Objective: We explored the association between cerebrospinal fluid (CSF) dopamine metabolites and transporter denervation in the development of depression in Parkinson Disease (PD).

Background: Depression is associated with significant burden in Parkinson’s disease, and the association between both conditions is complex and an area of active research [1]. Research links the severity of depressive symptoms with decreased dopaminergic metabolism in depressed patients, with or without PD [1,2]. However, results remain inconclusive regarding the relationship between dopamine transporter (DaT) striatal binding ratios (SBRs) and depressive symptoms in both PD and non-PD populations [3]. Prior studies have shown depression in non-PD patients is linked to hemispheric asymmetry in terms of anatomical, structural, EEG and metabolic activity; suggesting depression may be attributed to interhemispheric neurochemical imbalances [4, 5].

Method: 80 PD PPMI participants without baseline depression (Geriatric Depression Scale-15 (GDS) score <5) who had 10-years’ worth of follow up were identified. We compared normalized CSF concentrations of dopamine, its metabolites, and SBR values between PD participants with (PDw) or without (PDwo) suspected depression (SD) for the left and right, caudate, putamen and anterior putamen using a Welch’s t-test. The predictive accuracy of dopaminergic compounds for the likelihood of developing depression on follow up (any event of GDS score > 4) was assessed through three logistic regression models: 1) dopamine and metabolites, 2) SBR and 3) both models 1 and 2 combined (combined model).

Results: PDw (n= 39) had lower levels of 3,4-Dihydroxyphenylacetic acid (DOPAC) (p=0.038), and a lower ratio of DOPAC/DA (p=0.038) compared to PDwo (n=41). PDw had lower SBR in the right caudate (p=0.043), putamen (p=0.024), anterior putamen (p=0.024), and total right striatum (p=0.024) (Table 1). The combined model (AUC= 0.814) improved the prediction of depression compared to the individual models by an increase in sensitivity (Table 2).

Conclusion: Baseline lower levels of DOPAC and lower DOPAC/DA ratio were associated with a higher likelihood of suspected depression during 10-year follow up. This suggests PD patients at risk for depression may metabolize dopamine in a different way. Right striatal lower SBRs in PDw suggest that the right striatum may be involved.

Table 1

Table 2

References: 1. Prange S, Klinger H, Laurencin C, Danaila T, Thobois S. Depression in Patients with Parkinson’s Disease: Current Understanding of its Neurobiology and Implications for Treatment. Drugs Aging. 2022 Jun;39(6):417-439.
2. Meyer, J.H., et al., Lower dopamine transporter binding potential in striatum during depression. Neuroreport, 2001. 12(18): p. 4121-5.
3. Hsiao, M.C., et al., The interaction between dopamine transporter function, gender differences, and possible laterality in depression. Psychiatry Res, 2013. 211(1): p. 72-7.
4. Hecht, D., Depression and the hyperactive right-hemisphere. Neurosci Res, 2010. 68(2): p. 77-87.
5. Bruder, G.E., J.W. Stewart, and P.J. McGrath, Right brain, left brain in depressive disorders: Clinical and theoretical implications of behavioral, electrophysiological and neuroimaging findings. Neurosci Biobehav Rev, 2017. 78: p. 178-191.

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/characterizing-dopaminergic-correlates-of-depression-in-parkinsons-disease-the-ppmi-cohort/