Study participants were adult twins and their families recruited through the Australian Twin Registry (http://www.twins.org.au). Only unrelated individuals were included in MDD2000+. All participants provided written informed consent under study protocols approved by the QIMR Human Research Ethics Committee. MDD cases were identified through psychiatric questionnaires, either the shortened Composite International Diagnostic Interview16 or the SSAGA-OZ interview instrument (a version of the Semi-Structured Assessment for the Genetics of Alcoholism17 modified for use in Australia), a comprehensive psychiatric interview designed to assess MDD and other psychiatric disorders17 according to DSM-IIIR18 and DSM-IV19 criteria. Structured interviews were administered by trained telephone interviewers, closely supervised by a clinical psychologist. Briefly, from 1988 to 1990, study participants were mailed an extensive health and lifestyle questionnaire, which included the shortened revised Eysenck personality questionnaire.20 Sum scores of 12 item responses in each personality domain resulted in quantitative scores for neuroticism. Between 1992–2000, an unselected subset of these participants were interviewed by telephone using the SSAGA-OZ.21 Over the period 1996–9 sibling pairs that were either concordant or discordant for extreme neuroticism scores (one sibling in the
