Longitudinal relationship between adverse childhood experiences and depressive symptoms: the mediating role of physical pain

Abstract

Background
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).

Methods
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.

Results
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%.

Conclusions
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.

Clinical trial number
Not applicable.

Full text

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Bao and Ma BMC Psychiatry (2024) 24:947
https://doi.org/10.1186/s12888-024-06312-y BMC Psychiatry
*Correspondence:
Rongji Ma
rongji_ma@foxmail.com
1School of Public Health, Southeast University, Nanjing, Jiangsu, China
2Department of Medical Aairs, The Second Aliated Hospital of
Soochow University, Suzhou, Jiangsu, China
Abstract
Background 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).
Methods 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 eects were estimated by
combining mediation and outcome models, adjusting for relevant covariates. Bayesian network models were used
to visually demonstrate the interrelations between factors inuencing depressive symptoms, further verifying the
association between ACE, physical pain, and depressive symptoms.
Results 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% condence 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%.
Conclusions Physical pain partially mediated the association between ACE and depressive symptoms. The study
ndings highlighted the importance of early screening and intervention for physical pain in middle-aged and older
adults with ACE.
Clinical trial number Not applicable.
Keywords Physical pain, Adverse childhood experiences, Depressive symptoms, Middle-aged and elderly, China
Longitudinal relationship between adverse
childhood experiences and depressive
symptoms: the mediating role of physical pain
MinBao1 and RongjiMa2*
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Bao and Ma BMC Psychiatry (2024) 24:947
Introduction
With the intensication of social competition and the
acceleration of life pace, the number of individuals suf-
fering from depression is rapidly increasing. It is reported
that globally, around 322million people are aected by
depression [1]. Studies in the Chinese population indi-
cate that the prevalence of depression ranges from 1.5
to 7.9%, while the prevalence of signicant 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 signicant risk fac-
tor for cardiovascular diseases, disability, and mortality
[6–9]. Presently, the identication and control of risk fac-
tors are crucial for the primary and secondary prevention
of depressive symptoms.
Previous studies have shown that ACE are associ-
ated with a range of social disadvantages in adulthood,
and individuals with higher ACE scores are more likely
to engage in risky health behaviors [10–12]. People with
ACE undergo physical and psychological abnormali-
ties, 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 depres-
sive symptoms during the pandemic, and that there is a
combined eect between ACE and polygenic suscepti-
bility 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 asso-
ciation between the two [17]. Existing research [18–21]
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 verication
from long-term cohort studies. Current evidence over-
looks the potential roles of pain intensity and the num-
ber of pain sites, and there is a lack of exploration into
the underlying mechanisms, particularly the interactions
among inuencing factors.
Considering the potential long-term harm of ACE
on mental health, understanding its relationship with
depressive symptoms in middle-aged and elderly indi-
viduals, and the mediating role of physical pain, could
provide a basis for promoting their physical and mental
health. erefore, this study aims to utilize data from
the China Longitudinal Study of Health and Retirement
(CHARLS) to explore the associations of ACE and physi-
cal pain with depressive symptoms among middle-aged
and elderly Chinese, and further analyze the mediat-
ing 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 veried the
association between ACE, physical pain, and depres-
sive 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 rst time. In terms of
methodology, this study not only uses traditional statisti-
cal models to analyze correlations, but also innovatively
uses Bayesian network models to visually demonstrate
complex correlations.
Methods
Study design and participants
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, fol-
lowing the initial survey in 2011. e life course survey
was conducted in 2014. is study included a total of
3,840 participants (Fig.1), excluding those who, at base-
line, had depression, other aective psychiatric issues, or
memory-related diseases (conrmed cases of Alzheimer’s
disease, cerebral atrophy, Parkinson’s disease).
Assessment of adverse childhood experiences
In the CHARLS, ACE before the age of 17 were assessed
using the 2014 life history questionnaire. 14 ACE, includ-
ing 11 intra-familial ACE (emotional neglect, family vio-
lence, parental separation or divorce, parental substance
abuse, parents incarcerated, parental mental illness,
