Background. Neuroticism and self-esteem, two commonly used personality constructs, are thought to reflect a person's underlying vulnerability to major depression. The relative strength of these predictors is not known.

Method. Information was gathered on 2163 individual women from an epidemiological sample of female–female twin pairs. Neuroticism was assessed by the Eysenck Personality Questionnaire and global self-esteem by the Rosenberg Self-Esteem Scale. Major depression (DSM-III-R criteria) and stressful life events were also assessed. The personality constructs were studied in relation to major depression by logistic regression and structural equation modelling.

Results. Both cross-sectionally and prospectively, examined individually, neuroticism was a stronger predictor of risk for major depression than was self-esteem. When examined together, the predictive power of neuroticism remained substantial, while that of self-esteem largely disappeared. The same pattern of findings was obtained when a subset of subjects who had recently experienced stressful life events was analysed. By trivariate twin modelling, we found that the covariation of self-esteem, neuroticism and major depression was due largely to genetic factors. When self-esteem was the ‘upstream’ variable, a substantial genetic correlation remained between neuroticism and major depression. By contrast, when neuroticism was the ‘upstream’ variable, the genetic correlation between self-esteem and major depression disappeared.

Conclusions. The personality construct of neuroticism is a substantially better index of a woman's underlying vulnerability to major depression than is self-esteem. These findings suggest that overall emotionality or emotional reactivity to the environment reflects risk for depression better than does global self-concept.