Childhood maltreatment and risk of endocrine diseases: an exploration of mediating pathways using sequential mediation analysis

Abstract

Background: Adverse childhood experiences (ACEs), including childhood maltreatment, have been linked with increased risk of diabetes and obesity during adulthood. A comprehensive assessment on the associations between childhood maltreatment and all major endocrine diseases, as well as the relative importance of different proposed mechanistic pathways on these associations, is currently lacking.

Methods: Based on the UK Biobank, we constructed a cohort including 151,659 participants with self-reported data on childhood maltreatment who were 30 years of age or older on/after January 1, 1985. All participants were followed from the index date (i.e., January 1, 1985, or their 30th birthday, whichever came later) until the first diagnosis of any or specific (12 individual diagnoses and 9 subtypes) endocrine diseases, death, or the end of follow-up (December 31, 2019), whichever occurred first. We used Cox models to examine the association of childhood maltreatment, treated as continuous (i.e., the cumulative number of experienced childhood maltreatment), ordinal (i.e., 0, 1 and ≥ 2), or binary (< 2 and ≥ 2) variable, with any and specific endocrine diseases, adjusted for multiple covariates. We further examined the risk of having multiple endocrine diseases using Linear or Logistic Regression models. Then, sequential mediation analyses were performed to assess the contribution of four possible mechanisms (i.e., suboptimal socioeconomic status (SES), psychological adversities, unfavorable lifestyle, and biological alterations) on the observed associations.

Results: During an average follow-up of 30.8 years, 20,885 participants received a diagnosis of endocrine diseases. We observed an association between the cumulative number of experienced childhood maltreatment and increased risk of being diagnosed with any endocrine disease (adjusted hazard ratio (HR) = 1.10, 95% confidence interval 1.09-1.12). The HR was 1.26 (1.22-1.30) when comparing individuals ≥ 2 with those with < 2 experienced childhood maltreatment. We further noted the most pronounced associations for type 2 diabetes (1.40 (1.33-1.48)) and hypothalamic-pituitary-adrenal (HPA)-axis-related endocrine diseases (1.38 (1.17-1.62)), and the association was stronger for having multiple endocrine diseases, compared to having one (odds ratio (95% CI) = 1.24 (1.19-1.30), 1.35 (1.27-1.44), and 1.52 (1.52-1.53) for 1, 2, and ≥ 3, respectively). Sequential mediation analyses showed that the association between childhood maltreatment and endocrine diseases was consistently and most distinctly mediated by psychological adversities (15.38 ~ 44.97%), while unfavorable lifestyle (10.86 ~ 25.32%) was additionally noted for type 2 diabetes whereas suboptimal SES (14.42 ~ 39.33%) for HPA-axis-related endocrine diseases.

Conclusions: Our study demonstrates that adverse psychological sequel of childhood maltreatment constitutes the main pathway to multiple endocrine diseases, particularly type 2 diabetes and HPA-axis-related endocrine diseases. Therefore, increased access to evidence-based mental health services may also be pivotal in reducing the risk of endocrine diseases among childhood maltreatment-exposed individuals.

Keywords: Childhood maltreatment; Endocrine diseases; Psychological adversities; Sequential mediation analysis.

Fig. 1

Study design

Fig. 2

Hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between childhood maltreatment (≥ 2 vs < 2) and specific (individual or subtypes) endocrine diseases. * Cox models were adjusted for sex, birth year, ethnicity, country of birth, number of siblings, maternal smoking, being breastfed, and family history of diabetes

Fig. 3

The proposed casual diagram with possible temporal orders and the summarized mediated proportion of four hypothesized pathways from the sequential mediation analyses. * The selected mediators for each hypothesized pathway were Townsend Deprivation Index for suboptimal SES, self-rated mental problem for psychological morbidities, body mass index for unfavorable lifestyle, and high-density lipoprotein for biological alternations in the cohorts for mediation analyses of any endocrine diseases and type 2 diabetes, as well as employment, self-rated mental problem, alcohol and triglycerides in the cohort for mediation analyses of HPA-axis-related endocrine diseases, according to the results of simple mediation analyses