Traumatic life events as predictors for depression in middle-aged men and women: A Finnish twin study

Traumatic life events as predictors for depression in middle-aged men and women: A Finnish twin study | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Traumatic life events as predictors for depression in middle-aged men and women: A Finnish twin study View ORCID Profile Piirtola Maarit , Haravuori Henna , Kiviruusu Olli , Viertiö Satu , Suvisaari Jaana , Marttunen Mauri , Kaprio Jaakko , Korhonen Tellervo doi: https://doi.org/10.1101/2024.04.18.24306034 Piirtola Maarit 1 Institute for Molecular Medicine Finland (FIMM), University of Helsinki , Helsinki, Finland 2 UKK Institute for Health Promotion Research , Tampere, Finland Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Piirtola Maarit For correspondence: maarit.piirtola{at}helsinki.fi Haravuori Henna 3 Mental Health Team, Department of Public Health and Welfare, Finnish Institute for Health and Welfare (THL) , Helsinki, Finland 4 Psychiatry, University of Helsinki and Helsinki University Hospital , Helsinki, Finland 5 Wellbeing services county of Lapland , Rovaniemi, Finland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kiviruusu Olli 3 Mental Health Team, Department of Public Health and Welfare, Finnish Institute for Health and Welfare (THL) , Helsinki, Finland 4 Psychiatry, University of Helsinki and Helsinki University Hospital , Helsinki, Finland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Viertiö Satu 3 Mental Health Team, Department of Public Health and Welfare, Finnish Institute for Health and Welfare (THL) , Helsinki, Finland 4 Psychiatry, University of Helsinki and Helsinki University Hospital , Helsinki, Finland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Suvisaari Jaana 3 Mental Health Team, Department of Public Health and Welfare, Finnish Institute for Health and Welfare (THL) , Helsinki, Finland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marttunen Mauri 3 Mental Health Team, Department of Public Health and Welfare, Finnish Institute for Health and Welfare (THL) , Helsinki, Finland 4 Psychiatry, University of Helsinki and Helsinki University Hospital , Helsinki, Finland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kaprio Jaakko 1 Institute for Molecular Medicine Finland (FIMM), University of Helsinki , Helsinki, Finland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Korhonen Tellervo 1 Institute for Molecular Medicine Finland (FIMM), University of Helsinki , Helsinki, Finland Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Supplementary material Data/Code Preview PDF ABSTRACT Background We examined the exposure to adulthood traumatic life events (TLEs) and analysed their associations with depression in women and men. Then we examined whether the associations of TLEs are independent of exposure loading and vulnerability including familial confounding. Methods Total of 8410 individuals (45% men, mean age 60 years) participated in the fourth survey of the population-based Finnish Twin Cohort conducted in 2011. Depression was assessed using the Center for Epidemiologic Studies Depression (CES-D) scale (cut-off value ≥20). Participants reported exposure to TLEs during adulthood. Logistic regression adjusted for multiple covariates was used as the individual-based analyses. The effect of shared familial factors was tested using conditional logistic regression in 399 twin pairs discordant for depression. Results Depression was more common in women (15%) than in men (11%). Men reported more traffic accidents (men: 11.8%, women: 7.4%), other serious accidents (11.8%, 5.8%), and violent crime (3.1%, 2.0%) whereas women reported more sexual assault (0.7%, 10.6%). Violent crime (Odds Ratio 3.86; 95% Confidence Intervals 2.59, 5.73), sexual assault (3.49; 2.67, 4.55), physical assault (3.10; 2.45, 3.93), and other serious accidents (1.36; 1.01, 1.85) were associated with depression. These associations, except other serious accidents, remained statistically significant after adjusting for multiple covariates including TLEs load and shared familial factors. The associations did not differ by sex. Conclusions Women and men differ in exposure to TLEs but, if exposed, they are equally vulnerable for depression. Because traumatic life events are robustly associated with depression, they should be considered in prevention and treatment. INTRODUCTION Among adults, depression disorders are highly prevalent globally, and twice as prevalent in women than in men ( Bebbington, 1996 , Bromet et al ., 2011 , Salk, Hyde and Abramson, 2017 , Steel et al ., 2014 ), for reasons still poorly understood ( Hyde, Mezulis and Abramson, 2008 , Salk et al ., 2017 ). Depression is a complex multifactorial