Director: Akira Sawa, MD, Ph.D.
The Conte Center for Schizophrenia Research at The Johns Hopkins School of Medicine is designed to conduct interdisciplinary studies towards understanding the molecular pathology of schizophrenia. The ultimate goal is to elucidate the disease ‘pathways’ to better understanding the disease, build appropriate models for mechanistic studies and future therapeutic strategies, and eventually to identify novel ways to treat the disease.
Schizophrenia is a debilitating disorder with onset in young adulthood. Many lines of evidence have indicated that pre- and peri-natal brain disturbances underlie the initial risks for the disease. It is possible that these initial risks may affect postnatal cortical maturation, resulting in the delayed onset of the disorder. Prodromal stages of schizophrenia in adolescence and young adulthood may reflect the dynamic pathophysiology of disturbed brain maturation.
Thus, the overall goal of this Center is to address the key question of how defects of cortical development elicited by combinations of genetic and environmental risk factors for the disease lead to molecular, histological, and behavioral deficits, in particular those associated with the frontal cortex, relevant to this disease.
Our collaborative team has obtained evidence that a set of genetic susceptibility factors for schizophrenia (DISC1 interactome) mediate several distinct processes of neurodevelopment by functionally interacting with environmental risk factors and that their overall disturbance affects postnatal brain maturation, resulting in defects of the frontal cortex and behavioral abnormalities in adulthood. Therefore, we are conducting systematic studies to elucidate these mechanisms in association with genetic/environmental factors for schizophrenia and to link such mechanistic observations to clinical conditions.
P1: Synaptic formation and pruning in the postnatal maturation of the cerebral cortex.
P2: Centrosomal and cilial organization in the developing cerebral cortex.
P3: Axonal growth and environmental stressors in the developing cerebral cortex.
P4: Dendritic organization in the postnatal maturation of the cerebral cortex.
P5: Gene-environmental interactions for the postnatal maturation of the cerebral cortex with animal models.
P6: Roles for immune molecules in the postnatal maturation of the cerebral cortex.
These projects are supported by cores (administration, animal behavior, human genetics, and human tissue resources).