Abstract
The comorbidity of depression and overweight is a manifestation of mental-physical multimorbidity, a marker of complex healthcare needs. We sought to examine how adverse childhood experiences (ACEs) are associated with depression-overweight comorbidity in the period of adolescence and early adulthood, and the extent to which associations are sensitive to age, sex, and socioeconomic background. Using data from 4734 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, we estimated relative risk ratios (RRR) for the associations of multiple ACEs (physical, emotional, and sexual abuse, emotional neglect, being bullied, parental substance abuse, violence between parents, parental criminal conviction, parental separation, parental mental illness, or suicide) with depression only, overweight only or their comorbidity at ages 17 and 24. We tested whether associations differed by sex and socioeconomic background, indicated by parental education. Most ACEs were associated with depression-overweight comorbidity, and there was a dose–response relationship whereby a greater number of ACEs was associated with greater risk, and this continued from adolescence to young adulthood. Some ACEs associations with comorbidity appeared to be influenced by sex: at age 17, females had stronger associations for parental separation and mental health problems, and at age 24, sexual abuse had a stronger association in males. We did not find evidence that the sensitivity to ACEs varied by parental education. ACEs across childhood are associated with depression and depression-overweight comorbidity in late adolescence, which indicates their potential impact on the early manifestation of complex healthcare needs.
Introduction
Adverse childhood experiences (ACEs), such as experiences of neglect and emotional, physical, and sexual abuse, are significant risk factors for poor mental and physical health outcomes [1–9]. Evidence from adulthood shows that ACEs are associated with depression [1, 5] and higher body mass index (BMI) [6], including early in life [9–13], but less is known about their association with depression-overweight comorbidity. Depression and overweight are major contributors to the global burden of ill health [14, 15]. They are important public health problems due to the impact that both can have on individual well-being as well as societal costs, e.g., in terms of health spending and economic productivity [16, 17]. Depression and overweight tend to emerge in adolescence or young adulthood and carry a high likelihood of tracking into later adulthood [18, 19]. Depression and overweight commonly co-occur, which may follow from shared risk factors as well as reciprocal effects between depressive symptoms and BMI [20]. Depression-overweight comorbidity is a manifestation of mental-physical multimorbidity, defined as the presence of at least one mental health condition and at least one physical health condition, that can often emerge early in the life course. Importantly, mental-physical multimorbidity is a marker of complex healthcare needs and is strongly linked to socioeconomic circumstances and deprivation [21, 22].
Two previous studies have explored the association between ACEs and depression-overweight comorbidity, showing that ACEs are associated with a higher risk of depression-overweight comorbidity in adolescence (ages 14 and 17) [23] and adulthood (ages 23, 33, and 42 years) [24]. ACEs are linked to poverty and other measures of adverse socioeconomic circumstances [13, 25, 26], which are associated with both depression and overweight [27]. The differential vulnerability hypothesis posits that socioeconomic disadvantage increases sensitivity to risk exposures such as ACEs, as those with fewer socioeconomic resources have fewer of the associated wider resources that could buffer from the negative effects of adversity [28–30]. Previous studies show that socioeconomic position is associated with depression-overweight comorbidity [31], and one previous study found little evidence of effect modification by parental income in the association between ACEs and depression-obesity comorbidity in adolescence [23].
In this study, we expand on this literature using data from a UK birth cohort to investigate the associations of ACEs with depression-overweight comorbidity in both adolescence and later in young adulthood, with a more comprehensive set of ACEs. We examine whether the association of ACEs with comorbidity varies across males and females and by family socioeconomic background, measured by parental education, which is a more stable and fundamental measure of the relevant socioeconomic resources available in a young person's family than social class or income. We use rich data on ACEs between birth and age 16, reported by the mother and the participants themselves [32], and measures of depression-overweight comorbidity in adolescence (age 17) and early adulthood (age 24).
Methods
We use data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort, which enrolled pregnant women resident in Avon, UK, with expected dates of delivery between 1 April 1991 and 31 December 1992 [33–35]. The initial number of pregnancies enrolled was 14 541, of which 13 988 children were alive at 1 year, which our sample is based on as due to data requirements. However, when the oldest children were ∼7 years of age, an attempt was made to bolster the initial sample with eligible cases who had failed to join the study originally. The total sample size for analyses using any data collected after the age of seven is therefore 15 447 pregnancies, of which 14 901 children were alive at 1 year of age. Study data were collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at the University of Bristol [36]. REDCap is a secure, web-based software platform designed to support data capture for research studies. Please note that the study website contains details of all the available data through a fully searchable data dictionary and variable search tool (http://www.bristol.ac.uk/alspac/researchers/our-data/). Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees. Informed consent for the use of data collected via questionnaires and clinics was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time.
In 2008–2011, at a target age of 17.5 years, 5217 ALSPAC participants took part in a clinic assessment where weight and height were measured, and 4500 participants responded to an online questionnaire with data on depressive symptoms. A further clinic assessment in 2015–2017 was attended by 4026 participants at ∼24 years of age, and 4222 ALSPAC participants completed a questionnaire including questions on depressive symptoms at ∼23 years of age. The selected sample for the present study includes participants who had data on depressive symptoms and/or BMI at the age 17 wave, and at least 10% of ACE questions answered (N = 4734 Flow diagram in Supplementary Fig. S1).
