women with inflammation in mood-regulating areas of the brain.
Scientists believe the findings could help them solve the mystery of the distressing condition, which is still poorly understood.
An estimated 15 per cent of new mothers experience postnatal depression - also known as post-partum depression - after giving birth.
Having post-natal depression can prevent a mother bonding with her baby, and cause feelings of overwhelming fatigue and helplessness.
Dr Benedetta Leuner, from Ohio State University in the US, who led the new study, said: "Gaining a better understanding of the factors that contribute to this serious and prevalent disorder will be key to finding ways to better help women who are struggling."
The research focused on the medial prefrontal cortex, a mood-regulating brain region previously shown to be linked with post-natal depression.
Rats were first stressed during pregnancy to mimic a well-known risk factor for the condition.
After giving birth the animals showed distinct signs of depression similar to those seen in humans, including reduced attentiveness to their pups.
The scientists discovered that unlike their unstressed companions, the stressed rats had raised levels of inflammatory biomarkers in their brains.
There was also evidence linking stress to changes in the functioning of brain immune cells called microglia.
Co-author Dr Kathryn Lenz, also from Ohio State, said: "It was especially interesting that we found no evidence of increased inflammation in the blood, but we did find it in this area of the brain that is important for mood regulation.
"We're really excited because this suggests that inflammation in the brain may be a potential contributor to post-partum depression."
The findings were presented at the Society for Neuroscience annual meeting in San Diego.
