Depression in Parkinson’s disease: Reduced α4β2 nicotinic acetylcholine receptor (α4β2) binding in limbic and paralimbic regions

Abstract

14

Objectives: Depression is common and negatively impacts the quality of life in Parkinson’s disease. To better understand the role of α4β2 in the pathophysiology of depression in Parkinson's disease (dPD), patients with dPD and Parkinson’s disease without depression (PD) matched for age, cognitive impairment and disease severity were analyzed using α4β2 specific 2-[F-18]F-A85380 (2FA) PET.

Methods: Ten dPD (Beck Depression Inventory, BDI: 18.3±4.1; 64±9y; MMSE: 27.4±2.3, Hoehn&Yahr: 2.6±0.7), 23 PD (BDI: 6.6±3.1; 63±8y; MMSE: 27.8±1.9; Hoehn&Yahr: 2.6±0.8) and 10 age-matched normal subjects (N, 56±12y), all non-smokers, underwent PET for 7h after short infusion of 370 MBq 2FA. Binding potentials (2FA-BP) were calculated using Logan plot after correction of the arterial input function for plasma protein binding and radioactive metabolites and VOI-analysis with the corpus callosum as reference region.

Results: Compared with N, 2FA-BP was reduced in the caudate nucleus, midbrain, insular and middle/posterior cingulate cortex in both dPD or PD, and additionally in the amygdala, anterior cingulate cortex and pons in dPD. Compared with PD, in dPD, 2FA-BP was decreased in the caudate nucleus, putamen, pallidum, thalamus, frontal lobe (superior, orbitofrontal, rectus), superior temporal lobe, insular and posterior cingulate cortex (for all tests: p<0.05).

Conclusions: Patients with dPD demonstrate greatest reductions of α4β2 binding in multiple limbic and paralimbic regions (amygdala, cingulate cortex, basal ganglia, frontal/temporal lobe), which are highly involved in the pathophysiology of depression. Therefore, α4β2 may become a pivotal target for diagnostic PET and drug therapy in dPD.

Research Support: IZKF (C27)