In transition : a longitudinal exploration of the adolescent brain at risk for psychosis

The overall aim of this thesis was to detect potential neurobiological vulnerability markers for psychosis in adolescents putatively at risk for developing the disorder. This knowledge can be used to improve prediction and ultimately lead to improved early intervention. A longitudinal research design was used in which multiple brain imaging methods (structural magnetic resonance imaging, neurophysiological recordings) were assessed over a two-year period in young adolescents (12-18 years) at ultra-high risk (UHR) for psychosis and typically developing adolescents. The following research aims were addressed: 1) determine the validity of UHR criteria in predicting the development of subsequent psychosis in a group of adolescent individuals; 2) explore whether UHR in adolescence is associated with a presence of neurobiological vulnerability markers before the onset of psychosis, as measured by structural MRI and neurophysiology; 3) explore whether neurobiological vulnerability markers become more apparent over time in UHR adolescents, in particular for those individuals who develop psychosis. The results showed that 15.6% of UHR adolescents made a transition to psychosis. However, the remission rate was about three times higher, rendering the predictive validity of the UHR paradigm currently insufficient to guide specialized early interventions. Furthermore, subtle neurobiological vulnerability markers may already be present in UHR adolescents and these are best identified within a longitudinal study design. While some markers may be more indicative of a general vulnerability for psychopathology (e.g., reduced prepulse inhibition, restricted white matter growth), others may be more specific to the actual transition to psychosis (e.g., increased cortical thinning). Future prediction models would benefit from multi-level, multi-method assessments to optimize identification of individuals with the highest need for intervention. In doing so, the aim should not be restricted to preventing the transition to an arbitrary threshold to psychosis, but rather focussed on long-term functional outcome.