Objective: To investigate structural changes associated with depression in glucocerebrosidase (GBA) mutation carriers.

Background: Depression is a common non-motor symptom in Parkinson’s disease (PD); however, less is known about the prevalence and the neuropathology underlying depression in GBA carriers.

Method: The Parkinson’s Progression Markers Initiative database was utilised to identify 37 GBA carriers with manifest PD (GBA-PD) and 395 matched idiopathic PD (iPD) patients. The presence of depression was defined as a score of ≥1 on MDS-UPDRS-I subitem 1.3 for depressive mood. We explored the relationship between depression and microstructural changes (diffusion tensor imaging; DTI), within limbic regions-of-interest, in GBA-PD patients with depression compared to matched iPD patients with depression. Age, disease duration and anxiety (state-trait anxiety inventory) were included as covariates. P values were FDR corrected.

Results: Depression was present in 35% (n=13) of GBA-PD and 25% (n=106) of iPD patients. Depressed GBA-PD patients had decreased fractional anisotropy (FA) in the thalamus (P<0.0001), pons (P=0.013), medulla (P=0.030) and posterior cingulate (P=0.013) compared to GBA-PD without depression. GBA-PD patients with depression showed decreased FA in the putamen (P=0.049), ventral striatum (P=0.036), substantia nigra (P=0.018), anterior (P=0.041) and posterior (P=0.015) cingulate; and increased mean diffusivity (MD) in the caudate (P=0.038), insula (P=0.006), hippocampus (P=0.035) and locus coeruleus (P=0.048) compared with matched iPD patients with depression.

Conclusion: Our findings indicate that depression in GBA-PD is associated with microstructural damages in the limbic system. The GBA-PD depressive phenotype is associated greater microstructural changes, higher FA reductions and MD increases, compared with the iPD depressive phenotype. Future studies in asymptomatic GBA carriers and longitudinal analysis could provide insights into the utility of microstructural changes to monitor and predict depression in GBA carriers.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/microstructural-changes-in-gba-mutation-carriers-with-depression/