Harsh family climate in early life presages the emergence of a proinflammatory phenotype in adolescence

Abstract

A growing body of evidence indicates that children reared in harsh families are prone to chronic diseases and premature death later in life. To shed light on the mechanisms potentially underlying this phenomenon, we evaluated the hypothesis that harsh families engender a proinflammatory phenotype in children that is marked by exaggerated cytokine responses to bacterial stimuli and resistance to the anti-inflammatory properties of cortisol. We repeatedly measured psychological stress and inflammatory activity in 135 female adolescents on four occasions over 1.5 years. To the extent that they were reared in harsh families, participants displayed an increasingly proinflammatory phenotype during the follow-up analyses. This phenotype was marked by increasingly pronounced cytokine responses to in vitro bacterial challenge and a progressive desensitization of the glucocorticoid receptor, which hampered cortisol's ability to properly regulate inflammatory responses. If sustained, these tendencies may place children from harsh families on a developmental trajectory toward the chronic diseases of aging.

Figure 1

Early-life family climate and inflammatory trajectory in adolescence. To the extent that they were reared in a harsh family climate, participants had increasing stimulated IL-6 production over the follow-up (upper panel), and became less sensitive to cortisol’s anti-inflammatory properties (lower panel).

Figure 2

Participants who were raised in harsher family climates had greater stimulated production of IL-6 at times when they had been exposed to a major life event, relative to times when they had not. By contrast, participants raised in warmer family climates showed little change in IL-6 production (and perhaps even a small decline) after being exposed to a life event.