Key Points
Question
Are adverse stress responses (ASRs) or posttraumatic stress disorder (PTSD) transmitted from parents to offspring, and if so, to what extent is the transmission due to genes vs rearing?
Findings
This cohort study of 2 194 171 individuals found that ASRs or PTSD was transmitted from parents to offspring through rearing and genes. Shared traumatic event exposure was likely important in transmission; however, correlations with rearing remained substantial even when controlling for potential shared exposures.
Meaning
Parent-offspring transmission of ASRs or PTSD was correlated with both rearing and genes. Even after accounting for potential shared index traumas, correlations were similar for both rearing and genes.
Abstract
Importance
Twin studies have found that posttraumatic stress disorder (PTSD) is influenced by both genetic and environmental factors within a generation. No study has used an adoption design, which can address questions about the degree and sources of cross-generational transmission of adverse stress responses (ASRs) and PTSD.
Objectives
To examine whether ASRs or PTSD are transmitted from parents to offspring, and to clarify the relative importance of genes and rearing.
Design, Setting, and Participants
This cohort study used nationwide Swedish registry data from parents and offspring (n = 2 194 171, born 1960-1992) of 6 types of families (intact; had not lived with biological father; had not lived with biological mother; lived with stepfather; lived with stepmother; and adoptive). Follow-up occurred on December 31, 2018, and data were analyzed from March 3, 2023, to January 16, 2024.
Exposures
Three sources of parent-offspring resemblance: genes plus rearing, genes only, and rearing only.
Main Outcomes and Measures
Diagnoses of ASRs or PTSD were obtained from national inpatient, outpatient, and primary care medical registries. Parent-child resemblance was assessed by tetrachoric correlation. Sensitivity analyses were conducted to control for possible shared traumatic events.
Results
The study population included 2 194 171 individuals of 6 family types (1 146 703 [52.3%] male; median [range] age, 42 [20-63] years). The weighted tetrachoric correlations across family types were 0.15 (95% CI, 0.15-0.16) for genes plus rearing, 0.08 (95% CI, 0.06-0.11) for genes only, and 0.10 (95% CI, 0.07-0.12) for rearing only. Controlling for potential shared traumatic events, sensitivity analyses found that the correlation for rearing decreased, with the most conservative control (exclusion of parent-offspring dyads with onset of ASRs or PTSD within 1 year) suggesting equal correlations with genes and rearing.
Conclusions and Relevance
Diagnosis of ASRs or PTSD demonstrated cross-generational transmission, including both genetic and rearing correlations. Sensitivity analyses suggested that shared traumatic events partially accounted for the observed rearing correlations.
This cohort study using nationwide Swedish registry data examines whether parent-offspring transmission of adverse stress responses or posttraumatic stress disorder is correlated with genes or rearing.
Introduction
Twin studies of posttraumatic stress disorder (PTSD) have demonstrated moderate heritability, with estimates ranging from 26% (95% CI, 12%-40%) to 72% (95% CI, 41%-85%),1,2,3,4 and that unique, but not shared, environmental influences account for variance in PTSD.2,3,4 Several factors correlate with liability to PTSD.5 Family history of mood disorders increases the risk for exposure to trauma6 and for PTSD.7,8,9 Epidemiological studies suggest that familial environmental factors, such as job instability, parental poverty, separation or divorce of parents prior to age 10 years, and early adversity, correlate with PTSD.10 Thus, familial factors and shared genes are important in PTSD etiology.
These studies largely rely on intact families who share both genes and environment, limiting their ability to separate out the influence of these 2 sources. This leaves questions unanswered: do the familial environmental factors (ie, rearing) that correlate with risk for PTSD have a causal relationship, or are they accounted for by parental susceptibilities that are transmitted genetically to their offspring? These questions can be addressed in an adoption design where information on PTSD is available across 2 generations, allowing us to determine the degree and sources of cross-generational transmission.
