Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression
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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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The working memory disturbance in major depression is likely related to an initial hyperactivity of the dopaminergic system that eventually leads to long-term downregulation of dopamine activity in the basal ganglia, thereby contributing to anhedonia and lack of motivation.
“This is likely related to an initial hyperactivity of the dopaminergic system that eventually leads to long-term downregulation of dopamine activity in BG, thereby contributing to anhedonia and lack of motivation (Grace, 2016).”
From Baseline-dependent effect of dopamine’s precursor L-tyrosine on working memory gating but not updating (2020) · cites this paper as Grace, 2016
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Experimental — accuracy not yet measuredDysregulation of the DA system is linked to these disorders.
“Conversely, dysregulation of the DA system is linked to these disorders (Grace, 2016).”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Grace, 2016
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Abnormal Stress Responsivity in a Rodent Developmental Disruption Model of Schizophrenia
Zimmerman, E. C., Bellaire, M., Ewing, S. G., & Grace, A. A. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.110 · Cited by 63 · see citing works
Self-citationBerretta, S., Lange, N., Bhattacharyya, S., Sebro, R., Garces, J., & Benes, F. M. (2004) · Hippocampus · doi:10.1002/hipo.20002 · Cited by 61 · see citing works
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The contribution of drug research to investigating the nature of endogenous depression.
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Self-citationThe Contribution of Drug Research to Investigating the Nature of Endogenous Depression*
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Self-citationDevelopmental dysregulation of the dopamine system and the pathophysiology of schizophrenia
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Self-citationDouble Jeopardy: Psychopathology of Black Mentally Ill Returned Migrants to Jamaica
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“Grace, A. A. (2016).”
BackgroundInfluentialda Silveira, V. T., de Castro Medeiros, D., Ropke, J., Guidine, P. A., Rezende, G. H., Moraes, M. F. D., Mendes, E. M. A. M., Macedo, D., Moreira, F. A., & de Oliveira, A. C. P. (2017) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2017.01.009 · Cited by 51 · see citing works
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“Conversely, dysregulation of the DA system is linked to these disorders (Grace, 2016).”
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de la Fuente Revenga, M., Zhu, B., Guevara, C. A., Naler, L. B., Saunders, J. M., Zhou, Z., Toneatti, R., Sierra, S., Wolstenholme, J. T., Beardsley, P. M., et al. (2021) · doi:10.1101/2021.02.24.432725 · Cited by 11 · see citing works
- Authors
- Grace, A. A.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Grace, Anthony A.
- ORCID
- Grace, Anthony A.
- Venue
- Nature Reviews Neuroscience
- Published
- 2016-06-03
- Volume
- 17
- Issue
- 8
- Pages
- 524-532
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- PMC
- PMC5166560
- OpenAlex
- W2411013142
- Cited by
- 1,166
- References
- 127
- Citations by year
- 2026: 109 · 2025: 153 · 2024: 150 · 2023: 136 · 2022: 140 · 2021: 116 · 2020: 117 · 2019: 97 · 2018: 81 · 2017: 56 · 2016: 10 · 2013: 1
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (2r01mh057440-26a1, 5r01mh101180-05)
- National Institute of Mental Health (R01-MH101180, R01-MH057440, R21MH104320, R37MH057440)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dopaminergic system, schizophrenia, depression, stress, pathophysiology, neuromodulation
- MeSH terms
- Animals, Brain, Depression, Depressive Disorder, Dopamine, Humans, Neurons, Schizophrenia
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