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Association of childhood maltreatment and adverse lifetime experiences with post-injury psychopathology: evidence from the China Severe Trauma Cohort

BMC Medicine volume 23, Article number: 29 (2025) Cite this article

Abstract

Background

Adverse life experiences have been associated with increased susceptibilities to psychopathology in later life. However, their impact on psychological responses following physical trauma remains largely unexplored.

Methods

Based on the China Severe Trauma Cohort, we conducted a cohort study of 2937 patients who were admitted to the Trauma Medical Center of West China Hospital between June 2020 and August 2023. Adverse life experiences, including childhood maltreatment (5 subtypes, measured by Childhood Trauma Questionnaire-Short Form) and adverse lifetime experiences (17 subtypes, by Life Events Checklist) were assessed. Generalized linear mixed models were used to examine the associations of childhood maltreatment and adverse lifetime experiences with symptoms of psychopathology measured at multiple time-points after the index injury (i.e., at recruitment, 1-, 3-, 6-, and 12-month follow-ups), adjusted for important confounders. We further stratified the analyses by level of genetic predisposition to a given psychological symptom quantified by polygenic risk score (PRS) based on publicly available GWAS summary statistics. Mediation analyses were performed to assess the role of adverse lifetime experiences in connecting childhood maltreatment and post-injury psychopathology.

Results

The mean age of participants was 47.95 years with a predominance of males (61.39%). During the whole follow-up period, the incidence of symptoms of stress-related disorders, anxiety, and depression was 13.86%, 29.89%, and 36.57%, respectively. We observed associations between the cumulative number of those studied adversities and increased risk of post-injury psychopathology, particularly stress-related disorder (odds ratio [OR] = 2.78, 95% confidence interval [CI] 1.87–4.12 for ≥ 2 vs no childhood maltreatment; 2.65 [1.67–4.20] for ≥ 4 vs 0–1 adverse lifetime experiences). By subtype, positive associations were observed for most studied life adversities, with the most pronounced estimates for childhood emotional abuse (ORs = 1.71–2.52) and lifetime life-threatening illness/injury (ORs = 1.87–2.89). We found basically comparable estimates among traumatized individuals with different PRSs for studied psychopathology. Moreover, adverse lifetime experiences may partially (mediation proportion: 22.52–27.48%) explain the associations between various childhood maltreatment and post-injury psychopathology.

Conclusions

Both childhood maltreatment and adverse lifetime experiences were associated with post-injury psychopathology, irrespective of genetic susceptibility. Such findings highlight the importance of close surveillance and timely psychological interventions for injury patients with adverse life experiences.

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Background

Worldwide, trauma injury is the leading cause of disability-adjusted life years in individuals aged 10–49 years [1], as well as the top cause of death among the economically productive age group (i.e., < 45 years) [2]. It has also been reported to account for 7.0% of total deaths and 10.0% of all-cause disability-adjusted life years in China [3]. Besides direct impacts on physical health [3, 4], increased attention has been paid to post-injury psychopathology [5, 6], such as depression and anxiety [6], which may subsequently contribute to poorer wound recovery [6], long-term disability [7], social and work functional impairment [5, 6], cognitive disability [8], undermined life satisfaction [6], and even suicidality [5].

Despite substantial sequelae, the understanding of risk factors associated with post-injury psychopathology remained limited, with few established but unmodifiable characters such as the type of injury, injury severity, and socioeconomic status (SES) [5, 6]. With variations by country, the worldwide prevalence of lifetime trauma exposure was estimated to be 24% ~ 85% [9], and the data from Chinese community-dwelling surveys were 67.1%−88.7% [10, 11], leading to a large proportion of the population with such an issue. Additionally, it has been proposed that prior trauma-related experiences might accumulatively exaggerate psychological reactions to the next trauma (i.e., the “stress accumulation model” [12, 13]) through possibly increased baseline activity level of the sympathetic nervous system and hypothalamus-pituitary-adrenocortical (HPA) axis [14]. It is therefore plausible that adverse early life experiences, as well as the accumulation of adversity across the lifespan, may jointly increase individuals’ susceptibility to post-trauma psychopathology after trauma injury [5, 14,15,16,17,18,19]. Nevertheless, studies concerning on adverse life experiences prior to post-injury psychopathology have primarily discussed the associations between childhood adversities (e.g., childhood maltreatment [15, 18]) and subsequently one specific type of psychopathology (e.g., depression) [16, 19], with methodological shortcomings such as small sample size [15, 19], cross-sectional data [17, 19], and inadequate control of confounders [14, 19]. Data from prospective cohorts with detailed information on childhood maltreatment and other trauma experiences, as well as longitudinal measures of various psychological symptoms at multiple post-trauma time-points are highly warranted to elucidate the relationships.