To our knowledge, PTSD has yet to be studied using an adoption design. Substance use disorders, which like PTSD’s conditional relationship with trauma exposure are conditional on exposure to the relevant substances, has been examined with an adoption design, finding evidence for both genetic and rearing transmission.11,12,13 Adoption studies have also been applied to similarly heritable phenotypes (eg, major depressive disorder [MDD], anxiety disorders [ADs]).14,15,16,17,18,19,20 Results from research using data from the registries used herein suggest that ADs and MDD are transmitted from parents to offspring via a combination of genetic (67% and 57%, respectively) and rearing (33% and 43%, respectively) influences.21 These findings of rearing influences contrast with twin studies wherein shared environmental effects on these conditions are generally not found.14,15,16 However, the estimates of shared environment within a generation, as estimated by twin studies, differ from rearing effects across a generation; they reflect a wide range of influences, with rearing being only a small part and with other notable sources of influence (eg, sibling interactions, peer and school influences, and community and cohort associations). Twin studies have found that the proportion of sibling resemblance for psychopathology due to parenting is modest (ie, <4% for many disorders and <2% for some disorders).22
An innovation to the adoption design has been the inclusion of other familial constellations beyond adoptions. Termed the extended adoption design, these constellations include biological parents who never live with their offspring and stepparents who raise children who are genetically unrelated to them. Examining these forms of parent-offspring families increases statistical power and provides the ability to replicate findings within the same study. Furthermore, while adoptive parents are carefully selected in Sweden and tend to have quite low rates of psychopathology,23 this does not apply to stepparents. The extended adoption design has been used in the study of other disorders21 but, to our knowledge, has yet to be applied to PTSD.
Thus, our aims are to assess whether PTSD is transmitted from parents to offspring and, if so, to determine to what extent the transmission is due to genes vs rearing using an extended adoption design applied to a nationwide Swedish sample. We also aimed to examine the influence of potential shared traumatic events across parents and their children as another source of environmental cross-generational transmission of PTSD.
Methods
Information for this study was collected from nationwide Swedish registries (eMethods in Supplement 1). Ethical approval was obtained, and as approved by the Swedish ethical authorities, informed consent was not obtained. Each person’s unique identification number, having been replaced with serial numbers for confidentiality, was used for registry linkages. Using the Swedish Hospital Discharge Register, Outpatient Care Register, and nationwide primary care data, a definition of adverse stress responses (ASRs) and PTSD encapsulating stress reaction disorders was defined using International Classification of Diseases, Ninth Revision (ICD-9) code 308 and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes F43.1, F43.0, and F62.0. Additional analyses used the strict definition, using only ICD-10 code F43.1.
We included all individuals born in Sweden from 1960 through 1992 who were alive and resided in Sweden at least until age 20 years. For having a chance of being diagnosed with ASRs or PTSD, individuals had to have some follow-up time beyond 1987, when ICD-9 codes began to be used in the Swedish registries. Study end was set at December 31, 2018, for reasons of the availability of medical registry data. In the registries, we searched for the number of years, during ages 0 to 15 years, that the individuals, herein called offspring, resided in the same household and geographic area as their biological mother, biological father, and possible stepfather, stepmother, adoptive mother, and adoptive father. From 1960 to 1985 (every fifth year), we used household identification numbers from the Population and Housing Census to define family types.
We defined the following types of families: intact families that included offspring residing from ages 0 to 15 years in the same household with both the biological mother and biological father; families with not-lived-with (NLW) father or NLW mother that included offspring who never resided in the same household or Statistical Area Market Survey area (eMethods in Supplement 1) as the biological father or biological mother; 2 types of stepfamilies (stepfather or stepmother) that included offspring who did not reside the entire period between ages 0 to 15 years with the biological father or biological mother and resided at least 10 of these years with a biologically unrelated man or woman 18 to 50 years older; and adoptive families that included offspring adopted before age 5 years with information on both adoptive parents and at least 1 biological parent. The adoptive parents had to be biologically unrelated to the offspring, and the offspring had to reside with each adoptive parent for at least 10 years between ages 0 to 15 years. As domestic adoptions declined in Sweden in recent decades, we defined our adoption cohort to maximize sample size, including offspring born from 1955 to 1992 (the birth cohorts of 1955-1959 were not included for the other family types as household information was available from 1960 onward). The NLW parents and stepparents were defined so that their relationships with their offspring resembled those seen between an adoptee and his or her biological and adoptive parents. To be recorded as a biological mother in the NLW father or stepfather families or a biological father in the NLW mother or stepmother families, where the aim was for the biological mother or father to reflect a genes plus rearing relationship with her or his offspring, the offspring had to reside with the biological mother or father from ages 0 to 15 years.