disorder ( Bromet et al ., 2011 , Hyde et al ., 2008 , Kendler, Kuhn and Prescott, 2004a , Köhler et al ., 2018 , Markkula et al ., 2015 ). It is, however, particularly common among individuals exposed to stressful and traumatic life events (TLEs) ( Kessler, 1997 , McCutcheon et al ., 2009 , Vibhakar, Allen, Gee and Meiser-Stedman, 2019 , Xiang and Wang, 2021 ). Even though men report higher overall number of TLEs than women ( Hatch and Dohrenwend, 2007 ) it is possible that women underreport some TLEs, such as domestic violence ( Attila et al ., 2023 ). Overall, there are not many population-based studies analysing association of TLEs with depression separately in men and women ( Kendler et al ., 2004a , McLaughlin, Conron, Koenen and Gilman, 2010 , Xiang and Wang, 2021 ). Even fewer studies have considered multiple potential confounders, such as personality and shared familial factors ( Kendler and Gardner, 2014 , Kendler, Thornton and Prescott, 2001 ). Despite many shared risk factors for depression and TLEs ( Hatch and Dohrenwend, 2007 , Otten et al ., 2021 ), gender-based differences exist. It has been suggested that neuroticism and failures in interpersonal relationships play a larger role in the development of major depression in women whereas substance abuse, prior history of depression, and childhood sexual abuse play a greater role in men ( Kendler and Gardner, 2014 ). Gender-based sensitivity for depression is, however, most likely modified by both socio-cultural factors as gender-based expectations and marital status, and traits like temperament and personality ( Maji, 2018 , Parker and Brotchie, 2010 ). Though, higher education, being married and having fewer previous TLEs have been found to protect against subsequent TLEs in general ( Benjet et al ., 2016 ), the evidence for TLEs as gender-based risks for depression is sparse. Generally, the relationship between TLEs and depression has been analysed in women only ( Kendler, Kuhn and Prescott, 2004b ) or gender has been adjusted for in the analyses ( Richardson, Carr, Netuveli and Sacker, 2020 ). There are several theories related to impact of TLEs on depression among men and women. According to exposure hypothesis ( Denton, Prus and Walters, 2004 ), women and men differ by their exposure to TLEs which would then partly explain gender differences in depression. However, adverse childhood experiences (ACE) have been reported to associate equally with adult TLEs in both genders ( Bürgin et al ., 2021 ). Notably, even if exposure would differ, the same TLE might not be equally traumatic to everyone ( Pearlin, Schieman, Fazio and Meersman, 2005 ), and not all individuals exposed to TLEs suffer from depression ( Baldwin, Reuben, Newbury and Danese, 2019 , McLaughlin et al ., 2010 ). Therefore, gender, personality, socioeconomic factors, social relationships, exposure to ACE and genetic liability, including biological sex, are likely to confound or modify the complex aetiology of exposure to TLEs and of depression onset ( Kendler et al ., 2004a , Kessler, 1997 , Luo, Zhang and Roberts, 2021 , Pearlin et al ., 2005 ). Hence, differences in depression have also been explained through interaction with individual-based vulnerability, such as sensitivity to adverse experiences ( Bilodeau, Marchand and Demers, 2020 , Piccinelli and Wilkinson, 2000 ). In addition, an exposure load (sensitivity/sensitization) hypothesis has been proposed ( Hammen, Henry and Daley, 2000 , McLaughlin et al ., 2010 ) suggesting that individuals facing TLEs during adulthood are more sensitive for depression if they have also experienced ACEs ( Bandoli et al ., 2017 , Kendler et al ., 2004b , McLaughlin et al ., 2010 ). Further, it has been reported that individuals who experience adversities, such as traumas, are at an increased risk of experiencing further adversities during their life span ( Pearlin et al ., 2005 ). Notably, also a dose-response relationship between stressors and depression has been shown indicating that more frequent or more severe stressors either in childhood or in adulthood lower the threshold for depression ( Bandoli et al ., 2017 , Kendler et al ., 2004b , McLaughlin et al ., 2010 ). Familial liability for depression cannot been ruled out in the development of depression after adverse life events ( Zimmermann et al ., 2008 ). Twin and family studies indicate a moderate heritability of depression ( Flint and Kendler, 2014 , Kendall et al ., 2021 , Polderman et al ., 2015 ), which may be higher in women ( Flint and Kendler, 2014 ). Likewise, there is evidence for a heritable component in trauma exposure ( Lyons et al ., 1993 , Power et al ., 2013 ), and this may be shared with the heritable component of depression (Coleman 