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Recently, a new locus (PARK8) for autosomal dominant parkinsonism has been identified in one large Japanese family. Linkage has been shown to a 16-cM centromeric region of chromosome 12, between markers D12S1631 and D12S339. We tested 21 white families with Parkinson disease and an inheritance pattern compatible with autosomal dominant transmission for(More)
Placebo responses occur in a wide range of medical conditions, yet the underlying mechanisms remain poorly understood. On the basis of our observations of patients in Parkinson's disease, we have argued that the placebo effect is partly mediated by the activation of reward circuitry and that mesocorticolimbic dopamine release, particularly in the ventral(More)
OBJECTIVE Although dopaminergic hyperactivity has been implicated in mania, the precise location in the brain of the abnormality is unclear. This study assessed presynaptic dopamine function in neuroleptic- and mood-stabilizer-naive nonpsychotic first-episode manic patients before and after treatment with divalproex sodium by measuring(More)
An increase in dopamine turnover has been shown to occur early in Parkinson's disease (PD). This study investigated changes of dopamine turnover as a function of PD duration using the effective distribution volume (EDV) for dopamine, determined by positron emission tomography with 6-[18F]-fluoro-L-dopa, and compared them with changes in dopamine synthesis(More)
Treatment-related motor complications in Parkinson's disease have been previously linked to disease-induced pre-synaptic alterations: dopaminergic denervation and changes in dopamine (DA) release patterns. The occurrence of such complications is also known to be partly dependent on the age of disease onset, occurring more frequently in patients with disease(More)
Increase in dopamine (DA) turnover was found to occur early in symptomatic Parkinson's disease (PD) and to be functionally related to the dopamine transporter (DAT). The objectives of this study were to examine changes in DA turnover in the asymptomatic PD phase; to compare them with changes in other dopaminergic markers, and to investigate a possible(More)
BACKGROUND Parkinson's disease (PD) is an adult-onset, neurodegenerative disorder characterized by a selective loss of the dopaminergic cells of the substantia nigra and by progressive motor decline. Studies have shown aberrant oxidative stress metabolism within the substantia nigra and other dopaminergic regions of the brain in patients with PD. (More)
INTRODUCTION Mutations in dynactin DCTN1 (p150(glued)) have previously been linked to familial motor neuron disease or Perry syndrome (PS) consisting of depression, parkinsonism and hypoventilation. METHODS We sequenced DCTN1 in 636 Caucasian patients with parkinsonism (Parkinson's disease and Parkinson-plus syndromes) and 508 healthy controls. Variants(More)
BACKGROUND Parkinson's disease is a common disorder that becomes more prevalent with advanced age. The cardinal features are related to dopamine deficiency, arising from loss of neurons projecting from the substantia nigra in the midbrain to the striatum. Therapies based on dopamine replacement are well established but while highly effective, leave a number(More)