Thalamic Volume Is Associated with Dopaminergic Degeneration and Depressive Symptoms in Parkinson's Disease

The thalamus is a core node of the basal ganglia-thalamocortical circuit implicated in Parkinson's disease (PD) and depression. This study examined associations among thalamic volume ratio (TVR), nigrostriatal dopaminergic degeneration, and depressive symptoms in PD.

We included 170 PD patients with 4‑year follow‑up data from a prospective cohort. TVR was derived from automated thalamic segmentation; depressive symptoms were assessed using the Geriatric Depression Scale (GDS), and dopamine transporter (DAT) availability was quantified. Multivariable regression, linear mixed‑effects models, mediation, and ordinal logistic regression sensitivity analyses were performed.

TVR correlated positively with caudate (r = 0.249, p = 0.001), putamen (r = 0.197, p = 0.010), and anterior putamen (r = 0.230, p = 0.003) DAT availability, but inversely with GDS at Years 1-4 (p < 0.05), not at baseline. After FDR adjustment, TVR remained independently associated with GDS at Year 2 (β = -0.655, p = 0.006, q = 0.036), but the association at Year 1 did not survive correction (β = -0.445, p = 0.037, q = 0.100). A significant TVR‑by‑time interaction emerged (β = -0.163, p = 0.008), suggesting that lower TVR was associated with a steeper increase in GDS scores over time. Mediation analyses demonstrated significant indirect effects of caudate DAT on GDS at Years 1 and 2, with direct effects marginal at Year 1 (β = -0.840, p = 0.050) and significant at Year 2 (β = -1.181, p = 0.017), indicating partial mediation.

TVR may represent an imaging correlate of dopaminergic dysfunction and depressive progression in PD, with a mediating pathway linking caudate degeneration, thalamic alterations, and depressive symptoms. Independent validation is warranted.