Objective: (1) To evaluate the existing neuroimaging studies of depression, anxiety and apathy in Parkinson’s disease (PD) and (2) to determine the key neural pathway associated with the three mood symptoms in PD based on previous findings.

Background: Depression, anxiety, and apathy are common mood symptoms in PD, but their pathophysiology is unclear. Advanced neuroimaging has been increasingly used to unravel neural substrates linked to these symptoms. We provide a systematic review of neuroimaging findings in depression, anxiety and apathy in PD.

Methods: We searched PubMed, MEDLINE, and EMBASE for peer-reviewed original research articles using the combinations of the following keywords: “depression”, “anxiety”, “apathy”, “mood symptoms”, “Parkinson’s disease”, “Parkinson’s disease”, “neuroimaging”, “magnetic resonance imaging (MRI)”, “functional MRI”, “diffusion tensor imaging (DTI)”, “resting state functional MRI”, “single-photon emission computed tomography (SPECT)”, “position emission tomography (PET)”, and “transcranial sonography (TCS)”. We identified 38 studies on depression, 8 on anxiety, and 14 on apathy.

Results: Most of the imaging studies used either PET or SPECT 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 with metabolism or activity in 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.

Conclusions: Both nigrostriatal and extra-nigrostriatal pathways (in particular the frontal 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 pathophysiologic clues for the development of better therapeutic targets for affected patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/depression-anxiety-and-apathy-in-parkinsons-disease-insights-from-neuroimaging-studies/