PROGRESSION OF GRAY MATTER LOSS AND ITS CLINICAL CORRELATES IN FIRST EPISODE SCHIZOPHRENIA

Overall Abstract: One of the most striking changes in schizophrenia research has been the increasing evidence for progression of brain changes in the time before clinical onset (prodrome) and in the time immediately after onset. This symposium brings together new data presented by leaders of research teams who have been at the forefront of this dramatic change in our perception of schizophrenia. There is a striking concurrence of data from Europe (Kahn), USA (McCarley), Japan (Kasai) and Australia (Pantelis) that underscores the validity of the findings. This symposium will offer the SIRS attendees a state-of-the-art window into the latest results and research methods on the individuals at risk (the "who" in the title), where in the brain changes occur, when they occur, and indicate the "why" is not due to medication effects. The discussant (DeLisi), a pioneer in the study of progression, will lead the discussion of these findings. SPEAKER 1 ABSTRACT: Pantelis and colleagues used MRI to examine gray matter (GM) volume of the insular before psychosis onset in 97 individuals at risk for psychosis (UHR; 31 later developed psychosis [UHR-P]) and 55matched controls. 31UHR (11UHR-P) and 20 controls examined longitudinally. Cross-sectionally: UHR-P had significantly smaller insular bilaterally comparedwithUHR-NP (nonpsychotic UHR) and on left compared with controls. Longitudinally: UHR-P showed greater GM reduction (-5%/year) compared with controls (-0.4%/year) or UHR-NP (-0.6%/year). Results will be compared with findings at later stages of psychosis. SPEAKER 2 ABSTRACT:McCarley and colleagues analyzed longitudinal data from 21 first episode schizophrenics (FESZ) & 23matched healthy controls using a new algorithm (DARTEL) providing improved VBMmorphological resolution. GrayMatter (GM) loss over 1.5 yearswas observed in frontal, temporal and parietal gyri. Progressive GM loss in different regions showeddistinct clinical correlations, themore loss, theworse the symptoms. Examples: Heschl gyrus/STG loss & Thinking disturbance/hallucinations; Inferior Frontal gyrus/insula and negative symptoms. VBM findings were validated by cingulate & STG longitudinal ROI analyses. Concurrent electrophysiological changes (mismatch and gamma band) further indicate the functional relevance of the MRI changes. SPEAKER 3 ABSTRACT: Kasai and coworkers have conducted longitudinal, integrative neuroimaging assessments in people at ultra-high risk for developing psychosis and at first-episode of psychosis. The integrative neuroimaging assessments include structural and functional MRI, MR spectroscopy, diffusion tensor imaging, near-infrared spectroscopy (NIRS), and event-related potentials (ERPs). In their preliminary analysis on cross-sectional samples of at risk mental state (ARMS), first-episode, and chronic patients, they found that fMRI and NIRSmay be useful in tracking functional brain abnormalities and its progression through the clinical stages in schizophrenia. SPEAKER 4 ABSTRACT: Kahn and coworkers examined cortical thickness in patients with schizophrenia over time. Measures of functional outcome, and cumulative intake of antipsychotic medication were also assessed. Two MRI scans were obtained over a 5-year interval of 96 schizophrenia patients and 113 healthy subjects between 16 and 56 years. Excessive cortical thinning was found in widespread areas on the cortical mantle, most pronounced bilaterally in the temporal and in the left frontal cortex. Poorer outcome was associated with more pronounced cortical thinning. Thus, the cortex shows excessive thinning over time, most pronounced in the frontal and temporal areas and progresses across the entire course of the illness.