For all family types, parents had to be alive throughout 1986 and had to reside in Sweden during some period from 1987 onward. Overlaps exist in the parent-offspring pairs, with a genes plus rearing relationship, between the NLW families and the stepfamilies. When doing joint statistical analyses across family types, overlapping biological mothers (n = 20 843) or biological fathers (n = 365) were only included in the stepfather or stepmother families and no longer in the NLW father or NLW mother families, so that each relationship was calculated only once. In descriptive tables and familywise analyses, the pairs were included in both types of families.
Statistical Analysis
In our parent-offspring pairs, we calculated tetrachoric correlations—which represent the correlation in relatives for a latent underlying normally distributed liability to illness24—for ASR or PTSD transmission. We used this measure because of its ease of interpretability25 and its insensitivity to changes in base rates.26 For the primary analyses, we used the escalc and rma functions (eTable 1 in Supplement 1) from the R package metafor (R Foundation).27 We tested for heterogeneity in tetrachoric correlations across families using a significance level of P < .05, and we used a Bonferroni correction. As the tests of heterogeneity did not detect significant differences, we used a meta-analysis fixed-effects (instead of random-effects) model to calculate weighted tetrachoric correlations28 for the transmissions labeled genes plus rearing, genes only, and rearing only. The tetrachoric correlations across the different relationships were tested for heterogeneity. When calculating the correlations, we made the simplified assumption that parent-offspring pairs were independent of each other, which could lead to a slight underestimation in the width of confidence intervals. Notably, when including robust standard errors in the Cox regression models, confidence intervals for the hazard ratios (HRs) were almost identical to when not applying robust standard errors.
A sensitivity analysis was conducted in which we excluded parent-offspring pairs who developed ASRs or PTSD likely in response to a shared traumatic event. To do so, we calculated the difference in onset times of the ASR or PTSD diagnoses for the parent-offspring pairs; if this difference was shorter than a specific time frame (ie, 3, 6, or 12 months), those pairs were excluded from analyses that were conducted using the same methods as described earlier for the full sample. In another sensitivity analysis, we included only the ICD-10 code F43.1 to define PTSD. As this code can be found in registries from 1997 onward, offspring and parents had to have some follow-up time from 1997 or later to be included. Also, to increase power, we included offspring born from 1993 through 1995. For this definition of PTSD, we recalculated the tetrachoric correlations across families. Data analysis was conducted from March 3, 2023, to January 16, 2024. Statistical analyses were performed using R version 4.2.1 (R Foundation) (eTable 1 in Supplement 1) and SAS version 9.4 (SAS Institute Inc) statistical software.
Results
Descriptive Analyses
The study population included 2 194 171 individuals (1 146 703 [52.3%] male). The sample sizes by type of parents and offspring, born from 1960 through 1992 (1955-1992 in adoptive families) are shown in Table 1. The mean (SD) age of the offspring was 41.5 (10.0) years (median [range], 42 [20-63] years). Table 2 presents the prevalence of ASRs or PTSD, which in offspring appeared to be lowest in intact families compared with other types of families, highest in disrupted families (NLW and stepparent families), and moderate in offspring from adoptive families. The prevalence of ASRs or PTSD was lowest among adoptive parents, which is expected, as these parents are screened prior to approval for adoption. Higher prevalence of ASRs or PTSD was found in women compared with men across all family types.