Depression-overweight comorbidity
Depression-overweight comorbidity was constructed as a multinomial variable with categories of (i) neither depression nor overweight (reference), (ii) depression only, (iii) overweight only, and (iv) depression-overweight comorbidity. We used the Short Moods and Feelings Questionnaire (SMFQ), a 13-item self-reported questionnaire used for screening depressive symptoms in adolescents and young adults [37], to identify depressed mood or depression. Participants were asked to rate statements about experiences of low mood and other correlates in the past two weeks as ‘not true’, ‘sometimes’, or ‘true’. Total scores range between 0 and 26, with higher scores indicating more depressive symptoms. A score threshold of ≥11 was used to identify depression [38]. BMI (kg/m2) was calculated from measured weight and height. Height was measured to the nearest millimetre using a Harpenden stadiometer, and weight was measured either to the nearest 0.05 kg with a Tanita Body Fat Analyser (age 17) or to the nearest 0.1 kg using Tanita TBF-401A electronic body composition scales (age 24). Being overweight was identified with the BMI threshold ≥25 kg/m2.
Adverse childhood experiences
Several questionnaires throughout the cohort follow-up have probed into ACEs. We included ACEs occurring between birth and age 16, and included measures of physical, emotional, and sexual abuse, emotional neglect, being bullied, parental substance abuse, violence between parents, parental conviction of criminal offence, parental separation, parental mental illness, or suicide [32]. From age 8 onwards, some ACEs were self-reported by the participants, and at earlier ages, the measures derive mainly from questionnaires filled out by the participants’ mothers. The definition and source of information for each of the ACEs are summarized in Supplementary Table S1. The detailed list of the specific questions, who they were reported by, and at what ages can be found in a data note by Houtepen et al. [32]. We considered the 10 different types of ACEs separately with dichotomous indicators of whether the participant reported having experienced the specific type of ACE. We considered any report of an experience to indicate the presence of an ACE, regardless of inconsistencies with later reporting. The number of different types of ACEs was counted, and the score was categorized into (i) no ACEs, (ii) one ACE, (iii) two or three ACEs, or (iv) four or more ACEs reported.
Socioeconomic background
Family socioeconomic background was measured by the highest reported parental educational qualifications from mother and partner responses to questionnaires at 32 weeks’ gestation. We grouped education into (i) university degree, (ii) Advanced (A)-level (examinations around age 18), and (iii) Ordinary (O)-level (examinations taking place at approximately age 16, the UK minimum school leaving age when the mothers were at school), or (iv) CSE (Certificate of Secondary Education), vocational degree or lower qualifications. For interaction analyses, we generated a binary measure of high parental education: (i) high—university degree and (ii) low—less than university degree.
Covariates
Covariates included in adjusted models were ethnicity, social class, financial difficulties, and maternal age (centred at the mean age). Ethnicity was reported by the mother (white/non-white). Social class was derived from questionnaires during pregnancy and measured by the highest occupational class based on Registrar General’s Social Class classification: (i) I—professional, (ii) II—managerial/technical, (iii) III—skilled manual or nonmanual, and (iv) IV—semiskilled manual/V—unskilled manual. Financial difficulties were assessed in a questionnaire at 32 weeks' gestation, when mothers were asked ‘How difficult at the moment do you find it to afford these items’ for food, heating, and rent or mortgage. We constructed a binary measure of reporting experiencing none or only some difficulties, versus reporting affording any as ‘fairly difficult’ or ‘very difficult’.
Missing data
There was missing data on the outcomes, exposures, and covariates. After examining patterns of missingness, we decided to impute data with a missing at random (MAR) assumption. Multiple imputation (MI) models included data on all outcomes and variables used in the analysis models, as well as auxiliary variables (Supplementary Table S2), and we stratified the main imputation models by sex and the interaction models by the binary measure of parental education. We generated 50 imputed datasets with 20 cycles and combined coefficients across imputed datasets using Rubin’s rules.
Statistical methods
We used multinomial logistic regression to examine the associations of the ACE score and different ACEs with depression-overweight comorbidity. We tested for different effects by sex using a joint interaction test using a threshold of P < .05. To test for interaction between parental education and ACE score, we tested interactions in imputed data that had been stratified by the binary measure of parental education. We also repeated the main analyses in unimputed data as a sensitivity analysis.
Results
The characteristics of the sample are described in Table 1. A fifth of the participants had no report of any of the ACEs studied, 28% had experienced one ACE, 36% had experienced two or three, and 16% had experienced four or more. The most common type of ACE reported was parental mental health problems or suicide (42%), followed by experiences of being bullied (26%), and parental separation (25%). At age 17, 59% of females and 66% of males had neither depression nor overweight, whilst this decreased to 47% for both at age 24 (Table 1). The prevalence of the ‘depression only’ group decreased while the prevalence of ‘overweight only’ and depression-overweight comorbidity increased substantially, the latter from 7% in females and 3% in males to 12% and 8%, respectively.
Table 1.