2020). Therefore, in addition to individual-based risk factors for depression, familial factors including both childhood environmental factors and genetic vulnerability are potential confounders when analysing associations between TLEs and depression. For this purpose, twin studies provide a powerful design allowing control of familial factors ( McGue, Osler and Christensen, 2010 ). AIMS First, we report sex-differences in prevalence of depression based on the Center for Epidemiologic Studies Depression (CES-D) scale and in the exposure to TLE during adulthood. Second, we analyse sex differences in the associations of TLEs with depression. Third, we test if the associations are independent of variables increasing vulnerability for depression such as personality, socioeconomic factors, other negative life events, and ACEs, as well as familial factors including genetic liability. METHODS Participants The fourth survey of the population-based Finnish Twin Cohort of like-sexed twin pairs was conducted in 2011 ( Kaprio, 2013 ). Participation rate was 72% and the full data included 8,410 participants (46% men, age range: 53 to 68 years) ( Figure 1a ). We had information only on biological sex from the registered birth certificates. Gender was not inquired in the questionnaires of the twin cohort. Participant characteristics by sex and depressive symptoms are described in Table 1 . Download figure Open in new tab Figure 1a. Flow chart of samples included in the individual-based analyses. View this table: View inline View popup Download powerpoint Table 1. Characteristics of participants (n=8,165) with CES-D information by sex in the Finnish Twin Cohort in 2011. The prevalence of depression was calculated for 8,165 participants who completed the CES-D assessment ( Figure 1a ). The prevalence of TLEs was calculated for those 7,250 who had also reported exposure (yes/no) to at least one TLEs during adulthood (44% men). The Individual-based association analyses were performed for those 6,002 (44% men) participants who had information on depressive symptoms, TLEs and relevant covariates. Within-pair data came from 2,253 same-sexed twin pairs (40% male pairs) where both twins had information about their depression status and at least one mention about their exposure to TLEs during adulthood ( Figure 1b ). We identified 399 pairs (35% male) who were discordant for depression (as defined below), of whom 264 were dizygotic (DZ) and 135 monozygotic (MZ). Download figure Open in new tab Figure 1b. Flow chart of twin pairs included in the within-pair analyses. Ethics All procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. The study protocol was approved by the Ethical Committee of the University of Helsinki, Department of Public Health. Analyses of the present study did not involve contact with the study participants. A returned and completed questionnaire was considered as consent from the participant. The study participants were provided with information about the study aims and their right to withdraw from the study at any time. Measures Depression Depressive symptoms were assessed using the sum score of the self-reported 20-item Center for Epidemiologic Studies Depression (CES-D) scale (range 0-60 points). A higher score reflects more current depressive symptoms ( Radloff, 1977 ). If one or two items were missing, they were imputed by replacing the mean of the non-missing items before computing the sum score (616 participants, 7% of the total sample). The process is described in detail elsewhere ( Piirtola et al ., 2021 ). As the sum score was skewed with a floor effect (Fig S1), we coded depression as a dichotomous variable (yes/no) with a cut off value ≥20. This classifies an individual with a clinically relevant level of depression ( Vilagut, Forero, Barbaglia and Alonso, 2016 ). Traumatic life events Exposure (yes/no) to traumatic life events (TLEs) during adulthood was assessed using the Trauma History Screen measure ( Carlson et al ., 2011 ). We asked exposure to six items: involvement in a serious traffic accident, involvement in any other serious accident, being a witness to a fire or natural disaster, being injured by a physical assault, being a victim of a sexual assault, and being a victim of or witness to a violent crime. Cumulative number of TLEs was calculated both as a sum and categorized as none, one or two, and at least three TLEs in adulthood. The corresponding items were asked from childhood and calculated both as cumulative sum and categorized ACE (none vs. at least one). A total of 6,527 participants (90%) of those reporting information at least one TLE (n=7,268) had no missing information in any of their adulthood TLEs. In the whole cohort, missing information varied from 15.8% to 