The stressed-​​out brain

Clin­ical studies of ado­les­cents suf­fering from depres­sion have shown an inter­esting con­nec­tion between early life stress and the immune system.

“Those who have expe­ri­enced child­hood trauma and adver­sity tend to have higher levels of inflam­ma­tion bio­markers in their blood,” explained Heather Bren­house, an assis­tant pro­fessor of psy­chology at North­eastern University.

Many of the emo­tional and behav­ioral prob­lems asso­ci­ated with early life stress don’t appear until ado­les­cence, she said, “so you’ve got this group of kids who will go on to be sick, but you can’t iden­tify them early.” If, how­ever, those inflam­ma­tion bio­markers are present before clin­ical prob­lems arise, then doc­tors could use them to pre­dict future mental illness.

Backed by a new grant from the National Insti­tutes of Health, Bren­house is inves­ti­gating whether such bio­markers are present in rat models that expe­ri­ence early life stress as well as how inflam­ma­tion may be linked to neural cir­cuitry prob­lems that give rise to mental ill­ness. Under­standing that con­nec­tion, she said, could reveal new treat­ment options in addi­tion to early detec­tion oppor­tu­ni­ties pro­vided by biomarkers.

In pre­vious research, Bren­house found evi­dence of inflam­ma­tion in the brains of ado­les­cent ani­mals that were sep­a­rated from their mothers during their youth. When she looked for sim­ilar evi­dence in juve­nile ani­mals, how­ever, she came up empty handed.

For her new study, Bren­house will be taking small blood sam­ples to test for cytokines—molecules released during an immune response—at var­ious points before ado­les­cence. Over time, she will closely mon­itor for signs of cog­ni­tive dis­or­ders during adolescence.

At the same time, she will inves­ti­gate how early life stress changes the brain’s neural cir­cuitry in these ado­les­cents, par­tic­u­larly focusing on iden­ti­fying how sig­nif­i­cant the role of the NR2A—of a par­tic­ular type of neu­ro­trans­mitter receptor in the pre­frontal cortex—plays in mental ill­ness caused by early life stress. These recep­tors, she said, bind a mol­e­cule called glu­ta­mate, which is impli­cated in dis­eases such as schiz­o­phrenia. In ani­mals with early life stress, the con­cen­tra­tion of NR2As is higher.

“We know that NR2A is upreg­u­lated,” she said, we just don’t know if it’s impor­tant yet.”

Brenhouse’s work will also involve ana­lyzing whether blocking inflam­ma­tion changes how these NR2A recep­tors functions.

“Our ner­vous system and our immune system are con­stantly in com­mu­ni­ca­tion, for good reason,” Bren­house said. “Think about it: when you’re sick, you need to behave dif­fer­ently.” So-​​called “sick­ness behavior,” she said, is one of the eas­iest ways to think about the con­nec­tion between the two systems.

When it comes to stress, how­ever, the story is a little more com­pli­cated. In some cases, stress acti­vates the immune system, while in others it deac­ti­vates it. “We’re trying to figure out how early life stress, in par­tic­ular, changes the devel­op­ment of the immune system and how that winds up leading to neu­roin­flam­ma­tion later on.”