Characteristics of the unimputed and imputed data (N = 4734)
| Unimputed | Imputed |
|||
|---|---|---|---|---|
| All | All | Females | Males | |
| % (N) | % | % | % | |
| Sex | ||||
| Male | 43.8 (2074) | 43.8 | ||
| Female | 56.2 (2660) | 56.2 | ||
| Ethnicity | ||||
| White | 93.4 (4420) | 95.8 | 95.9 | 95.7 |
| Other | 4.0 (189) | 4.2 | 4.1 | 4.3 |
| Missing | 2.6 (125) | |||
| Highest parental education | ||||
| Degree | 29.7 (1408) | 30.0 | 28.7 | 31.8 |
| A-level | 35.2 (1668) | 35.6 | 35.7 | 35.5 |
| O-level | 24.3 (1152) | 24.7 | 25.6 | 23.6 |
| CSE/vocational/none | 9.4 (445) | 9.7 | 10.0 | 9.1 |
| Missing | 1.4 (61) | |||
| Social class | ||||
| I | 13.5 (639) | 13.7 | 12.7 | 15.0 |
| II | 44.8 (2123) | 45.7 | 45.6 | 45.8 |
| III/IV/V | 39.7 (1877) | 40.6 | 41.7 | 39.2 |
| Missing | 2.0 (95) | |||
| Financial difficulties | ||||
| Some/none | 83.1 (3932) | 87.2 | 86.9 | 87.5 |
| Fairy/very difficult | 12.0 (570) | 12.8 | 13.1 | 12.5 |
| Missing | 4.9 (232) | |||
| ACEs | ||||
| No ACEs | 13.1 (620) | 20.5 | 21.1 | 19.7 |
| 1 ACE | 17.0 (804) | 27.7 | 26.4 | 29.4 |
| 2–3 ACEs | 20.5 (973) | 36.0 | 36.7 | 35.1 |
| 4 or more ACEs | 7.8 (368) | 15.8 | 15.8 | 15.8 |
| Missing | 41.6 (1969) | |||
| Physical abuse | 13.2 (626) | 17.6 | 17.8 | 17.4 |
| Missing | 23.0 (1091) | |||
| Sexual abuse | 3.5 (165) | 3.8 | 5.8 | 1.3 |
| Missing | 6.4 (301) | |||
| Emotional abuse | 15.0 (712) | 19.5 | 20.2 | 18.5 |
| Missing | 21.0 (994) | |||
| Emotional neglect | 15.0 (712) | 18.8 | 17.6 | 20.4 |
| Missing | 17.8 (844) | |||
| Being bullied | 23.2 (1099) | 26.5 | 23.0 | 31.0 |
| Missing | 11.5 (543) | |||
| Parental substance abuse | 6.7 (319) | 9.3 | 9.2 | 9.5 |
| Missing | 19.1 (903) | |||
| Violence between parents | 12.7 (600) | 18.6 | 19.2 | 17.8 |
| Missing | 25.9 (1225) | |||
| Parental criminal offence | 5.7 (271) | 7.1 | 7.3 | 7.0 |
| Missing | 16.6 (784) | |||
| Parental separation | 17.4 (823) | 24.8 | 25.8 | 23.4 |
| Missing | 23.3 (1102) | |||
| Parental mental health problems or suicide attempt | 34.2 (1617) | 42.2 | 43.2 | 41.0 |
| Missing | 16.8 (797) | |||
| Comorbidity at 17 | ||||
| Has neither depression nor overweight | 51.3 (2429) | 62.0 | 58.6 | 66.3 |
| Depression only | 13.3 (629) | 16.4 | 18.6 | 13.7 |
| Overweight only | 13.7 (649) | 16.4 | 15.8 | 17.3 |
| Depression-overweight comorbidity | 4.2 (200) | 5.2 | 7.0 | 2.7 |
| Missing | 17.5 (827) | |||
| Comorbidity at 24 | ||||
| Has neither depression nor overweight | 23.2 (1097) | 46.8 | 47.1 | 46.5 |
| Depression only | 5.9 (278) | 12.8 | 14.1 | 11.1 |
| Overweight only | 12.2 (579) | 30.1 | 26.7 | 34.4 |
| Depression-overweight comorbidity | 4.3 (206) | 10.3 | 12.1 | 8.0 |
| Missing | 54.4 (2574) | |||
The ACE score and several individual ACEs were associated with depression-overweight comorbidity at age 17 in unadjusted results (Supplementary Table S3) as well as when adjusted for socioeconomic covariates (Table 2), with a slight attenuation of associations with adjustment. There was a dose–response relationship between the number of ACEs and comorbidity, and participants with four or more ACEs had a nearly three-fold increased risk of depression-overweight comorbidity compared to those with no ACEs (RRR 2.92, 95% CI 1.71, 5.00) (Table 2).
Table 2.