18.1% per TLE, with no sex-difference ( Table 2 ). Persons with depression, irrespective of sex, had about twice as much missing information in each TLE than those without depression. View this table: View inline View popup Download powerpoint Table 2. Prevalence of self-reported adulthood traumatic life events, adverse childhood experiences and negative life events in the whole cohort by sex (n=8,410) and by sex and depressive symptoms (n=7,118) * in the Finnish Twin cohort in 2011. Background variables and covariates Register data provided sex and date of birth. Age was computed using date of response and birthdate. Relevant covariates associated with depression and TLEs were chosen based on previous literature ( Bromet et al ., 2011 , Kendler et al ., 2004a , Kendler et al ., 2004b , Klein, Kotov and Bufferd, 2011 , Köhler et al ., 2018 , Santini et al ., 2016 , Vinkers et al ., 2014 , Zhou et al ., 2019 ) and tested if they were associated with both depression and TLEs (data not shown). Sex, marital status and working status ( Kaprio and Koskenvuo, 1988 , Koskenvuo, Langinvainio, Kaprio and Sarna, 1984 ), emotional support ( Dalgard, Bjørk and Tambs, 1995 , Romanov, Varjonen, Kaprio and Koskenvuo, 2003 ) and ACE ( Carlson et al ., 2011 ) were used as sum or categorical/dichotomous variables (any vs. none). Age, formal education years until 1981 ( Silventoinen, Krueger, Bouchard, Kaprio and McGue, 2004 ), a 10-item neuroticism scale ( Floderus, 1974 , Rose, Koskenvuo, Kaprio, Sarna and Langinvainio, 1988 ), and time-weighted (during the last six months [highest points], during the last 5 yrs, earlier, never) sum of 12 negative life events (death of a spouse, close relative or a friend, individual health or sexual problems, family member’s poor health, substantial conflicts, divorce or legal separation with a spouse, problems in other human relationships, considerable interpersonal conflicts at work, loss of job, serious financial problems, and other serious problem, range) ( Romanov et al ., 2003 ) were used as continuous variables. Formations of the variables are described in detail elsewhere ( Piirtola et al ., 2021 , Romanov et al ., 2003 ). Table 1 describes the covariates by sex and depression status. Statistical methods Individual-based analyses Depression sum score could be calculated for 97% (n=8,165) of the cohort (Figure 1). Prevalence of depression and TLEs were calculated for the total cohort and separately for men and women. Difference between sexes was analysed using chi-squared tests. Odds Ratios (OR) with 95% Confidence Intervals (CI) from logistic regression models assessed the strength of associations between TLE and depression. Analyses were restricted to those individuals who had information about all covariates (n=6,002, Figure 1). Analyses were performed for each TLE separately at four stages. Model 1 was adjusted for age and sex. Model 2 was adjusted for age, sex, education, neuroticism, and emotional support. Model 3 was adjusted for covariates in model 2 plus other negative life events, whereas Model 4 was additionally adjusted for any ACE instead of negative life events, because we wanted to observe confounding effects of those 2 variables separately. Regression analyses were performed first separately for men and women ( Heidari, Babor, De Castro, Tort and Curno, 2016 ). Then interactions between sex and TLE, ACE and TLE, and ACE sum and TLE on depression were analysed with Likelihood-ratio test comparing two nested models with and without interaction term. If no sex interaction was found (p>0.05), analyses were performed by pooling men and women. A drop-out analysis using age- and sex-adjusted logistic regression analyses related to depression was performed for those excluded from the main analyses (Figure 1, Table S1). In all analyses of individuals, we corrected for the statistical dependence of twins within the twin pairs ( Williams, 2000 ). Within-pair analyses Twin pairs generally share the same childhood environment and experiences. DZ pairs are genetically full siblings whereas MZ pairs are almost identical at the genomic sequence ( Jonsson et al ., 2021 ). Therefore, twin pairs discordant for depression are informative concerning the contribution of familial confounding (genetics and shared environmental) in the association between TLE and depression. In such pairs, one twin has depression and the other does not, and the analysis examines the distribution of TLE in such pairs, using principles and approaches described earlier ( Piirtola et al ., 2021 , van Dongen, Slagboom, Draisma, Martin and Boomsma, 2012 ). Results from the within-pair analyses are compared with the results from individual-based analyses. If familial confounding plays a