Twin studies have made four major contributions to our understanding of the genetic etiology of PTSD. First, they indicate that genetic factors influence exposure to PTEs. This is referred to as gene-environment correlation, whereby selection of environment, and subsequently potential for exposure to trauma, is partly determined by genetic factors [
Kendler and Eaves, 1986]. For example, twin studies have demonstrated that genetic factors influence exposure to PTEs such as combat exposure [
Lyons et al., 1993] and assaultive violence [
Stein et al., 2002]. These gene-environmental correlations are likely due in part to individual differences in personality. Personality characteristics are moderately heritable and influence the tendency for individuals to select themselves into potentially harmful environments. For example, longitudinal investigations have found that childhood adjustment and neuroticism predicted subsequent stressful life events in adulthood [
Van Os and Jones, 1999]. Similarly, research has found that childhood externalizing is prospectively associated with both risk of trauma exposure and with PTSD in adulthood [
Koenen et al., 2007b]. One investigation found that genetic factors partially mediated the association between personality variables (such as antisocial personality traits, psychoticism, and openness to novelty) and exposure to violent traumatic events [
Jang et al., 2003].
Second, twin studies suggest genetic influences explain a substantial proportion of vulnerability to PTSD even after accounting for genetic influences on trauma exposure. The first twin study to estimate heritability of PTSD was conducted by
True et al. [1993] on members of the Vietnam Era Twin (VET) Registry. The authors found that approximately 30% of the variance in PTSD was accounted for by genetic factors, even after controlling for combat exposure. Genetic influences on PTSD were similar for twins who did not serve in Southeast Asia, suggesting heritability of PTSD has generalization to traumatic events other than combat exposure. The second twin study of PTSD was conducted on a sample of male and female civilian volunteers [
Stein et al., 2002]. Consistent with True and colleagues, the authors found moderate heritability in PTSD symptoms, with additional variance accounted for by non-shared environmental factors. The findings from these two twin studies support suggest that genetic factors play a substantial role in vulnerability to developing PTSD.
Third, twin studies have demonstrated that genetic influences on PTSD overlap with those for other mental disorders. The extent of the overlap varies with the disorder studied. For example, genetic influences on major depression account for the majority of the genetic variance in PTSD [
Fu et al., 2007;
Koenen et al., 2007a]. Genetic influences common to generalized anxiety disorder and panic disorder symptoms account for approximately 60% of the genetic variance in PTSD [
Chantarujikapong et al., 2001] and those common to alcohol and drug dependence [
Xian et al., 2000] and nicotine dependence [
Koenen et al., 2005a] account for over 40% of the variance associated with PTSD. Thus, the limited data available suggest that the majority of genes that affect risk for PTSD also influence risk for other psychiatric disorders and vice versa.
Fourth, twin studies can provide important information regarding possible biological “endophenotypes,” or intervening phenotypes inmultifactorial disorders that may be more proximal to genetic variants. Toward the examination of these endophenotypes, twin studies have employed monozygotic (MZ) discordant design, in which individuals with and without PTSD are compared
across twin pairs on a specific biological correlate to determine whether that marker is associated with the PTSD diagnosis. The design includes four participant groups: (1) trauma-exposed index twins who developed PTSD; (2) their “high-risk” trauma-unexposed co-twins who did not have PTSD (considered high risk because their identical twin developed PTSD when exposed to trauma); (3) trauma-exposed index twins with no PTSD; and (4) “low risk” trauma unexposed co-twins who did not have PTSD (deemed low risk because their identical twin did not develop PTSD when exposed to trauma).
Pitman et al. [2006] have used the MZ discordant design to test whether commonly found biological correlates of PTSD are actually risk factors for developing the disorder. Investigations have generally emerged from established concomitants of chronic PTSD [
Kitayama et al., 2005;
Smith, 2005] and have identified smaller hippocampal volume [
Gilbertson et al., 2002] and abnormally large CSP [
May et al., 2004] in twins with chronic PTSD and in their non-combat exposed cotwins, as compared to combat veterans who did not develop the disorder. Similarly, neurological soft signs (NSS), or subtle indices of neurological function thought to represent “subtle cortical dysfunction,” are more prevalent in combat exposed index twins with PTSD than those without PTSD and high-risk co-twins had greater NSS than low-risk co-twins [
Gurvits et al., 2006]. These investigations provide important information regarding biological endophenotypes of PTSD that, given unique data afforded by MZ discordant design, likely represents pre-trauma risk factors rather than consequences of PTSD.
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