Table 1. Sample Size, Birth Year, Age, and Sex Distributions Across the 6 Family Types Included in the Study.
| Characteristic | Intact families | NLW father families | NLW mother families | Stepfather families | Stepmother families | Adoptive families |
|---|---|---|---|---|---|---|
| Sample size, No. | ||||||
| Offspring | 2 000 648 | 106 032 | 5824 | 93 432 | 17 007 | 12 392 |
| Biological mother | 2 000 648 | 77 541 | 5824 | 68 777 | NA | 12 240 |
| Biological father | 2 000 648 | 106 032 | 964 | NA | 4385 | 7747 |
| Offspring | ||||||
| Year of birth, mean (SD) | 1975.7 (9.5) | 1974.3 (9.6) | 1968.7 (8.0) | 1973.8 (8.4) | 1972.6 (8.6) | 1964.6 (7.7) |
| Age, mean (SD) [range], y | 41.3 (9.9) [20-58] | 42.5 (10.1) [20-58] | 47.7 (9.3) [20-58] | 43.0 (9.2) 20-58] | 43.9 (9.5) [20-58] | 51.9 (9.1) [20-63] |
| Sex, No. (%) | ||||||
| Female | 952 363 (47.6) | 52 180 (49.2) | 2683 (46.1) | 46 697 (50.0) | 7787 (45.8) | 5825 (47.0) |
| Male | 1 048 285 (52.4) | 53 852 (50.8) | 3141 (53.9) | 46 735 (50.0) | 9220 (54.2) | 6567 (53.0) |
| Average parental level of education, No. (%)a | ||||||
| Biological parent | ||||||
| Presecondary | 284 336 (14.2) | 13 131 (12.4) | 1633 (28.0) | 13 520 (14.5) | 4343 (25.5) | 4654 (37.6) |
| Secondary | 988 299 (49.4) | 59 903 (56.5) | 2965 (50.9) | 54 063 (57.9) | 8192 (48.2) | 5788 (46.7) |
| Postsecondary | 727 748 (36.4) | 32 960 (31.1) | 1188 (20.4) | 25 643 (27.4) | 3904 (23.0) | 1854 (15.0) |
| Lived-with parent | ||||||
| Presecondary | 284 336 (14.2) | 26 431 (24.9) | 2235 (38.4) | 31 797 (19.1) | 5216 (30.7) | 3377 (27.3) |
| Secondary | 988 299 (49.4) | 52 150 (49.2) | 2071 (35.6) | 41 351 (54.3) | 7393 (43.5) | 5578 (45.0) |
| Postsecondary | 727 748 (36.4) | 27 191 (25.6) | 1084 (18.6) | 20 152 (26.6) | 4358 (25.6) | 3406 (27.5) |
Abbreviations: NA, not applicable; NLW, not-lived-with.
When the average level fell between 2 categories, it was rounded to the higher educational level.
Table 2. Prevalence of ASRs or PTSD in the Relatives From the 6 Family Types Included in the Study.
| Relative | No. with ASRs or PTSD/total No. (%) | ||||||
|---|---|---|---|---|---|---|---|
| Intact families | NLW father families | NLW mother families | Stepfather families | Stepmother families | Adoptive families | Alla | |
| All offspring | 106 711/2 000 648 (5.3) | 10 313/106 032 (9.7) | 563/5824 (9.7) | 8652/93 432 (9.3) | 1831/17 007 (10.8) | 1076/12 392 (8.7) | 125 029/2 194 171 (5.7) |
| Female offspring | 72 860/952 363 (7.7) | 6977/52 180 (13.4) | 366/2683 (13.6) | 5844/46 697 (12.5) | 1126/7787 (14.5) | 707/5825 (12.1) | 85 197/1 047 468 (8.1) |
| Male offspring | 33 851/1 048 285 (3.2) | 3336/53 852 (6.2) | 197/3141 (6.3) | 2808/46 735 (6.0) | 705/9220 (7.6) | 369/6567 (5.6) | 39 832/1 146 703 (3.5) |
| Biological mother | 67 276/2 000 648 (3.4) | 5434/77 541 (7.0) | 231/5824 (4.0) | 4155/68 777 (6.0) | NA | 339/12 240 (2.8) | 76 359/2 144 187 (3.6) |
| Biological father | 26 824/2 000 648 (1.3) | 2889/106 032 (2.7) | 11/964 (1.1) | NA | 81/4385 (1.8) | 90/7747 (1.2) | 29 892/2 119 411 (1.4) |
| Stepmother or adoptive mother | NA | NA | NA | NA | 597/17 007 (3.5) | 186/12 392 (1.5) | 783/29 399 (2.7) |
| Stepfather or adoptive father | NA | NA | NA | 1851/93 432 (2.0) | NA | 60/12 392 (0.5) | 1911/105 824 (1.8) |
Abbreviations: ASRs, adverse stress responses; NA, not applicable; NLW, not-lived-with; PTSD, posttraumatic stress disorder.
