Posttraumatic stress disorder and the genetic structure of comorbidity.

This study used structural equation modeling to examine the genetic and environmental architecture of latent dimensions of internalizing and externalizing psychiatric comorbidity and explored structural associations between posttraumatic stress disorder (PTSD) and these dimensions. Data were drawn from the Vietnam Era Twin Registry and included lifetime diagnoses for PTSD and a range of other psychiatric disorders for 3,372 male-male twin pairs. Examination of the phenotypic structure of these disorders revealed that PTSD cross-loaded on both Internalizing and Externalizing common factors. Biometric analyses suggested largely distinct genetic risk factors for the latent internalizing and externalizing comorbidity dimensions, with the total heritability of the Externalizing factor (69%) estimated to be significantly stronger than that for Internalizing (41%). Nonshared environment explained the majority of the remaining variance in the Internalizing (58%) and Externalizing (20%) factors. Shared genetic variance across the 2 dimensions explained 67% of their phenotypic correlation (r = .52). These findings have implications for conceptualizations of the etiology of PTSD and its location in an empirically based nosology.

[1]  M. Miller,et al.  Posttraumatic stress disorder: anxiety or traumatic stress disorder? , 2009, Journal of traumatic stress.

[2]  R. Krueger,et al.  Externalizing disorders: Cluster 5 of the proposed meta-structure for DSM-V and ICD-11 , 2009, Psychological Medicine.

[3]  G. Andrews,et al.  Emotional disorders: Cluster 4 of the proposed meta-structure for DSM-V and ICD-11 , 2009, Psychological Medicine.

[4]  K. Markon,et al.  Modeling psychopathology structure: a symptom-level analysis of Axis I and II disorders , 2009, Psychological Medicine.

[5]  B. Lahey,et al.  Public health significance of neuroticism. , 2009, The American psychologist.

[6]  D. Watson Differentiating the mood and anxiety disorders: a quadripartite model. , 2009, Annual review of clinical psychology.

[7]  E. Willcutt,et al.  Behavioral Disinhibition: Liability for Externalizing Spectrum Disorders and Its Genetic and Environmental Relation to Response Inhibition across Adolescence the Nature and Etiology of Behavioral Disinhibition , 2022 .

[8]  M. Miller,et al.  DSM-V: should PTSD be in a class of its own? , 2009, British Journal of Psychiatry.

[9]  J. Bukszár,et al.  Catechol-O-Methyltransferase Contributes to Genetic Susceptibility Shared Among Anxiety Spectrum Phenotypes , 2008, Biological Psychiatry.

[10]  K. Bucholz,et al.  Posttraumatic stress disorder; combat exposure; and nicotine dependence, alcohol dependence, and major depression in male twins. , 2008, Comprehensive psychiatry.

[11]  A. Caspi,et al.  The developmental mental-disorder histories of adults with posttraumatic stress disorder: a prospective longitudinal birth cohort study. , 2008, Journal of abnormal psychology.

[12]  L. Bierut,et al.  Using dimensional models of externalizing psychopathology to aid in gene identification. , 2008, Archives of general psychiatry.

[13]  M. Miller,et al.  The internalizing and externalizing structure of psychiatric comorbidity in combat veterans. , 2008, Journal of traumatic stress.

[14]  M. Tsuang,et al.  Common genetic liability to major depression and posttraumatic stress disorder in men. , 2008, Journal of affective disorders.

[15]  D. Dick Identification of Genes Influencing a Spectrum of Externalizing Psychopathology , 2007 .

[16]  Stephen D. Benning,et al.  Linking antisocial behavior, substance use, and personality: an integrative quantitative model of the adult externalizing spectrum. , 2007, Journal of abnormal psychology.

[17]  T. Brown Temporal course and structural relationships among dimensions of temperament and DSM-IV anxiety and mood disorder constructs. , 2007, Journal of abnormal psychology.

[18]  M. Miller,et al.  Internalizing and externalizing subtypes in female sexual assault survivors: implications for the understanding of complex PTSD. , 2007, Behavior therapy.

[19]  Richie Poulton,et al.  Juvenile mental health histories of adults with anxiety disorders. , 2007, The American journal of psychiatry.

[20]  Richie Poulton,et al.  Early childhood factors associated with the development of post-traumatic stress disorder: results from a longitudinal birth cohort , 2006, Psychological Medicine.

[21]  D. Watson,et al.  The structure of common DSM-IV and ICD-10 mental disorders in the Australian general population , 2006, Psychological Medicine.

[22]  Terence M Keane,et al.  PTSD and substance-related problems: the mediating roles of disconstraint and negative emotionality. , 2006, Journal of abnormal psychology.

[23]  R. Krueger,et al.  Reinterpreting comorbidity: a model-based approach to understanding and classifying psychopathology. , 2006, Annual review of clinical psychology.

[24]  D. Watson Rethinking the mood and anxiety disorders: a quantitative hierarchical model for DSM-V. , 2005, Journal of abnormal psychology.

[25]  Andrew Smolen,et al.  A genome-wide search for quantitative trait Loci that influence antisocial drug dependence in adolescence. , 2005, Archives of general psychiatry.

[26]  B. Pennington,et al.  Testing hypotheses regarding the causes of comorbidity: examining the underlying deficits of comorbid disorders. , 2005, Journal of abnormal psychology.

