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BMC Psychiatry volume 24, Article number: 947 (2024)
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This study explored the relationship between Adverse Childhood Experiences (ACE), physical pain, and depressive symptoms, and examined the mediating role of pain in the correlation between ACE and depressive symptoms among middle-aged and elderly Chinese (over the age of 45).
Cox proportional hazards regression models were used to analysis the association between ACE, physical pain, and depressive symptoms. To assess the mediating role of physical pain in the relationship between ACE and depressive symptoms, mediation analysis was conducted. Indirect, direct, and total effects were estimated by combining mediation and outcome models, adjusting for relevant covariates. Bayesian network models were used to visually demonstrate the interrelations between factors influencing depressive symptoms, further verifying the association between ACE, physical pain, and depressive symptoms.
In the fully adjusted model, middle-aged and elderly individuals reporting ACE had a higher risk of developing depressive symptoms (hazard ratios [HR] and 95% confidence intervals [95% CI], 1.379 [1.266–1.503]). Compared to those without physical pain, individuals reporting severe physical pain were at an increased risk of depressive symptoms (HR [95% CI], 1.438 [1.235–1.673]). The risk was even higher for those with both ACE and severe physical pain compared to those with neither (HR [95% CI], 2.020 [1.630–2.505]). The intensity of pain explained 7.48% of the association between ACE and depressive symptoms, while the number of pain sites accounted for 7.86%.
Physical pain partially mediated the association between ACE and depressive symptoms. The study findings highlighted the importance of early screening and intervention for physical pain in middle-aged and older adults with ACE.
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With the intensification of social competition and the acceleration of life pace, the number of individuals suffering from depression is rapidly increasing. It is reported that globally, around 322 million people are affected by depression [1]. Studies in the Chinese population indicate that the prevalence of depression ranges from 1.5 to 7.9%, while the prevalence of significant depressive symptoms varies from 1.5–60.3%.2–5 Depression not only severely impacts the quality of life of middle-aged and elderly individuals but also serves as a significant risk factor for cardiovascular diseases, disability, and mortality [6,7,8,9]. Presently, the identification and control of risk factors are crucial for the primary and secondary prevention of depressive symptoms.
Previous studies have shown that ACE are associated with a range of social disadvantages in adulthood, and individuals with higher ACE scores are more likely to engage in risky health behaviors [10,11,12]. People with ACE undergo physical and psychological abnormalities, with adult physical pain and depressive symptoms potentially being long-term health consequences of ACE. Chronic physical pain is characterized by high prevalence and substantial social burden, and it is also a leading cause of disability [13, 14]. Previous studies have shown that ACE is an important predictor of increased depressive symptoms during the pandemic, and that there is a combined effect between ACE and polygenic susceptibility to major depressive disorder [15, 16]. In addition, physical pain often occurs at the same time as depressive symptoms, suggesting that there may be a two-way association between the two [17]. Existing research [18,19,20,21] indicates that both ACE and physical pain are associated with depressive symptoms, but the role of physical pain in mediating the impact of ACE on depressive symptoms in middle-aged and elderly periods lacks verification from long-term cohort studies. Current evidence overlooks the potential roles of pain intensity and the number of pain sites, and there is a lack of exploration into the underlying mechanisms, particularly the interactions among influencing factors.
Considering the potential long-term harm of ACE on mental health, understanding its relationship with depressive symptoms in middle-aged and elderly individuals, and the mediating role of physical pain, could provide a basis for promoting their physical and mental health. Therefore, this study aims to utilize data from the China Longitudinal Study of Health and Retirement (CHARLS) to explore the associations of ACE and physical pain with depressive symptoms among middle-aged and elderly Chinese, and further analyze the mediating roles of the number of pain sites and the intensity of physical pain in the relationship between ACE and depression. In terms of content, this study verified the association between ACE, physical pain, and depressive symptoms through a cohort study design, and also explored the mediating role of physical pain between ACE and depressive symptoms in the middle-aged and elderly population in China for the first time. In terms of methodology, this study not only uses traditional statistical models to analyze correlations, but also innovatively uses Bayesian network models to visually demonstrate complex correlations.
CHARLS is a nationally representative longitudinal survey of adults over the age of 45. More details about CHARLS have been reported in previous studies [22]. In the 2011 baseline survey of this study, face-to-face interviews were conducted with individuals from 10,257 households across 28 provinces, utilizing the probability ratio sampling method. Subsequent follow-up surveys have been carried out in 2013, 2015, 2018, and 2020, following the initial survey in 2011. The life course survey was conducted in 2014. This study included a total of 3,840 participants (Fig. 1), excluding those who, at baseline, had depression, other affective psychiatric issues, or memory-related diseases (confirmed cases of Alzheimer’s disease, cerebral atrophy, Parkinson’s disease).
Flow-chart of the selection of study participants. Abbreviations: ACE, adverse childhood experiences
In the CHARLS, ACE before the age of 17 were assessed using the 2014 life history questionnaire. 14 ACE, including 11 intra-familial ACE (emotional neglect, family violence, parental separation or divorce, parental substance abuse, parents incarcerated, parental mental illness, parental disability, parental death, sibling death, physical abuse, and economic adversity) and 3 extra-familial ACE (bullying, loneliness, and community violence) were identified based on our previous research. Utilizing dichotomous items, we further constructed a composite variable (≥ 4 ACE vs. <4 ACE). This threshold was chosen because previous studies have reported that having four or more ACE increases the risk of various adverse health outcomes, making it a widely accepted benchmark [23, 24]. Additionally, this study also considered the relationship between continuous ACE scores and depressive symptoms.
Depressive symptoms were measured using the CES-D scale, whose reliability in Chinese adults has been widely validated [25, 26]. Participants were asked about their mood and behavior over the past week, including eight negative and two positive questions. Each question was scored from 0 to 3, with a total score ranging from 0 to 30. Higher depressive scores refer to more depressive symptoms. The cutoff score for depressive symptoms was 10.
During the baseline survey, participants were asked about the frequency of physical pain, the locations of the pain, and its intensity. The listed pain locations included the head, shoulders, arms, wrists, fingers, chest, stomach, back, waist, hips, legs, knees, ankles, toes, and neck. If participants experienced more than one type of pain, they were instructed to report the severity of the most severe pain.
At baseline, sociodemographic factors, personal lifestyle, and health status were collected through questionnaire surveys, physical examinations, and blood tests. Potential confounding factors considered included sociodemographic factors (age, sex, urban/rural residence, education level, marital status, body mass index), personal lifestyle factors (smoking, alcohol consumption, social participation, exercise habits), relevant blood test indicators, and health status. The latter encompasses self-reported histories of 12 chronic diseases: hypertension, dyslipidemia, diabetes, cancer and other malignancies, chronic lung diseases, liver diseases, heart diseases, stroke, kidney diseases, stomach diseases, arthritis or rheumatism, and asthma, defined based on whether a doctor had informed the participants of having these diseases.
Baseline characteristics of participants were described by mean values for continuous variables and proportions for categorical variables. Data are presented as frequency (%) and mean (SD). T tests were used for continuous variables, and Chi-square tests for categorical variables. Considering missing data, variables with a missing proportion over 5% were assigned NA dummy variables, while those with less than 5% missing data underwent multiple imputation. Details of missing data are shown in supplementary material (see Table S1 published as supplementary material online).
Cox proportional hazards regression models were used to calculate HR [95% CI] for the association between ACE, physical pain, and depressive symptoms. Three models progressively revealed the correlations between ACE, physical pain, and depressive symptoms, comparing HR before and after adjusting for confounding factors. The effects of combinations of ACE and physical pain on depressive symptoms were further stratified. To assess the mediating role of physical pain in the relationship between ACE and depressive symptoms, mediation analysis was conducted. Indirect, direct, and total effects were estimated by combining mediation and outcome models, adjusting for relevant covariates.
Several sensitivity analyses were performed to test the robustness of the results. Firstly, participants who developed depression within two years of recruitment were excluded to reduce the possibility of reverse causation. Secondly, continuous ACE scores and the number of pain sites were used instead of categorical ACE and pain intensity in the primary analysis. Thirdly, based on the results of the Cox regression models, variables with statistical significance were included, and those with over 5% missing data were excluded. Bayesian network models were used to visually demonstrate the interrelations between factors influencing depressive symptoms, further verifying the association between ACE, physical pain, and depressive symptoms.
A two-sided P-value of < 0.05 was considered statistically significant. Analyses were conducted using R statistical software version 9.4 (R Foundation for Statistical Computing) and SPSS version 26.0 (IBM SPSS Statistics). Data analysis was carried out from November 2023 to January 2024.
