Genetic Determinants of PTSD in Women

Summary

Principal Investigator: Karestan Koenen
Affiliation: Harvard University
Country: USA
Abstract: One in nine American women will meet criteria for the diagnosis of posttraumatic stress disorder (PTSD) in their lifetime. Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder. We propose to use the unique resource of the Nurses Health Study II, a prospective epidemiologic cohort of 68,518 women, to conduct what promises to be the largest candidate gene association study of PTSD to date. The entire cohort will be screened for trauma exposure and PTSD; 3,000 women will be selected for PTSD diagnostic interviews based on the screening data. Our nested case-control study will genotype lOOO women who developed PTSD following a history of trauma exposure; 1000 controls will be selected from women who experienced similar traumas but did not develop PTSD. The primary aim of this study is to detect genetic variants that predict the development of PTSD following trauma. We posit inherited vulnerability to PTSD is mediated by genetic variation in three specific neurobiological systems whose alterations are implicated in PTSD etiology: the hypothalamic-pituitary- adrenal axis, the locus coeruleus/noradrenergic system, and the limbic-frontal neuro-circuitry of fear. The secondary, exploratory aim of this study is to dissect genetic influences on PTSD in the broader genetic and environmental context for the candidate genes that show significant association with PTSD in detection analyses. This will involve: conducting conditional tests to identify the causal genetic variant among multiple correlated signals; testing whether the effect of PTSD genetic risk variants is moderated by age of first trauma, trauma type, and trauma severity; and exploring gene-gene interactions using a novel gene-based statistical approach. Identification of liability genes for PTSD would represent a major advance in understanding the pathophysiology of the disorder. Such understanding could advance the development of new pharmacological agents for PTSD treatment and prevention. Moreover, the addition of PTSD assessment data will make the NHSII cohort an unparalleled resource for future genetic studies of PTSD as well as provide the unique opportunity for the prospective examination of PTSD-disease associations.
Funding Period: 2007-09-25 - 2011-04-30
more information: NIH RePORT

Top Publications

  1. ncbi Genetics of posttraumatic stress disorder: Review and recommendations for future studies
    Karestan C Koenen
    Department of Society, Human Development, and Health and Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
    J Trauma Stress 20:737-50. 2007
  2. ncbi A prospective study of sex differences in the lifetime risk of posttraumatic stress disorder among abused and neglected children grown up
    Karestan C Koenen
    Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, USA
    J Trauma Stress 22:566-74. 2009
  3. ncbi Variation in RGS2 is associated with suicidal ideation in an epidemiological study of adults exposed to the 2004 Florida hurricanes
    Ananda B Amstadter
    Department of Psychiatry and Behavioral Science, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Arch Suicide Res 13:349-57. 2009
  4. ncbi The posttraumatic stress disorder project in Brazil: neuropsychological, structural and molecular neuroimaging studies in victims of urban violence
    Rodrigo A Bressan
    Laboratório Interdisciplinar de Neurosciencias Clínicas LiNC, Sao Paulo, Brazil
    BMC Psychiatry 9:30. 2009
  5. ncbi Protocol for investigating genetic determinants of posttraumatic stress disorder in women from the Nurses' Health Study II
    Karestan C Koenen
    Department of Society, Human Development and Health, Harvard School of Public Health, Boston, MA 02115, USA
    BMC Psychiatry 9:29. 2009
  6. ncbi Is posttraumatic stress disorder related to development of heart disease? An update
    Laura D Kubzansky
    Department of Soci ety, Human Development and Health, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
    Cleve Clin J Med 76:S60-5. 2009
  7. ncbi Modification of the association between serotonin transporter genotype and risk of posttraumatic stress disorder in adults by county-level social environment
    Karestan C Koenen
    Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, USA
    Am J Epidemiol 169:704-11. 2009
  8. ncbi Posttraumatic stress symptoms and trajectories in child sexual abuse victims: an analysis of sex differences using the national survey of child and adolescent well-being
    Andrea Kohn Maikovich
    Department of Psychology, University of Pennsylvania, 3720 Walnut Street, Philadelphia, PA 19104, USA
    J Abnorm Child Psychol 37:727-37. 2009
  9. ncbi A prospective study of posttraumatic stress disorder symptoms and coronary heart disease in women
    Laura D Kubzansky
    Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, USA
    Health Psychol 28:125-30. 2009
  10. ncbi Variant in RGS2 moderates posttraumatic stress symptoms following potentially traumatic event exposure
    Ananda B Amstadter
    Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA
    J Anxiety Disord 23:369-73. 2009

