Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression.

BACKGROUND: Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role in the interaction between the central and peripheral inflammation. Here we aimed to investigate CP volume alterations in depression and their associations with inflammation. METHODS: 51 depressed participants (HDRS score > 13) and 25 age- and sex-matched healthy controls (HCs) from the Wellcome Trust NIMA consortium were re-analysed for the study. All the participants underwent full peripheral cytokine profiling and simultaneous [11C]PK11195 PET/structural MRI imaging for measuring neuroinflammation and CP volume respectively. RESULTS: We found a significantly greater CP volume in depressed subjects compared to HCs (t(76) = +2.17) that was positively correlated with [11C]PK11195 PET binding in the anterior cingulate cortex (r = 0.28, p = 0.02), prefrontal cortex (r = 0.24, p = 0.04), and insular cortex (r = 0.24, p = 0.04), but not with the peripheral inflammatory markers: CRP levels (r = 0.07, p = 0.53), IL-6 (r = -0.08, p = 0.61), and TNF-α (r = -0.06, p = 0.70). The CP volume correlated with the [11C]PK11195 PET binding in CP (r = 0.34, p = 0.005). Integration of transcriptomic data from the Allen Human Brain Atlas with the brain map depicting the correlations between CP volume and PET imaging found significant gene enrichment for several pathways involved in neuroinflammatory response. CONCLUSION: This result supports the hypothesis that changes in brain barriers may cause reduction in solute exchanges between blood and CSF, disturbing the brain homeostasis and ultimately contributing to inflammation in depression. Given that CP anomalies have been recently detected in other brain disorders, these results may not be specific to depression and might extend to other conditions with a peripheral inflammatory component

Comparison of phosphodiesterase 10A and dopamine transporter levels as markers of disease burden in early Parkinson's disease

BACKGROUND: Recent work has shown loss of phosphodiesterase 10A levels in middle-stage and advanced treated patients with PD, which was associated with motor symptom severity. OBJECTIVES: To assess phosphodiesterase 10A levels in early PD and compare with loss of dopamine transporter as markers of disease burden. METHODS: Seventy-eight subjects were included in this study (17 early de novo, 15 early l-dopa-treated, 24 moderate-advanced l-dopa-treated patients with PD, and 22 healthy controls). All participants underwent [11 C]IMA107 PET, [11 C]PE2I PET, and 3-Tesla MRI scan. RESULTS: Early de novo PD patients showed loss of [11 C]IMA107 and of [11 C]PE2I binding in caudate and putamen (P < 0.001); early l-dopa-treated PD patients showed additional loss of [11 C]IMA107 in the caudate (P < 0.001; annual decline 3.6%) and putamen (P < 0.001; annual decline 2.8%), but loss of [11 C]PE2I only in the putamen (P < 0.001; annual decline 6.8%). Lower [11 C]IMA107 correlated with lower [11 C]PE2I in the caudate (rho = 0.51; P < 0.01) and putamen (rho = 0.53; P < 0.01). Longer disease duration correlated with lower [11 C]IMA107 in the caudate (rho = -0.72; P < 0.001) and putamen (rho = -0.48; P < 0.01), and with lower [11 C]PE2I only in the putamen (rho = -0.65; P < 0.001). Higher burden of motor symptoms correlated with lower [11 C]IMA107 in the caudate (rho = -0.42; P < 0.05) and putamen (rho = -0.41; P < 0.05), and with lower [11 C]PE2I only in the putamen (rho = -0.69; P < 0.001). CONCLUSION: Our findings demonstrate loss of phosphodiesterase 10A levels very early in the course of PD and is associated with the gradual and progressive increase of motor symptoms. Phosphodiesterase 10A imaging shows similar potential with dopamine transporter imaging to follow disease progression. © 2019 International Parkinson and Movement Disorder Society

Neuroimaging of Sleep Disturbances in Movement Disorders

Sleep dysfunction is recognized as a distinct clinical manifestation in movement disorders, often reported early on in the disease course. Excessive daytime sleepiness, rapid eye movement sleep behavior disorder and restless leg syndrome, amidst several others, are common sleep disturbances that often result in significant morbidity. In this article, we review the spectrum of sleep abnormalities across atypical Parkinsonian disorders including multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), as well as Parkinson's disease (PD) and Huntington's disease (HD). We also explore the current concepts on the neurobiological underpinnings of sleep disorders, including the role of dopaminergic and non-dopaminergic pathways, by evaluating the molecular, structural and functional neuroimaging evidence based on several novel techniques including magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), single-photon emission computed tomography (SPECT) and positron emission tomography (PET). Based on the current state of research, we suggest that neuroimaging is an invaluable tool for assessing structural and functional correlates of sleep disturbances, harboring the ability to shed light on the sleep problems attached to the limited treatment options available today. As our understanding of the pathophysiology of sleep and wake disruption heightens, novel therapeutic approaches are certain to transpire