Offspring included in more than 1 type of family are counted once.
Cross-Generational Transmission
Tetrachoric correlations for ASR or PTSD transmission were calculated for mothers and fathers across the family types (eTable 2 in Supplement 1). The test for heterogeneity examines whether the correlations used to determine the weighted estimate were statistically heterogeneous, and none were. Cross-generational transmission for ASRs or PTSD was highest among mothers and fathers providing genes plus rearing (r = 0.16 [95% CI, 0.15-0.17] and 0.14 [95% CI, 0.13-0.15], respectively), intermediate in mothers and fathers providing rearing only (r = 0.11 [95% CI, 0.06-0.15] and 0.10 [95% CI, 0.07-0.13], respectively), and lowest in mothers and fathers providing genes only (r = 0.06 [95% CI, 0.00-0.12] and 0.09 [95% CI, 0.06-0.11], respectively). The weighted estimate from parents reflecting genes plus rearing was 0.15 (95% CI, 0.15-0.16); genes only, 0.08 (95% CI, 0.06-0.11); and rearing only, 0.10 (95% CI, 0.07-0.12) (Table 3). The weighted estimate was significantly higher for genes plus rearing compared with both genes only and rearing only, whereas estimates of genes only and rearing only were not significantly different. Concordance rates for parent-offspring pairs are provided in eTable 3 in Supplement 1. Analyses were rerun using only ICD-10 code F43.1 (eTables 4-7 in Supplement 1), and the pattern of results was highly consistent.
Table 3. Tests of Transmission of Adverse Stress Responses or Posttraumatic Stress Disorder From Mothers and Fathers Using Weighted Estimates Across All Family Types.
| Exclusion cutoff for shared traumatic event | Estimate (95% CI) | Nominal P value for test of heterogeneitya | ||
|---|---|---|---|---|
| Mothers | Fathers | Weighted estimate | ||
| None | ||||
| Genes plus rearing | 0.16 (0.15-0.17) | 0.14 (0.13-0.15) | 0.15 (0.15-0.16)b,c | <.001d |
| Genes only | 0.06 (0.00-0.12) | 0.09 (0.06-0.11) | 0.08 (0.06-0.11)b | .51 |
| Rearing only | 0.11 (0.06-0.15) | 0.10 (0.07-0.13) | 0.10 (0.07-0.12)c | .58 |
| <3 mo | ||||
| Genes plus rearing | 0.12 (0.11-0.13) | 0.10 (0.09-0.11) | 0.11 (0.11-0.12)b,c | <.001d |
| Genes only | 0.06 (−0.01 to 0.12) | 0.08 (0.05-0.10) | 0.07 (0.05-0.10)b | .57 |
| Rearing only | 0.07 (0.02-0.12) | 0.08 (0.05-0.11) | 0.08 (0.05-0.10)c | .99 |
| <6 mo | ||||
| Genes plus rearing | 0.10 (0.10-0.11) | 0.09 (0.08-0.10) | 0.10 (0.10-0.11)b | <.001d |
| Genes only | 0.04 (−0.02 to 0.10) | 0.07 (0.04-0.09) | 0.06 (0.04-0.09)b | .47 |
| Rearing only | 0.06 (0.01-0.11) | 0.07 (0.04-0.10) | 0.07 (0.04-0.09) | .95 |
| <1 y | ||||
| Genes plus rearing | 0.08 (0.07-0.09) | 0.07 (0.07-0.08) | 0.08 (0.07-0.08) | .03 |
| Genes only | 0.03 (−0.03-0.09) | 0.05 (0.03-0.08) | 0.05 (0.02-0.07) | .81 |
| Rearing only | 0.05 (0.00-0.10) | 0.05 (0.02-0.09) | 0.05 (0.03-0.08) | .89 |
Significance threshold after Bonferroni correction for 12 tests was P < .05/12 = .004.