Scientific Experts

Detail Information

Publications17

  1. ncbi Genetics of posttraumatic stress disorder: Review and recommendations for future studies
    Karestan C Koenen
    Department of Society, Human Development, and Health and Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
    J Trauma Stress 20:737-50. 2007
    ..Recommendations for future studies are presented with emphasis on study design and assessment issues particular to the field of trauma and PTSD. Clinical implications of PTSD genetic studies are discussed...
  2. ncbi A prospective study of sex differences in the lifetime risk of posttraumatic stress disorder among abused and neglected children grown up
    Karestan C Koenen
    Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, USA
    J Trauma Stress 22:566-74. 2009
    ..Future research should identify mechanisms that make female victims particularly vulnerable to revictimization and the development of PTSD...
  3. ncbi Variation in RGS2 is associated with suicidal ideation in an epidemiological study of adults exposed to the 2004 Florida hurricanes
    Ananda B Amstadter
    Department of Psychiatry and Behavioral Science, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Arch Suicide Res 13:349-57. 2009
    ..59 times increased risk of having current ideation. No gene-by-environment interactions were found, perhaps due to low power. RGS2 rs4606 is related to risk of current suicidal ideation in stressor-exposed adults...
  4. ncbi The posttraumatic stress disorder project in Brazil: neuropsychological, structural and molecular neuroimaging studies in victims of urban violence
    Rodrigo A Bressan
    Laboratório Interdisciplinar de Neurosciencias Clínicas LiNC, Sao Paulo, Brazil
    BMC Psychiatry 9:30. 2009
    ..This paper shows the research rationale and design for these three case-control studies...
  5. ncbi Protocol for investigating genetic determinants of posttraumatic stress disorder in women from the Nurses' Health Study II
    Karestan C Koenen
    Department of Society, Human Development and Health, Harvard School of Public Health, Boston, MA 02115, USA
    BMC Psychiatry 9:29. 2009
    ..Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder...
  6. ncbi Is posttraumatic stress disorder related to development of heart disease? An update
    Laura D Kubzansky
    Department of Soci ety, Human Development and Health, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
    Cleve Clin J Med 76:S60-5. 2009
    ..A better understanding of the relationship will increase prevention and intervention efforts. Cardiologists may be most effective when they can recognize and manage emotional distress in practice...
  7. ncbi Modification of the association between serotonin transporter genotype and risk of posttraumatic stress disorder in adults by county-level social environment
    Karestan C Koenen
    Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, USA
    Am J Epidemiol 169:704-11. 2009
    ..These results suggest that social environment modifies the effect of 5-HTTLPR genotype on PTSD risk...
  8. ncbi Posttraumatic stress symptoms and trajectories in child sexual abuse victims: an analysis of sex differences using the national survey of child and adolescent well-being
    Andrea Kohn Maikovich
    Department of Psychology, University of Pennsylvania, 3720 Walnut Street, Philadelphia, PA 19104, USA
    J Abnorm Child Psychol 37:727-37. 2009
    ..Implications for theory and intervention are discussed...
  9. ncbi A prospective study of posttraumatic stress disorder symptoms and coronary heart disease in women
    Laura D Kubzansky
    Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, MA 02115, USA
    Health Psychol 28:125-30. 2009
    ..No study has tested this hypothesis in women even though PTSD is more prevalent among women than men. This study aims to examine whether higher levels of PTSD symptoms are associated with increased risk of incident CHD among women...
  10. ncbi Variant in RGS2 moderates posttraumatic stress symptoms following potentially traumatic event exposure
    Ananda B Amstadter
    Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA
    J Anxiety Disord 23:369-73. 2009
    ..RGS2 rs4606 modifies risk of postdisaster and lifetime PTSD symptoms under conditions of high stressor exposure. This is the first demonstration of gene-environment interaction for this locus...
  11. ncbi Childhood IQ and adult mental disorders: a test of the cognitive reserve hypothesis
    Karestan C Koenen
    Department of Society, Human Development, and Health, Harvard School of Public Health, Kresge 613, 677 Huntington Ave, Boston, MA 02115, USA
    Am J Psychiatry 166:50-7. 2009
    ..The authors tested the hypothesis that low childhood IQ is associated with increased risk and severity of adult mental disorders...
  12. ncbi RGS2 and generalized anxiety disorder in an epidemiologic sample of hurricane-exposed adults
    Karestan C Koenen
    Department of Society, Human Development and Health, Harvard School of Public Health, Boston, MA 02115, USA
    Depress Anxiety 26:309-15. 2009
    ..We examined whether rs4606, a single nucleotide polymorphism (SNP) in the 3' UTR of RGS2, was associated with GAD in an epidemiologic sample of adults exposed to the 2004 Florida Hurricanes...
  13. ncbi The developmental mental-disorder histories of adults with posttraumatic stress disorder: a prospective longitudinal birth cohort study
    Karestan C Koenen
    Department of Society Human Development and Health, Harvard School of Public Health, Boston, MA 02115, USA
    J Abnorm Psychol 117:460-6. 2008
    ..Juvenile mental-disorder histories may help indicate which individuals are most likely to develop PTSD in populations at high risk of trauma exposure...
  14. ncbi Genetics of post-traumatic stress disorder: informing clinical conceptualizations and promoting future research
    Nicole R Nugent
    Brown Medical School and Bradley Hasbro Children s Research Center, USA
    Am J Med Genet C Semin Med Genet 148:127-32. 2008
    ..Finally, we summarize findings from molecular genetic studies, which have the potential to inform our understanding of underlying biological mechanisms for the development of PTSD...
  15. ncbi Persisting posttraumatic stress disorder symptoms and their relationship to functioning in Vietnam veterans: a 14-year follow-up
    Karestan C Koenen
    Departments of Society, Human Development, and Health and Epidemiology, Harvard School of Public Health, Boston, MA, USA
    J Trauma Stress 21:49-57. 2008
    ..Further investigation is needed to determine whether the PTSD-functioning relationship is causal and if successful treatment of PTSD is associated with improvement in functioning...
  16. ncbi Gene-environment interaction in posttraumatic stress disorder: review, strategy and new directions for future research
    Karestan C Koenen
    Department of Society, Human Development, and Health and Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
    Eur Arch Psychiatry Clin Neurosci 258:82-96. 2008
    ..Finally, we propose some promising new directions for PTSD G x E research. We suggest that G x E research in PTSD is essential to understanding vulnerability and resilience following exposure to a traumatic event...
  17. ncbi Association between COMT, PTSD, and increased smoking following hurricane exposure in an epidemiologic sample
    Ananda B Amstadter
    Department of Psychiatry and Behavioral Science, Medical University of South Carolina in Charleston, USA
    Psychiatry 72:360-9. 2009
    ..This study represents the first genetic association study (to our knowledge) of smoking behavior following an acute stressor...