Breast milk from mothers with postpartum depression may negatively impact infants’ brain development, a Chinese study has found. 

The study, published Oct. 27 in the top academic journal Cell Metabolism, was led by a team at Nanjing University, in the eastern Jiangsu province. Through a mouse model, it shows, for the first time, how depression-related changes in levels of microRNA, a type of gene-regulating molecule, contained in structures called extracellular vesicles in breast milk can affect offspring brains.

Between 10% and 20% of mothers worldwide experience postpartum depression. Children of affected mothers are more likely to face challenges in cognition, language, behavior, and school performance, and are at a higher risk of developing depression themselves. 

Past research has implicated genetics and the way mothers with postpartum depression bond with, and care for, their infants as contributing to this phenomenon, but the broad and long-lasting effects of postpartum depression on child development remain unclear, according to the researchers.

Because breast milk is increasingly viewed as a “signaling system orchestrating infant development,” the researchers wrote, they looked at the relationship between milk-based microRNAs and extracellular vesicles, key parts of this signaling. Because babies’ blood-brain barrier is more permeable than adults’, these vesicles can enter the brain during nursing, making its development more sensitive to diet. 

The researchers compared the breast milk of 40 human mothers clinically diagnosed with postpartum depression, and 51 without, finding that those with depression had elevated levels of three types of microRNA implicated in psychiatric illness. The same was true of the breast milk of depressed mice.

To test nursing’s role in brain development, swapping mouse pups between healthy and depressed mouse mothers. Pups born to healthy mice but nursed by their depressed counterparts showed worse cognitive and emotional behavior than pups born to depressed mothers but nursed by healthy ones. 

They also found that neurons in pups nursed by depressed mothers had shorter dendrites and fewer branches in the hippocampal dentate gyrus, a part of the brain believed to play a role in memory development and depression. The problems arose mainly as the neurons matured, were detectable by day 21 after birth, and persisted into adulthood, suggesting that early nursing-environment effects can last into later development. 

Giving milk from depressed mothers to healthy pups was also enough to cause cognitive impairment after weaning, while milk where the vesicles had been removed had no such effect, the researchers found.

When the team inhibited Rab27a, a protein and key factor in vesicle secretion, in the mammary glands of depressed mothers, vesicle secretion fell by 58%, and the cognitive and neurodevelopmental deficits in their pups improved significantly.

The researchers also found that microRNA in milk vesicles from depressed mothers blocks a “brake” receptor called mGluR8 in pups’ brains. Without this brake, brain regions can become overstimulated, impairing the development of neural connections. As a result, new brain cells are more active overall but respond more weakly to memory tasks, helping explain the cognitive problems seen in pups nursed by depressed mothers.

The study offers the key findings of both a new communication pathway and a microRNA-based mechanism of inheritance between mothers and babies, according to the researchers.

Breastfeeding is widely seen as good for babies’ brain development, but this study also suggests that breastfeeding by mothers with postpartum depression may have a “double-edged effect on offspring health,” the researchers wrote. 

“Elucidating the molecular mechanisms linking maternal postnatal depression to offspring neurological outcomes therefore holds considerable public health value and underscores the urgent need for targeted maternal mental health interventions during lactation,” they added.

Editor: Marianne Gunnarsson.

(Header image: VCG)