Serotonergic loss in motor circuitries correlates with severity of action-postural tremor in PD

Abstract

Objective: The underlying pathophysiology of tremor in Parkinson disease (PD) is unclear; however, it is known that tremor does not appear to be as responsive to dopaminergic medication as bradykinesia or rigidity. It is suggested that serotonergic dysfunction could have a role in tremor development.Methods: Using 11 C-DASB PET, a marker of serotonin transporter binding, and clinical observations, we have investigated function of serotonergic terminals in 12 patients with tremor-predominant and 12 with akinetic-rigid PD. Findings were compared with those of 12 healthy controls.Results: Reductions of 11 C-DASB in caudate, putamen, and raphe nuclei significantly correlated with tremor severity on posture and action, but not with resting tremor. The tremor-predominant group also showed reductions of 11 C-DASB in other regions involved in motor circuitry, including the thalamus and Brodmann areas 4 and 10. Conclusions:

Serotonin transporter in Parkinson's disease: A meta‐analysis of positron emission tomography studies

“…[25][26][27][28][29][30] The development of tremor in PD has been speculated to be underlined by non-dopaminergic mechanisms attributed to the fluctuating response of this symptom to dopaminergic supplementation and the lack of correlations with dopaminergic molecular imaging markers. 23 These findings complement earlier results, which demonstrated a correlation between reduced raphe 5-HT 1A binding and severity of resting tremor in patients with PD. Moreover, caudate, putamen, and raphe nuclei SERT levels correlated with postural and action tremor.…”

“…Serotonergic pathology has been associated with the development of motor symptoms 23,24 and complications. [25][26][27][28][29][30] The development of tremor in PD has been speculated to be underlined by non-dopaminergic mechanisms attributed to the fluctuating response of this symptom to dopaminergic supplementation and the lack of correlations with dopaminergic molecular imaging markers.…”

Treadmill exercise alleviates depressive symptoms in rotenone-induced Parkinson disease rats

“…Altered serotonergic neurotransmission contributes to the motor and non-motor features commonly associated with PD (Loane et al, 2013). Changes in the 5-HT system are associated with psychiatric disorders, including major depression and bipolar disorder (Fava and Kendler, 2000).…”

Deep brain stimulation of the subthalamic nucleus: All that glitters isn't gold?

“…Nevertheless, creating a fixed, not adaptable, surgical schedule is difficult, particularly for patients with a 6‐ to 7‐year disease history. Why should a similar therapeutic timetable apply to an early asymmetric akinetic patient, to a late‐onset postural instability gait disorder, or to a tremulous PD whose mixed tremor could be explained by l ‐dopa resistance?Are we using reliable indicators to monitor DBS therapeutic effectiveness? A recent contribution stressed how the QoL is “not designed specifically to assess home and community mobility”; not surprisingly, the significant motor improvement afforded by STN‐DBS at 6 to 9 months did not “translate systematically to improvement in all measures of QoL or life‐space.” The studied cohort consisted of classical 12 years' PD patients (receiving approximately 400 mg l ‐dopa equivalent daily dose), suffering from an “ingrained sedentary lifestyle.” In other words, the well‐known difficulty in modifying behavior of advanced PD patients may represent an argument for performing the intervention earlier in the course of the disease (as far as we aim at modifying significantly the daily life‐space).…”