A population-based twin study of the relationship between neuroticism and internalizing disorders.
OBJECTIVE
The anxiety and depressive disorders exhibit high levels of lifetime comorbidity with one another. The authors examined how genetic and environmental factors shared by the personality trait neuroticism and seven internalizing disorders may help explain this comorbidity.


METHODS
Lifetime major depression, generalized anxiety disorder, panic disorder, agoraphobia, social phobia, animal phobia, situational phobia, and neuroticism were assessed in over 9,000 twins from male-male, female-female, and opposite-sex pairs through structured diagnostic interviews. Multivariate structural equation models were used to decompose the correlations between these phenotypes into genetic and environmental components, allowing for sex-specific factors.


RESULTS
Genetic factors shared with neuroticism accounted for between one-third and one-half of the genetic risk across the internalizing disorders. When nonsignificant gender differences were removed from the models, the genetic correlations between neuroticism and each disorder were high, while individual-specific environmental correlations were substantially lower. In addition, the authors could identify a neuroticism-independent genetic factor that significantly increased risk for major depression, generalized anxiety disorder, and panic disorder.


CONCLUSIONS
There is substantial, but not complete, overlap between the genetic factors that influence individual variation in neuroticism and those that increase liability across the internalizing disorders, helping to explain the high rates of comorbidity among the latter. This may have important implications for identifying the susceptibility genes for these conditions.
Hettema
John M
JM
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, P.O. Box 980126, Richmond, VA 23298-0126, USA. jhettema@hsc.vcu.edu
Neale
Michael C
MC
Myers
John M
JM
Prescott
Carol A
CA
Kendler
Kenneth S
KS
D000328:Adult; D000368:Aged; D001008:Anxiety Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D004200:Diseases in Twins / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009497:Neurotic Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D016584:Panic Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D010551:Personality / Q000145:classification* / Q000235:genetics*; D010641:Phenotype; D010698:Phobic Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D012931:Social Environment; D014768:Virginia / Q000453:epidemiology