Psychological stress during childhood and adolescence and its association with inflammation across the lifespan: A critical review and meta-analysis.

Abstract

Psychological stress during childhood and adolescence increases risk of health problems across the lifecourse, and inflammation is implicated as an underlying mechanism. To evaluate the viability of this hypothesis, we used meta-analysis to quantify the association between childhood/adolescent stress and inflammation over the lifecourse. Furthermore, we addressed three unresolved conceptual questions: (a) Does the strength of this association change over the lifecourse? (b) Are different types of childhood/adolescent stressors differentially associated with inflammation? (c) And which components of the inflammatory response are involved? A systematic search identified 187 articles reporting 922 associations. Meta-analyses were conducted using a three-level multilevel approach and controlled for study quality, conversion confidence, and whether effect sizes were unadjusted or adjusted (n = 662, 72%). Results indicated a small but reliable overall adjusted association (rfalse^ = .04). The magnitude of the association strengthened across the lifecourse—effect sizes were smallest in studies that measured inflammation in childhood (rfalse^ = .02) and became progressively larger in studies of adolescence (rfalse^ = .04) and adulthood (rfalse^ = .05), suggesting the impact of early stress strengthens with time. By contrast, effect sizes did not vary by adversity type (socioeconomic disadvantage, maltreatment, other interpersonal stressors, and cumulative exposure across stressors), or component of inflammation (circulating biomarkers of low-grade inflammation vs. cytokine responses to microbial stimuli). Implications and future directions are discussed.

A molecular framework for autistic experiences: Mitochondrial allostatic load as a mediator between autism and psychopathology

“…Post-mortem studies also found a significant upregulation of microglial-specific genes (226), increased microglial density (224,230) and excessive microglial activation (225,231) in ASC brain tissue, while two recent systematic reviews report consistent evidence for disrupted microglial morphology, organization and activation in autism (220,232). Although the precise nature of neuroimmune dysregulation is context-specific and pleiotropic in both ASC and ELS (204,233), these data reveal an interesting mechanistic overlap between ASC neurology and stress-related psychopathology.…”

“…Extensive synaptic remodeling also occurs during adolescence, and CAS is known to disrupt synaptic plasticity and myelination with long-term implications for psychology, cognition and behavior (73,279). These neurophysiological differences have largely been attributed to signaling between the HPA axis, GCs and neurogenic factors (e.g., Brain-derived neurotrophic factor and Wnt) (233,234). However, just as the concept of MAL is becoming increasingly established in stress research, mitochondria are also emerging as central regulators of neurodevelopment and physiology (Figure 3).…”

A Molecular Framework for Autistic Experiences: Mitochondrial Allostatic Load as A Mediator between Autism and Psychopathology

“…Post-mortem studies also found a significant upregulation of microglial-specific genes (208), increased microglial density (206,212) and excessive microglial activation (207,213) in ASC brain tissue, while two recent systematic reviews report consistent evidence for disrupted microglial morphology, organization and activation in autism (202,214). Although the precise nature of neuroimmune dysregulation is context-specific and pleiotropic in both ASC and ELS (215,216), these data reveal an interesting mechanistic overlap between ASC neurology and stress-related psychopathology.…”

Socioeconomic disadvantage, chronic stress, and proinflammatory phenotype: an integrative data analysis across the lifecourse

“…Elevations in these biomarkers take time to accumulate, and their association with stress might, therefore, be expected to strengthen with age. Indeed, in other investigations, we have demonstrated that socioeconomic disparities in circulating inflammation strengthens with age using an integrative data analysis approach ( 53 ) and a meta-analytical approach ( 54 ). These findings point to the importance of considering both the developmental timing of stress exposure and the nature of the inflammatory parameter being considered.…”