Distinct Fractional Amplitude of Low-Frequency Fluctuation in Parkinson’s Disease Patients with Comorbid Anxiety and Depression: A Resting-State fMRI Study

Background: Anxiety and depression symptoms are prevalent and persistent in patients with Parkinson’s disease (PD). Most neuroimaging studies have examined PD patients presenting with isolated anxiety or depression, whereas few studies have specifically investigated patients with concurrent anxiety and depression, a clinically more severe subtype. The present study therefore sought to unravel the neural mechanisms underlying PD with comorbid anxiety and depression (PD-A&D). Methods: This study enrolled 35 PD-A&D patients, 32 PD patients without anxiety and depression (PD), and 38 healthy control subjects (HCs), who underwent resting-state functional magnetic resonance imaging using a 3.0T scanner. Fractional amplitude of low-frequency fluctuation (fALFF) analysis was used to assess spontaneous brain activity across the three groups. Correlations between fALFF alterations and the Hamilton Anxiety Rating Scale (HAMA) as well as the Hamilton Depression Rating Scale (HAMD) scores were examined within the PD-A&D group. Results: Relative to the PD group, PD-A&D patients exhibited significant fALFF reductions primarily in the right putamen/caudate, right superior frontal gyrus, right precuneus, and right inferior parietal lobe. Furthermore, relative to HCs, PD-A&D patients displayed widespread fALFF alterations in the left cerebellar Crus I/lobule VI, left precuneus and so on. Notably, the fALFF values in left cerebellar Crus I/lobule VI were positively correlated with the HAMA scores (r = 0.48, p = 0.0035, 95% CI = [0.17, 0.70]), while those in the right precuneus showed a negative correlation with the HAMD scores (r = −0.39, p = 0.021, 95% CI = [−0.64, −0.07]) in PD-A&D patients. Conclusions: This research indicates that anxiety and depression symptoms in PD patients are correlated with abnormal spontaneous neuronal activities across multiple brain regions, particularly the frontoparietal and basal ganglia networks. These findings provide preliminary and exploratory insights into the neural heterogeneity of PD-A&D patients. However, given the modest sample size and the cross-sectional design, these potential neuroimaging correlates require future longitudinal validation.