News and Commentary | Published:

News & Commentary

The role of genes and family in trauma exposure and posttraumatic stress disorder

Molecular Psychiatry volume 6, pages 360362 (2001) | Download Citation


Most human behavioral traits are likely to result from an interplay of genes and environment. The field of psychiatric genetics, in this regard, is rapidly growing. Since the anxiety disorders, including posttraumatic stress disorder (PTSD), have a complex genetic basis and are not inherited in strict Mendelian fashion, factors such as incomplete penetrance (an individual who carries the disease allele may not become ill, or the onset may be extremely late), pleiotropy (multiple effects of a single gene), heterogeneity (similar phenotype from different genotypes), and epistatic interactions (several genes interacting in the same individual), amongst others, must be accounted for.1 Although the precise weighting of genes for anxiety disorders is undetermined, twin studies have demonstrated that genetic factors are at least as important as familial aggregation for some anxiety disorders (eg panic disorder and generalised anxiety disorder).

PTSD is a peculiar anxiety disorder in that it requires the presence of exposure to an extremely traumatic environmental event. Previous research has focused on identifying factors that put exposed persons at ‘risk’: female gender, previous trauma exposure, neuroticism, and pre-existing anxiety and depression.2,3 However, more recent data indicate that both the risk of trauma exposure and PTSD may be influenced by genetic make-up and family environment; for example, studies show an increased prevalence of PTSD in the adult children of Holocaust survivors even though these children as a group did not have greater exposure to life-threatening events.4

Furthermore, population prevalence studies have demonstrated a markedly disproportionate risk between trauma exposure and PTSD, suggesting that other environmental and genetic factors also contribute to one's liability to develop the disorder. While trauma exposure rates vary between 40–80%, the prevalence rate of PTSD in exposed individuals is only 8%.3 The contribution of genes in PTSD is further supported in animal models of the stress response: genetic differences in sensitivity to environmental stress have been noted in rhesus monkeys5 and variations in the fear response to inescapable shocks have been documented in different mice strains reared in identical environments.6 The results of fear-conditioning studies in animals are consistent with a model of PTSD in humans that posits pathological dysfunction within a network of brain regions.

Both twin and family studies have been used to explore genetic influence in PTSD but, to date, the adoption method has not been applied. Additionally, there is the issue of trying to separate hereditary predisposition to trauma exposure from hereditary predisposition to PTSD. Two elegant twin studies, however, provide fairly robust support for the heritability of PTSD. The Vietnam Era Twin Registry project of 4029 male–male Vietnamese twin pairs (2224 monozygotic pairs, 1818 dizygotic pairs) was an informative design for studying genetic and non-genetic factors that influenced wartime exposure to trauma.7 The project examined specific variables such as volunteering for service in Vietnam, time served in Southeast Asia, combat experiences, and combat decoration awards. Genetic factors accounted for 36% of the variance in service in Southeast Asia, 47% of the variance in combat exposure, and 54% of the variance in the likelihood of receiving a combat medal. In addition, genes accounted for approximately 30% of the variance in liability for most PTSD symptoms in all three symptom clusters: re-experiencing, avoidance, and hyperarousal, even after differences in concordance for combat exposure between monozygotic (MZ) and dizygotic (DZ) twin pairs were accounted for.8 Significantly, family environment (such as family upbringing, schooling, and parental socio-economic status) shared by twin siblings did not contribute to the development of PTSD.

In another twin study of DSM-IIIR anxiety disorders that compared MZ (n = 20) and DZ (n = 29) co-twins of anxiety disorder probands with a group of co-twins (MZ and DZ) (n = 32) with other non-psychotic mental disorders, PTSD was only found in co-twins of anxiety probands and was twice as prevalent in MZ (20%) vs DZ (7%) twins.9

As regards familial susceptibility to PTSD, knowledge derives largely from studies of family history research rather than genetically informative family designs, and full pedigrees for PTSD have not been obtained. One of the earliest observations of familial predisposition in PTSD was reported in a study of World War I veterans (n = 100) with war neurosis who were matched with control subjects (n = 100) with war-related physical injuries.10 Approximately 75% of the war neurosis patients, and none of the controls, had a family history of ‘psychoneurosis’ comprising such conditions as nervousness, alcoholism, epilepsy, and insanity. Subsequent studies of World War I/ World War II veterans also reported high rates (45–70%) of familial psychopathology (depression, alcoholism, and anxiety).11,12

A more recent study of male military veterans comparing family history of a PTSD proband group with three other proband groups (mixed anxiety disorders, coexisting anxiety and depressive disorders, and normal controls) found that family history variables distinguished PTSD from the other proband groups.13 Furthermore, a family history of major depression and DSM-III ‘dramatic personality disorder’ also predicted experience of combat situations. Epidemiological investigations in civilian populations have likewise shown higher rates of depression, anxiety, and antisocial behaviour in family members of PTSD probands, but not higher rates of family alcohol/substance use problems. However, in a study of chronic PTSD patients (n = 36), Davidson and colleagues reported a higher prevalence of alcoholic siblings in PTSD probands than in a retrospectively derived control group of depressed and anxious male patients.14

Aside from twin and family studies, genetic marker studies in PTSD are few, and findings are conflicting. Allelic associations at the D2 dopamine receptor gene (DRD2) exist for various psychiatric disorders including alcoholism, Tourette's syndrome, attention deficit hyperactivity disorder, and autism.15 While some studies have shown an association between the DRD2 and PTSD,15,16 there have been other reports of no allelic association.17