The main sample included 3840 middle-aged and elderly individuals, with an average age of 58.03 (SD = 8.32) years, of whom 1935 (50.39%) were female. During the 9-year follow-up period, 2095 (54.56%) reported new onset of depressive symptoms, with the cumulative incidence shown in supplementary material (see Table S2 published as supplementary material online). As indicated in Table 1, compared to those without depressive symptoms, participants who reported new onset of depressive symptoms were more likely to be older, male, from rural areas, have lower education levels, be in a single status, have unhealthier lifestyles, more chronic diseases, higher ACE scores, and experience more intense physical pain.
Table 2 displays the associations between ACE, physical pain, and depressive symptoms in the Cox regression model. Compared to individuals with ACE scores less than 4, those with scores of 4 or higher had a significantly increased risk of developing depressive symptoms. The HR (95% CI) before and after adjusting for confounders were 1.439 (1.319–1.570) and 1.379 (1.266–1.503), respectively. Compared to those without physical pain, individuals with mild, moderate, and severe physical pain had progressively higher risks of developing depressive symptoms, with adjusted HR (95% CI) of 1.275 (1.094–1.486), 1.418 (1.209–1.665), and 1.438 (1.235–1.673), respectively. Compared to individuals with low ACE scores and no physical pain, those with high ACE scores and severe physical pain had a significantly increased risk of developing depressive symptoms, with an adjusted HR (95% CI) of 2.020 (1.630–2.505).
Considering the potential for reverse causality, this study excluded participants who developed depressive symptoms within two years of recruitment and then reanalyzed using Cox regression. As illustrated in Fig. 2, the associations between ACE, physical pain, and depressive symptoms remained. To address collinearity issues, continuous ACE scores, the presence or absence of physical pain, and the number of pain sites were used instead of categorical ACE and pain intensity in the primary analysis. After adjusting for confounders, the results remained unchanged, consistent with previous conclusions (see Table S3 published as supplementary material online). Bayesian networks visually demonstrated the interrelations among factors influencing depressive symptoms, further verifying the association between ACE, physical pain, and depressive symptoms (see Figure S1 published as supplementary material online). When both ACE and physical pain scores were high, the probability of middle-aged and elderly individuals suffering from depressive symptoms was 76.70% (see Figure S2 published as supplementary material online).
Relationship between adverse childhood experiences, physical pain and new-onset depressive symptoms during the period 2013–2020. Abbreviations: HR, hazard ratio; CI, confidence interval; ACE, adverse childhood experiences
a adjusted for age, sex, residents, education, marital status, BMI, smoking, drinking, ADL, IADL, social activity, exercise, number of chronic diseases, Cystatin C, high density lipoprotein cholesterol
The results of the mediation analysis are shown in Fig. 3. We found that physical pain partially mediated the association between ACE and depressive symptoms. The intensity of pain explained 7.48% of the association between ACE and depressive symptoms, while the number of pain sites accounted for 7.86%. Subgroup analyses by type of residence revealed that this mediating effect persisted in both urban and rural middle-aged and elderly populations (see Figure S3 and Figure S4 published as supplementary material online). However, the mediation effect was relatively increased in urban populations and decreased in rural populations.
Effect of physical pain on the Association between ACE and the Aew-onset of Aepressive Aymptoms. Abbreviations: ACE, adverse childhood experiences. *p < 0.001. Adjusted for age, sex, residents, education, marital status, BMI, smoking, drinking, ADL, IADL, social activity, exercise, number of chronic diseases, Cystatin C, high density lipoprotein cholesterol.
This study explored the association between ACE, physical pain, and depressive symptoms in middle-aged and older adults in China. It further analyzed the mediating role of the number of pain locations and the intensity of physical pain in the relationship between ACE and depression. The results indicated that both ACE and physical pain were significantly associated with a higher risk of depressive symptoms, with the risk positively correlated with the intensity of physical pain. Examination of the mediating effects revealed that both the intensity and the number of pain sites mediated the association between ACE and depressive symptoms to some extent, with this mediating effect being more pronounced in urban middle-aged and elderly populations.
