Association of Choroid Plexus Enlargement With Cognitive, Inflammatory, and Structural Phenotypes Across the Psychosis Spectrum

Lizano, Paulo; Lutz, Olivia; Ling, George M.; Lee, Adam M.; Eum, Seenae; Bishop, Jeffrey R.; Kelly, Sinéad; Pasternak, Ofer; Clementz, Brett A.; Pearlson, Godfrey D.; Sweeney, John A.; Gershon, Elliot S.; Tamminga, Carol A.; Keshavan, Matcheri S.

doi:10.1176/appi.ajp.2019.18070825

Cited by 115 publications

(114 citation statements)

References 37 publications

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“…The choroid plexus, located in brain ventricles, is responsible for production of cerebrospinal fluid (CSF) and its volume is related with pathogenesis of neurodegenerative diseases, such as the clearance of CSF proteins ( Tadayon et al, 2020 ). Larger choroid plexus volume is also related to smaller total gray matter and larger lateral ventricle volumes ( Lizano et al, 2019 ). Recently, there is a report that an increased volume of choroid plexus is associated with increased vascular burden ( Egorova et al, 2019 ), which could be related to an increase in cerebrovascular pulsatility.…”

Section: Discussionmentioning

confidence: 99%

Cardiac-induced cerebral pulsatility, brain structure, and cognition in middle and older-aged adults

Kim

Agarwal

et al. 2021

NeuroImage

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Changes of cardiac-induced regional pulsatility can be associated with specific regions of brain volumetric changes, and these are related with cognitive alterations. Thus, mapping of cardiac pulsatility over the entire brain can be helpful to assess these relationships. A total of 108 subjects (age: 66.5 ± 8.4 years, 68 females, 52 healthy controls, 11 subjective cognitive decline, 17 impaired without complaints, 19 MCI and 9 AD) participated. The pulsatility map was obtained directly from resting-state functional MRI time-series data at 3T. Regional brain volumes were segmented from anatomical MRI. Multidomain neuropsychological battery was performed to test memory, language, attention and visuospatial construction. The Montreal Cognitive Assessment (MoCA) was also administered. The sparse partial least square (SPLS) method, which is desirable for better interpreting high-dimensional variables, was applied for the relationship between the entire brain voxels of pulsatility and 45 segmented brain volumes. A multiple holdout SPLS framework was used to optimize sparsity for assessing the pulsatility-volume relationship model and to test the reliability by fitting the models to 9 different splits of the data. We found statistically significant associations between subsets of pulsatility voxels and subsets of segmented brain volumes by rejecting the omnibus null hypothesis (any of 9 splits has p < 0.0056 (=0.05/9) with the Bonferroni correction). The pulsatility was positively associated with the lateral ventricle, choroid plexus, inferior lateral ventricle, and 3rd ventricle and negatively associated with hippocampus, ventral DC, and thalamus volumes for the first pulsatility-volume relationship. The pulsatility had an additional negative relationship with the amygdala and brain stem volumes for the second pulsatility-volume relationship. The spatial distribution of correlated pulsatility was observed in major feeding arteries to the brain regions, ventricles, and sagittal sinus. The indirect mediating pathways through the volumetric changes were statistically significant between the pulsatility and multiple cognitive measures ( p < 0.01). Thus, the cerebral pulsatility, along with volumetric measurements, could be a potential marker for better understanding of pathophysiology and monitoring disease progression in age-related neurodegenerative disorders.

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Section: Discussionmentioning

confidence: 99%

Cardiac-induced cerebral pulsatility, brain structure, and cognition in middle and older-aged adults

Kim

Agarwal

et al. 2021

NeuroImage

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“…↑ Expression of genes related to immune function and inflammation associated with the disease status [296] ↑ CP volume [297] Chorionic Stress ↓ 5HT2C, glucocorticoid receptor, cilia genes IFT88 expression ↑ 5HT2A, BDNF, TNFα, IL-1β expression [298] CP papilloma, but not between CP papilloma and CP carcinoma. These changes include villous hypertrophy and diffuse enlargement of the CP with normal histological appearance [278].…”

Section: Schizophreniamentioning

confidence: 99%

“…Increased CP volume and an associated upregulation of genes related to immune function in the CP has been observed in patients suffering from schizophrenia [296,297].…”

Section: Effect Of Schizophrenia and Chronic Stress On Cpmentioning

confidence: 99%

Choroid plexus and the blood–cerebrospinal fluid barrier in disease

Solar

Zamani

Kubíčková

et al. 2020

Fluids Barriers CNS

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142

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The choroid plexus (CP) forming the blood-cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research. Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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“…3 We also found that dysbiosis of the gut induced depressive-like behaviors by means of the microbiota/gut/ brain axis. 4,5 A recent trial showed that CP volume was significantly increased in psychosis probands, 6 suggesting involvement of the CP across the psychosis spectrum with a latent pathophysiological mechanism. However, function of the CP in neuropsychiatric disease remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Different Serotypes of Adeno-Associated Virus Vector- and Lentivirus-Mediated Tropism in Choroid Plexus by Intracerebroventricular Delivery

Chen

Tian

et al. 2020

Human Gene Therapy

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Regulation of gene expression by viral vectors is an effective method for researchers to explore the function of gene products in a target tissue. The choroid plexus (CP) is an important target for gene therapy of neuropsychiatric diseases such as Alzheimer's disease and major depressive disorder. However, viral tropism in CP has not been well studied as a result of limited viral vector applications. To identify CP-specific viral vectors, we intracerebroventricularly administered six different serotypes of adeno-associated virus (AAV) vectors (AAV2/1, AAV2/5, AAV2/8, AAV2/9, AAV2-BR1, and AAV2-PHP.eB) and lentivirus in adult mice. Tropism in CP was compared among these viruses. We found that AAV2/5 and AAV2/8 displayed remarkable infections in CP, while AAV2/1 infected both ependymal cells and cells in the CP. Except for the low infection intensity of AAV2/9 and lentivirus in the CP, no infection intensity was found for CP tissues injected with AAV2-BR1 or AAV2-PHP.eB. Green fluorescence protein expression in the CP after AAV2/5 infection was confirmed by Western blotting. AAV2/5-mediated tropism in epithelial cells of the CP was verified by immunostaining with transthyretin. In this study, we identified for the first time that serotype-specific AAVs 5 and 8 may be robust research tools for intracerebroventricular gene delivery.

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Association of Choroid Plexus Enlargement With Cognitive, Inflammatory, and Structural Phenotypes Across the Psychosis Spectrum

Cited by 115 publications

References 37 publications

Cardiac-induced cerebral pulsatility, brain structure, and cognition in middle and older-aged adults

Cardiac-induced cerebral pulsatility, brain structure, and cognition in middle and older-aged adults

Choroid plexus and the blood–cerebrospinal fluid barrier in disease

Different Serotypes of Adeno-Associated Virus Vector- and Lentivirus-Mediated Tropism in Choroid Plexus by Intracerebroventricular Delivery

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