Stress in Childhood Leads to Lifelong Vulnerability in Brain

First Posted: Jun 23, 2017 03:36 AM EDT

Stress hurts us. Stress early in life hurts us more.

Researchers at Mount Sinai recently discovered that early life stress activates certain molecules that dictate to what degree and when particular genes are expressed. Specific proteins that attach themselves to certain DNA codes, which either initiate or cease a genetic expression, regulate this transcription process.

This is important as much of research has shown again and again how early life stress triggers chronic behavioral and physiological repercussions, such as depression and anxiety. Now, we know that these tiny molecules are at the heart of connecting the experience to the reaction in the ventral tegmental area of the brain (VTA).

"Our work identifies a molecular basis for stress during a sensitive developmental window that programs a mouse's response to stress in adulthood," explains Dr. Catherine Peña, lead investigator of the study. "We discovered that disrupting maternal care of mice produces changes in levels of hundreds of genes in the VTA that primes this brain region to be in a depression-like state, even before we detect behavioral changes. Essentially, this brain region encodes a lifelong, latent susceptibility to depression that is revealed only after encountering additional stress."

The study, which was published in Science, enforced stress on baby mice. Those that were stressed during the day they were born to day 10-20 displayed an inactive orthodenticle homeobox 2 (Otx2) in the VTA. Otx2 serves as the basis for transcribing the molecules that turn on and off certain genes. What is more, even though OtX2 did activate through adulthood, the damage was done. Genetic changes had lasted through adulthood, showing that early life stress permeates throughout one's life.

How does this change manifest in behavioral symptoms? In comparison to mice that were not stressed as babies, the experimental group showed signs of depression when stressed again during adulthood. This means that OtX2 in childhood is essential for dealing with stress later in life.

"We anticipated that we would only be able to ameliorate or mimic the effects of early life stress by changing Otx2 levels during the early sensitive period," Dr. Peña further said. "This was true for long-lasting effects on depression-like behavior, but somewhat to our surprise we could also change stress sensitivity for short amounts of time by manipulating Otx2 in adulthood."

As it turns out, there is more to attend to than language development in children. "This mouse paradigm will be useful for understanding the molecular correlates of increased risk of depression resulting from early life stress and could pave the way to look for such sensitive windows in human studies," states Dr. Eric J. Nestler, senior investigator of the study. "The ultimate translational goal of this research is to aid treatment discoveries relevant to individuals who experienced childhood stress and trauma."

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