Adjusted associations between adverse childhood experiences and depression-overweight comorbidity at age 17
| Outcome ref: neither depression nor overweight | Depression only |
Overweight only |
Depression-overweight comorbidity |
P-value for sex interaction | ||||
|---|---|---|---|---|---|---|---|---|
| Exposure | RRR | RRR | 95% CI | RRR | 95% CI | RRR | 95% CI | |
| Ref: 0 ACEs | 1 | 1 | 1 | 1 | .418 | |||
| 1 ACE | 1.41 | 1.04, 1.91 | 1.31 | 1.01, 1.69 | 1.33 | 0.77, 2.31 | ||
| 2–3 ACEs | 2.01 | 1.52, 2.65 | 1.23 | 0.96, 1.58 | 2.09 | 1.29, 3.40 | ||
| 4 or more ACEs | 3.38 | 2.46, 4.63 | 1.18 | 0.87, 1.62 | 2.92 | 1.71, 5.00 | ||
| Physical abuse | 1 | 1.85 | 1.47, 2.32 | 1.15 | 0.91, 1.46 | 1.73 | 1.16, 2.59 | .4845 |
| Sexual abuse | 1 | 1.79 | 1.17, 2.74 | 1.28 | 0.81, 2.03 | 2.00 | 1.14, 3.51 | .2081 |
| Emotional abuse | 1 | 1.74 | 1.41, 2.16 | 0.95 | 0.75, 1.21 | 1.23 | 0.81, 1.86 | .3095 |
| Emotional neglect | 1 | 1.40 | 1.10, 1.78 | 1.21 | 0.97, 1.52 | 2.20 | 1.54, 3.14 | .9783 |
| Being bullied | 1 | 1.85 | 1.52, 2.26 | 1.00 | 0.82, 1.22 | 1.82 | 1.33, 2.49 | .8891 |
| Parental substance abuse | 1 | 1.38 | 1.02, 1.86 | 0.92 | 0.66, 1.29 | 0.95 | 0.54, 1.69 | .4798 |
| Violence between parents | 1 | 1.42 | 1.12, 1.80 | 0.96 | 0.75, 1.23 | 1.17 | 0.78, 1.77 | .8341 |
| Parental criminal conviction | 1 | 1.02 | 0.70, 1.47 | 1.02 | 0.73, 1.42 | 0.90 | 0.48, 1.69 | .5245 |
| Parental separation | 1 | 1.39 | 1.10, 1.75 | 0.96 | 0.77, 1.19 | 1.23 | 0.85, 1.79 | .0348 |
| Parental mental health problems or suicide attempt | 1 | 1.41 | 1.17, 1.71 | 1.07 | 0.89, 1.28 | 1.53 | 1.13, 2.08 | .0105 |
Note: Adjusted for sex, ethnicity, parental education, social class, financial difficulties, and maternal age.
Abbreviations: ACE, adverse childhood experiences; CI, confidence interval; RRR, relative risk ratio.
When assessing individual ACEs, there was evidence of an association with depression-overweight comorbidity for physical abuse, sexual abuse, emotional neglect, being bullied, and parental mental health problems or suicide attempt (Table 2). The magnitude of the estimates was similar across these ACEs. The associations between ACEs and comorbidity were similar to those of the ‘depression only’ group, while associations with the ‘overweight only’ group were weaker or null. For example, the association of physical abuse with depression-overweight comorbidity was RRR 1.73 (95% CI 1.16, 2.59), whilst the association with depression was RRR 1.85 (95% CI 1.47, 2.32) and with overweight RRR 1.15 (95% CI 0.91, 1.46). Tests of interactions by sex suggested that parental separation (P = .0348) and mental health problems (P = .0105) had stronger associations with comorbidity in females than males, whilst ACE score and other ACEs did not have different associations by sex (see Supplementary Tables S4 and S5 for sex-specific results).
As with depression-overweight comorbidity at age 17, ACEs were also associated with comorbidity at age 24 in unadjusted models (Supplementary Table S6), with some attenuation of estimates in adjusted models (Table 3). Similarly, comorbidity had more similar estimates to the ‘depression only’ group, and ACEs had weaker associations with the ‘overweight only’ group. Four or more ACES were associated with 2.5 times increased risk of comorbidity versus having neither depression nor overweight (95% CI 1.58, 3.92) relative to having no ACEs. Of the individual ACEs, physical abuse, sexual abuse, emotional abuse, being bullied, and parental mental health problems were associated with comorbidity at age 24 (Table 3). Sexual abuse was associated with comorbidity particularly strongly for males (P-values for sex difference .0094, RRR for females 2.45, 95% CI 1.46, 4.11, RRR for males 22.63, 95% CI 3.38, 151.74, see Supplementary Tables S7 and S8 for sex-specific results).
Table 3.
Adjusted associations between adverse childhood experiences and depression-overweight comorbidity at age 24
| Outcome ref: neither depression nor overweight | Depression only |
Overweight only |
Depression-overweight comorbidity |
P-value for sex interaction | ||||
|---|---|---|---|---|---|---|---|---|
| RRR | RRR | 95% CI | RRR | 95% CI | RRR | 95% CI | ||
| Ref: 0 ACEs | 1 | 1 | 1 | 1 | .9348 | |||
| 1 ACE | 1.33 | 0.94, 1.88 | 1.13 | 0.89, 1.43 | 1.07 | 0.72, 1.58 | ||
| 2–3 ACEs | 1.78 | 1.26, 2.51 | 1.13 | 0.90, 1.41 | 1.67 | 1.14, 2.45 | ||
| 4 or more ACEs | 2.91 | 1.91, 4.44 | 1.07 | 0.80, 1.44 | 2.48 | 1.58, 3.92 | ||
| Physical abuse | 1 | 1.95 | 1.44, 2.65 | 0.99 | 0.78, 1.25 | 1.93 | 1.44, 2.59 | .8871 |
| Sexual abuse | 1 | 2.27 | 1.36, 3.78 | 1.41 | 0.90, 2.21 | 3.25 | 2.00, 5.28 | .0094 |
| Emotional abuse | 1 | 1.59 | 1.17, 2.16 | 1.03 | 0.82, 1.28 | 1.50 | 1.11, 2.02 | .9395 |
| Emotional neglect | 1 | 1.04 | 0.77, 1.40 | 1.01 | 0.80, 1.26 | 1.29 | 0.94, 1.76 | .0707 |
| Being bullied | 1 | 1.55 | 1.18, 2.05 | 1.00 | 0.83, 1.20 | 1.51 | 1.10, 2.07 | .6347 |
| Parental substance abuse | 1 | 1.40 | 0.91, 2.15 | 0.84 | 0.61, 1.17 | 0.81 | 0.49, 1.34 | .7026 |
| Violence between parents | 1 | 1.49 | 1.06, 2.09 | 1.14 | 0.91, 1.44 | 1.44 | 1.00, 2.06 | .993 |
| Parental criminal conviction | 1 | 1.30 | 0.83, 2.04 | 0.86 | 0.61, 1.22 | 1.28 | 0.76, 2.16 | .7463 |
| Parental separation | 1 | 1.32 | 0.98, 1.77 | 1.00 | 0.81, 1.23 | 1.23 | 0.89, 1.70 | .4504 |
| Parental mental health problems or suicide attempt | 1 | 1.47 | 1.14, 1.90 | 1.05 | 0.89, 1.24 | 1.58 | 1.21, 2.08 | .1403 |
Note: Adjusted for sex, ethnicity, parental education, social class, financial difficulties, and maternal age.
