Depression, anxiety, and apathy in Parkinson's disease: insights from neuroimaging studies

Abstract

Depression, anxiety and apathy are common mood disturbances in Parkinson's disease (PD) but their pathophysiology is unclear. Advanced neuroimaging has been increasingly used to unravel neural substrates linked to these disturbances. A systematic review is provided of neuroimaging findings in depression, anxiety and apathy in PD. A PubMed, MEDLINE and EMBASE search of peer‐reviewed original research articles on these mood disturbances in PD identified 38 studies on depression, eight on anxiety and 14 on apathy in PD. Most of the imaging studies used either position emission tomography or single‐photon emission computed tomography techniques. These studies generally suggest increased neural activity in the prefrontal regions and decreased functional connectivity between the prefrontal−limbic networks in depressed patients. Functional imaging studies revealed an inverse correlation between dopaminergic density in the caudate and putamen with the severity of anxiety in PD. There was no consistent correlation between dopaminergic density of thalamus and anxiety. Studies demonstrated both positive and inverse correlations between apathy and metabolism or activity in the striatum, amygdalar, prefrontal, temporal and parietal regions. The clinical variability of study subjects and differences in image pre‐processing and analytical strategies may contribute to discrepant findings in these studies. Both nigrostriatal and extra‐nigrostriatal pathways (in particular the frontal region and its connecting areas) are affected in mood disorders in PD. Identifying the relative contributions of these neural pathways in PD patients with overlapping motor and mood symptoms could provide new pathophysiological clues for the development of better therapeutic targets for affected patients.

Can anxiety increase tremors in patients with Parkinson’s disease? An experimental model

“…Furthermore, the cerebellum and locus coeruleus are a part of this complex mechanism of the motor system 24 . It is of note that these areas are also directly associated with mood symptoms 25 and anxiety in PD 26 , thereby corroborating the influence of non-motor symptoms in tremors.…”

Impaired long contact white matter fibers integrity is related to depression in Parkinson's disease

“…Resting‐state functional MRI (RS‐fMRI) shows that PDD patients have increased spontaneous neural activity in orbitofrontal cortex, while reduced network functional connectivity of the prefrontal‐limbic system. These results suggest the abnormalities of prefrontal‐limbic network may be involved in the complex pathophysiological mechanisms in PDD patients …”

“…Depression is one of the most common mood disturbances in PD, but its pathogenesis is unclear . Studies using advanced neuroimaging generally suggest increased neural activity in the prefrontal regions and decreased functional connectivity between the prefrontal‐limbic networks in depressed PD patients . Most of these studies have adopted position emission tomography, single‐photon emission computed tomography, structural MR, or RS‐fMRI.…”

Grey matter abnormalities in Parkinson’s disease: a voxel‐wise meta‐analysis

“…Neuroimaging studies have also demonstrated widespread reduced functional connectivity in the basal ganglia network in PD patients compared with HCs . Moreover, functional neuroimaging studies have also detected that increased or decreased neural activities of the striatum in PD patients were related to mood disturbances, such as depression, apathy and anxiety . Considerable evidence has shown that the basal ganglia dysfunction may also give rise to aberrant cognition .…”