In addition, the role of genetic architectures in the development of various psychiatric disorders, including posttraumatic stress disorder (PTSD), has been revealed in previous genome-wide association studies (GWASs) [20]. Recent research also suggested the predictive role of genetic liability (e.g., polygenic risk scores [PRS]) of major depressive disorder on PTSD symptoms after brain trauma injury [21, 22], implying complex interactions between general psychiatry disorders and post-trauma psychopathology. However, no prior study assessed the association of childhood adversities with post-injury psychopathology in the context of genetic background, leading to further uncertainties of interested associations (i.e., childhood maltreatment and post-trauma psychopathology in later life).

Leveraging data from the China Severe Trauma Cohort (CSTC) [23], which collected enriched information on adverse life experiences (i.e., childhood maltreatment and adverse lifetime experiences), details of trauma injury that led to hospitalization, lifestyles, and somatic and psychiatric history, with prospective psychological assessments scheduled at multiple time points within 12 months after the injury, we conducted a cohort study to assess the associations of life adversities that occurred at different periods with various post-injury psychopathology. In addition, benefiting from the availability of individual-level genotyping data in the CSTC database, our study, for the first time, explored whether the observed associations could be modified by individuals’ genetic predispositions to psychopathology. Furthermore, considering the complexity and interplay between those studied advertises [16, 24], we made additional efforts on estimating the mediating proportions of adulthood adverse experiences on the link from childhood maltreatment to post-injury psychopathology. Thus, the findings of our study might provide a valuable temporal perspective on the potential influence of lifetime adverse experiences on the occurrence of different types of post-injury psychopathology in the Chinese population, aiding in the identification of psychologically vulnerable patients after physical trauma for tailored and timely interventions.

Methods

Study design

The study was based on the ongoing CSTC, which recruited patients aged 12–80 years who underwent sudden and serious injuries within 3 months and were admitted to the Trauma Center of West China Hospital since June 1st, 2020. Details of the CSTC have been described elsewhere [23] (cohort website: https://biomedbdc.wchscu.cn/JoylabErasePM/hx-portals/#/queue/02/index.). In brief, at the time of hospital admission, baseline data on sociodemographic characteristics, lifestyle, adverse life experiences, and details of the index injury (i.e., the trauma injury that led to this hospitalization) were collected through face-to-face interviews using touchscreen questionnaires (implanted in the Cohort Data Collection and Management System [CD-CMS] [Version 1.0, Build 2021SR0484324. ©West China Hospital, Sichuan, China]). Follow-ups for those participants were scheduled at 1, 3, 6, and 12 months after recruitment via phone calls or online questionnaires sent through the official WeChat account. We measured trauma-related psychological symptoms using well-established scales (see below “ascertainment of post-injury psychopathology” for details) both at recruitment and each follow-up point. In addition, at baseline, participants were invited to donate 11 ml blood samples within 24 h after recruitment. We also linked questionnaire data to the electronic medical records of West China Hospital, to obtain information about medical interventions and laboratory test results, and plan to derive long-term health-related consequences (i.e., diagnoses of subsequent diseases, and mortality) from established administrative databases. CSTC study was featured by its stringent data quality control process, which primarily included a 14-day training program for full-time data collectors and multistep quality checks to ensure data accuracy [23]. Until August 2023, among 4115 eligible patients, a total of 3607 were successfully enrolled in the cohort (response rate: 87.65%). The rate for blood sample donation was 93.90% (3387/3607).

In the present study, we included 3060 adults (i.e., age ≥ 18 years) who experienced the index injury within 2 weeks and were recruited from the CSTC between June 2020 and August 2023. We excluded participants who had a self-reported history of mental illness (n = 107) or who withdrew their informed consent (n = 12). We further removed individuals without data on the studied adversities, leaving 2930 participants in the analytic cohort for childhood maltreatment and 2937 participants in the cohort for adverse lifetime experiences analysis (Fig. 1). The follow-up rates, accounting for the proportion of participants who responded to at least one psychological assessment at each follow-up, were 79.78–90.44% among individuals included in childhood maltreatment analyses, and 79.64–90.36% among those in the analyses of adverse lifetime experiences. In addition, the genetic analyses included 2072 patients whose available genotyping data passed quality checks (Fig. 1).

Fig. 1
figure 1

Study design

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Written informed consent was obtained from all participants before the baseline data collection. The CSTC and the present study were approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University (2020.243).