Abbreviations: ACE, adverse childhood experiences; CI, confidence interval; RRR, relative risk ratio.
The number of ACEs a person had encountered was associated with an increased risk of comorbidity in a dose–response manner in participants with both high and low parental education (Table 4). Stratum-specific estimates were imprecise, particularly for high parental education, but there was no statistical evidence of interaction between parental education and ACEs in their association with comorbidity at either age.
Table 4.
The adjusted risk of having depression-overweight comorbidity versus having neither depression nor overweight, associated with the ACE score by level of parental education
| Age 17 |
Age 24 |
||||
|---|---|---|---|---|---|
| RRR | 95% CI | RRR | 95% CI | ||
| Low parental education | Ref: 0 ACEs | 1 | 1 | ||
| 1 ACE | 1.29 | 0.66, 2.52 | 1.15 | 0.71, 1.86 | |
| 2–3 ACEs | 2.12 | 1.18, 3.80 | 1.69 | 1.06, 2.70 | |
| 4 or more ACEs | 3.07 | 1.67, 5.63 | 2.33 | 1.38, 3.95 | |
| High parental education | Ref: 0 ACEs | 1 | 1 | ||
| 1 ACE | 1.38 | 0.43, 4.41 | 0.92 | 0.42, 1.99 | |
| 2–3 ACEs | 2.17 | 0.77, 6.11 | 1.46 | 0.72, 2.96 | |
| 4 or more ACEs | 2.01 | 0.44, 9.10 | 2.40 | 0.97, 5.97 | |
| P-value for interaction with parental education | 0.9329 | 0.9904 | |||
Note: Models are adjusted for sex, ethnicity, social class, financial difficulties, and maternal age.
Abbreviations: ACE, adverse childhood experiences; CI, confidence interval; RRR, relative risk ratio.
The main results using unimputed complete case data were similar to when using the imputed data (Supplementary Tables S9–S11).
Discussion
We found that ACEs across childhood are associated with depression-overweight comorbidity in adolescence, and these associations continue into young adulthood. The risk of depression-overweight comorbidity associated with having four or more ACEs, which comprised 16% of this sample, was over three-fold compared to those who reported none. The effects were overall similar at the two ages and in males and females, though a few sex-specific associations were observed. We did not find evidence that parental education moderated the impact of the ACE score on depression-overweight comorbidity, but the estimates were imprecise.
When exploring the associations between individual ACEs and depression-overweight comorbidity, at age 17, associations were observed for physical abuse, sexual abuse, emotional neglect, being bullied, and parental mental health problems. With the exception of emotional neglect, these associations were also observed at age 24, in addition to associations with emotional abuse and violence between parents. We replicated the associations found between experiences of bullying and parental mental health problems with comorbidity at age 17 found in the Millennium Cohort Study (MCS) [23], although note that we looked at comorbidity of depression and overweight rather than obesity. Having experienced four or more ACEs was a strong risk factor for comorbidity at both ages. The results from MCS had suggested that between ages 14 and 17, the association between ACEs with depression-obesity comorbidity attenuated [23], but used different questionnaires to identify depression at ages 14 and 17. We were able to use the same measurement tool for depression at ages 17 and 24 as well as a comprehensive set of ACEs, and the results suggested little attenuation of associations to young adulthood. In the 1958 National Child Development Study, associations between two or more ACEs with depression-overweight comorbidity were similar at ages 23 and 33 years, but decreased at age 42 years [24]. There was an increase in comorbidity with age, mainly due to an increase in overweight prevalence, especially in males. Nevertheless, the association of ACEs with comorbidity was more similar to the association with depression than the association with overweight status. In our analysis, the associations of the ACE score and the individual ACEs with depression-overweight comorbidity largely mirrored the associations for ‘depression only’, with associations between ACEs and ‘overweight only’ being small or absent. In a previous study, despite little evidence of association between ACEs and overweight only was observed, the association between ACEs and overweight-depression comorbidity was stronger than the association between ACEs and depression only [24]. Overall, we had hypothesized that ACEs may have a strong association with the co-occurrence of depression and overweight, because some of the suggested mechanisms linking stressful experiences with greater BMI, such as impaired self-regulation, poor sleep, overeating and food addiction [39, 40], may be heightened by the presence of depression or depressed mood. ACEs could also heighten the relationship between depression and overweight, amplifying their co-occurrence in a ‘vicious cycle’. However, our results indicate that the association with comorbidity at these ages is likely mainly driven by depression. It remains possible that depression could mediate any stronger association between ACEs and overweight emerging later in life, as previous evidence suggests that the impact of ACEs on BMI/obesity is stronger in adulthood than in childhood [2, 8]. The impact ACEs may have on the intersecting trajectories of depressive symptoms and BMI from adolescence to adulthood would require further investigation.
