Higher Inflammation Associated with Lower Resting State Functional Connectivity in Emotion Regulation and Executive Networks

• In Event: 1-015 - Translational Perspectives on the Role of Inflammation in Brain Development and Function

Integrative Statement

Growing evidence documents bidirectional signaling between the brain and immune system in the pathogenesis of emotional health problems. For example, preclinical research implicates neuroimmune signaling in the acquisition and expression of behaviors related to anxiety, and antidepressants diminish stress-induced inflammation and anxiety and depressive behaviors. Neuroimmune signaling is amplified and dysregulated in animal models of multiple psychiatric disorders, ranging from depression and anxiety, autism and schizophrenia, and substance use. Furthermore, the transition from adolescence to adulthood is a period of risk for the dysregulation of neuroimmune signaling and the onset of psychiatric illness, more generally.

Despite the strength of preclinical findings, there are only a handful of studies examining brain functioning and inflammatory signaling in humans. To extend this work, this talk presents results from two independent studies examining the relationship between tonic inflammatory signaling and resting state functional connectivity (rsFC), as measured by fMRI within African American participants. Our aims for these studies were to first assess the nature of brain-immune associations in young adults, and then to extend this work to an adolescent sample to determine whether these associations are present across the developmental spectrum.

We focus on tonic activity because chronic low-grade inflammation is involved in the onset and course of a heterogeneous set of mental and physical illnesses. Study 1 involved 90 rural young adults, age 25 years (52% female), and measured 4 circulating inflammatory biomarkers (CRP, IL6, IL10, TNFα), which were averaged to form a composite. The Study 1 sample was working poor; primary caregivers worked an average of 39.4 hours per week, yet 46.3% of the sample lived below federal poverty standards. In line with predictions, higher scores on this composite were associated with lower rsFC within an emotion regulation network, controlling for sex and age. Study 2 involved 82 urban African Americans, ages 13-14 (66% female). In terms of socioeconomic conditions, 22% percent of youth resided in households whose income was below the federal poverty threshold (i.e., an income-to-poverty ratio < .99). Another 35.4 percent had income-poverty ratios typically considered as low income. It replicated Study 1, showing that higher scores on the inflammatory composite were associated with lower rsFC within the emotion regulation network, controlling for sex, age and pubertal status, and found a similar pattern for rsFC within a frontoparietal central executive network. Study 2 also enumerated a key leukocyte sub-population involved in immune-brain signaling - classical monocytes - and found that higher circulating numbers of these cells were associated with lower rsFC within both the emotion regulation and central executive networks. There was no relationship between rsFC in the default mode or the anterior salience networks with inflammatory signaling in either study. These findings document relationships between peripheral inflammatory signaling and rsFC within an emotion regulation and central executive network, and replicate the association between rsFC in the emotion regulation network and inflammatory signaling across the developmental spectrum. These findings have implications for understanding the development of neuroimmune signaling and the pathogenesis of emotional and physical health problems.

Authors

• Robin Nusslock, Northwestern University
  Presenting Author

• Gene Brody, University of Georgia
  Non-Presenting Author

• Casey Armstrong, Northwestern University
  Non-Presenting Author

• Ann Carroll, Northwestern University
  Non-Presenting Author

• Yu Tianyi, University of Georgia
  Non-Presenting Author

• Allen Barton, University of Georgia
  Non-Presenting Author

• Edith Chen, Northwestern University
  Non-Presenting Author

• James Higgins, Northwestern University
  Non-Presenting Author

• Todd Parrish, Northwestern University
  Non-Presenting Author

• Lei Wang, Northwestern University
  Non-Presenting Author

• Greg Miller, Northwestern University
  Non-Presenting Author