Measurement of adverse life experiences

At recruitment, adverse life experiences (i.e., childhood maltreatment and adverse lifetime experiences) were measured using well-validated scales [23]. Specifically, the 28-item Childhood Trauma Questionnaire-Short Form (CTQ-SF) with five subscales (i.e., emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect), was used to assess childhood maltreatment [25]. Each subscale ranged from 5 to 25, and we used established cut-off scores for defining the presence of such a subtype [26, 27]. The cumulative number of childhood maltreatment was also calculated.

Adverse lifetime experiences were assessed with the Life Events Checklist (LEC), which had 17 domains of self-reported potentially traumatic experiences throughout an individual’s lifetime [28]. The cumulative number of adverse lifetime experiences was calculated based on identified exposure (i.e., “happened to me,” “witnessed it,” or “learned about it”) [28], with a limited time happening before the present trauma experience. Detailed information on the scales is shown in the Additional file 1: Table S1.

Ascertainment of post-injury psychopathology

We considered post-injury psychopathology as the presence of symptoms of stress-related disorder, anxiety, and depression, which were determined by scores on corresponding psychological scales (Additional file 1: Table S1) measured at recruitment and each follow-up point (1, 3, 6, and 12 months) [23]. Symptoms of anxiety and depression were measured by the 7-item Generalized Anxiety Disorder Scale (GAD-7) [29], and the 9-item Patient Health Questionnaire-9 (PHQ-9) [30], respectively, with a cut-off point for caseness of ≥ 5. In a sub-analyses for assessing the risks associated with varying degrees of anxiety and depression, we re-classified the GAD-7 and PHQ-9 scores into three categories: normal (0–4), mild (5–9), and moderate to severe (≥ 10). In line with our previous work [23], stress-related disorder was defined as experiencing a probable acute stress disorder (i.e., a dissociation cluster score of ≥ 9 and a total score ≥ 28 encompassing reexperiencing, avoidance, and arousal clusters, measured by the 19-item Acute Stress Disorder Scale [31]) at recruitment and/or probable posttraumatic stress disorder (PTSD, endorsing at least moderate levels for 1 intrusion symptom, 1 avoidance symptom, 2 negative alterations in cognitions and mood, and hyperarousal symptoms, according to the 20-item Posttraumatic Stress Disorder Checklist for DSM-5 [PCL-5]), at any follow-up. All scales had good test–retest reliability and validity in the Chinese population (see details in previous cohort profile [23]).

Covariates

Information on demographic characteristics (i.e., age, sex, and ethnicity), SES (i.e., marital status, education attainment, occupation, and monthly family income), lifestyles (i.e., body mass index [BMI, calculated as weight in kilograms divided by height in meters squared], status of smoking, drinking, and substance use), and the condition of the index injury (i.e., trauma causes [traffic accident, exploration, high fall, hitting by objectives, machine-related accident, fall/wrench, cutting, and other], severity of trauma assessed by doctors/nurses [rated as low (the rating score of severity: 1–2), moderate (3), and high (4–5)], and days since the index injury) were collected at the baseline interview and well documented in the CD-CMS.

Genetic data and assessment on genetic predisposition to post-injury psychopathology

Among the 2937 included participants, DNA was successfully extracted from 2084 blood samples. Then, genotyping was performed by the WeGene Clinical Laboratory in Shenzhen, China, using the Illumina Infinium Chinese Genotyping Array (WeGene V3) which covers approximately 700k variants. After the quality control and imputation using the Rapid Imputation and Computational Pipeline for GWAS [32], 2072 eligible samples with 9,955,686 single-nucleotide polymorphisms (SNPs) on autosomes remained. We additionally applied a post-imputation quality control, leaving a final set of 6,412,640 SNPs from 2072 samples for the genetic analyses of the present study (see more detailed steps in the Additional file 1: Supplementary method) [32, 33].

We calculated PRS, serving as a proxy of an individual’s genetic susceptibility to each studied psychopathology, based on publicly available GWAS summary statistics (i.e., effect sizes and standard errors for the variants) for the corresponding psychological disorder [20, 34, 35] using the least absolute shrinkage and selection operator (LASSO) approach [36]. Especially, the analysis was restricted to SNPs available in both the base dataset (e.g., GWAS summary statistics for SRD from iPSYCH [34]) and the target dataset (i.e., CTSC genotyping data) after removing ambiguous SNPs (i.e., symmetric/strand-ambiguous A/T, T/A, C/G, and G/C SNPs). We demonstrated positive associations between standardized PRSs for each psychopathology and the corresponding phenotype in CTSC (measured by logistic regression models, adjusted odds ratio [OR] = 1.15, 95% confidence interval [CI] [1.01–1.31] for a unit [i.e., standard deviation] increase in the PRS of stress-related disorder [n = 2072]; OR = 1.03, 95% CI [0.94–1.14] for anxiety PRS [n = 2040]; OR = 1.10, 95% CI [1.00–1.21] for depression PRS [n = 2041]).