Despite sex differences in the prevalence of ACEs, depression, and overweight, we did not find strong evidence that the association of ACEs with comorbidity varied substantially across sexes. Some differences found for individual ACEs were that parental separation and mental health problems had associations with depression-overweight comorbidity in females but not males at age 17, and sexual abuse had a stronger association with comorbidity in males than females at age 24, although the latter was estimated imprecisely due to small numbers. In the MCS, no sex differences were found for the association of cumulative ACE score with depression-obesity comorbidity at age 17 [23], and in the 1958 Cohort, sex differences were only observed at age 42 [24]. Previous evidence of sex differences in the long-term mental health effects of ACEs has been mixed [1, 2, 5, 6]. In the MCS, no differences were found in the association between parent-reported ACEs prior to age 4 and internalizing or externalizing symptoms up to age 14 [10]. For overweight status, a systematic review of studies of childhood obesity reported a greater impact of ACEs in females [11].
We also did not find any interaction between parental education and ACEs on their effects on comorbidity, but the stratum-specific estimates were imprecise. If these results can be replicated in other samples, this would indicate that resources linked to parental education do not alter sensitivity to ACE exposure or mitigate the negative effects of adversity.
The study strengths include that the data on ACEs throughout childhood have been both prospectively and retrospectively reported. We did not rely solely on parental reports of ACEs, which could underestimate their occurrence. Other advantages were that depression was identified based on a validated depressive symptom score rather than a self-reported clinical diagnosis, which could be more strongly affected by socioeconomic biases in seeking care, and overweight was based on measured BMI. However, it should be noted that the measure of depression we used is more sensitive than a clinical diagnosis, and we do not suggest that it corresponds to major depressive disorder as clinically defined.
One limitation of the study is the potential effects of reverse causation, limiting straightforward causal inference. Depressive symptoms or overweight before age 17 can influence the likelihood of exposure to ACEs such as bullying. In addition, potential bias is introduced by study attrition and missing data, which we mitigated using MI. There was missingness in the ACE exposure, and there was high missingness in the outcomes, especially in young adulthood, with those with more ACEs and depressive symptoms and overweight being more likely to drop out of the study. This is likely to bias estimates towards the null, although it is unclear in what direction interaction results would be affected. Whilst the MAR assumption for missing data is unverifiable, we included a range of auxiliary variables in our imputation model, including multiple sociodemographic indicators measured at baseline on most cohort participants, which makes this assumption more plausible. The sample remains also a more advantaged sample than the general population at the time, which may also result in an underestimation of any ACE effects. Unmeasured confounding, including genetics or disability, could have influenced the associations. However, methods to account for genetic confounding have not been developed for multinomial outcomes, and the prevalence of disability is low in this general population cohort.
Conclusions
This study confirms that ACEs are associated with depression-overweight comorbidity in adolescence and young adulthood. The findings point to the early emergence of complex healthcare needs and mental-physical multimorbidity in a proportion of people exposed to childhood adversity, but also suggest that this is mainly driven by increased depression risk.
Supplementary Material
Acknowledgements
We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. We thank Dr Lindsey Hines for help with MI scripts. For the purpose of open access, the author(s) have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.
Contributor Information
Fanny Kilpi, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Ana Goncalves Soares, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Laura D Howe, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Supplementary data
Supplementary data are available at EURPUB online.
Conflict of interest: None declared.
Funding
F.K. was funded by an Economic and Social Research Council grant (ES/T013923/1). A.G.S. was supported by the Dynamic Longitudinal Exposome Trajectories in Cardiovascular and Metabolic Non-communicable Diseases (H2020-SC1-2019-Single-Stage-RTD, project ID 874739). The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z), and the University of Bristol provide core support for ALSPAC. A comprehensive list of grant funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). The collection of some of the variables used in this study was specifically funded by the Wellcome Trust and MRC (076467/Z/05/Z and MR/L022206/1). This publication is the work of the authors, and F.K. will serve as guarantor for the contents of this article.
Data availability
The informed consent obtained from ALSPAC participants does not allow the data to be made freely available through any third-party maintained public repository. However, data used for this submission can be made available on request to the ALSPAC Executive. The ALSPAC data management plan describes in detail the policy regarding data sharing, which is through a system of managed open access. Full instructions for applying for data access can be found here: http://www.bristol.ac.uk/alspac/researchers/access/. The ALSPAC study website contains details of all the data that are available (http://www.bristol.ac.uk/alspac/researchers/our-data/).
Key points.
Both individual ACEs and cumulative exposure to multiple ACEs are associated with increased risk of depression-overweight comorbidity in adolescence and young adulthood.
People who experience four or more ACEs have an almost three-fold risk of depression-overweight comorbidity in adolescence and young adulthood compared with people who experience no ACEs.
