DESCRIPTION (provided by applicant): One in four adult Americans experiences a mental health disorder in a given year. About 2.4 million Americans live with schizophrenia. There are considerable and growing evidences suggesting schizophrenia may originate from early neurodevelopment involving abnormal neuronal circuits. However, schizophrenia still cannot be diagnosed until young adulthood at the earliest when the most rapid phase of neurodevelopment has already completed. The lack of earlier risk assessment has severely limited our understanding of the developmental trajectory of the disease thus preventing more effective intervention before symptom onset. This project will develop a novel non-invasive MRI technique that will provide the necessary sensitivity and resolution (10 micron) to detect potential developmental abnormalities associated with neuronal circuits. Our preliminary studies have demonstrated a markedly improved sensitivity and resolution compared to state-of- the-art MRI techniques. We will further develop this novel technique and determine its molecular basis of the improved sensitivity. We will test the technique on transgenic mouse models of schizophrenia and investigate its ability to detect abnormalities in neuronal circuits before symptoms occur. In particular, we will determine the relationship between the new image contrast and abnormalities of myelination and synapses associated with corticostriatal and corticohippocampal connectivity. The rationale of the research is that the proposed multidisciplinary imaging-genetics study would help us to better understand the genetic and developmental components of the disease, to detect circuit abnormalities before behavioral symptoms, and to eventually guide treatment strategies.

PUBLIC HEALTH RELEVANCE: This research will develop an in vivo MRI-based technique for assessing brain development. In addition to the study of normal brain development and schizophrenia, this technique could be relevant for applications to many brain disorders, including demyelination diseases and brain trauma. If our hypotheses are correct, this may save lives by providing earlier diagnosis of developmental brain disorders.