parental disability, parental death, sibling death, physi-
cal abuse, and economic adversity) and 3 extra-familial
ACE (bullying, loneliness, and community violence)
were identied based on our previous research. Utilizing
dichotomous items, we further constructed a composite
variable (≥ 4 ACE vs. <4 ACE). is threshold was cho-
sen 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 rela-
tionship between continuous ACE scores and depressive
symptoms.
Assessment of 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
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Bao and Ma BMC Psychiatry (2024) 24:947
symptoms. e cuto score for depressive symptoms was
10.
Assessment of physical pain
During the baseline survey, participants were asked
about the frequency of physical pain, the locations of the
pain, and its intensity. e listed pain locations included
the head, shoulders, arms, wrists, ngers, chest, stom-
ach, 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.
Covariates
At baseline, sociodemographic factors, personal lifestyle,
and health status were collected through questionnaire
surveys, physical examinations, and blood tests. Poten-
tial confounding factors considered included sociode-
mographic factors (age, sex, urban/rural residence,
education level, marital status, body mass index), per-
sonal lifestyle factors (smoking, alcohol consumption,
social participation, exercise habits), relevant blood test
indicators, and health status. e latter encompasses
self-reported histories of 12 chronic diseases: hyperten-
sion, dyslipidemia, diabetes, cancer and other malignan-
cies, chronic lung diseases, liver diseases, heart diseases,
Fig. 1 Flow-chart of the selection of study participants. Abbreviations: ACE, adverse childhood experiences
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Bao and Ma BMC Psychiatry (2024) 24:947
stroke, kidney diseases, stomach diseases, arthritis or
rheumatism, and asthma, dened based on whether a
doctor had informed the participants of having these
diseases.
Statistical analysis
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 pro-
portion 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 sup-
plementary material online).
Cox proportional hazards regression models were used
to calculate HR [95% CI] for the association between
ACE, physical pain, and depressive symptoms. ree
models progressively revealed the correlations between
ACE, physical pain, and depressive symptoms, compar-
ing HR before and after adjusting for confounding fac-
tors. e eects of combinations of ACE and physical
pain on depressive symptoms were further stratied. To
assess the mediating role of physical pain in the relation-
ship between ACE and depressive symptoms, mediation
analysis was conducted. Indirect, direct, and total eects
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 causa-
tion. Secondly, continuous ACE scores and the number
of pain sites were used instead of categorical ACE and
pain intensity in the primary analysis. irdly, based on
the results of the Cox regression models, variables with
statistical signicance were included, and those with
over 5% missing data were excluded. Bayesian network
models were used to visually demonstrate the interrela-
tions between factors inuencing depressive symptoms,
further verifying the association between ACE, physical
pain, and depressive symptoms.
A two-sided P-value of < 0.05 was considered statisti-
cally signicant. Analyses were conducted using R sta-
tistical 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.
Results
Participant characteristics
e 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 pub-
lished as supplementary material online). As indicated
in Table1, compared to those without depressive symp-
toms, 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.
Adverse childhood experiences and physical pain and
depressive symptoms
Table 2 displays the associations between ACE, physi-
cal 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 signicantly
increased risk of developing depressive symptoms. e
HR (95% CI) before and after adjusting for confound-
ers 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 signicantly increased risk
of developing depressive symptoms, with an adjusted HR
(95% CI) of 2.020 (1.630–2.505).
Sensitivity analyses
Considering the potential for reverse causality, this study
excluded participants who developed depressive symp-
toms within two years of recruitment and then reana-
lyzed using Cox regression. As illustrated in Fig. 2, the
associations between ACE, physical pain, and depressive
symptoms remained. To address collinearity issues, con-
tinuous 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 analy-
sis. 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 interrela-
tions among factors inuencing 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
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Bao and Ma BMC Psychiatry (2024) 24:947
Characteristics Depressive symptoms p Value
No (n,1745) Yes (n,2095)
Age, mean (SD) 57.47 (7.85) 58.49(8.68) < 0.001
Sex, n (%) < 0.001
Male 992 (56.85) 913 (43.58)
Female 753 (43.15) 1182 (56.42)
Residents, n (%) < 0.001
Rural 886 (50.77) 1183 (56.47)
