Serotonergic dysregulation is linked to sleep problems in Parkinson's disease

INTRODUCTION: Sleep disturbances are common non-motor symptoms in Parkinson's disease (PD). Experimental studies suggest involvement of the serotonergic system in the regulation of sleep and arousal. Using [(11)C]DASB positron emission tomography, a marker of serotonin transporter availability, we investigated whether sleep dysfunction is associated with serotonergic dysfunction in PD. METHODS: We studied 14 PD patients with sleep dysfunction, 14 PD without sleep dysfunction, and 12 healthy controls. Groups were matched for age, disease duration, severity of motor symptoms, daily intake of levodopa equivalent units, body-mass-index, depression and fatigue. [(11)C]DASB non-displaceable binding potential (BP(ND)) was calculated for regions with a role in the regulation of sleep and arousal. RESULTS: [(11)C]DASB BP(ND) was reduced by 32–49% in PD patients with sleep dysfunction, and 14–25% in PD without sleep dysfunction, compared to healthy controls. PD patients with sleep dysfunction had lower [(11)C]DASB BP(ND) in caudate (P < 0.01), putamen (P < 0.001), ventral striatum (P < 0.001), thalamus (P < 0.05), hypothalamus (P < 0.001) and raphe nuclei (P < 0.01), compared to PD without sleep dysfunction. Higher severity of sleep symptoms (assessed with Parkinson Disease Sleep Scale) correlated with lower [(11)C]DASB binding in caudate (r = 0.77; P < 0.001), putamen (r = 0.84; P < 0.001), ventral striatum (r = 0.86; P < 0.001), thalamus (r = 0.79; P < 0.001), hypothalamus (r = 0.90; P < 0.001) and raphe nuclei (r = 0.83; P < 0.001). CONCLUSIONS: Our findings demonstrate that sleep dysfunction in PD is associated with reduced serotonergic function in the midbrain raphe, basal ganglia and hypothalamus. Strategies to increase serotonin levels in the brain could be a promising approach to treat sleep dysfunction in PD, and may also have relevance in other neurodegenerative disorders.