Anxiety and depression in twin and sib pairs extremely discordant and concordant for neuroticism: prodromus to a linkage study.

Multivariate modelling of anxiety and depression data in twins has suggested that the two phenotypes are largely underpinned by one genetic factor, while other studies have indicated a relationship between these disorders and the neuroticism personality trait. As part of a study to identify quantitative trait loci for anxiety and depression, questionnaire responses and interviews of 15,027 Australian twins and 11,389 of their family members conducted during the past 20 years were reviewed to identify individuals with neuroticism, anxiety and depression scores in the upper or lower deciles of the population. This information was then used to identify extreme discordant and concordant (EDAC) sib pairs. 1373 high-scoring and 1571 low-scoring subjects (2357 sib pairs) were selected for participation, and extremely high participation rates were achieved, with over 90% of contactable prospective participants completing the interview phase, and over 90% of these providing blood or buccal samples. Participation bias arising from the nature of the selection variables was minimal, with only a small difference between rates of interview participation among prospective participants with high and low selection scores (89.4% vs 91.6%). The interview permitted the diagnosis of depression and several anxiety disorders (OCD, agoraphobia, panic disorder, generalised anxiety disorder) in this sample according to DSM-IV criteria. The methodology for selection of prospective subjects was demonstrated to be extremely successful, with highly significant differences in depression and anxiety disorder prevalence rates between individuals in the two selection groups. The success of this EDAC sampling scheme will enhance the power for QTL linkage and association analysis in this sample.