Maternal mental illness and frequent change of caregivers were shown to be significantly associated with overactivation of the hypothalamic-pituitary-adrenal (HPA) axis in children, adolescents, and young adults in institutional care, according to a pilot study published in Psychiatry Research. Early-life stress caused by adverse childhood experiences (ACEs) has been linked to alterations in HPA axis activity that persist into adulthood, which may play a role in mental illness, including depression.

The researchers examined the correlation between HPA axis dysregulation and ACEs in 138 participants (age range, 7-25 years) living in institutional care facilities in German-speaking regions of Switzerland. However, only 65.5% (n=91) of the recruited participants provided complete samples for analysis. The researchers assessed HPA axis dysregulation by measuring the ratio between cortisol and dehydroepiandrosterone (DHEA) levels from participants’ hair samples and assessed mental health with the Child Behavior Checklist (CBCL). Hair sample-derived cortisol/DHEA ratios may offer a more accurate measurement of HPA axis activity without the confounds of daily fluctuations present in plasma and salivary cortisol levels.

Both maternal mental illness and frequent change of caregivers were associated with HPA axis activation. The researchers found a significant increase in the ratio of cortisol/DHEA from the hair samples of the 13 (39.3%) participants who reported maternal mental illness (mean 0.09±0.35 vs -0.18±0.31; P =.02) and the 27 (29.7%) participants who self-reported frequent change of caregivers (mean 0.03±0.36 vs. -0.17±0.30; P =0.02) compared with those who did not. Frequent change of caregivers was further associated with elevated CBCL total scores (mean 68.92±7.26 vs 62.47±8.95; P =.01). Additionally, increased cortisol/DHEA ratios were correlated with mental health problems (standardized coefficient=0.28; P =.02), particularly anxiety and depressive symptoms (standardized coefficient, 0.29; P =.01).

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Study limitations included low sample size and the reliance on 1 method to measure HPA axis activity.  Sample size between variables ranged from 20 to 91 participants due to missing data, and low sample size did not allow for control variable analysis such as age and sex, which may have introduced bias.

The results of this study may have implications for interventions for teens and adolescents in institutional care. The researchers concluded, “when children are already at high risk, [for example] coming from families with mentally ill mothers, permanency planning that avoids frequent changes of caregivers should be one main priority in order to reduce the physiological changes and devastating consequences that are going along with these adverse experiences.”


Clemens V, Bürgin D, Eckert A, et al. Hypothalamic-pituitary-adrenal axis activation in a high-risk sample of children, adolescents and young adults in residential youth care: associations with adverse childhood experiences and mental health problems. Psychiatry Res. 2020;284:112778.