A recent study found that childhood adversity may be associated with dysregulated biological functioning and increased risk for numerous serious health problems in adulthood. The effects differed based on sex, type of adversity experienced, and specific health outcomes examined.

In the study, published in Brain, Behavior, and Immunity, investigators analyzed the data of 2,111 participants (54.8% female, mean age 53.04 years, standard deviation [SD] = 12.57). They examined associations between childhood stressors and 25 stress- and disease-related biomarkers as well as 20 major health conditions in adulthood.

The investigators utilized data from the MIDUS 2 (n = 1,250) and MIDUS Refresher (n = 861) studies, including biomarker data. Childhood stressors assessed included financial distress, welfare status, abuse, neglect, frequency of moving, and living away from biological parents. The study controlled for age and sex effects on class membership probability.

Latent class analysis was used to identify unobserved groups based on childhood stressor exposure. Associations between latent classes and biomarkers were examined using the three-step method. Cox proportional hazards models tested associations with health conditions.

Multivariate effect sizes were computed using Mahalanobis distances. Harmonic mean P analyses controlled for multiple comparisons.

Sex-specific latent class analyses identified different childhood stressor profiles:

• Among males: Low stress (n = 791) and high stress (n = 163)
• Among females: Low stress (n = 643), moderate stress (n = 358), and high stress (n = 156).

The high-stress groups showed greater inflammation and poorer metabolic health compared with the low-stress groups:

• High-stress males had higher levels of interleukin (IL)-6 (P = .02, Cohen's d = 0.20), C-reactive protein (CRP) (P = .004, d = 0.25), intercellular adhesion molecule 1 (I-CAM) (P = .01, d = 0.26), and diastolic blood pressure (P = .006) compared with low-stress males.
• High-stress females had higher IL-6 (P = .004, d = 0.32), CRP (P = .004, d = 0.39), fibrinogen (P < .001, d = 0.26), E-selectin (P = .004), and waist-to-hip ratio (P = .006) levels compared with low-stress females.

The high-stress groups exhibited an increased risk for numerous health conditions compared with the low-stress groups:

• High-stress males showed increased risk for conditions including high blood pressure (adjusted hazard ratio [HR] = 1.71, 95% confidence interval [CI] = 1.25–2.32), circulation problems (adjusted HR = 2.61, 95% CI = 1.40–4.86), and depression (adjusted HR = 3.09, 95% CI = 2.22–4.31).
• High-stress females showed increased risk for 18 of 20 health conditions assessed, with adjusted HR ranging from 1.51 to 9.28. Notably, high-stress females had higher risk of emphysema/COPD (adjusted HR = 4.01, 95% CI = 1.56–10.20).

The effects of specific stressors differed by sex. For instance, emotional abuse and neglect showed stronger associations with some biomarkers and health conditions in males.

Inflammation biomarkers: High-stress males had higher IL-6 (P = .02), CRP (P = .004), and I-CAM (P = .01) levels compared with low-stress males. High-stress females had higher IL-6 (P = .004), CRP (P = .004), and fibrinogen (P < .001) levels compared with low-stress females.

Metabolic biomarkers: High-stress males had higher body mass index (BMI) (P = .003, d = 0.28), insulin levels (P = .001, d = 0.33), insulin resistance (P = .002, d = 0.31), triglycerides (P = .01, d = 0.25), and low-density lipoprotein (LDL) cholesterol (P = .048, d = 0.19), and lower high-density lipoprotein (HDL) cholesterol (P = .02, d = 0.26) compared with low-stress males. High-stress females showed higher BMI (P = .005), insulin levels (P = .001), insulin resistance (P = .007), and triglycerides (P = .005) compared with low-stress females. High-stress females had lower urinary cortisol levels than low-stress females (P = .04, d = 0.25).

High-stress males showed an increased risk for high blood pressure (adjusted HR = 1.71, 95% CI = 1.25–2.32), circulation problems (adjusted HR = 2.61, 95% CI = 1.40–4.86), cholesterol problems (adjusted HR = 1.52, 95% CI = 1.13–2.05), thyroid disease (adjusted HR = 3.65, 95% CI = 1.87–7.12), cancer (adjusted HR = 2.41, 95% CI = 1.52–3.83), arthritis (adjusted HR = 1.81, 95% CI = 1.30–2.53), and depression (adjusted HR = 3.09, 95% CI = 2.22–4.31).

High-stress females showed increased risk for 18 of 20 health conditions assessed, with adjusted HRs ranging from 1.51 to 9.28. Notably, high-stress females had higher risk of emphysema/COPD (adjusted HR = 4.01, 95% CI = 1.56–10.20).

The investigators also examined associations between specific childhood stressors and health outcomes. Welfare status during childhood was associated with elevated inflammatory activity, with larger effect sizes for males. Physical abuse showed stronger associations with glucose metabolism and anthropometric measurements in females. Emotional abuse was more strongly related to several health conditions for males, particularly thyroid conditions, mental/behavioral issues, blood disorders, and glaucoma.

Multivariate effect sizes (Mahalanobis's D) among males were 0.43 for inflammation biomarkers and ranged from 0.32 to 0.33 for metabolic biomarkers. Among females, these values were 0.59 for inflammation biomarkers and ranged from 0.32 to 0.47 for metabolic biomarkers.

Robustness checks using harmonic mean P analyses showed that effects on 22 out of 25 biomarkers remained significant after adjusting for multiple comparisons. All omnibus tests with health conditions as outcomes survived adjustment for multiple comparisons, except for glaucoma.

Limitations included the cross-sectional design, potential recall bias in retrospective childhood adversity measures, and the nonrepresentative nature of the MIDUS sample.

The authors declare no conflicts of interest related to this research. All funding sources and potential biases have been disclosed and accounted for in accordance with the relevant guidelines.