Psychological Medicine

Neuroticism, major depression and gender: a population-based twin study

A.  FANOUS  a1 c1, C. O.  GARDNER  a1, C. A.  PRESCOTT  a1, R.  CANCRO  a1 and K. S.  KENDLER  a1
a1 From the Departments of Psychiatry and Human Genetics, Medical College of Virginia, Virginia Commonwealth University and Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA; and Department of Psychiatry, New York University School of Medicine, New York, NY, USA


Background. A portion of the genetic risk factors for the personality trait neuroticism (N) may also increase risk for major depression (MD). Females have both higher levels of N and higher rates of MD than males, suggesting that these traits may be more genetically correlated in females.

Methods. Structured interviews, including a lifetime assessment for MD by DSM-III-R criteria, were administered to 863 male–male MZ (monozygotic), 649 male–male DZ (dizygotic), 506 female–female MZ, 345 female–female DZ, and 1408 opposite-sex twin pairs. N was assessed using the short-form of the Eysenck Personality Questionnaire. A sex-limited Cholesky model was fitted which allowed us to decompose into additive genetic, common environmental, and individual-specific environmental components two main classes of correlations: within-sex between-variable and between-sex within-variable.

Results. Our best-fitting model contained only additive genetic and individual-specific environmental factors for both N and MD. The within-sex genetic correlations between N and MD were estimated at +0·68 in men and +0·49 in women. This model fitted only slightly better than one in which the N–MD within-sex genetic correlation was constrained to be equal across the sexes, and estimated at +0·55. There may be sex-specific genes influencing both N and MD.

Conclusion. Our best-fitting model failed to establish a significant sex difference in the genetic correlation between N and MD. These results, as well as evidence for sex-specific genetic factors for both traits, have implications for the diagnosis, classification, and treatment of the affective disorders, and molecular genetic approaches to the study of these traits.

c1 Address for correspondence: Dr Ayman Fanous, Box 980126, Richmond, VA 23298-0126, USA.