Reduced striatal dopamine transmission as a transdiagnostic substrate of psychomotor retardation

Journal article : Review

Psychomotor retardation, defined as generalized slowing of movement and speech, is a feature of several neurological and psychiatric disorders. In this review, we discuss the hypothesis that reduced striatal dopaminergic transmission is a transdiagnostic substrate for psychomotor retardation underlying the motor features of conditions such as Parkinson’s disease, drug-induced parkinsonism, neuroleptic malignant syndrome, catatonia and depression. We examine the evidence across clinical, epidemiological, neuroimaging, laboratory and therapeutic studies. Parkinsonian disorders share slowed movement and a reduction in verbal output with catatonia and depression. Bradyphrenia, slowed cognitive processing, also occurs in Parkinson’s disease and depression. In addition, there are close epidemiological relationships between depression and Parkinson’s disease, and between catatonia and neuroleptic malignant syndrome. Neuroimaging studies also generally support the association of psychomotor retardation with reduced dopaminergic transmission, particularly in the dorsal striatum. CSF measurement of homovanillic acid (a dopamine catabolite) yields inconsistent results and is non-specific. Parkinson’s disease and catatonia generally respond well to dopaminergic medication. In contrast, dopamine antagonists can induce both parkinsonism and catatonia. Our review is limited by the variability in measurement of psychomotor retardation and difficulty distinguishing between cognitive and motor slowing. It is also likely that other neurotransmitters, such as GABA and serotonin, play an important role in psychomotor speed. It is possible that dopaminergic deficits in psychiatric disorders represent functional disruptions, in contrast to the structural damage to the substantia nigra in Parkinson’s disease. We propose further research be conducted into the effects of levodopa and dopamine agonists in depression with psychomotor retardation. Alternative neuroimaging methods such as PET sequences with shorter imaging protocols and neuromelanin-MRI should also be explored.

Authors: Leong, IL; Ng, TH; Sen, K; Burchill, E; Costello, H

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: Brain
• Volume: 149
• Issue: 1
• Pages: 18-36
• Publication date: 2025-09-12
• Acceptance date: 2025-08-14
• DOI: 10.1093/brain/awaf335
• EISSN: 1460-2156
• ISSN: 0006-8950
• Language: English
• Keywords: striatum; movement disorders; basal ganglia; cognitive slowing; bradykinesia
• Subtype: Review