Anissa Abi-Dargham, MD
The unifying hypothesis of the Center is that schizophrenia is associated with an imbalance of dopamine (DA) systems. This imbalance is characterized by a persistent deficit in prefrontal cortical DA function (contributing to the cognitive impairment observed in these patients) and an intermittent excess of subcortical DA function (contributing to the emergence of psychotic states). The imbalance might stem from altered prefrontal cortical (PFC) connectivity involving GLU transmission and from a failure of PFC to appropriately modulate DA function.
The overall goal of the Center is to combine clinical imaging with Positron Emission Tomography and epigenetic and transgenic animal models in mice and rhesus monkeys to test this hypothesis. A set of interrelated clinical and preclinical investigations aim to:
- better characterize the existence of a DA imbalance in schizophrenia;
- explore the underlying biological mechanisms that might account for this DA phenotype; and
- understand the consequence of this imbalance for brain functions, clinical symptoms, and treatment.
Projects include two clinical imaging projects in patients with schizophrenia and four preclinical projects performed in rhesus monkeys or mice. Research investigates this single hypothesis about the association of schizophrenia and imbalances in dopamine with state-of-the art methodologies and prominent collaborators from three institutions. By integrating basic and clinical research in a unique way, the Center fundamentally advances our understanding of the neural substrates underlying schizophrenia, the developmental etiology of this phenotype, and the implications of these findings for the development of new treatment modalities.
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