Background. Concordance for major depressive disorder (MDD) between parents could happen for different reasons. Regardless of the origin and the frequency of the concordance, the effect on offspring of having two parents affected with MDD may be serious. The sex of the affected parent and offspring may also be a important risk factor for MDD in offspring.

Methods. We examined the increased risk of psychopathology among offspring of the four parental mating groups: both parents affected with MDD (N = 53); only mother affected (N = 31); only father affected (N = 65); and, neither parents affected (N = 33). Parents and offspring were assessed by direct interview, conducted blind and independently of each other.

Results. Among the four parental mating groups, offspring of both parents affected had the highest risk of MDD, anxiety disorder and alcohol dependence, and the earliest age of onset for MDD. There were two exceptions: the highest risk of conduct disorder and of drug dependence was in the groups where only the father was affected and where only the mother was affected, respectively. Mother's MDD was a stronger predictor of MDD in male compared to female offspring. Father's MDD was a stronger predictor of MDD in female compared to male offspring.

Conclusion. Having two parents with MDD increases the risk of psychiatric disorders in offspring. A clear dose–response relationship between the number of affected parents and psychiatric disorders in offspring was observed. The sex of the affected parent and of the offspring is important in determining the risk to offspring. For an examination of the risk to psychopathology in offspring, diagnosis status of both parents should be considered.