ACE and physical pain were identified as risk factors for depressive symptoms in middle-aged and older adults, aligning with findings from previous studies. A study in Germany during the Covid-19 pandemic identified ACE as a significant predictor of increased depressive symptoms, suggesting that individuals with ACE might be at risk for mental health issues during the current and potential future pandemics [15]. The UK’s aging longitudinal study confirmed that both ACE and polygenic susceptibility to major depression are associated with higher depressive symptoms, and the combined effect of ACE and polygenic susceptibility further increases the risk of depression [16]. Previous research has shown that physical pain often co-occurs with depressive symptoms, suggesting a bidirectional association [17, 27,28,29,30]. Building on these studies, our research further determined that in the Chinese middle-aged and elderly population, the intensity of physical pain and the number of pain sites explained 7.48% and 7.86%, respectively, of the association between ACE and depressive symptoms. Therefore, timely attention by Chinese health service personnel to the comprehensive assessment of physical pain in middle-aged and elderly people is more conducive to the prevention and control of depressive symptoms. Additionally, the Bayesian network showed that gender is a common influencing factor for both ACE and the intensity of physical pain, with physical pain not only directly affecting depressive symptoms but also influencing depressive symptoms through pathways including chronic diseases and social participation.
The internal mechanisms linking ACE and physical pain with depressive symptoms remain unclear. Compared to normal individuals, those with high ACE scores experience more physical and psychological abnormalities during childhood, which may lead to physical pain in adulthood and a more closed and vulnerable psychological state. Biologically, chronic physical pain and depressive symptoms may share common neural circuits and brain modulators [31, 32]. Furthermore, research suggests that chronic inflammation is a risk factor for depression, and both ACE and physical pain are associated with some level of inflammation [33,34,35,36,37]. Longitudinal studies and meta-analyses evaluating evidence suggest that stress and immune system dysregulation due to ACE exposure are significantly associated with elevated inflammatory biomarkers, with a mechanophysiological response to trauma [38]. Long-term inflammation can cause peripheral sensitization, leading to hyperalgesia and chronic generalized pain [39]. Therefore, it is crucial to pay attention to the mental health of individuals with ACE who suffer from physical pain. China’s aging population is deepening, and the development of community health service centers is becoming more and more comprehensive, the results of this study provide guidance for the prevention and control of physical and mental health in the elderly. Measures should be taken to prevent and control the risk of depressive symptoms in potentially susceptible individuals, including regular screening and timely care for chronic physical pain in middle-aged and elderly people by community health centers [40].
This study has several significant strengths. Firstly, this cohort study integrates the intensity of physical pain and the number of pain sites to examine the association between ACE and depressive symptoms, which helps in better understanding the potential mechanisms. Secondly, the extended period of follow-up and the application of multiple imputation methods further ensure the accuracy of the causal relationships. Finally, multiple different sensitivity analyses enhance the reliability of our results.
The study also has limitations. Firstly, ACE was measured by asking about experiences prior to age 18, and due to the relatively older age of the study subjects, there may be bias in recalling childhood trauma, and a certain amount of recall bias may not be eliminated. Secondly, although we adjusted for as many confounding factors as possible, the impact of residual confounders, such as genetic factors, cannot be entirely eliminated. Finally, pain in this study was self-rated by the subjects, so there may be information bias in the evaluation of pain degree.
In this cohort study, we found that both ACE and physical pain were associated with a higher risk of developing depressive symptoms, particularly when both were present. Physical pain partially mediated the association between ACE and depressive symptoms in middle-aged and elderly individuals, indicating that adverse experiences in childhood can have long-term negative effects on mental health. Focusing on physical pain as a phenotypic factor may help mitigate these effects. Importantly, the development and promotion of physical pain screening and intervention measures within communities may enhance the physical and mental health of the middle-aged and elderly population with ACE.
All data and materials are available from the corresponding author on reasonable request.
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This analysis used data or information from the CHARLS. The authors thank all staff and participants of this study for their important contributions.
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School of Public Health, Southeast University, Nanjing, Jiangsu, China
Min Bao
Department of Medical Affairs, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Rongji Ma
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Min Bao was in charge of study conceptualization, drafting of manuscript, carrying out statistical analyses, and interpretation of results. Rongji Ma revised the manuscript and offered constructive feedback.
Correspondence to Rongji Ma.
The study was approved by the Ethics Review Committee of Peking University, and all CHARLS participants provided written informed consent. All methods were carried out by the principle embodied in the Declaration of Helsinki.
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Bao, M., Ma, R. Longitudinal relationship between adverse childhood experiences and depressive symptoms: the mediating role of physical pain. BMC Psychiatry 24, 947 (2024). https://doi.org/10.1186/s12888-024-06312-y
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