title: Pathway-Specific Dopamine Abnormalities in Schizophrenia.
abstract: In light of the clinical evidence implicating dopamine in schizophrenia and the prominent hypotheses put forth regarding alterations in dopaminergic transmission in this disease, molecular imaging has been used to examine multiple aspects of the dopaminergic system. We review the imaging methods used and compare the findings across the different molecular targets. Findings have converged to suggest early dysregulation in the striatum, especially in the rostral caudate, manifesting as excess synthesis and release. Recent data showed deficit extending to most cortical regions and even to other extrastriatal subcortical regions not previously considered to be "hypodopaminergic" in schizophrenia. These findings yield a new topography for the dopaminergic dysregulation in schizophrenia. We discuss the dopaminergic innervation within the individual projection fields to provide a topographical map of this dual dysregulation and explore potential cellular and circuit-based mechanisms for brain region-dependent alterations in dopaminergic parameters. This refined knowledge is essential to better guide translational studies and efforts in early drug development.
authors.affiliation: Department of Psychiatry, Columbia University, New York; Divisions of Translational Imaging, New York State Psychiatric Institute, New York, New York. Electronic address: jodi.j.weinstein@aya.yale.edu.
authors.forename: Jodi J
authors.initials: JJ
authors.lastname: Weinstein
authors.affiliation: Integrative Neuroscience, New York State Psychiatric Institute, New York, New York.
authors.forename: Muhammad O
authors.initials: MO
authors.lastname: Chohan
authors.affiliation: Department of Psychiatry, Columbia University, New York; Divisions of Translational Imaging, New York State Psychiatric Institute, New York, New York.
authors.forename: Mark
authors.initials: M
authors.lastname: Slifstein
authors.affiliation: Department of Psychiatry, Columbia University, New York; Divisions of Translational Imaging, New York State Psychiatric Institute, New York, New York.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kegeles
authors.affiliation: Department of Psychiatry, Columbia University, New York; Integrative Neuroscience, New York State Psychiatric Institute, New York, New York.
authors.forename: Holly
authors.initials: H
authors.lastname: Moore
authors.affiliation: Department of Psychiatry, Columbia University, New York; Divisions of Translational Imaging, New York State Psychiatric Institute, New York, New York.
authors.forename: Anissa
authors.initials: A
authors.lastname: Abi-Dargham
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D002421:Caudate Nucleus / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D049268:Positron-Emission Tomography; D011954:Receptors, Dopamine / Q000378:metabolism / Q000502:physiology; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology*; D013569:Synapses / Q000378:metabolism / Q000502:physiology; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; D004298:Dopamine
keywords: Cortex; Dopamine; Neuroanatomy; PET imaging; Schizophrenia; Striatum