significant role in the association between TLE and depression, we should see an association among all individuals but not within twin pairs. Examining MZ and DZ pairs separately assesses whether familial confounding is due to shared environment or genetic influences. Within-pair analyses were done using conditional logistic regression by zygosity in twin pairs discordant for depression ( Figure 1b ), first for all pairs, and then separately by zygosity. We tested for heterogeneity by zygosity using the matched-pair cohort method (csmatch test in Stata)( Cummings and McKnight, 2004 ). Within-pair analyses were performed first separately for men and women. If no sex differences in the OR estimates were found, men and women were analysed together. Notably, in addition to age, sex is automatically controlled for in the same-sexed twin pairs. Stata SE version 18 (StataCorp, College Station, Texas, USA) was used for all the analyses. We report two-tailed p-values, unless otherwise stated. RESULTS Individual-based analyses The prevalence of depression in the whole cohort was 13.3%, being higher among women (15.0%) compared with men (11.2%), p<0.001 ( Table 1 ). Distributions of the CES-D scale sum in the whole cohort and by sex are shown in the Supplement Figure 1. Of the 7,250 participants providing information about TLEs, most (70.8%) reported no TLEs in adulthood (men 69.4%; women 71.9%). One or two different kinds of TLEs were reported by 27.5% (men 29.1%; women 26.3%) and at least three TLEs by 1.7% (1.6% men; 1.8% women) of the participants. The mean sum of TLEs in adulthood was 0.40 (SD 0.71, range 0-6) in men and 0.38 (SD 0.70, range 0-4) in women. Men reported more involvements in serious traffic accidents and other serious accidents and being a victim of or witness to a violent crime than women ( Table 2 ). Women reported 10 times more often sexual assault than men. There were no other major differences in the exposure to the reported TLEs between sexes. Depression was generally more common among those men and women reporting TLEs, but the frequencies varied greatly across the TLEs ( Table 2 ). In the age- and sex-adjusted analyses (Model 1), we found evidence of associations of serious accidents (OR 1.36; 95% CI 1.01, 1.85), physical assault (OR 3.10; 95% CI 2.45, 3.93), sexual assault (OR 3.49; 95% CI 2.67, 4.55), and violent crime (OR 3.86; 95% CI 2.59, 5.73) with depression ( Table 3 ). The associations of physical assault, sexual assault, and violent crime remained substantial with no attenuation of the strength of association in any of the adjusted models (Models 2 – 4). Overall, we did not find evidence for sex interactions (i.e., sex differences in the OR estimates) (Table S2). View this table: View inline View popup Table 3. Associations (Odds Ratio [OR] with 95% Confidence Intervals [CI]) of adulthood traumatic life events with depression (The Center for Epidemiological Studies-Depression [CES-D] ≥20) in 6,002 participants of the Finnish Twin Cohort in 2011. The likelihood for depression was higher among those reporting more TLEs. In age- and sex-adjusted analyses, those reporting one to two TLEs had about 2-times higher likelihood for depression (OR 1.92; 95% CI 1.61, 2.29) than those with no TLEs, and the odd ratios were 4-fold for those reporting at least three TLEs (OR 4.54; 95% CI 2.83, 7.28). There was no statistical interaction between the number of TLEs and sex on depression. In the multivariate adjusted analyses (models 2-4), the strength of odds ratios attenuated slightly in one/two TLE category on depression (ORs varied from 1.23 to 1.52) but among those with at least three TLEs the association with depression attenuated (ORs varied from 2.29 to 3.26) (detailed data not shown). A statistical interaction (p=0.018) was found between the numbers of TLEs and of ACEs on depression. Among specific TLEs, a statistically significant interaction was found only between sum on ACEs and involvement in other serious accidents (p=0.006) but not between any other TLEs. Further, interaction between ACE sum and involvement in other serious accidents was statistically significant only in men (p=0.036). Results from the drop-out analysis related to depression are shown in Table S1. Within-pair analyses Altogether, there were 399 pairs discordant for depression (264 DZ, 135 MZ) ( Fig 1b ). The within-pairs associations of physical assault and sexual assault were elevated and statistically significant in all pairs, DZ pairs and MZ pairs ( Table 4 ). The associations of violent crime with depression were of the same strength across the three groups of pairs, though not significant for MZ pairs. Associations of involvement in other serious accidents with depression was seen only in DZ pairs. Overall, within-pair associations between TLEs and depression did not differ by sex (Table S3). View this table: View inline View popup Download powerpoint Table 4. Within-pair associations (Odds Ratio [OR] with 95% Confidence Intervals [CI]) of adulthood traumatic life events with depression (The Center for Epidemiological Studies-Depression [CES-D] ≥20) in pairs discordant for depression. All pairs and by zygosity in the Finnish Twin Cohort in 2011. DISCUSSION In this study, we examined the sex-based prevalence of adulthood traumatic life events and analysed whether the associations of TLEs with depression were independent of vulnerability, exposure loading, measured covariates or familial confounding. We found support for sex-based trauma exposure differences but not for sex-based vulnerability for depression after trauma experience. Men were exposed more often to traffic accidents, other serious accidents, and violent crime than women, whereas women reported ten times more sexual assault than men. Thus, the exposure to various TLEs seems to differ by sex which, at least partly, supports the exposure hypothesis. However, some traumas were more strongly associated with depression than others. In our study, serious accidents, physical assault, sexual assault, and violent crime were all associated with depression whereas being involved in a serious traffic accident, or in other serious accidents, or witnessing fires or natural disasters were not associated with depression. The associations were robust to adjustment for individual covariates or for shared familial factors. Further, even though depression was more common among women compared with men, we did not find evidence that associations between TLEs and depression were modified by sex. Therefore, our results implicate that if exposed to TLEs, both men and women have similar vulnerability for depression. The associations appear to be independent of several individual covariates, including ACEs and neuroticism, as well of shared familial factors including genetic vulnerability. We observed that the prevalence of depression was higher in women than in men. This sex ratio is consistent with most earlier studies ( Bebbington, 1996 , Bromet et al ., 2011 , Markkula et al ., 2015 , Salk et al ., 2017 , Steel et al ., 2014 ). Most (70%) people worldwide report exposure to at least one TLE during their lifespan ( Benjet et al ., 2016 , Kessler et al ., 2017 ). In our study, the proportion was 32% in adulthood. Notably, there is great variation in TLE prevalence across countries ( Benjet et al ., 2016 ), which may be partly accounted for by which TLEs are assessed. In addition, social unrest, conflicts, and natural catastrophes, affect some countries more than others. We included only a relatively small number of serious TLEs in our analyses, while other adverse life events were categorized as negative life events. When we combined lifelong TLEs with negative life events, their combined prevalence was 78%. Globally, the most common TLEs have been events that cause bodily harm for someone ( Benjet et al ., 2016 ). This finding is in line with our results. In line with the exposure hypothesis ( Denton et al ., 2004 ), we observed sex-based differences in exposure to traumas. Men were more exposed to traffic accidents, other serious accidents, and violent crime than women, who were more exposed to sexual assault. Exposure to domestic violence and sexual assault has been reported to be higher in females than in males ( Attila et al ., 2023 , Fergusson, Swain-Campbell and Horwood, 2002 ). In previous studies, men reported more TLE categories overall than women during the life span ( Hatch and Dohrenwend, 2007 ), but we did not observe this for either TLEs in adulthood or ACEs in childhood. Altogether, men and women seem to be exposed equally to traumatic and adverse life events, but the type of event varies. In a meta-analysis, over half of individuals with current post-traumatic stress disorder had also major depressive disorder ( Rytwinski, Scur, Feeny and Youngstrom, 2013 ). In our study, both the cumulative load of TLEs and some specific TLEs were associated with depression, as observed earlier ( Kessler, 1997 , McCutcheon et al ., 2009 , Wang et al ., 2023 , Xiang and Wang, 2021 ). We found that three traumas were associated with depression among both men and women: being injured by physical assault, being victim of sexual assault and being victim or witnessing to a violent crime. The associations remained substantial with no attenuation of the strength of association in all adjusted models. A high prevalence of sexual assault has been reported in many countries ( Kessler et al ., 2017 ). We found that sexual assault was reported