Statistical analysis

We first compared the distribution of baseline characteristics across different levels of adverse life experiences using ANOVA or Kruskal–Wallis tests (for continuous variables), or chi-square tests (for categorical variables). To assess the association of childhood maltreatment and adverse lifetime experiences, treated as cumulative number (i.e., as continuous and ordinal [number = 0, 1, ≥ 2 childhood maltreatment; 0–1, 2–3, and ≥ 4 adverse lifetime experiences]) or subtypes (5 and 17 subtypes for childhood maltreatment and adverse lifetime experiences, respectively), with psychopathology at recruitment (i.e., with 2 weeks after the injury) and each follow-up (at 1, 3, 6, and 12 months after the recruitment), we calculated the ORs and 95% CIs using logistic regression, adjusted for age at recruitment (as continuous variable), sex (male or female), ethnicity (Han or others), marital status (married, unmarried, divorced/widowed, or unknown), educational attainment (collage and above, junior school, senior/secondary school, elementary and lower, or unknown), occupation (full-time job, part-time or unemployed, or unknown), monthly family income (≤ 3000, 3001–6000, 6001–9000, ≥ 9001 Yuan), BMI (< 18.5, 18.5–25, 25–30, ≥ 30 kg/m2), smoking (yes, no, or unknown), alcohol (yes, no, or unknown), substance use (yes, no or unknown), trauma causes (fall/wrench, traffic accident, or other), severity of trauma assessed by doctors/nurses (low, moderate, high, or unknown), and days since the index injury (as continuous variable).

Taking into account post-injury psychopathology measured at multiple time-points together, we constructed generalized linear mixed models (GLMMs) with random intercepts to each participant [37] to examine the associations of adverse life experiences with any post-injury psychopathology, with the same covariates as stated above. To explore the possible modification effect of age, sex, and the condition of the present trauma, we conducted subgroup analyses by sex (male and female), age (< 45 and ≥ 45 years) [38], trauma causes (fall/wrench, traffic accident and other), and severity of trauma (low, moderate and high). Importantly, we also performed separate analyses for individuals with low (< 1st tertile) and high (> 2nd tertile) PRS levels [39, 40], to clarify if the observed associations could be differed by varied genetic susceptibilities to psychopathology. To assess the associations with different severities of anxiety and depressive symptoms, we recalculated estimates for mild (5–9) and moderate to severe (≥ 10) cases separately.

Furthermore, with the assumption that most lifetime adversities captured by LEC actually occurred after childhood and thereby could be on the pathway from identified childhood maltreatment to post-injury psychopathology, we conducted mediation analyses where the mediation proportions of each adverse lifetime experience (as ordinal variable) were assessed for any and subtypes of childhood maltreatment that associated with post-injury psychopathology, using “CMAverse” package based on a weighting-based approach [41, 42] (adjusted for age, sex and ethnicity and bootstrap setting of 1000 times).

In the sensitivity analyses, we repeated the analyses of PRS stratification by redefining the genetic susceptibility level using the median of the corresponding PRS (“<median” for low and “≥median” for high). Also, to test if the observed associations were heavily driven by participants with shorter follow-up periods, we re-run the GLMM analyses after restricting to participants with a follow-up of more than 6 months (n = 2250 for the childhood maltreatment cohort, n = 2253 for the adverse lifetime experiences).

All analyses were performed with R software (version 4.10). A two-sided P value < 0.05 was considered statistically significant.

Results

The mean (standard deviation [SD]) ages of the participants in the analyses of childhood maltreatment (n = 2930) and adverse lifetime experiences (n = 2937) were 47.93 (15.47) and 47.95 (15.48) years, respectively, with a predominance proportion of males (61.40% and 61.39% in the two groups) and Han ethnicity (96.42%) (Table 1). The mean time since the index injury was 3.79 (3.16) and 3.80 (3.16) days, respectively. In brief, while factors related to lifestyles and injury causes were comparable, participants exposed to higher levels of childhood maltreatment were more likely to be older (mean age = 52.07 for ≥ 2 vs. 44.49 years for 0 childhood maltreatment, P < 0.001), married (84.53% vs. 75.97%, P < 0.001), but having lower SES (presenting as lower proportions of individuals with collage and above education [12.27% vs. 29.07%] and ≥ 9001 Yuan monthly household income [18.13% vs 27.79%], all P < 0.001). In contrast, with similar marital status, SES, and age at recruitment, participants with more adverse lifetime experiences were more likely to be male (72.68% for ≥ 4 vs. 52.67% for 0–1 adverse lifetime experiences, P < 0.001), current drinkers (25.15% vs. 14.23%, P < 0.001) or smokers (25.39% vs. 15.00%, P < 0.001) (Table 1).

