There are no known biological measures that accurately predict future development of psychiatric disorders in individual at-risk adolescents. We investigated whether machine learning and fMRI could help to: 1. differentiate healthy adolescents genetically at-risk for bipolar disorder and other Axis I psychiatric disorders from healthy adolescents at low risk of developing these disorders; 2. identify those healthy genetically at-risk adolescents who were most likely to develop future Axis I disorders.

16 healthy offspring genetically at risk for bipolar disorder and other Axis I disorders by virtue of having a parent with bipolar disorder and 16 healthy, age- and gender-matched low-risk offspring of healthy parents with no history of psychiatric disorders (12–17 year-olds) performed two emotional face gender-labeling tasks (happy/neutral; fearful/neutral) during fMRI. We used Gaussian Process Classifiers (GPC), a machine learning approach that assigns a predictive probability of group membership to an individual person, to differentiate groups and to identify those at-risk adolescents most likely to develop future Axis I disorders.

Using GPC, activity to neutral faces presented during the happy experiment accurately and significantly differentiated groups, achieving 75% accuracy (sensitivity = 75%, specificity = 75%). Furthermore, predictive probabilities were significantly higher for those at-risk adolescents who subsequently developed an Axis I disorder than for those at-risk adolescents remaining healthy at follow-up.

We show that a combination of two promising techniques, machine learning and neuroimaging, not only discriminates healthy low-risk from healthy adolescents genetically at-risk for Axis I disorders, but may ultimately help to predict which at-risk adolescents subsequently develop these disorders.