Parental education does not seem to moderate the association between ACEs and depression-overweight comorbidity.
This highlights the early emergence of mental-physical multimorbidity, a marker of complex healthcare needs, in some people exposed to childhood adversity.
References
- 1. Chapman DP, Whitfield CL, Felitti VJ et al. Adverse childhood experiences and the risk of depressive disorders in adulthood. J Affect Disord 2004;82:217–25. 10.1016/j.jad.2003.12.013 [DOI] [PubMed] [Google Scholar]
- 2. Danese A, Tan M. Childhood maltreatment and obesity: systematic review and meta-analysis. Mol Psychiatry 2014;19:544–54. 10.1038/mp.2013.54 [DOI] [PubMed] [Google Scholar]
- 3. Felitti VJ, Anda RF, Nordenberg D et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The adverse childhood experiences (ACE) study. Am J Prev Med 1998;14:245–58. 10.1016/s0749-3797(98)00017-8 [DOI] [PubMed] [Google Scholar]
- 4. Goncalves Soares A, Zimmerman A, Zammit S et al. Abuse in childhood and cardiometabolic health in early adulthood: evidence from the Avon Longitudinal Study of Parents and Children. J Am Heart Assoc 2021;10:e021701. 10.1161/JAHA.121.021701 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Gondek D, Patalay P, Lacey RE. Adverse childhood experiences and multiple mental health outcomes through adulthood: a prospective birth cohort study. SSM—Mental Health 2021;1:100013. 10.1016/j.ssmmh.2021.100013 [DOI] [Google Scholar]
- 6. Hemmingsson E, Johansson K, Reynisdottir S. Effects of childhood abuse on adult obesity: a systematic review and meta-analysis. Obes Rev 2014;15:882–93. 10.1111/obr.12216 [DOI] [PubMed] [Google Scholar]
- 7. Hughes K, Bellis MA, Hardcastle KA et al. The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. Lancet Public Health 2017;2:e356–e66. 10.1016/S2468-2667(17)30118-4 [DOI] [PubMed] [Google Scholar]
- 8. Power C, Pinto Pereira SM, Li L. Childhood maltreatment and BMI trajectories to mid-adult life: follow-up to age 50 y in a British birth cohort. PLoS One 2015;10:e0119985. 10.1371/journal.pone.0119985 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Houtepen LC, Heron J, Suderman MJ et al. Associations of adverse childhood experiences with educational attainment and adolescent health and the role of family and socioeconomic factors: a prospective cohort study in the UK. PLoS Med 2020;17:e1003031. 10.1371/journal.pmed.1003031 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Bevilacqua L, Kelly Y, Heilmann A et al. Adverse childhood experiences and trajectories of internalizing, externalizing, and prosocial behaviors from childhood to adolescence. Child Abuse Negl 2021;112:104890. 10.1016/j.chiabu.2020.104890 [DOI] [PubMed] [Google Scholar]
- 11. Schroeder K, Schuler BR, Kobulsky JM et al. The association between adverse childhood experiences and childhood obesity: a systematic review. Obes Rev 2021;22:e13204. 10.1111/obr.13204 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Soares ALG, Matijasevich A, Menezes AMB et al. Adverse childhood experiences (ACEs) and adiposity in adolescents: a cross-cohort comparison. Obesity (Silver Spring) 2018;26:150–9. 10.1002/oby.22035 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Straatmann VS, Lai E, Law C et al. How do early-life adverse childhood experiences mediate the relationship between childhood socioeconomic conditions and adolescent health outcomes in the UK? J Epidemiol Community Health 2020;74:969–75. 10.1136/jech-2020-213817 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Afshin A, Forouzanfar MH, Reitsma MB; GBD 2015 Obesity Collaborators et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 2017;377:13–27. 10.1056/NEJMoa1614362 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease study 2019. Lancet 2020;396:1204–22. 10.1016/S0140-6736(20)30925-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Konig H, Konig HH, Konnopka A. The excess costs of depression: a systematic review and meta-analysis. Epidemiol Psychiatr Sci. 2019; 29:e30. 10.1017/S2045796019000180 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Withrow D, Alter DA. The economic burden of obesity worldwide: a systematic review of the direct costs of obesity. Obes Rev 2011;12:131–41. 10.1111/j.1467-789X.2009.00712.x [DOI] [PubMed] [Google Scholar]
- 18. Mulraney M, Coghill D, Bishop C et al. A systematic review of the persistence of childhood mental health problems into adulthood. Neurosci Biobehav Rev 2021;129:182–205. 10.1016/j.neubiorev.2021.07.030 [DOI] [PubMed] [Google Scholar]
- 19. Simmonds M, Llewellyn A, Owen CG et al. Predicting adult obesity from childhood obesity: a systematic review and meta-analysis. Obes Rev 2016;17:95–107. 10.1111/obr.12334 [DOI] [PubMed] [Google Scholar]
- 20. Milaneschi Y, Simmons WK, van Rossum EFC et al. Depression and obesity: evidence of shared biological mechanisms. Mol Psychiatry 2019;24:18–33. 10.1038/s41380-018-0017-5 [DOI] [PubMed] [Google Scholar]
- 21. Barnett K, Mercer SW, Norbury M et al. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet 2012;380:37–43. 10.1016/S0140-6736(12)60240-2 [DOI] [PubMed] [Google Scholar]
- 22. MacRae C, Mercer SW, Henderson D et al. Age, sex, and socioeconomic differences in multimorbidity measured in four ways: UK primary care cross-sectional analysis. Br J Gen Pract 2023;73:e249–e56. 10.3399/BJGP.2022.0405 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Karamanos A, Khanolkar AR. Adverse childhood experiences and mental ill-health—obesity comorbidity among British adolescents—a national cohort study. J Multimorb Comorb 2023;13:26335565231215638. 10.1177/26335565231215638 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Ugarteche Pérez A, Berger EA-O, Kelly-Irving M et al. Early life stress in relation with risk of overweight, depression, and their comorbidity across adulthood: findings from a British birth cohort. Psychol Med 2024;54:1853–66. 10.1017/S0033291723003823 [DOI] [PubMed] [Google Scholar]