Table 1 Baseline characteristics of study participants
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In the cohort for childhood maltreatment analyses, we observed the highest incidence of post-injury psychopathology at recruitment (i.e., within 2 weeks of the index injury, 9.59%, 20.61%, and 25.19% for stress-related disorder, anxiety, and depression, respectively), which then declined over time, particularly within the first month of follow-up (Fig. 2). According to the fully adjusted logistic regression models, we observed an elevated risk of various post-injury psychopathology measured at each time point among patients with higher exposure levels of the cumulative number of childhood maltreatment (Fig. 2), with the most pronounced associations for the period more adjacent to the index injury (e.g., ORs = 1.39–1.79 and 1.90–2.27 for 1, and ≥ 2 childhood maltreatment at recruitment, respectively). Analyses on subtypes of childhood maltreatment revealed basically comparable results (Additional file 1: Fig. S1, in which the gradient of the red color indicates the magnitude of the associations). However, sexual abuse and emotional abuse/neglect gained stable or increasing trends of relative risk over time, whereas the associations for physical abuse and neglect seemed attenuated by time (Additional file 1: Fig. S1). We observed similar phenomena for adverse lifetime experiences, presenting as increased ORs for participants with a higher cumulative number of adverse lifetime experiences (Fig. 2), particularly within 2 weeks after injury (ORs = 1.59–1.68 and 2.40–2.72 for 2–3, and ≥ 4 adverse lifetime experiences, respectively). By subtype, life-threatening illness/injury, captivity, and sudden violent death (witnessed or learned about) were the top three with the highest estimates (Additional file 1: Fig. S1). Again, those adversities, which were traditionally considered desperate (i.e., sexual assault, assault with a weapon, and combat or war zone), showed prolonged effects on risk of post-injury psychopathology (i.e., notable estimates at the 12-month follow-up).

Fig. 2
figure 2

The association of childhood maltreatment and adverse lifetime experiences with post-injury psychopathology at different time points

No., number; OR, odd ratio; CI, confidence interval aORs and 95% CIs were derived from logistic regressions, adjusted for age, gender, ethnicity, marital status, education attainment, occupation, monthly family income, body mass index, smoking, alcohol, substance use, trauma causes, severity of this trauma, and days since index injury

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During the whole follow-up period, the incidence of symptoms of stress-related disorders, anxiety, and depression was 13.79% (404/2930), 29.83% (874/2930), and 36.52% (1070/2930), respectively, in the cohort of childhood maltreatment analyses, and 13.86% (407/2937), 29.89% (878/2937), and 36.57% (1074/2937) in the cohort of adverse lifetime experiences analyses (Fig. 3). Results derived from the fully adjusted GLMMs corroborated those from logistic regression models (Fig. 3), revealing significant associations of childhood maltreatment and adverse lifetime experiences with post-injury psychopathology, in a dose–response manner and with similar magnitudes for all specific psychopathology (i.e., stress-related disorders, anxiety and depression, see results of the partly adjusted models in the Additional file 1: Table S2). By subtype of adversity, the most pronounced estimates were obtained for emotional abuse (ORs = 1.71–2.52) and emotional neglect (ORs = 1.53–2.37) among the studied childhood maltreatment, and life-threatening illness/injury (ORs = 1.87–2.89) and sudden violent death (witnessed or learned about, ORs = 1.66–1.96) among studied lifetime adversities (Fig. 4). Subgroup analyses indicated slightly higher, albeit not significantly, risk elevations of post-injury psychopathology among younger (i.e., < 45 years at recruitment), whilst comparable estimates were retrieved when analyzing by sex, trauma causes, and severity of trauma rated by doctors/nurses (Additional file 1: Fig. S2–S3). Likewise, by PRS level for each studied psychopathology, we found basically similar estimates among individuals with low or high genetic predisposition (Table 2). We also found slightly higher but basically comparable estimates for mild and moderate-to-severe symptoms (Additional file 1: Table S3).

