CAM-15-004 The N400 brainwave, elicited by meaningful stimuli like words or pictures, is smaller for stimuli more related to previous ones. This “N400 priming effect” is reduced in schizophrenia. In this study we found the same abnormality in patients with milder schizophrenia-like symptoms placing them at “clinical high risk” (CHR) of developing this disorder. Our finding suggests that this abnormality reflects brain dysfunction underlying schizophrenia rather than medication or chronic illness effects, indicating a potential target for new treatments or preventive interventions. We will present preliminary results from ongoing follow-up study of whether the degree of this abnormality predicts which CHR patients will develop schizophrenia, which could help target treatment to those most at risk.

CAM-15-004 Schizophrenia is a chronic mental illness that affects 1% of people and costs $7 billion per year in Canada. Thus, efforts to identify persons at “clinical high risk” (CHR) of developing schizophrenia and to prevent this outcome are crucial. CHR patients, who have milder forms of schizophrenia symptoms, have 400 times the normal risk of developing schizophrenia. Yet, a majority of CHR patients will not develop schizophrenia, while providing them with psychiatric treatment is costly and time-consuming, and can cause side effects and stigma. To target treatment to those most in need, new tests are needed to predict which CHR patients are most likely to develop schizophrenia. We propose that one such test could use the scalp-recorded N400 brainwave, which people exhibit in response to any meaningful stimulus like a word or picture. N400 is normally smaller when the stimulus is more related to other, preceding stimuli. This size difference in the N400 to related and unrelated stimuli (“N400 semantic priming effect”) is reduced in schizophrenia. We hypothesized that CHR patients exhibit a similar N400 abnormality and that its severity predicts their risk of developing schizophrenia. We found that CHR patients indeed exhibit this abnormality, suggesting that it reflects brain dysfunction predisposing to schizophrenia rather than medication or chronic illness effects, and indicating a potential target for new treatments or preventive interventions. We continue to follow patients longitudinally to study whether the degree of this N400 abnormality predicts which CHR patients will develop schizophrenia. If this hypothesis is confirmed, the N400 could be a low-cost, easy-to-obtain measure for helping to further predict CHR patients’ schizophrenia risk, and thus to target treatment to those most at risk.