Depression in Parkinson's disease: loss of dopamine and noradrenaline innervation in the limbic system

TLDR

Depression and anxiety are common in Parkinson’s disease, yet the underlying mechanisms are poorly understood, and loss of non‑dopaminergic neurotransmitter systems may contribute. The study employed [11C]RTI‑32 PET imaging to compare dopamine and noradrenaline transporter binding in eight depressed and twelve non‑depressed Parkinson’s patients matched for age, disease duration, and medication. Depressed patients showed reduced [11C]RTI‑32 binding in the locus coeruleus and limbic structures, and anxiety severity correlated inversely with binding, indicating that depression and anxiety in Parkinson’s disease are linked to selective loss of dopamine and noradrenaline innervation in the limbic system.

Abstract

The reason for the high frequency of depression and anxiety in Parkinson's disease is poorly understood. Degeneration of neurotransmitter systems other than dopamine might play a specific role in the occurrence of these affective disorders. We used [11C]RTI-32 PET, an in vivo marker of both dopamine and noradrenaline transporter binding, to localize differences between depressed and non-depressed patients. We studied eight and 12 Parkinson's disease patients with and without a history of depression matched for age, disease duration and doses of antiparkinsonian medication. The depressed Parkinson's disease cohort had lower [11C]RTI-32 binding than non-depressed Parkinson's disease cases in the locus coeruleus and in several regions of the limbic system including the anterior cingulate cortex, the thalamus, the amygdala and the ventral striatum. Exploratory analyses revealed that the severity of anxiety in the Parkinson's disease patients was inversely correlated with the [11C]RTI-32 binding in most of these regions and apathy was inversely correlated with [11C]RTI-32 binding in the ventral striatum. These results suggest that depression and anxiety in Parkinson's disease might be associated with a specific loss of dopamine and noradrenaline innervation in the limbic system.