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.

Keywords: Parkinson's disease; anxiety; apathy; depression; frontostriatal pathway; neuroimaging.

Figure 1

Flow diagram of study selection.

Figure 2

Simplified schemes of the depression, anxiety and apathy networks in PD. Generally, as PD pathology defined by dopaminergic deficiency progresses, the implicated neural areas that are associated with mood symptoms involve the prefrontal cortex including orbitofrontal cortex and medial prefrontal cortex and then extend to some regions in the anterior temporal and parietal lobes, and subcortical areas. Amongst the three mood symptoms, the shared brain regions are mainly within the frontostriatal pathway. Blocks in grey refer to the frontostriatal pathway; ACC, anterior cingulate cortex; AMG, amygdala; DA, dopamine; HIPP, hippocampus; PCC, posterior cingulate cortex; SMC, supplementary motor cortex; SNr, substantia nigra.