Striatal dopamine D2 receptors in tardive dyskinesia: PET study.

Abstract

SUMMARY The dopamine D2 receptors were investigated in vivo in eight neuroleptic-free patients with persistent tardive dyskinesia using positron emission tomography and 76Br-bromospiperone. The striatal receptor density, estimated by the striatum/cerebellum radioligand concentration ratio, was not elevated in patients as compared with age-matched controls but was positively correlated with the severity of orofacial dyskinesia assessed with the Abnormal Involuntary Movement Rating Scale. These results indicate that tardive dyskinesia is associated with normal levels of striatal D2 receptors but the severity of orofacial movements may depend on the relative density of striatal D2 receptors.Tardive dyskinesia (TD) is a protracted, sometimes permanent, complication of long-term neuroleptic treatment, affecting 13% to 31% of treated schizophrenic patients.'2 It is a distressing condition as the involuntary movements affect the orofacial musculature and often do not respond to therapy save for reintroduction or increased dosage of neuroleptics. There is no established preventive measure other than restricting prescription, and limiting both dosage and duration, of neuroleptic treatment as much as possible.3Brain dopamine receptor hypersensitivity is the most widely accepted hypothesis for the development of TD: it resembles levodopa-induced dyskinesia; it is both caused and controlled by dopaminergic antagonists and aggravated by dopaminergic agonists; during and following chronic neuroleptic treatment, rodents show increased behavioural responses to dopaminergic agonists with correlated increase in dopamine D2 receptor density in the striatum.4 Until now, however, no direct evidence for this role of striatal D2 receptors has been obtained in prospectively selected TD patients. We have evaluated striatal D2 receptors in TD patients in vivo using positron emission tomography (PET) and 76Br-bromospiperone to investigate the following hypothesis: (1) the striatal D2 receptors are increased in TD, and (2) the D2 receptor density is correlated to the severity of TD. Eight dyskinetic patients were studied after giving informed consent (table 1). The eight TD patients (7 women and I man, mean age 64-3 years, SD 4 7) were compared with eight agematched controls (3 women and 5 men, mean age 63 5, SD 2 6). The diagnosis of TD was established when abnormal involuntary movements (AIMS) (of a choreic nature), without other neurological abnormalities, had been permanent for the past 3 months, affecting in all cases the oro-linguofacial area and sometimes also the limbs or trunk, and had begun following a minimum of 3 months of exposure to neuroleptics, persisting at least 9 days after withdrawal of the neuroleptics (the type of which not being relevant). Neuroleptics had been prescribed, sometimes for many years, by general practitioners for reasons not always clear, particularly in the six chronically depressed patients. The characteristics ofdyskinesia and the plasma concentration of prolactin (as an index of neuroleptic medicati...

Effect of Age on D2 Dopamine Receptors in Normal Human Brain Measured by Positron Emission Tomography and 11C-Raclopride

“…A significant decrease with age of the index for specific tracer uptake was found in putamen and caudate nucleus. The decrease was steep until 30 years, but slower afterward. After approximately 30 years of age, the decline of specific 11C-raclopride binding in putamen was found to be 0.6% per year.…”

Amphetamine-Induced Dopamine Release and Post-Synaptic Specific Binding in Patients with Mild Tardive Dyskinesia

“…A PET study examining patients with Parkinson's Disease also failed to find any difference in D 2 receptor binding in patients who had developed dyskinesias (Turjanski et al 1997). Moreover, although Blin et al (1989) observed correlation between orofacial dyskinesia and D 2 receptor density, no correlation between global dyskinesia and D 2 binding was found.…”

“…Brains of schizophrenic patients with TD examined post-mortem have not demonstrated an increase in striatal D 2 receptor density (Cross et al 1985;Kornhuber et al 1989). Similarly, two in vivo positron emission tomography (PET) studies using N-[ 11 C]-methylspiperone and [ 76 Br]-bromospiperone failed to demonstrate increased D 2 receptor density in individuals with TD, both compared with individuals exposed to neuroleptics without TD, and in a cohort of age matched controls (Blin et al 1989;Andersson et al 1990). A PET study examining patients with Parkinson's Disease also failed to find any difference in D 2 receptor binding in patients who had developed dyskinesias (Turjanski et al 1997).…”

A Review of Epilepsy Diagnosis Using PET Parameters

“…For partial seizures and other types of seizures that originate from a specific focus, however, functional imaging can be useful for localizing the primary site. Functional imaging also helps in the understanding of the pathophysiology of seizure disorders [34,35]. SPECT is widely used in the localization of epileptogenic focus.…”

“…These parameters on image data are analyzed with various data processing tools, which include asymmetry, SUV statistical analysis, and Image enhancement, postprocessing of image data, besides image visualization in 2D and 3D mode. Various PET parameters [32][33][34][35][36][37] used to diagnose the epileptic patients are as follows:…”