- 25. Lacey RE, Howe LD, Kelly-Irving M et al. The clustering of adverse childhood experiences in the Avon Longitudinal Study of Parents and Children: are gender and poverty important? J Interpers Violence 2022;37:2218–41. 10.1177/0886260520935096 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Walsh D, McCartney G, Smith M et al. Relationship between childhood socioeconomic position and adverse childhood experiences (ACEs): a systematic review. J Epidemiol Community Health 2019;73:1087–93. 10.1136/jech-2019-212738 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Reiss F. Socioeconomic inequalities and mental health problems in children and adolescents: a systematic review. Soc Sci Med 2013;90:24–31. 10.1016/j.socscimed.2013.04.026 [DOI] [PubMed] [Google Scholar]
- 28. Anderson LR, Monden CWS, Bukodi E. Stressful life events, differential vulnerability, and depressive symptoms: critique and new evidence. J Health Soc Behav 2022;63:283–300. 10.1177/00221465211055993 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Kessler RC. A strategy for studying differential vulnerability to the psychological consequences of stress. J Health Soc Behav 1979;20:100–8. [PubMed] [Google Scholar]
- 30. Oude Groeniger J, Houweling TA, Jansen PW et al. Social inequalities in child development: the role of differential exposure and susceptibility to stressful family conditions. J Epidemiol Community Health 2023;77:74–80. 10.1136/jech-2022-219548 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Khanolkar AR, Patalay P. Socioeconomic inequalities in co-morbidity of overweight, obesity and mental ill-health from adolescence to mid-adulthood in two national birth cohort studies. Lancet Reg Health Eur 2021;6:100106. 10.1016/j.lanepe.2021.100106 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Houtepen LC, Heron J, Suderman MJ et al. Adverse childhood experiences in the children of the Avon Longitudinal Study of Parents and Children (ALSPAC). Wellcome Open Res 2018;3:106. 10.12688/wellcomeopenres.14716.1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Boyd A, Golding J, Macleod J et al. Cohort profile: the ‘children of the 90s’—the index offspring of the Avon Longitudinal Study of Parents and Children. Int J Epidemiol 2013;42:111–27. 10.1093/ije/dys064 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Fraser A, Macdonald-Wallis C, Tilling K et al. Cohort profile: the Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort. Int J Epidemiol 2013;42:97–110. 10.1093/ije/dys066 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Northstone K, Lewcock M, Groom A et al. The Avon Longitudinal Study of Parents and Children (ALSPAC): an update on the enrolled sample of index children in 2019. Wellcome Open Res 2019;4:51. 10.12688/wellcomeopenres.15132.1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Harris PA, Taylor R, Thielke R et al. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81. 10.1016/j.jbi.2008.08.010 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Messer SC, Angold A, Costello EJ et al. Development of a short questionnaire for use in epidemiological studies of depression in children and adolescents: factor composition and structure across development. International Journal of Methods in Psychiatric Research 1995;5:251–62. [Google Scholar]
- 38. Kwong ASF. Examining the longitudinal nature of depressive symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC). Wellcome Open Res 2019;4:126. 10.12688/wellcomeopenres.15395.2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39. Tomiyama AJ. Stress and obesity. Annu Rev Psychol 2019;70:703–18. 10.1146/annurev-psych-010418-102936 [DOI] [PubMed] [Google Scholar]
- 40. Wiss DA, Brewerton TD. Adverse childhood experiences and adult obesity: a systematic review of plausible mechanisms and Meta-Analysis of Cross-Sectional studies. Physiol Behav 2020;223:112964. 10.1016/j.physbeh.2020.112964 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The informed consent obtained from ALSPAC participants does not allow the data to be made freely available through any third-party maintained public repository. However, data used for this submission can be made available on request to the ALSPAC Executive. The ALSPAC data management plan describes in detail the policy regarding data sharing, which is through a system of managed open access. Full instructions for applying for data access can be found here: http://www.bristol.ac.uk/alspac/researchers/access/. The ALSPAC study website contains details of all the data that are available (http://www.bristol.ac.uk/alspac/researchers/our-data/).
Key points.
Both individual ACEs and cumulative exposure to multiple ACEs are associated with increased risk of depression-overweight comorbidity in adolescence and young adulthood.
People who experience four or more ACEs have an almost three-fold risk of depression-overweight comorbidity in adolescence and young adulthood compared with people who experience no ACEs.
Parental education does not seem to moderate the association between ACEs and depression-overweight comorbidity.
This highlights the early emergence of mental-physical multimorbidity, a marker of complex healthcare needs, in some people exposed to childhood adversity.