Fig. 3
figure 3

The association of childhood maltreatment and adverse lifetime experiences with post-injury psychopathology, based on generalized linear mixed models

No., number; OR, odd ratio; CI, confidence interval. aThe mean (standard deviation, SD) number of adverse life experiences (i.e., childhood maltreatment and adverse lifetime experiences) in individuals with/without the corresponding post-injury psychopathology. bORs and 95%CIs were derived from generalized linear mixed models, adjusted for age, gender, ethnicity, marital status, education attainment, occupation, monthly family income, body mass index, smoking, alcohol, substance use, trauma causes, severity of this trauma, and days since index injury

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Fig. 4
figure 4

The association of subtypes of childhood maltreatment and adverse lifetime experiences, with post-injury psychopathology, based on generalized linear mixed models

OR, odds ratio. aORs were derived from logistic regressions, adjusted for age, gender, ethnicity, marital status, education attainment, occupation, monthly family income, body mass index, smoking, alcohol, substance use, trauma causes, severity of this trauma, and days since index injury

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Table 2 The association of childhood maltreatment and adverse lifetime experiences with post-injury psychopathology, stratified by polygenic risk score (PRS) level for the corresponding psychopathology
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The results of the mediation analyses noted significant mediating proportions of adverse lifetime experiences (as ordinal variable) on the associations of any (22.52–27.48%) and some subtypes (i.e., 13.86–21.95%, 29.55–55.61%, and 27.92–36.28% for emotional abuse, physical abuse, and physical neglect, respectively) of childhood maltreatment with all studied post-injury psychopathology (Table 3).

Table 3 The mediation proportion of adverse lifetime experience on the association of childhood maltreatment and post-injury psychopathology
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In sensitivity analyses, the observed associations remained largely identical after changing the grouping strategy of PRS stratification analysis (Additional file 1: Table S4), as well as when restricting to participants with follow-ups of more than 6 months (Additional file 1: Fig. S4).

Discussion

To the best of our knowledge, this is the first prospective cohort study to explore the associations of adverse lifespan experiences with various post-injury psychopathologies in a Chinese population, using both individual-level phenotypic and genotypic data. Our study clearly demonstrated that individuals with prior exposure to childhood maltreatment or lifetime adversities were at increased risk of developing both short- and long-term psychopathology after experiencing severe injury. Importantly, such associations were constantly observed among individuals with different age, sex, injury causes, and severity, as well as those with different genetic predispositions to psychiatry disorders, highlighting a general need for close surveillance or intervention for psychopathology among injury patients with adverse life experiences. Moreover, our study analyzed how lifetime adversity, primarily occurring in adulthood, may mediate the association between childhood maltreatment and post-injury psychopathology, indicating that adulthood adversities could contribute to approximately one-fourth of the observed associations. Such findings underscore the interplay and complexity between lifespan adversities, and aid interpretations of the profound influences of early life experiences, possibly through both cumulative stressors and stress-related biological alternations, on increased susceptibility to post-injury psychopathology in later life.

Despite the lack of comparable data from studies with similar designs, our findings gained support from some prior investigations, mostly with a small sample size, indicating individuals with early-life adversities might pose an excess risk of adverse psychological consequences after experiencing a subsequent traumatic event. In a US cohort study of 999 patients from 29 urban emergency departments, all studied childhood maltreatment, particularly emotional abuse, was associated with a doubled relative risk of 3-month posttraumatic neuropsychiatric sequelae after a motor vehicle collision [15]. Similarly, another US prospective cohort of 713 trauma survivors suggested a notable predictive value of a history of PTSD symptoms induced by prior life adversities on 6-month PTSD after being admitted to emergency departments for the current trauma [14]. However, some cross-sectional studies, such as the one conducted among the 580 aged survivors (i.e., ≥ 65) in the 2011 Japan earthquake and tsunami [19], failed to demonstrate such associations. Moreover, most existing evidence has focused exclusively on post-injury PTSD [14], or psychopathology as a whole [15], and studies with comprehensive assessments on the impacts of multiple lifespan adversities and various post-injury psychopathology were lacking. In addition, it is notable that we found the impact of these life adversities on post-injury psychopathology was broadly consistent across different genetic risk levels, which indicates that individuals with both low and high genetic susceptibility to psychiatric disorders may benefit from early screening and intervention. Although prior efforts have shown the predictive role of genetics (e.g., PRS [21] or the apolipoprotein E gene [43]) on PTSD, such findings underscore the need for an integrative approach that combines genetic, trauma-related, and other environmental factors in understanding psychological vulnerability after injury.

