Control subjects were mainly from the NTR, which has collected longitudinal data from twins and their families since 1991 (total cohort of ∼22,000 participants from 5,546 families). The majority of families were recruited when the twins were adolescents or young adults through city council registrations along with alternative efforts to recruit older twins. Longitudinal phenotyping includes assessment of depressive symptoms (via multiple instruments), anxiety, neuroticism, and other personality measures. Inclusion required availability of both survey data and biological samples, no report of MDD at any measurement occasion, and low genetic liability for MDD. No report of MDD was determined by specific queries about medication use or whether the subject had ever sought treatment for depression symptoms and/or via the CIDI interview. Low genetic liability for MDD was determined by the use of a factor score derived from longitudinal measures of neuroticism, anxiety, and depressive symptoms (28) (mean 0, std 0.7); controls were required never to have scored highly (≥0.65) on this factor score. Finally, controls and their parents were required to have been born in the Netherlands or western Europe.
