Abstract

In order to understand the pathophysiology of schizophrenia we carried out a number of brain imaging studies in both medicated and unmedicated patients. In addition, to help unravel the pathophysiological mechanisms without the confound of prior exposure to antipsychotic medication or chronicity, we enrolled a large group of antipsychotic medication-naïve first episode psychosis patients at first treatment contact, and performed longitudinal multimodal neuroimaging studies over several months.In unmedicated patients we found both functional and structural connectivity alterations. Similarly, in medication-naïve patients we replicated many of our prior findings, suggesting that functional and structural connectivity alterations are core pathological features of the illness. We found that a longer duration of untreated psychosis, i.e. the time between first symptom onset and initial treatment contact, was associated with greater structural and functional connectivity abnormalities, which in turn was associated with worse subsequent clinical response to treatment.These results underscore the critical importance of early identification and treatment in patients with psychosis spectrum disorders.

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