Early-life stress exposure linked to neural inflammation and psychiatric effects

Children exposed to severe, chronic stress may be at increased risk for developing neural inflammation that can affect their mental health, according to study results published in American Journal of Psychiatry.

“Children exposed to severe, chronic stressors are vulnerable to a plethora of health problems across the lifespan,” Gregory E. Miller, PhD, of the Institute for Policy Research at Northwestern University in Illinois, and colleagues wrote. “These problems span the continuum of what are traditionally understood to be mental (eg, depression, posttraumatic stress, substance misuse) and physical (eg, coronary heart disease, some cancers, autoimmune conditions) illnesses. Little is known about the behavioral and biological pathways underlying risk for this heterogeneous set of health problems.”

In a prior study, researchers proposed the neuroimmune network hypothesis to explain how mental and physical health problems across the lifespan may develop in relation to severe and chronic stress exposure in childhood. According to the hypothesis, early-life stress initiates a positive feedback loop between peripheral inflammatory cells and networked brain regions associated with reward and threat processing.

To test this hypothesis, Miller and colleagues analyzed data of 207 urban children from diverse socioeconomic backgrounds. The children had a mean age of 13.9 years and 63% were girls, 33% were Black and 30% were Hispanic. The researchers focused on poverty as a stressor. They drew participants’ fasting blood to quantify five inflammatory biomarkers, which were C-reactive protein, tumor necrosis factor-a and interleukins-6, -8 and -10, and they averaged results to form a composite score. Miller and colleagues’ measured participants’ amygdala responsivity to angry facial expressions, as well as their ventral striatum responsivity to monetary rewards, using two functional MRI tasks.

Results showed a statistical interaction between poverty status and neural responsivity that predicted inflammation. Children living in poverty exhibited a positive association between amygdala threat responsivity and inflammation, as well as with ventral striatum responsivity and reward. These brain-immune associations weakened as children’s socioeconomic conditions improved. Results of sensitivity analyses revealed these patterns were robust to alternative measure of socioeconomic status. Further, they were independent of age, racial and ethnic identity, sex and pubertal status. The researchers noted that the associations were condition specific, since they observed no interactions for amygdala responsivity to neutral faces, nor did they observe striatal responsivity to monetary losses.

“As the neuroimmune network hypothesis suggests, these neural and behavioral changes might, in turn, initiate a positive feedback loop that worsens psychiatric symptoms and extends them into other realms,” Miller and colleagues wrote. “Of course, longitudinal studies are needed to evaluate this scenario’s validity, but in the meantime, it provides a framework for conceptualizing how vulnerability arises. In the long term, this work could facilitate a next generation of interventions that improve psychiatric outcomes by targeting brain-to-immune and/or immune-to-brain signaling.”