[27]  Olga V. Demler,et al.  Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. , 2005, Archives of general psychiatry.

[28]  J. Kaprio,et al.  Understanding the Covariation Among Childhood Externalizing Symptoms: Genetic and Environmental Influences on Conduct Disorder, Attention Deficit Hyperactivity Disorder, and Oppositional Defiant Disorder Symptoms , 2005, Journal of abnormal child psychology.

[29]  Kenneth S. Kendler,et al.  Personality and comorbidity of common psychiatric disorders , 2005, British Journal of Psychiatry.

[30]  M. Tsuang,et al.  Juvenile conduct disorder as a risk factor for trauma exposure and posttraumatic stress disorder. , 2005, Journal of traumatic stress.

[31]  Michael C Neale,et al.  The structure of genetic and environmental risk factors for anxiety disorders in men and women. , 2005, Archives of general psychiatry.

[32]  M. Miller,et al.  Externalizing and internalizing subtypes of combat-related PTSD: a replication and extension using the PSY-5 scales. , 2004, Journal of abnormal psychology.

[33]  K. Kendler,et al.  The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. , 2003, Archives of general psychiatry.

[34]  R. Krueger,et al.  A cross-cultural study of the structure of comorbidity among common psychopathological syndromes in the general health care setting. , 2003, Journal of abnormal psychology.

[35]  M. Miller,et al.  Multidimensional Personality Questionnaire profiles of veterans with traumatic combat exposure: externalizing and internalizing subtypes. , 2003, Psychological assessment.

[36]  C. Patrick,et al.  Etiologic connections among substance dependence, antisocial behavior, and personality: modeling the externalizing spectrum. , 2002, Journal of abnormal psychology.

[37]  Ming Tsuang,et al.  A TWIN REGISTRY STUDY OF FAMILIAL AND INDIVIDUAL RISK FACTORS FOR TRAUMA EXPOSURE AND POSTTRAUMATIC STRESS DISORDER , 2002, The Journal of nervous and mental disease.

[38]  B. Cox,et al.  Posttraumatic stress disorder and the structure of common mental disorders , 2002, Depression and anxiety.

[39]  H. Xian,et al.  A twin study of generalized anxiety disorder symptoms, panic disorder symptoms and post-traumatic stress disorder in men , 2001, Psychiatry Research.

[40]  J Ormel,et al.  The structure and stability of common mental disorders: the NEMESIS study. , 2001, Archives of general psychiatry.

[41]  R. Krueger,et al.  The higher-order structure of common DSM mental disorders: internalization, externalization, and their connections to personality , 2001 .

[42]  M. Tsuang,et al.  A twin study of the association between pathological gambling and antisocial personality disorder. , 2001, Journal of abnormal psychology.

[43]  J. Meyer,et al.  Genetic and Environmental Influences on the Relationship Among Combat Exposure, Posttraumatic Stress Disorder Symptoms, and Alcohol Use , 2001, Journal of traumatic stress.

[44]  M. Tsuang,et al.  Genetic and environmental influences on posttraumatic stress disorder, alcohol and drug dependence in twin pairs. , 2000, Drug and alcohol dependence.

[45]  K S Krauter,et al.  Genetic and environmental influences on behavioral disinhibition. , 2000, American journal of medical genetics.

[46]  S. Young,et al.  Heritability and the Comorbidity of Attention Deficit Hyperactivity Disorder With Behavioral Disorders and Executive Function Deficits: A Preliminary Investigation , 2000, Developmental neuropsychology.

[47]  R. Krueger The structure of common mental disorders. , 1999, Archives of general psychiatry.

[48]  K. Kendler,et al.  Fears and phobias: reliability and heritability , 1999, Psychological Medicine.

[49]  P. Bentler,et al.  Cutoff criteria for fit indexes in covariance structure analysis : Conventional criteria versus new alternatives , 1999 .

[50]  S. Faraone,et al.  A registry-based twin study of depression in men. , 1998, Archives of general psychiatry.

[51]  K. Bucholz,et al.  Long-term reliability and validity of alcoholism diagnoses and symptoms in a large national telephone interview survey. , 1998, Alcoholism, clinical and experimental research.

[52]  T. Brown,et al.  Structural relationships among dimensions of the DSM-IV anxiety and mood disorders and dimensions of negative affect, positive affect, and autonomic arousal. , 1998, Journal of abnormal psychology.

[53]  Phil A. Silva,et al.  The structure and stability of common mental disorders (DSM-III-R): a longitudinal-epidemiological study. , 1998, Journal of abnormal psychology.

[54]  S. Mineka,et al.  Comorbidity of anxiety and unipolar mood disorders. , 1998, Annual review of psychology.

[55]  M C Neale,et al.  Models of comorbidity for multifactorial disorders. , 1995, American journal of human genetics.

[56]  W R True,et al.  The Vietnam Era Twin Registry: a resource for medical research. , 1990, Public health reports.

[57]  John P. Rice,et al.  Determining zygosity in the Vietnam Era Twin Registry: an approach using questionnaires , 1989, Clinical genetics.

[58]  M. Drake Diagnostic and Statistical Manual of Mental Disorders (3rd ed. rev.) , 1988 .