by ten times more women than men. Nonetheless, the association with depression was of the same magnitude in men and women and was independent of measured covariates. In the within-pair analyses, shared exposures and experiences between twin siblings did not attenuate the association, nor did control of genetic relatedness. Thus, possible shared genetic liability between TLEs and depression does not account for the association. Indeed, we provide further evidence for a causal path from sexual assault to depression. In addition to sexual assault, being injured by physical assault or being victim or witnessing to a violent crime can be categorized as type II traumas ( Wang et al ., 2023 ). Because these specific traumas were associated with depression both in men and women, our findings do not support gender vulnerability hypothesis for depression due these traumas ( Bilodeau et al ., 2020 , Piccinelli and Wilkinson, 2000 ). The individual-based modelling of covariates and within-pair analyses are consistent with a causal role of violent crime victimization in the development of depression. We further considered cumulative load of ACEs, TLEs and weighted sum of other negative life events during the adulthood in our analyses, but they did not substantially impact the association of adult TLEs and depression. However, we found statistically significant sex-interaction on depression between sum on ACEs and involvement in other serious accidents in adulthood, yet only in males. In previous studies, individuals who have experienced ACEs or TLEs, have been reported to be at an increased risk of further TLEs and this cumulative chain of adversities can affect individual’s later well-being and depression risk ( Bürgin et al ., 2021 , Kendler et al ., 2004b , McLaughlin et al ., 2010 , Pearlin et al ., 2005 ). Also, a dose-response relationship between stressors and depression has been shown indicating that higher amount or ACEs or TLS in adulthood lower the threshold for depression ( Bandoli et al ., 2017 , Kendler et al ., 2004b , McLaughlin et al ., 2010 ). Personality traits and emotional dysregulation have been proposed as important modifiers between men and women for the onset of depression explaining some part of prevalence differences of depression between genders ( Parker and Brotchie, 2010 ). Women with high neuroticism scores have reported health problems through different kinds of TLEs ( Iacovino, Bogdan and Oltmanns, 2016 ). In our analyses, including neuroticism in the model weakened modestly the association of depression with all kinds of traumas, however, with a statistically significant effect only for involvement in other serious accidents. Thus, our analyses slightly support previous findings about the role of personality in the development of depression after stressful life events ( Iacovino et al ., 2016 ). Even though TLEs increase the risk of major depression in later life ( McCutcheon et al ., 2009 , Vibhakar et al ., 2019 , Xiang and Wang, 2021 ), not all individuals develop depressive disorders, and multiple protective factors and pathways to resilience exist ( Bonanno, 2004 , Smith and Hayslip Jr, 2012 ). We did not test the resilience hypothesis as such, but we adjusted our analyses for several factors related to resilience in relation to depressive disorders. Strengths Our data is a relatively large population-based sample with high participation rate including both men and women. We have information about multiple potential covariates. Uniquely, we could take account familial factors including genetics. Limitations Our data came from a survey where depressive symptoms were reported cross-sectionally using the CES-D scale, and we have not compared it to diagnostic measures of major depressive disorder. However, a sensitivity of 0.83 and specificity of 0.78 for individuals with clinically relevant level of depression has been shown with a cut off value ≥20 ( Vilagut et al ., 2016 ). However, reverse causation cannot rule out as a limitation. The age group in this study represents late adulthood (mean age 60) and there may be some bias if those with severe depression have not replied. The TLEs were reported retrospectively. However, retrospective reports are shown to be useful risk indicators of TLEs associated with incidence of psychopathology and its course of illness ( Baldwin et al ., 2019 ). Depressive disorders can increase reporting previous traumatic life event ( Baldwin et al ., 2019 , Schraedley, Turner and Gotlib, 2002 ). On the other hand, both depressive individuals and those who experienced TLEs might be missing from the analyses. We do not know whether respondents were not answering some TLE items because they have not experienced any TLEs or whether they