Pathway-Specific Dopamine Abnormalities in Schizophrenia

Biol Psychiatry. 2017 Jan 1;81(1):31-42. doi: 10.1016/j.biopsych.2016.03.2104. Epub 2016 Mar 31.

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.

Keywords: Cortex; Dopamine; Neuroanatomy; PET imaging; Schizophrenia; Striatum.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / physiopathology
  • Caudate Nucleus / metabolism
  • Caudate Nucleus / physiopathology
  • Corpus Striatum / metabolism
  • Corpus Striatum / physiopathology*
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopamine Plasma Membrane Transport Proteins / physiology
  • Humans
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Positron-Emission Tomography
  • Receptors, Dopamine / metabolism
  • Receptors, Dopamine / physiology
  • Schizophrenia / metabolism
  • Schizophrenia / physiopathology*
  • Synapses / metabolism
  • Synapses / physiology
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Receptors, Dopamine
  • Dopamine