Although without clear explanations, several possible underlying mechanisms have been proposed for the observed associations. The “biological embedding” notion emphasizes the changes of epigenetic components [44], stress axis dysregulation [45], truncated immune response [46], and functional and structural alterations of brain structure [47] following life adversities, which may escalate over time and thus facilitate the development of psychopathology after exposure to later trauma. For instance, prior studies implied that exposure to childhood maltreatment, especially emotional abuse, was associated with NR3C1 methylation, which is in relation to HPA axis alterations and overactivity of the cortisol awakening response, and thus interfaces with the pathogenesis of psychiatric disorders such as depression [48]. Consistent with this finding, our results found emotional abuse/neglect presenting as one of the most influential childhood maltreatment that poses notable and prolonged impacts on post-injury psychopathology in later life. Likewise, a meta-analysis pooling the results of 57 observational studies also demonstrated a stronger magnitude of associations between emotional abuse and major depression, than other subtypes of childhood maltreatment [49]. Similarly, human and animal studies also indicated the activated HPA axis and peripheral adaptations (e.g., suppressed cortisol metabolism and increased cortisol availability) in response to other lifetime traumatic experiences, such as life-threatening illness/injury [50]. Besides the biological reasoning, it is also plausible that undermined SES [47] and maladaptive coping strategies [19, 27] that have been linked to childhood adversities may indirectly influence individuals’ psychological responses to a subsequent injury. Indeed, a prospective study suggested a mediating role of emotional problems, hyperactivity, and prosocial behaviors in the association between emotional abuse experienced during childhood and psychopathology [27]. In addition, our finding of adverse lifetime experiences serving an important role in linking childhood maltreatment to post-injury psychopathology gained support from previous studies, indicating that childhood adversities may heighten vulnerability to further adversities and perceived burdensomeness in adulthood [13, 51, 52]. Theories such as the biological embedding of childhood maltreatment and life-course stress theories, including cumulative inequality and stress proliferation [16, 45], support this pathway. Taken together, those biosocial alternations induced and possibly accumulated by prior life adversities may affect psychological vulnerability to subsequent trauma (e.g., injury).

The present study has several strengths. First, our study benefits from the stringent quality control process and thereby high-quality and reliable data, as well as the relatively large sample size of injury patients (the largest in the Chinese population), in the CSTC database. Second, the combined use of enriched phenotypic data and individual-level genotyping data provides a unique chance to control for a wide range of important confounders and to explore the possible modification role of genetic background when analyzing the interested associations. Third, through the application of mediation analyses, we aimed to elucidate if the correlations/co-occurrence of early and late life adversities (i.e., the cumulative of traumatic events through one’s lifespan) could, to some extent, explain the elevated vulnerabilities to psychopathology when exposed to a subsequent physical injury.

The present study also has notable limitations. First, although the applied scales for collecting life adversities have been well-validated and widely used in the Chinese population [23], those retrospective measurements were inevitably subject to recall bias. Second, the old age (mean age = 47.95 years) of the CTSC participants (i.e., introversion tendency of the old Chinese generation) might contribute to underestimated exposure rates of some culturally sensitive adversities, such as sexual abuse or assault [53]. Additionally, as those scales were self-rated during a face-to-face interview process, it is possible that respondents were more prone to give socially desirable responses rather than honest ones, with the concern of embarrassment. Indeed, the prevalence of sexual abuse was much lower in our study (1.13%) than that reported in Chinese college students (5.4 ~ 20.2%) [27]. Third, it is notable that those screening scales for post-injury psychopathology were not diagnostic tools, and future studies using more precise approaches for psychological assessments are highly warranted. Last, considering that the CTSC recruited participants from a single medical center in the Southwest China area and thus lacked national representativeness, the generalizability of our findings to injury patients in other areas or the whole China needs further evaluation.

Conclusions

In conclusion, based on the prospective cohort of Chinese injury patients, our study reveals an excess risk of post-injury psychopathology among individuals exposed to childhood maltreatment or adverse lifetime experiences, irrespective of their genetic predisposition. Mediation analyses further highlight the critical role of adulthood adversities in linking childhood maltreatment to post-injury psychopathology, underscoring the long-lasting impact of trauma-related biosocial changes that which may accumulate over time. Accordingly, clinicians are encouraged to expand their assessments beyond the immediate physical trauma to consider histories of childhood maltreatment and adult adversities. Such an approach could help identify individuals at higher risk and guide the development of more comprehensive and personalized care strategies.

Data availability

Currently, the data of CSTC are not available to the public for data protection and privacy policy. However, we welcome clinicians and researchers to contact us for initiating collaborative projects. Please visit our website at https://biomedbdc.wchscu.cn/JoylabErasePM/hx-portals/#/queue/02/index for more details, and contact the corresponding author HS (songhuan@wchscu.cn) for collaboration requests.