found it too intimate or painful to answer. We chose a relatively small set of relevant TLEs from the Trauma History Screen measure ( Carlson et al ., 2011 ), while other studies have assessed more traumas and adverse life events ( Kessler, 1997 , Kessler et al ., 2017 , McCutcheon et al ., 2009 , Vibhakar et al ., 2019 , Wang et al ., 2023 , Xiang and Wang, 2021 ). We did analyse the effect of cumulative sum of TLEs on depression, but we have no information when or in which order TLEs have happened to a person during adulthood and whether someone has experienced several events of the same nature. Further studies Even though there is evidence that TLEs increase the risk of major depression in later life ( McCutcheon et al ., 2009 , Vibhakar et al ., 2019 , Xiang and Wang, 2021 ), not all individuals develop depressive disorders due to multiple protective factors ( Bonanno, 2004 , Smith and Hayslip Jr, 2012 ). We controlled for many resilience related factors like emotional support, but such adjustments did not substantially reduce the odds for depression especially among those injured by physical assault or being victims of sexual assault. The role of resilience related factors after a trauma as well as the type and order of cumulative load of traumatic events during lifespan warrants more studies. CONCLUSIONS Women seem to suffer from depression more than men during middle-age. Men are exposed more to traffic accidents and other serious accidents, as well as to violent crime, whereas women are exposed more to sexual assault. Traumatic life events are robustly associated with depression independently of sex and these associations appear to be independent of the variables increasing vulnerability for depression, such as personality, socioeconomic factors, other negative life events, and ACEs, as well as of familial influences, including shared genetic liability. Exposure to traumatic life events should be addressed in prevention and treatment of depression. Data Availability All data produced in the present study are available upon reasonable request to the authors Funding Statement This work was supported by the Academy of Finland (TK, JS and MM, grant number 309119), (JK, grant numbers 308248, 312073 and 352792), Biology of Trauma Initiative at Broad Institute of MIT and Harvard (grant to JK), and Sigrid Juselius Foundation (JK, Grant number 1057). Acknowledgements We acknowledge all twin participants for their valuable co-operation along the years. 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Share Traumatic life events as predictors for depression in middle-aged men and women: A Finnish twin study Piirtola Maarit , Haravuori Henna , Kiviruusu Olli , Viertiö Satu , Suvisaari Jaana , Marttunen Mauri , Kaprio Jaakko , Korhonen Tellervo medRxiv 2024.04.18.24306034; doi: https://doi.org/10.1101/2024.04.18.24306034 Share This Article: Copy Citation Tools Traumatic life events as predictors for depression in middle-aged men and women: A Finnish twin study Piirtola Maarit , Haravuori Henna , Kiviruusu Olli , Viertiö Satu , Suvisaari Jaana , Marttunen Mauri , Kaprio Jaakko , Korhonen Tellervo medRxiv 2024.04.18.24306034; doi: https://doi.org/10.1101/2024.04.18.24306034 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Epidemiology Subject Areas All Articles Addiction Medicine (573) Allergy and Immunology (865) Anesthesia (303) Cardiovascular Medicine (4457) Dentistry and Oral Medicine (445) Dermatology (383) Emergency Medicine (610) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1517) Epidemiology (15244) Forensic Medicine (30) Gastroenterology (1132) Genetic and Genomic Medicine (6620) Geriatric Medicine (669) Health Economics (1002) Health Informatics (4557) Health Policy (1372) Health Systems and Quality Improvement (1615) Hematology (543) HIV/AIDS (1272) Infectious Diseases (except HIV/AIDS) (15936) Intensive Care and Critical Care Medicine (1106) Medical Education (624) Medical Ethics (147) Nephrology (670) Neurology (6634) Nursing (346) Nutrition (999) Obstetrics and Gynecology (1148) Occupational and Environmental Health (957) Oncology (3348) Ophthalmology (980) Orthopedics (369) Otolaryngology (421) Pain Medicine (436) Palliative Medicine (130) Pathology (665) Pediatrics (1696) Pharmacology and Therapeutics (693) Primary Care Research (714) Psychiatry and Clinical Psychology (5463) Public and Global Health (9257) Radiology and Imaging (2210) Rehabilitation Medicine and Physical Therapy (1371) Respiratory Medicine (1198) Rheumatology (598) Sexual and Reproductive Health (716) Sports Medicine (532) Surgery (714) Toxicology (99) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a0344e80f8501b23',t:'MTc4MDA0NTIwNA=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();