Significant test of heterogeneity between genes plus rearing relationships and genes only relationships. Significance threshold after Bonferroni correction for 12 tests was P < .05/12 = .004.
Significant test of heterogeneity between genes plus rearing relationships and rearing only relationships. Significance threshold after Bonferroni correction for 12 tests was P < .05/12 = .004.
Statistically significant at P < .004.
To determine the relative risk of offspring ASRs or PTSD conferred by parental ASRs or PTSD, a Cox regression model was conducted (eMethods in Supplement 1). The HR from parents reflecting genes plus rearing was 3.08 (95 CI, 3.02-3.14); genes only, 2.11 (95% CI, 1.92-2.32); and rearing only, 2.31 (95% CI, 2.08-2.57).
Sensitivity Analysis
Diagnosis of ASRs or PTSD is unique in that exposure to a traumatic event is a criterion for the disorder, and exposure to the same trauma may confound the rearing estimates. If parent-offspring dyads were exposed to the same event, they would have similar ASR or PTSD onset. To disentangle the contribution of possible shared event exposure from rearing, dyads were excluded if the differences in their time at onset of ASR or PTSD diagnosis was shorter than a specified time frame (Table 4). eTable 2 in Supplement 1 shows the results for transmission across all family types using 3 different time frames. The weighted estimates are shown in Table 3 and the Figure. When excluding dyads with onset of within 3 months, the weighted estimate from parents reflecting genes plus rearing was 0.11 (95% CI, 0.11-0.12); genes only, 0.07 (95% CI, 0.05-0.10); and rearing only, 0.08 (95% CI, 0.05-0.10). When excluding dyads whose onset was within 6 months, the weighted estimate for genes plus rearing was 0.10 (95% CI, 0.10-0.11); genes only, 0.06 (95% CI, 0.04-0.09); and rearing only, 0.07 (95% CI, 0.04-0.09). When excluding dyads whose onset of ASRs or PTSD was within 1 year, the weighted estimate for genes plus rearing was 0.08 (95% CI, 0.07-0.08); genes only, 0.05 (95% CI, 0.02-0.07); and rearing only, 0.05 (95% CI, 0.03-0.08).
Table 4. Parent-Offspring Pairs Excluded Due to Possible Shared Traumatic Event.
| Time between onset of ASRs or PTSD for parent and offspring | Parent | No. excluded/total No. (%) | |||||
|---|---|---|---|---|---|---|---|
| Intact families | NLW father families | NLW mother families | Stepfather families | Stepmother families | Adoptive families | ||
| <3 mo | Biological mother | 1106/6851 (16.1) | 70/800 (8.8) | 28a | 54/571 (9.5) | NA | 38a |
| Biological father | 479/2781 (17.2) | 17 /389 (4.4) | a | NA | 11a | 13a | |
| Stepmother or adoptive mother | NA | NA | NA | NA | 11/90 (12.2) | 28a | |
| Stepfather or adoptive father | NA | NA | NA | 19/255 (7.5) | NA | 6a | |
| <6 mo | Biological mother | 1490/6851 (21.7) | 99/800 (12.4) | 28a | 85/571 (14.9) | NA | 5/38 (13.2) |
| Biological father | 610/2781 (21.9) | 31/389 (8.0) | a | NA | 11a | 13a | |
| Stepmother or adoptive mother | NA | NA | NA | NA | 15/90 (16.7) | 5/28 (17.9) | |
| Stepfather or adoptive father | NA | NA | NA | 29/255 (11.4) | NA | 6a | |
| <1 y | Biological mother | 2047/6851 (29.9) | 168/800 (21.0) | 28a | 137/571 (24.0) | NA | 7/38 (18.4) |
| Biological father | 787/2871 (28.3) | 56/389 (14.4) | a | NA | 11a | 13a | |
| Stepmother or adoptive mother | NA | NA | NA | NA | 18/90 (20.0) | 6/28 (21.4) | |
| Stepfather or adoptive father | NA | NA | NA | 45/255 (17.6) | NA | 6a | |
Abbreviations: ASRs, adverse stress responses; NA, not applicable; NLW, not-lived-with; PTSD, posttraumatic stress disorder.
