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Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression

Abstract

The dopamine system is unique among the brain's modulatory systems in that it has discrete projections to specific brain regions involved in motor behaviour, cognition and emotion. Dopamine neurons exhibit several activity patterns — including tonic and phasic firing — that are determined by a combination of endogenous pacemaker conductances and regulation by multiple afferent systems. Emerging evidence suggests that disruptions in these regulatory systems may underlie the pathophysiology of several psychiatric disorders, including schizophrenia and depression.

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Figure 1: Tonic and phasic dopamine neuron regulation.
Figure 2: Infralimbic prefrontal cortex-mediated modulation of dopamine neuron activity.
Figure 3: Ventral-subiculum dysfunction and schizophrenia symptomatology.
Figure 4: Depression circuitry and ketamine actions.

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Acknowledgements

The author thanks P. Belujon for her help in constructing the figures. This work was supported by US Public Health Service grants MH57440, MH191180 and MH104320.

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Correspondence to Anthony A. Grace.

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The author has received honoraria/research support from the following organizations: Johnson & Johnson, Lundbeck, Pfizer, GSK, Merck, Takeda, Dainippon Sumitomo, Otsuka, Lilly, Roche, Asubio, Abbott, Autofony and Janssen.

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Grace, A. Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. Nat Rev Neurosci 17, 524–532 (2016). https://doi.org/10.1038/nrn.2016.57

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