Early exposure to severe, chronic stress leaves children vulnerable to a series of health problems over the lifespan. Researchers recently tested the hypothesis that the stress created by conditions of poverty in childhood affects peripheral inflammatory cells and the brain regions involved in the processing of threats and rewards.
The study, led by psychologist Gregory Miller at Northwestern University, examined the connection between poverty, inflammation, and neural responses in a sample of urban youth from different socioeconomic backgrounds. Their results, published in the American Journal of Psychiatry, provide support for the “neuroimmune network hypothesis,” which suggests that children facing socioeconomic disadvantage are, on average, more likely to show inflammatory biomarkers and increased reactivity to threats and rewards in the environment.
These biological and behavior patterns may be adaptive, allowing for greater responsiveness in unpredictable contexts. However, the authors suggest that the long-term consequences of these neuroinflammatory responses can contribute to the development of physical health problems, “increases risk for fear-related symptoms (e.g., vigilance, worry, rumination) by modulating amygdala circuity, and motivation-related symptoms by modulating striatal circuitry (e.g., substance misuse, anhedonia, mania).”
“As the neuroimmune network hypothesis suggests,” Miller and his coauthors write, “these neural and behavioral changes might, in turn, initiate a positive feedback loop that worsens psychiatric symptoms and extends them into other realms.”
The results seem to underline the preventative effects of social programs and policies that address childhood poverty. Instead of addressing how to improve the environments that lead to the development of biological and behavioral changes that undermine public health, the authors instead focus on applying their results to “facilitate a next generation of interventions that improve psychiatric outcomes by targeting brain-to-immune and/or immune-to-brain signaling.”
Evidence abounds for the connection between adverse childhood experiences and mental and physical health problems. While studies have also revealed the strengths and resilience of children facing adversity, events like family member incarceration, exposure to pollution and economic deprivation, and other stressors tend to be associated with chronic inflammation, heightened immune responses, and mental health diagnoses.
Another way to understand these cumulative, complex effects in different health settings is “allostatic load,” which refers to the accumulating physical and mental health consequences of exposure to chronic stress. Much of this research is geared toward establishing correlations between experiences and health issues to influence the way we respond to these social issues, both proactively and retroactively.
In this latest study, Miller and his colleagues explore the neurological and immunological mechanisms involved by studying children from different socioeconomic backgrounds to test the neuroimmune hypothesis. This hypothesis suggests that chronic stress early in life sets in motion a positive feedback loop between inflammatory cells and networked brain regions that process threats and rewards.
To do this, the authors looked at the predictions of the neuroimmune network hypothesis in over 200 children in Chicago with an average age of 13.9 years (63% female; 33% Black, 30% Hispanic). They focused on poverty as a stressor because an incredible 41% of American children live near or below the poverty line, according to data from 2017.
They drew the blood of these children to quantify and determine a composite score of five biomarkers for inflammation, in addition to observing the fMRI data associated with two different tasks to measure responsivity to angry facial expressions and monetary rewards.
Miller and colleagues found that poverty status and neural responsivity together predicted inflammation:
“Among children living in poverty, amygdala threat responsivity was positively associated with inflammation, and the same was true for ventral striatum responsivity to reward. As children’s socioeconomic conditions improved, these brain-immune associations became weaker.”
They also ran sensitivity analyses, which showed that the observed patterns were present across different measures of SES and were “independent of age, sex, racial and ethnic identity, and pubertal status.” Moreover, neutral conditions of the fMRI studies did not provide evidence for an interaction between SES and neural reactivity. This indicates that these relationships are condition-specific, confirming prior research. They explain:
“These results provide initial support for the hypothesis that childhood stress amplifies crosstalk between peripheral inflammatory cells and brain regions involved in threat and reward. If substantiated, these patterns will have implications for understanding how early stressors, acting through neural-immune pathways, contribute to the development of a diverse set of health problems.”
Among other limitations, the authors caution that these results are only observational, meaning that no causal conclusions may be drawn. However, they also note that these results should be read together with experimental studies that reveal bidirectional signaling between threat circuitry and peripheral inflammatory cells, illustrating the plausibility of causal effects.
Adding to a robust body of research about the health effects of childhood poverty and lending novel, composite evidence to the neuroimmune network hypothesis, this study found early experiences of poverty to be associated with neural-immune patterns.
Miller GE, White SF, Chen E, Nusslock R. Association of Inflammatory Activity With Larger Neural Responses to Threat and Reward Among Children Living in Poverty. Am J Psychiatry. 2021 Apr 1;178(4):313-320. DOI: 10.1176/appi.ajp.2020.20050635 (LINK)