Effect of adverse childhood experiences on hypothalamic–pituitary–adrenal (HPA) axis function and antidepressant efficacy in untreated first episode patients with major depressive disorder

Background Depression is recognized globally as a leading cause of disability. Early-life adverse childhood experiences (ACEs) have been shown to have robust associations with poor mental health during adulthood. These effects may be cumulative, whereby a greater number of ACEs are progressively associated with worse outcomes. This study aimed to estimate the associations between ACEs and adult depression and suicidal ideation in a cross-sectional, population-based study of adults in Uganda. Methods and findings Between 2016 and 2018, research assistants visited the homes of 1,626 adult residents of Nyakabare Parish, a rural area in southwestern Uganda. ACEs were assessed using a modified version of the Adverse Childhood Experiences-International Questionnaire, and depression symptom severity and suicidal ideation were assessed using the Hopkins Symptom Checklist for Depression (HSCL-D). We applied a validated algorithm to determine major depressive disorder diagnoses. Overall, 1,458 participants (90%) had experienced at least one ACE, 159 participants (10%) met criteria for major depressive disorder, and 28 participants (1.7%) reported suicidal ideation. We fitted regression models to estimate the associations between cumulative number of ACEs and depression symptom severity (linear regression model) and major depressive disorder and suicidal ideation (Poisson regression models). In multivariable regression models adjusted for age, sex, primary school completion, marital status, self-reported HIV status, and household asset wealth, the cumulative number of ACEs was associated with greater depression symptom severity (b = 0.050; 95% confidence interval [CI], 0.039–0.061, p < 0.001) and increased risk for major depressive disorder (adjusted relative risk [ARR] = 1.190; 95% CI, 1.109–1.276; p < 0.001) and suicidal ideation (ARR = 1.146; 95% CI, 1.001–1.311; p = 0.048). We assessed the robustness of our findings by probing for nonlinearities and conducting analyses stratified by age. The limitations of the study include the reliance on retrospective self-report as well as the focus on ACEs that occurred within the household. Conclusions In this whole-population, cross-sectional study of adults in rural Uganda, the cumulative number of ACEs had statistically significant associations with depression symptom severity, major depressive disorder, and suicidal ideation. These findings highlight the importance of developing and implementing policies and programs that safeguard children, promote mental health, and prevent trajectories toward psychosocial disability.

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Supplemental Material for Cognitive Functioning in the First-Episode of Major Depressive Disorder: A Systematic Review and Meta-Analysis

Neuropsychology ◽

10.1037/neu0000319.supp ◽

2016 ◽

Keyword(s):

Systematic Review ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Cognitive Functioning ◽

Meta Analysis ◽

First Episode ◽

Major Depressive

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Major depressive disorder due to social isolation during the coronavirus disease 2019 pandemic: an elderly woman's first episode of major depressive disorder

Psychogeriatrics ◽

10.1111/psyg.12607 ◽

2020 ◽

Vol 20 (6) ◽

pp. 934-935

Author(s):

Yasuhiko Deguchi ◽

Shinichi Iwasaki ◽

Koki Inoue

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Social Isolation ◽

First Episode ◽

Major Depressive

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Adverse childhood experiences, daytime salivary cortisol, and depressive symptoms in early adulthood: a longitudinal genetically informed twin study

Translational Psychiatry ◽

10.1038/s41398-021-01538-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eleonora Iob ◽

Jessie R. Baldwin ◽

Robert Plomin ◽

Andrew Steptoe

Keyword(s):

Depressive Symptoms ◽

Hpa Axis ◽

Salivary Cortisol ◽

Adverse Childhood Experiences ◽

Emotional Abuse ◽

Early Adulthood ◽

Cumulative Exposure ◽

Childhood Experiences ◽

Adverse Childhood ◽

Cortisol Levels

AbstractDysregulated hypothalamic–pituitary–adrenal (HPA)-axis function might underlie the relationship between adverse childhood experiences (ACEs) and depression. However, limited research has examined the possible mediating role of the HPA-axis among young people using longitudinal data. Moreover, it remains unclear whether genetic influences could contribute to these associations. Participants were 290 children from the Twins Early Development Study. ACEs were assessed from age 3–11 years. We calculated a cumulative risk score and also derived different ACEs clusters using factor analysis and latent class analysis. HPA-axis activity was indexed by daytime salivary cortisol at age 11. Depressive symptoms were ascertained at age 21. Genetic liability to altered cortisol levels and elevated depressive symptoms was measured using a twin-based method. We performed causal mediation analysis with mixed-effects regression models. The results showed that ACEs cumulative exposure (b = −0.20, p = 0.03), bullying (b = −0.61, p = 0.01), and emotional abuse (b = −0.84, p = 0.02) were associated with lower cortisol levels at age 11. Among participants exposed to multiple ACEs, lower cortisol was related to higher depressive symptoms at age 21 (b = −0.56, p = 0.05). Lower cortisol levels mediated around 10–20% of the total associations of ACEs cumulative exposure, bullying, and dysfunctional parenting/emotional abuse with higher depressive symptoms. Genetic factors contributed to these associations, but the mediation effects of cortisol in the associations of ACEs cumulative exposure (b = 0.16 [0.02–0.34]) and bullying (b = 0.18 [0.01–0.43]) remained when genetic confounding was accounted for. In conclusion, ACEs were linked to elevated depressive symptoms in early adulthood partly through lower cortisol levels in early adolescence, and these relationships were independent of genetic confounding.

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