In summary, several factors need to be considered when examining the heritability issue in PTSD. Family studies are difficult to interpret since it is difficult to know to what extent the increased vulnerability to PTSD in family members results from genetic factors, other biological factors, or shared experience. Also, the relative contribution of genes and shared environment may well vary across the phenotype: nature of trauma, severity of trauma, gender, age of onset, comorbidity, and cultural background; for example, the genetics and family risk of PTSD arising in a child exposed to incest may differ from PTSD arising in an adult who is physically assaulted. Similarly, PTSD that is comorbid with depression may be associated with a different familial pattern to PTSD without depression. In a study of family risk factors among rape victims, Davidson and colleagues18 found that major depressive disorder was increased in first-degree relatives of female rape survivors with chronic PTSD compared with healthy control subjects. Furthermore, individual vulnerability to depression was an independent risk factor for chronic PTSD.

Future twin, family, and genetic marker studies must endeavour to tease out heritability factors for trauma exposure from heritability factors for PTSD. Exciting possibilities exist for exploring genetic mechanisms involved in conditioned fear responses in PTSD, sensitisation of CRH (corticotrophin releasing hormone) function, as well as deficits in hippocampal structure and function. In addition, molecular genetics might be useful in highlighting the contribution of heritability to the various pathogenic aspects of PTSD; for example, the relationship, if any, between aggression-proneness in PTSD and genetically-determined abnormalities in serotonin synthesis,19 and startle-proneness and chromosomal abnormalities.20


  1. 1.

    . Basic concepts in the study of diseases with complex genetics Biol Psychiatry 1999 45: 522–532

  2. 2.

    , , . Risk factors for PTSD-related traumatic events: a prospective analysis Am J Psychiatry 1995 152: 529–535

  3. 3.

    , , , , . Posttraumatic stress disorder in the National Comorbidity Survey Arch Gen Psychiatry 1995 52: 1048–1060

  4. 4.

    . Biological factors associated with susceptibility to posttraumatic stress disorder Can J Psychiatry 1999 44: 34–39

  5. 5.

    , , , . Inherited and experiential factors associated with individual differences in anxious behaviour displayed by rhesus monkeys. In: Klein DF, Rabkin J (eds) Anxiety: New Research and Changing Concepts Raven Press: New York, NY 1981 179–200

  6. 6.

    , , , , . Escape performance after inescapable shock in selectively bred lines of mice: response maintenance and catecholamine activity J Comp Physiol Psychol 1979 93: 229–241

  7. 7.

    , , , , , et al. Do genes influence exposure to trauma? A twin study of combat Am J Med Genet 1993 48: 22–27

  8. 8.

    , , , , , et al. A twin study of genetic and environmental contributions to liability of posttraumatic stress symptoms Arch Gen Psychiatry 1993 50: 257–264

  9. 9.

    , , , , . A twin study of DSM-III-R anxiety disorders Acta Psychiatr Scand 1993 88: 85–92

  10. 10.

    . The predisposing factors of war psycho-neuroses Lancet 1918 1: 177–180

  11. 11.

    . An analysis of ninety cases of functional disease in soldiers Arch Intern Med 1921 28: 586–602

  12. 12.

    , , . Neurocirculatory asthenia, anxiety neurosis or the effort syndrome Arch Intern Med 1948 81: 260–281

  13. 13.

    , , . Familial vulnerability factors to post-traumatic stress disorder in male military veterans Acta Psychiatr Scand 1996 93: 105–112

  14. 14.

    , , . Familial psychiatric illness in chronic posttraumatic stress disorder Compr Psychiatry 1989 30: 339–345

  15. 15.

    , , , , , et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders JAMA 1991 266: 1793–1800

  16. 16.

    , , . Dopamine D2 receptor (DRD2) gene and susceptibility to posttraumatic stress disorder: a study and replication Biol Psychiatry 1996 40: 368–372

  17. 17.

    , , , , , . No association between D2 dopamine receptor (DRD2) ‘A’ system alleles, or DRD2 haplotypes, and posttraumatic stress disorder Biol Psychiatry 1999 45: 620–625

  18. 18.

    , , , . A family study of post-traumatic stress disorder following rape trauma J Psychiatr Res 1998 32: 301–309

  19. 19.

    , , et al. Initial clinical evidence of genetic contributions to post-traumatic stress disorder. In: Danieli Y (ed) An International Handbook of Multigenerational Legacies of Trauma Plenum: New York 1996 657–667

  20. 20.

    , , , , , . Startle disease or hyperekplexia: response to clonazepam and assignment of the gene ((STHE) to chromosome 5 linkage analysis Ann Neurol 1992 31: 663–668

Download references


This work is supported by the MRC Unit on Anxiety and Stress Disorders, Medical Research Council of South Africa.

Author information


  1. Department of Psychiatry, Faculty of Medicine, University of Stellenbosch, PO Box 19063 Tygerberg 7505, Cape Town, South Africa

    • S Seedat
    • , D J Niehaus
    •  & D J Stein


  1. Search for S Seedat in:

  2. Search for D J Niehaus in:

  3. Search for D J Stein in:

Corresponding author

Correspondence to S Seedat.

About this article

Publication history