Abbreviations

SES:

Socioeconomic status

HPA:

Hypothalamus-pituitary-adrenocortical

CSTC:

China Severe Trauma Cohort

CD-CMS:

Cohort Data Collection and Management System

CTQ-SF:

Childhood Trauma Questionnaire-Short Form

LEC:

Life Events Checklist

GAD-7:

Generalized Anxiety Disorder Scale-7

PHQ-9:

9-Item Patient Health Questionnaire-9

PTSD:

Posttraumatic stress disorder

PCL-5:

Posttraumatic Stress Disorder Checklist for DSM-5

GWAS:

Genome-Wide Association Study

SNP:

Single-nucleotide polymorphism

PRS:

Polygenic risk score

LASSO:

Least absolute shrinkage and selection operator

OR:

Odds ratio

CI:

Confidence interval

GLMM:

Generalized linear mixed model

SD:

Standard deviation

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Acknowledgements

We express our sincere thanks to all the participants and data collectors of CSTC, as well as clinicians and team members of the Biomedical Big Data Center and Department of Orthopaedics in the West China Hospital of Sichuan University for their support.

Funding

This work was supported by the National Natural Science Foundation of China (grant No. 82471535 to HS), 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (grant No. ZYYC21005 to HS, grant No. ZYJC21004 to WZ), and Postdoctoral Research Fund of West China Hospital, Sichuan University (grant No. 2024HXBH144 to SW). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Trauma Medical Center, Department of Orthopedics Surgery and Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China

    Shu Wen

  2. Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China

    Shu Wen

  3. Med-X Center for Informatics, Sichuan University, Chengdu, China

    Shu Wen, Yu Zeng, Yueyao Xu, Shishi Xu, Wenwen Chen, Wei Zhang & Huan Song

  4. Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China

    Yu Zeng, Yueyao Xu, Shishi Xu, Wenwen Chen, Wei Zhang & Huan Song

  5. Division of Endocrinology & Metabolism, West China Hospital, Sichuan University, Chengdu, China

    Shishi Xu

  6. Trauma Medical Center, Department of Orthopedics Surgery, West China Hospital, Sichuan University, Chengdu, China

    Guanglin Wang

  7. Department of Orthopedics, Orthopedics Research Institute, West China Hospital, Sichuan University, Chengdu, China

    Guanglin Wang

  8. Mental Health Center, West China Hospital, Sichuan University, Chengdu, China

    Wei Zhang

  9. Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland

    Huan Song

  10. Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden

    Huan Song

Authors
  1. Shu Wen
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  2. Yu Zeng
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  4. Shishi Xu
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  5. Wenwen Chen
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  6. Guanglin Wang
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  7. Wei Zhang
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  8. Huan Song
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Contributions

HS and SW were responsible for the study’s concept and design. YX and YZ did the data and project management. YZ and SW did the data cleaning and analysis. HS, WZ, GW, SX and WC were involved in methodology and supervision. SW, WZ, GW and HS interpreted the data. SW, YZ, YX, GW, WZ and HS had full access to and verified the underlying data. SW and HS drafted the manuscript. All coauthors revised the manuscript. All coauthors read and approved the final manuscript.

Authors’ Twitter handles

Twitter handles: @JoyLab14169974 (Joy Lab)

Corresponding authors

Correspondence to Guanglin Wang, Wei Zhang or Huan Song.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Biomedical Research Ethics Committee of West China Hospital (reference number: 2020.243). Written informed consent was obtained from all the participants.

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Not applicable.

Competing interests

The authors declare no competing interests.

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Supplementary Information

12916_2025_3861_MOESM1_ESM.docx

Additional file 1. Tables S1-S4, Figures S1-S4, and Supplementary method. Table S1 The definition of childhood maltreatment, adverse lifetime experiences, and psychopathology. Table S2 The association of childhood maltreatment and adverse lifetime experiences and post-injury psychopathology, adjusted for different covariates and based on generalized linear mixed models. Table S3 The association of childhood maltreatment and adverse lifetime experiences, with different levels of post-injury anxiety and depression. Table S4 The association of childhood maltreatment and adverse lifetime experiences with post-injury psychopathology, stratified by polygenic risk score (PRS) level (< median, and ≥ median) for the corresponding psychopathology. Fig. S1 The association of subtypes of childhood maltreatment and adverse lifetime experience with post-injury psychopathology at different time points. Fig. S1 The association of subtypes of childhood maltreatment and adverse lifetime experience with post-injury psychopathology at different time points. Fig. S2 The association of childhood maltreatment and adverse lifetime experiences, with post-injury psychopathology, stratified by age and sex. Fig. S3 The association of childhood maltreatment and adverse lifetime experiences, with post-injury psychopathology, stratified by trauma cause and severity of trauma. Fig. S4 The association of childhood maltreatment and adverse lifetime experiences, with post-injury psychopathology, restricting to participants with follow-up of more than 6 months.

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Wen, S., Zeng, Y., Xu, Y. et al. Association of childhood maltreatment and adverse lifetime experiences with post-injury psychopathology: evidence from the China Severe Trauma Cohort. BMC Med 23, 29 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12916-025-03861-1

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BMC Medicine

ISSN: 1741-7015

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