Urban 859 (49.23) 912 (43.53)
Education, n (%) < 0.001
Primary school and below 924 (52.95) 1430 (68.26)
Secondary school and above 821 (47.05) 665 (31.74)
Marital status, n (%) 0.006
Single 103 (5.90) 172 (8.21)
Not single 1642 (94.10) 1923 (91.79)
BMI, n (%) 0.014
Normal 883 (50.60) 1063 (50.74)
Underweight 54 (3.10) 108 (5.16)
Overweight 567 (32.49) 650 (31.03)
Obesity 241 (13.81) 274 (13.08)
Smoking, n (%) < 0.001
No 972 (55.70) 1333 (63.63)
Yes 773 (44.30) 762 (36.37)
Drinking, n (%) < 0.001
No 1057 (60.57) 1416 (67.59)
Yes 688 (39.43) 679 (32.41)
ADL, n (%) < 0.001
No 806 (46.19) 1255 (59.90)
Yes 20 (1.15) 41 (1.96)
NA 919 (52.66) 799 (38.14)
IADL, n (%) < 0.001
No 1681 (96.33) 1952 (93.17)
Yes 64 (3.67) 143 (6.83)
Social activity, n (%) < 0.001
No 693 (39.71) 1045 (49.88)
Yes 1052 (60.29) 1050 (50.12)
Exercise, n (%) < 0.001
No 44 (2.52) 96 (4.58)
Low-intensity 157 (9.00) 169 (8.07)
Moderate-intensity 271 (15.53) 275 (13.13)
High-intensity 272 (15.59) 400 (19.09)
NA 1001 (57.36) 1155 (55.13)
Number of chronic diseases, mean (SD) 1.01 (1.18) 1.21 (1.26) < 0.001
Number of ACE, mean (SD) 3.25 (1.49) 3.74 (1.66) < 0.001
Number of ACE, n (%) < 0.001
< 4 1073 (61.49) 1031 (49.21)
≥ 4 672 (38.51) 1064 (50.79)
Pain, n (%) < 0.001
No 1486 (85.16) 1512 (72.17)
Yes 259 (14.84) 583 (27.83)
Pain degree, n (%) < 0.001
No 1486 (85.16) 1512 (72.17)
Mild 106 (6.07) 193 (9.21)
Moderate 85 (4.87) 208 (9.93)
Table 1 Comparison of baseline characteristics between participants with and without depressive symptoms
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Bao and Ma BMC Psychiatry (2024) 24:947
physical pain scores were high, the probability of middle-
aged and elderly individuals suering from depressive
symptoms was 76.70% (see Figure S2 published as sup-
plementary material online).
Mediation eects
e results of the mediation analysis are shown in Fig.3.
We found that physical pain partially mediated the
association between ACE and depressive symptoms.
e intensity of pain explained 7.48% of the association
between ACE and depressive symptoms, while the num-
ber of pain sites accounted for 7.86%. Subgroup analy-
ses by type of residence revealed that this mediating
eect persisted in both urban and rural middle-aged and
elderly populations (see Figure S3 and Figure S4 pub-
lished as supplementary material online). However, the
mediation eect was relatively increased in urban popu-
lations and decreased in rural populations.
Table 2 Relationship between adverse childhood experiences, Physical Pain and New-onset depressive symptoms over 9 years of
follow-up
Characteristics Reference New-onset depressive symptoms
HR (95% CI) aHR (95% CI) b
Model 1
Number of ACE Low (< 4)
High (≥ 4) 1.439 (1.319–1.570) 1.379 (1.266–1.503)
Model 2
Pain degree No
Mild 1.455 (1.252–1.690) 1.275 (1.094–1.486)
Moderate 1.671 (1.445–1.932) 1.418 (1.209–1.665)
Severe 1.680 (1.441–1.960) 1.438 (1.235–1.673)
Model 3
Number of ACE* Pain degree Low* No
Low* Mild 1.486 (1.189–1.858) 1.286 (1.027–1.610)
Low* Moderate 1.766 (1.436–2.172) 1.464 (1.184–1.741)
Low* Severe 1.670 (1.330–2.098) 1.379 (1.093–1.741)
High* No 1.440 (1.301–1.595) 1.385 (1.253–1.533)
High* Mild 1.897 (1.549–2.323) 1.738 (1.414–2.135)
High* Moderate 2.145 (1.750–2.629) 2.018 (1.638–2.486)
High* Severe 2.264 (1.838–2.790) 2.020 (1.630–2.505)
Abbreviati ons: HR, hazard rati o; CI, condence interva l; ACE, advers e childhood exper iences
a indicates that no inuencing factors have been included
b adjusted fo r age, sex, residents, education , marital status, BMI, smoking, drinking, AD L, IADL, social activity, exercise, number of chro nic diseases, Cystatin C, high
density lipoprotein cholesterol
Characteristics Depressive symptoms p Value
No (n,1745) Yes (n,2095)
Severe 68 (3.90) 182 (8.69)
Number of pain sites, mean (SD) 0.42 (1.33) 1.04 (2.28) < 0.001
Cystatin C (mg/l), mean (SD) < 0.001
Normal 968 (55.47) 1117 (53.32)
Low 15 (0.86) 15 (0.72)
High 236 (13.53) 400 (19.09)
NA 526 (30.14) 563 (26.87)
CRP (mg/l), mean (SD) 2.18 (5.05) 2.34 (5.69) 0.379
WBC (1000), mean (SD) 6.11 (2.04) 6.11 (1.96) 0.913
TG (mg/dl), mean (SD) 136.38 (113.46) 133.91 (115.88) 0.507
HDL (mg/dl), mean (SD) 48.37 (15.98) 50.03 (16.22) 0.002
LDL (mg/dl), mean (SD) 114.07 (37.69) 114.09 (38.63) 0.987
GLU (mg/dl), mean (SD) 107.51 (38.37) 107.24 (35.56) 0.820
Abbreviati ons: SD, standard deviat ion; BMI, body mass ind ex; ADL, activ ities of daily living; NA , Not Available; IADL, i nstrumental acti vity of daily livin g; ACE, adverse
childhood experiences; CRP, C-reactive protein; WBC, white blood cell; TG, Total Cholesterol (mg/dl); HDL, high density lipoprotein cholesterol; LDL, low density
lipoprotein cholesterol; GLU, glucose
Table 1 (continued)
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Bao and Ma BMC Psychiatry (2024) 24:947
Discussion
is study explored the association between ACE, physi-
cal pain, and depressive symptoms in middle-aged and
older adults in China. It further analyzed the mediat-
ing role of the number of pain locations and the inten-
sity of physical pain in the relationship between ACE
and depression. e results indicated that both ACE and
physical pain were signicantly associated with a higher
risk of depressive symptoms, with the risk positively cor-