Parent-offspring pairs less than 5 are not shown. Where applicable, the number shown indicates the total number (denominator).
Figure. Weighted Tetrachoric Correlations of Genes Plus Rearing, Genes Only, and Rearing Only for Cross-Generational Transmission of Adverse Stress Responses and Posttraumatic Stress Disorder.
The first set of bars represents the analyses in the full sample, with no exclusion for parent-offspring onset of adverse stress responses or posttraumatic stress disorder. The next estimates reflect the results from the models in which the sample was restricted if onset times of adverse stress responses or posttraumatic stress disorder for parents and offspring were within the time frame noted. These sensitivity analyses were conducted to examine the influence of potential shared traumatic events. Compared with genes plus rearing, differences were significant (P < .05) for genes only and rearing only in the groups with no exclusion and with exclusion for less than 3 months and for genes only in the group with exclusion for less than 6 months.
Discussion
This is, to our knowledge, the first adoption study of ASRs and PTSD as well as the first to apply an extended adoptive design. By using other familial constellations (eg, biological parents who did not live with offspring, stepparents), the present study is substantially more powered than traditional adoption designs. Moreover, including these familial constellations provides an opportunity for within-study replication of adoption findings. Indeed, our results support that NLW parents and stepparents are suitable proxies for biological parents and adoptive parents, respectively, in traditional adoption designs.
We first sought to determine the sources of cross-generational transmission of ASRs or PTSD in the full sample. ASRs or PTSD were moderately transmitted from parents to children in the full sample (ie, not adjusting for potential shared traumatic exposures). The weighted tetrachoric estimates across multiple family types and across mothers and fathers for genes plus rearing was 0.15 (95% CI, 0.15-0.16), significantly higher than the estimates for both genes only (0.08 [95% CI, 0.06-0.11]) and rearing only (0.10 [95% CI, 0.07-0.12]). Thus, approximately 45% of the parent-offspring resemblance for ASRs or PTSD was due to genetic transmission, and 55% of the resemblance was due to rearing. These genetic and rearing estimates are similar in strength to those found for MDD and AD, similarly heritable conditions.21 Our results of genetic influence across generations for ASRs or PTSD are consistent with evidence from twin studies that consistently find moderate genetic influences within a generation.29
Rearing correlations have also been found for MDD and AD using extended adoption designs.21 Our findings for ASRs and PTSD stand out in that the estimates for rearing were larger than those for genes, whereas the reverse is true for MDD and AD.21 ASRs and PTSD are unique, as exposure to a traumatic event is a necessary but not sufficient criterion. Family studies highlight the role of shared trauma in the etiology of the disorder in dyads for ranges of events,30 including disasters.31 A systematic review of parent-offspring PTSD found that parental PTSD was associated with youth outcomes also in nonshared traumas (eg, parental combat exposure).30 However, the extant studies are unable to determine whether the pattern of parent-offspring transmission is due to genetic or environmental effects. Adoption designs can clarify the sources of influence. To attempt to disentangle the degree to which the rearing estimates were confounded by potential shared trauma, we conducted sensitivity analyses. Across all sensitivity analyses, rearing estimates remained substantial (ie, 50%-54%). The modest attenuation of rearing estimates from the unadjusted model suggests a role of potential shared trauma in parent-offspring resemblance for ASRs or PTSD. However, even in the most conservative model, the rearing estimates were not statistically different from genetic estimates. Thus, aspects of the rearing environment beyond potential shared trauma are critical in ASR or PTSD etiology. We note that the sensitivity analyses may have removed dyads who were exposed to different traumas within the specified time frame, suggesting a possible role for other instrumental factors (eg, offspring may be at higher risk for trauma exposure if their parent has had acute trauma or PTSD).
