The relationship between the dopaminergic system and depressive symptoms in cervical dystonia

Abstract

PurposeCervical dystonia (CD) is associated with tremor/jerks (50%) and psychiatric complaints (17–70%). The dopaminergic system has been implicated in the pathophysiology of CD in animal and imaging studies. Dopamine may be related to the motor as well as non-motor symptoms of CD. CD is associated with reduced striatal dopamine D2/3 (D2/3) receptor and increased dopamine transporter (DAT) binding. There are differences in the dopamine system between CD patients with and without jerks/tremor and psychiatric symptoms.MethodsPatients with CD and healthy controls underwent neurological and psychiatric examinations. Striatal DAT and D2/3 receptor binding were assessed using [123I]FP-CIT and [123I]IBZM SPECT, respectively. The ratio of specific striatal to non-specific binding (binding potential; BPND) was the outcome measure.ResultsTwenty-seven patients with CD and 15 matched controls were included. Nineteen percent of patients fulfilled the criteria for a depression. Striatal DAT BPND was significantly lower in depressed versus non-depressed CD patients. Higher DAT BPND correlated significantly with higher scores on the Unified Myoclonus Rating Scale (UMRS). The striatal D2/3 receptor BPND in CD patients showed a trend towards lower binding compared to controls. The D2/3 BPND was significantly lower in depressed versus non-depressed CD patients. A significant correlation between DAT and D2/3R BPND was found in both in patients and controls.ConclusionsAlterations of striatal DAT and D2/3 receptor binding in CD patients are related mainly to depression. DAT BPND correlates significantly with scores on the UMRS, suggesting a role for dopamine in the pathophysiology of tremor/jerks in CD.

Dopamine transporter (DAT) knockdown in the nucleus accumbens improves anxiety- and depression-related behaviors in adult mice

“…However, when the density of DAT was assessed in other studies, the data indicated decreases in striatal DAT binding in depressed patients [24,94]. Likewise, in Parkinsonian patients, measures for anxiety and depression were associated with diminished left anterior putamen DAT binding [95], and striatal DAT binding was significantly lower in depressed versus non-depressed cervical dystonia patients [96]. The significant flaw in the results reported above is the absence of repeated cross-sectional studies that examine variations during phases of illness.…”

Lower serotonin transporter binding in patients with cervical dystonia is associated with psychiatric symptoms

“…Included subjects also participated in another study recently published [ 5 ]. In short, we included patients with idiopathic CD with stable disease severity for at least 1 year on the Tsui scale, age between 35 and 80 years, and ongoing treatment with botulinum neurotoxin (BoNT) injections, which is the current standard treatment for focal dystonia.…”

“…We recently showed normal striatal DAT binding but decreased D2/3 receptor binding in CD. We also showed a significant relationship between striatal DAT binding and jerks/tremor of the head, which is a common symptom in CD, and a significant and negative relationship between both striatal DAT and D2/3 receptor binding and depressive symptoms [ 5 ].…”

Randomised controlled trial of escitalopram for cervical dystonia with dystonic jerks/tremor

“…Using molecular imaging, abnormalities were found in dopaminergic signalling 7 8. We showed that lower striatal dopamine D 2/3 receptor and dopamine transporter (DAT) binding in CD is associated with depressive symptoms 8. We also found a clear trend towards lower serotonin transporter (SERT) binding in CD, particularly in patients with psychiatric symptoms.…”

“…After all videos of each subject were scored, physicians received the correct order for the videos and scored the CGI improvement for dystonia and jerks/tremor. Interobserver reliability was assessed in a subset of patients and was good (>80) for Tsui and TWSTRS and reasonable for UMRS (0.73) 8. The psychiatric interview was performed by trained investigators (EZ and YEMD) and consisted of the MINI International Neuropsychiatric Interview Plus (MINI-Plus), Montgomery-Åsberg Depression Rating Scale (MADRS) and the Y-BOCS Severity Scale.…”