related with the intensity of physical pain. Examination
of the mediating eects 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 eect being more pronounced in
urban middle-aged and elderly populations.
ACE and physical pain were identied as risk factors for
depressive symptoms in middle-aged and older adults,
aligning with ndings from previous studies. A study in
Germany during the Covid-19 pandemic identied ACE
as a signicant predictor of increased depressive symp-
toms, suggesting that individuals with ACE might be
at risk for mental health issues during the current and
potential future pandemics [15]. e UK’s aging longitu-
dinal study conrmed that both ACE and polygenic sus-
ceptibility to major depression are associated with higher
depressive symptoms, and the combined eect of ACE
and polygenic susceptibility further increases the risk of
depression [16]. Previous research has shown that physi-
cal pain often co-occurs with depressive symptoms, sug-
gesting a bidirectional association [17, 27–30]. 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 associa-
tion between ACE and depressive symptoms. erefore,
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 preven-
tion and control of depressive symptoms. Additionally,
the Bayesian network showed that gender is a common
inuencing factor for both ACE and the intensity of
physical pain, with physical pain not only directly aect-
ing depressive symptoms but also inuencing depressive
symptoms through pathways including chronic diseases
and social participation.
e internal mechanisms linking ACE and physical
pain with depressive symptoms remain unclear. Com-
pared to normal individuals, those with high ACE scores
experience more physical and psychological abnormali-
ties during childhood, which may lead to physical pain in
Fig. 2 Relationship between adverse childhood experiences, physical pain and new-onset depressive symptoms during the period 2013–2020. Abbre-
viations: HR, hazard ratio; CI, condence 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
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Bao and Ma BMC Psychiatry (2024) 24:947
adulthood and a more closed and vulnerable psychologi-
cal state. Biologically, chronic physical pain and depres-
sive symptoms may share common neural circuits and
brain modulators [31, 32]. Furthermore, research sug-
gests that chronic inammation is a risk factor for depres-
sion, and both ACE and physical pain are associated
with some level of inammation [33–37]. Longitudinal
studies and meta-analyses evaluating evidence suggest
that stress and immune system dysregulation due to
ACE exposure are signicantly associated with elevated
inammatory biomarkers, with a mechanophysiological
response to trauma [38]. Long-term inammation can
cause peripheral sensitization, leading to hyperalgesia
and chronic generalized pain [39]. erefore, it is crucial
to pay attention to the mental health of individuals with
ACE who suer from physical pain. China’s aging popu-
lation is deepening, and the development of community
health service centers is becoming more and more com-
prehensive, 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].
is study has several signicant 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. Sec-
ondly, the extended period of follow-up and the applica-
tion of multiple imputation methods further ensure the
accuracy of the causal relationships. Finally, multiple dif-
ferent sensitivity analyses enhance the reliability of our
results.
e study also has limitations. Firstly, ACE was mea-
sured 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.
Conclusions
In this cohort study, we found that both ACE and physi-
cal pain were associated with a higher risk of develop-
ing 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 experi-
ences in childhood can have long-term negative eects
Fig. 3 Eect 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.
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Page 9 of 10
Bao and Ma BMC Psychiatry (2024) 24:947
on mental health. Focusing on physical pain as a pheno-
typic factor may help mitigate these eects. Importantly,
the development and promotion of physical pain screen-
ing and intervention measures within communities may
enhance the physical and mental health of the middle-
aged and elderly population with ACE.
Supplementary Information
The online version contains supplementary material available at h t t p s : / / d o i . o r
g / 1 0 . 1 1 8 6 / s 1 2 8 8 8 - 0 2 4 - 0 6 3 1 2 - y .
Supplementary Material 1
Acknowledgements
This analysis used data or information from the CHARLS. The authors thank all
sta and participants of this study for their important contributions.
Author contributions
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 oered constructive feedback.
Funding
None.
Data availability
All data and materials are available from the corresponding author on
reasonable request.
Declarations
Ethics approval and consent to participate
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.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Received: 22 August 2024 / Accepted: 18 November 2024
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