An important next step will be to shed light on the source of the correlation with rearing found, with a focus on modifiable characteristics to inform prevention and intervention efforts. Social learning may play an important role, such as parental modeling of avoidance behaviors,32 an important factor of PTSD etiology. This modeling of avoidance could influence offspring risk of PTSD should they be exposed to traumatic events and thus could interrupt normative processing of the event. Further, distorted cognitions, such as exaggerated estimations of threat and safety, are common in PTSD,33 and if they are exhibited in the parents, they may also impact youth outcomes. Growing research is also examining the role of parental PTSD in family dysfunction and parenting behaviors, which have been found to influence offspring PTSD risk.31,34
Limitations
This study has several limitations. Cases of ASRs or PTSD were primarily detected from the primary care registry, which likely represents an underestimate as many do not seek care and/or do not report psychiatric symptoms to their physician. Our ASR or PTSD variable also included acute stress disorder and thus encompasses stress reactive disorders. However, the same pattern of results was found for analyses of a strict definition using ICD-10 code F43.1. Further, we were unable to disentangle the effects of trauma separately from those of ASRs or PTSD, although we strove to address potential shared trauma through sensitivity analyses. Thus, the genetic and rearing estimates reflect the combined risk for trauma and for ASRs or PTSD. Adoptive parents are selected (eg, good health, socioeconomic status; Table 1); rates of ASRs or PTSD are lowest in adoptive parents. The extended adoption design is an innovative methodological improvement, as stepparents and NLW parents undergo no formal selection, thus increasing generalizability. Indeed, while education was higher in adoptive parents compared with biological parents, this pattern was not true for stepparents. As our rearing estimates come largely from the stepparents, our rearing estimates may be less influenced by confounders of socioeconomic status. Additionally, our sample was restricted to native-born Swedish individuals, which limits generalizability. Other minor limitations include the birth cohort inclusion for offspring (born by 1955 for adoptive offspring and 1960 for other offspring due to household information availability). Our study also has strengths, including the novel design, statistical power, and representation of the country. Further, using diagnostic codes circumvents error that stems from self-report (eg, memory biases).
Conclusions
ASRs or PTSD are moderately transmitted across generations, and this is due to both genes and rearing. Rearing estimates are modestly confounded by potential shared trauma experiences between parents and offspring. However, rearing estimates outside of potential shared trauma exposure are still critically important in the etiology of ASRs and PTSD in offspring.
eMethods. Detailed Methods
eTable 1. Details on R-Packages Used in Statistical Analyses
eTable 2. Parent-Offspring Cross-Generational Transmission of ASR/PTSD: Tetrachoric Correlations, Weighted Estimates, and Heterogeneity Tests
eTable 3. Distribution of Parent-Offspring Pairs Across Families, in Relation to ASR/PTSD
eTable 4. Sample Size, Birth Year, Age and Sex Distributions Across the Six Family Types Included in the Study for Subanalyses of F43.1
eTable 5. Total Numbers, Prevalence, No. (%), of PTSD (F43.1) in the Relatives From the Six Family Types Included in This Study
eTable 6. Parent-Offspring Cross-Generational Transmission of PTSD (F43.1): Tetrachoric Correlations, Weighted Estimates, and Heterogeneity Tests
eTable 7. Tests of Transmission of PTSD (F43.1) From Mothers and Fathers Using Weighted Estimates Across All Family Types
Data Sharing Statement
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eMethods. Detailed Methods
eTable 1. Details on R-Packages Used in Statistical Analyses
eTable 2. Parent-Offspring Cross-Generational Transmission of ASR/PTSD: Tetrachoric Correlations, Weighted Estimates, and Heterogeneity Tests
eTable 3. Distribution of Parent-Offspring Pairs Across Families, in Relation to ASR/PTSD
eTable 4. Sample Size, Birth Year, Age and Sex Distributions Across the Six Family Types Included in the Study for Subanalyses of F43.1
eTable 5. Total Numbers, Prevalence, No. (%), of PTSD (F43.1) in the Relatives From the Six Family Types Included in This Study
eTable 6. Parent-Offspring Cross-Generational Transmission of PTSD (F43.1): Tetrachoric Correlations, Weighted Estimates, and Heterogeneity Tests
eTable 7. Tests of Transmission of PTSD (F43.1) From Mothers and Fathers Using Weighted Estimates Across All Family Types
Data Sharing Statement