Association Between Early Life Adversity and Risk for Poor Emotional and Physical Health in Adolescence: A Putative Mechanistic Neurodevelopmental Pathway

Abstract

Importance: Adverse childhood experiences (ACEs) have been associated with poor mental and physical health outcomes. However, the mechanism of this effect, critical to enhancing public health, remains poorly understood.

Objective: To investigate the neurodevelopmental trajectory of the association between early ACEs and adolescent general and emotional health outcomes.

Design, setting, and participants: A prospective longitudinal study that began when patients were aged 3 to 6 years who underwent neuroimaging later at ages 7 to 12 years and whose mental and physical health outcomes were observed at ages 9 to 15 years. Sequential mediation models were used to investigate associations between early ACEs and brain structure, emotion development, and health outcomes longitudinally. Children were recruited from an academic medical center research unit.

Exposure: Early life adversity.

Main outcomes and measures: Early ACEs in children aged 3 to 7 years; volume of a subregion of the prefrontal cortex, the inferior frontal gyrus, in children aged 6 to 12 years; and emotional awareness, depression severity, and general health outcomes in children and adolescents aged 9 to 15 years.

Results: The mean (SD) age of 119 patients was 9.65 (1.31) years at the time of scan. The mean (SD) ACE score was 5.44 (3.46). The mean (SD) depression severity scores were 2.61 (1.78) at preschool, 1.77 (1.58) at time 2, and 2.16 (1.64) at time 3. The mean (SD) global physical health scores at time 2 and time 3 were 0.30 (0.38) and 0.33 (0.42), respectively. Sequential mediation in the association between high early ACEs and emotional and physical health outcomes were found. Smaller inferior frontal gyrus volumes and poor emotional awareness sequentially mediated the association between early ACEs and poor general health (model parameter estimate = 0.002; 95% CI, 0.0002-0.056) and higher depression severity (model parameter estimate = 0.007; 95% CI, 0.001-0.021) in adolescence. An increase from 0 to 3 early ACEs was associated with 15% and 25% increases in depression severity and physical health problems, respectively.

Conclusions and relevance: Study findings highlight 1 putative neurodevelopmental mechanism by which the association between early ACEs and later poor mental and physical health outcomes may operate. This identified risk trajectory may be useful to target preventive interventions.

Figure 1.. Conceptual Model of Biological Embedding of Adversity With Mediating Associations

ACEs indicates adverse childhood events; S1, scan 1; T2, time 2; T3, time 3. a₁ Represents the association between early ACEs and prefrontal subregion volumes; a₂, the association between early ACEs and emotion/behaviors; b₁, the association between prefrontal subregion volumes and physical/emotional health outcomes; b₂, the association between emotion/behaviors and physical/emotional health outcomes; c′, the direct effect between early ACEs and physical/emotional health outcomes; d_1,2, the association between prefrontal subregion volumes and emotion/behaviors.

Figure 2.. Sequential Mediation Model Depicting Analysis of Mediating Associations Between ACEs and MDD Severity

Mediation model with parameter estimates was based on maximum likelihood procedures. ACEs indicates adverse childhood events; GPH, global physical health; MDD, major depressive disorder; PS, preschool; S1, scan 1; T2, time 2; T3, time 3; WBV, whole-brain volume. a₁ Represents the association between early ACEs and inferior frontal gyrus volume; a₂, the association between early ACEs and poor emotional awareness; b₁, the association between inferior frontal gyrus volume and MDD severity; b₂, the association between poor emotional awareness and MDD severity; c′, the direct effect between early ACEs and MDD severity; d_1,2, the association between inferior frontal gyrus volume and poor emotional awareness. ^aP < .05. ^bP < .01.

Figure 3.. Sequential Mediation Model Depicting Analysis of Mediating Associations Between Early ACEs and GPH Problems

Mediation model with parameter estimates was based on maximum likelihood procedures. ACEs indicates adverse childhood events; GPH, global physical health; MDD, major depressive disorder; S1, scan 1; T2, time 2; T3, time 3; WBV, whole-brain volume. a₁ Represents the association between early ACEs and inferior frontal gyrus volume; a₂, the association between early ACEs and poor emotional awareness; b₁, the association between inferior frontal gyrus volume and GPH problems; b₂, the association between poor emotional awareness and GPH problems; c′, the direct effect between early ACEs and GPH problems; d_1,2, the association between inferior frontal gyrus volume and poor emotional awareness. ^aP < .05. ^bP < .01.