Figure 1. Flowchart of participants in a stepwise sampling approach to narrow-down the early disease mechanisms in this high-risk sample.

In a high risk sample, we used a step by step sampling approach to narrow-down the early disease mechanisms. Upstream, we started with a 20-year follow-up of 48 densely affected multigenerational kindreds, including 1500 clinically characterized adult members who were all administered a consensus best-estimate lifetime diagnosis. From these, we then identified 400 members affected by a DSM-IV schizophrenia or bipolar disorder. Downstream, we finally focused on 65 offspring aged 7 to 22 having an affected parent, and the 65 were administered the neuropsychological battery.