Prospective observational study of young adults at ultra high risk for psychotic disorders
When established, schizophrenia can be a chronic, severe and disabling disorder characterized by positive symptoms such as hallucinations and delusions and negative symptoms such as passivity and decline in cognitive performance. There is evidence suggesting that early intervention can result in better outcomes but when is early enough?
Symptoms appear in adolescence and early adulthood and it is an open question as to whether the brain abnormalities are developmental and antedate clinical presentation or if they develop only around the time of conversion to the symptomatic phase.
Together with investigators at Institute of Mental Health Singapore, Duke University and the University of Melbourne, we will participate in a bench-to-bedside research programme (Translational Clinical Research programme). This will focus on young men at risk of developing psychotic symptoms around the time of conversion.
Our contribution to the TCR project will be to use structural and functional brain imaging to evaluate at-risk individuals for imaging abnormalities. It is hoped that we will uncover imaging bio-markers that could help identify young individuals at greatest risk of converting to psychosis so that preventative measures can be instituted early.
Structural brain imaging studies
Although pathological changes in the temporal and frontal lobes are well documented in established schizophrenia (Harrison, 1999; Harrison and Lewis, 2003), it is still unclear whether brain abnormalities precede the onset of psychotic illness or are the result of progressive neuropathological changes, especially at transition to illness (Pantelis et al 2005). In contrast to the abundant neuropsychological and fMRI data (Fusar-Poli 2007) pointing to frontal lobe dysfunction in schizophrenia, there is rather more modest evidence for structural abnormalities (Goldstein 1999, Narr 2004, Qiu 2007), particularly in UHR subjects (Pantelis 2003; Borgwardt 2007). We will be conducting one of the largest prospective studies in this regard.
Functional brain imaging studies
Brain changes that result in neuropsychological dysfunction may reflect changes in brain neurochemistry, synaptic connectivity, function or functional interaction between brain regions. These changes can be identified by functional MR imaging - a brain imaging technique that measures the haemodynamic response related to neural activity in the brain and allows us to visualize such changes in neurocircuitry. Using this non-invasive brain imaging technique we aim to evaluate task-related activation, which track cognitive functions known to be affected in schizophrenia, as indicated by prior studies on first onset schizophrenia (Tan 2005, Mendrek 2004, Snitz 2005, MacDonald III, 2005).
For more information on this study visit:
Singapore Translational and Clinical Research in Psychosis.
