The current investigation extends our understanding of the co-morbidity of PTSD and AD in women by characterizing common genetic and environmental contributions to the two disorders using a large, all-female community-based sample. Ours is the first known study to quantify the degree of overlap in the heritable and environmental influences on PTSD and AD in women and one of only a few to estimate heritability of PTSD in a sample that includes females. The existing literature is based primarily on an all-male twin sample in which combat was the traumatic event that led to PTSD. Our examination of PTSD and AD in an all-female population-based sample allows us both to uncover potential differences by gender in the relative role of genetics versus environment and to study the inter-relatedness of these heritable and environmental influences in the context of a broader range of trauma exposures.
Consistent with the existing literature, phenotypic analyses revealed elevated rates of lifetime AD diagnoses in women who had experienced traumatic events (Fergusson et al. 1996
; Kilpatrick et al. 1997
; Wilsnack et al. 1997
), with an even more pronounced elevation in women meeting lifetime criteria for PTSD (Kessler et al. 1995
; Breslau et al. 1997
; Danielson et al. 2009
). We also found that, among women who reported traumatic events but had no history of PTSD, the likelihood of meeting AD criteria was higher in those who experienced assaultive versus
only nonassaultive traumas (paralleling the elevated rates of PTSD in victims of assaultive events). Genetic analyses produced heritability estimates of 28%, 72% and 71% for trauma exposure, PTSD and AD respectively, and indicated that trauma exposure and PTSD were attributable to the same source of genetic variance. Whereas only additive genetic and individual-specific environmental influences were evident for PTSD and AD, shared environmental factors were also found to play a role in trauma exposure, accounting for 33% of variance. Of greatest relevance to our primary research question, we found that the genetic factors that contribute to trauma exposure and PTSD were correlated at 0.54 with those that contribute to AD, thus accounting for just under 30 % of the genetic variance in AD. Although we did not test a causal model of the PTSD–AD association (Chilcoat & Breslau, 1998
), our findings have implications for such models, specifically that they need to take into account the contribution of common genetic influences to the two disorders.
The relative contributions of genetic and environmental factors to AD observed in our sample are very similar to those reported in earlier studies, with additive genetic factors accounting for just over half of the variance in the disorder and individual-specific, but not shared, environmental influences accounting for just under half (Kendler et al. 1994
; van den Bree, 1998
; Prescott et al. 1999
). By contrast, the heritability estimate for PTSD in our sample is approximately twice that reported in earlier investigations. Xian et al.’s (2000)
study using the VETR sample, which is among the few to examine the full lifetime PTSD diagnosis, reported the heritability of PTSD to be 35%. Although not as directly comparable to our findings, similar values have been reported for PTSD symptoms. Stein et al. (2002)
, for example, found that 38 % of variance in PTSD symptoms was accounted for by genetic sources. Discrepancies between our findings and earlier reports cannot be attributed to the possible confounding effects of genetic contributions to trauma exposure itself, as we modeled trauma as a separate phenotype in our analyses. They are also not likely to be due purely to our exclusive focus on females or to the wider range of traumas represented in our sample, as the sample used by Stein et al. (2002)
was nonmilitary and 75 % female. However, given that Stein and colleagues did not test for gender differences in heritability estimates, it is possible that modest distinctions by gender in the relative contribution of genetic factors were present but not identified. Another factor to consider is that the prevalence of PTSD in our sample is lower than that reported for women in previous studies (Resnick et al. 1993
; Kessler et al. 1995
; Breslau et al. 1998
). If this reflects under-reporting, we may have identified only the most severe cases of PTSD. To the extent that severity is associated with heritability, categorizing only cases at the high end of the severity continuum as positive for PTSD could inflate the heritability estimate. Importantly, although we found a greater relative contribution of additive genetic influences to PTSD than has been reported previously, the support in our sample for an AE model is consistent with all prior genetically informative studies of PTSD.
Although intended to be a statistical control rather than a focus of the current study, the results of genetic modeling of the trauma exposure phenotype merit comment. We found that 28 % of variance in trauma exposure could be accounted for by genetic sources. In the VETR sample, Lyons et al. (1993)
reported 47% heritability for combat exposure. Stein et al. (2002)
found no evidence for genetic influences on nonassaultive trauma, but estimated heritability for assaultive trauma at 20%. Our finding that 33 % of variance in trauma exposure was accounted for by shared environmental factors is closely aligned with Stein et al
.’s estimates of 21 % and 39 % for assaultive and non-assaultive trauma respectively, but contrasts sharply with the absence of shared environmental influences reported in the VETR sample. With so few studies against which to compare our results, it is difficult to draw any definitive conclusions, but the greater similarity of our results to those of Stein et al. (2002)
Lyons et al. (1993)
suggests that the relative contribution of genetic and shared environmental influences may vary by gender and/or nature of the trauma. Again, although rarely reported in other studies, the high genetic correlation we found between trauma exposure and PTSD has also been documented previously (Stein et al. 2002
Despite our substantially higher heritability estimate for PTSD, the associations observed in our sample between genetic and environmental factors that influence PTSD and those that influence AD are highly comparable to results from the VETR sample (the only other sample in which genetic overlap between the disorders has been studied). In Xian et al.’s (2000)
study examining PTSD and AD in combination with drug dependence and also in Scherrer et al.’s (2008)
study examining PTSD and AD with combat exposure, common genetic contributions to PTSD and AD were evident. Also consistent with our findings, Scherrer et al. (2008)
found genetic overlap between combat exposure and PTSD.
Certain limitations should be kept in mind when interpreting the results from the current investigation. First, although the higher rate of PTSD in women who experienced assaultive versus only non-assaultive traumas supports the validity of this distinction as a crude severity indicator, we expect that a more direct measure of severity (e.g. subjective ratings of distress) would be more accurate. Second, our use of retrospective reports introduced potential retrospective reporting biases, although the adjustments made for age at time of report for all three phenotypes likely reduced their impact. Third, although integrating data from earlier waves of data collection and other sections of the interview with the Wave 4 trauma checklist enhanced the accuracy in establishing trauma status, only individuals who endorsed events on the trauma checklist (which, unlike the questions from early home environment and sexual maturation questions, were not worded behaviorally) were assessed for PTSD. As a result, PTSD diagnoses were missing for this subset of the sample. Fourth, although highly comparable to the lifetime prevalence of trauma exposure reported in studies using similar definitions, the rate of trauma exposure in our sample is lower than that reported in studies using broader definitions (e.g. learning about a loved one experiencing a traumatic event). Fifth, most, but not all, participants had passed the age of risk for AD. Similarly, some women in our study who had not yet been exposed to trauma or developed PTSD are likely to do so in the future, so we cannot assume that our findings are equally valid in older women.
Given the scarcity of the literature in this area, the first priority in this line of research is to attempt to replicate our findings in another genetically informative female sample. The next logical step is to test for gender differences in heritability of PTSD and its genetic overlap with AD in a civilian sample of men and women. Studies in this area are of particular interest in light of the absence of evidence of gender differences for other anxiety disorders (Hettema et al. 2005
; Kendler et al. 2003
) and mixed evidence for depression (Bierut et al. 1999
; Franic et al. 2010
). It is also important to address potential distinctions in both the link with AD and the relative contribution of genetic factors to childhood versus
adulthood trauma exposure and PTSD onset. With respect to identifying populations at high risk for substance-related problems, it is also important to determine the extent to which our findings generalize to other substances of abuse.