A preliminary choroid plexus volumetric study in individuals with psychosis

Şenay, Olcay; Seethaler, Magdalena; Makris, Nikos; Yeterian, Edward H.; Rushmore, Jarrett; Cho, Kang Ik K.; Rizzoni, Elizabeth; Heller, Carina; Pasternak, Ofer; Szczepankiewicz, Filip; Westin, Carl-Frederik; Lošák, Jan; Ustohal, Libor; Tomandl, Josef; Vojtíšek, Lubomír; Kudlicka, Peter; Kikinis, Zora; Holt, Daphne J.; Lewandowski, Kathryn Eve; Lizano, Paulo; Keshavan, Matcheri S.; Öngür, Döst; Kašpárek, Tomáš; Breier, Alan; Shenton, Martha E.; Seitz-Holland, Johanna; Kubicki, Marek

doi:10.1002/hbm.26224

Cited by 29 publications

(23 citation statements)

References 96 publications

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“…In patients with SZ, CP volume has been found consistently larger compared to controls [18][19][20] , whereas the enlargement has demonstrated a genetic component as it was intermediate in first-degree relatives 18 . This finding has been repeated trans-diagnostically as greater CP volume has also been demonstrated in patients with Major Depression Disorder (MDD) 20 . There is evidence of CP enlargement with measures of inflammation, either peripheral or central, and stress.…”

Section: Introductionmentioning

confidence: 92%

“…Recently, CP imaging abnormalities have been reported in psychiatric cohorts. In patients with SZ, CP volume has been found consistently larger compared to controls [18][19][20] , whereas the enlargement has demonstrated a genetic component as it was intermediate in first-degree relatives 18 . This finding has been repeated trans-diagnostically as greater CP volume has also been demonstrated in patients with Major Depression Disorder (MDD) 20 .…”

Section: Introductionmentioning

confidence: 92%

“…In patients with SZ - a positive association has been demonstrated with peripheral plasma IL-6 levels and allostatic load 18,19 . In MDD, CP volume has been associated with neuroinflammation measured with positron emission tomography (PET) in the anterior cingulate cortex, prefrontal cortex and insular cortex, but not with peripheral inflammatory markers 20 . Notably CP enlargement has been recently proposed as a transdiagnostic marker of brain inflammation in neurodegenerative conditions 21 .…”

Section: Introductionmentioning

confidence: 99%

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Histological examination of choroid plexus epithelia changes in schizophrenia

Williams¹,

MacDonald²,

Turkheimer

2023

Preprint

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Background. The choroid plexus (CP) is suggested to be involved in neuroimmune regulation avia the interaction between central and peripheral inflammation. Quantitative imaging has demonstrated volumetric CP change in psychosis, schizophrenia and depression. This study histologically examines CP epithelial cell morphology in these illnesses to identify the biological source of such volumetric changes. Methods. Formalin-fixed paraffin-embedded FFPE blocks were obtained bilaterally from the lateral ventricles of 13 cases of sex- and age-matched brains from each of schizophrenia (SZ) with psychosis, major depressive disorder (MDD) and matched controls. FFPE blocks were sectioned at 7μm and routinely stained for H&E. Morphological analysis of 180 CP epithelia/case was conducted blindly on digital images collected x600 magnification. Calcification was assessed in all CP regions manually. Results. Linear General Model analysis shows a significant effect of diagnosis on somal width (p=0.006, r2=0.33, adj=0.25), with a significant difference between SZ non-medicated v nonmedicated NPD controls (p=0.032), demonstrating increased somal width in SZ with psychotic medication but not in unmedicated SZ cases. No effects were observed in calcification. Discussion. Epithelial cells examined were adhered to CP fibrous surface so width expansion describes the primary methods for these cells to expand with adherence to this surface. The interaction of antipsychotic medication and diagnosis demonstrates that this is an illness specific change and mediated through the DA-system, although the mechanism is unclear at present.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Histological examination of choroid plexus epithelia changes in schizophrenia

Williams¹,

MacDonald²,

Turkheimer

2023

Preprint

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“…The present study showed abnormally elevated CSF and CP volumes in SCA3 patients compared to HCs. This enlargement in CSF and CP volume has been reported to be potentially linked to neuroinflammation and glymphatic impairment in neurodegenerative diseases [28, 31, 32] and psychosis spectrum [45, 46] . Therefore, the impaired glymphatic clearance mechanisms in SCA3 may mitigate glymphatic dysfunction by enhancing waste clearance through increased production and transmission of functional units in the CSF and CP [47] .…”

Section: Discussionmentioning

confidence: 99%

Regional Glymphatic Dysfunction is linked to Spinocerebellar Ataxia Type 3 pathophysiology

Hua,

Xu,

Zhang

et al. 2024

Preprint

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Spinocerebellar ataxia type 3 (SCA3) involves neuroinflammation and imbalance between production and clearance of proteins which affects the glymphatic system, the lymphatic-like, fluid-transport system in the brain. However, it is unclear whether SCA3 is related to impairments in glymphatic function. Using multimodal imaging data, 34 SCA3 patients and 36 age-, sex- and educational matched healthy controls (HCs) were compared using multiple glymphatic measurements, including choroid plexus (CP) and cerebrospinal fluid (CSF) volume, diffusion tensor imaging along the perivascular (DTI-ALPS) index, and coupling relationship between blood-oxygen-level-dependent signals and CSF flow (BOLD-CSF coupling). Then, we evaluated regional glymphatic function by dividing DTI-ALPS and BOLD-CSF coupling into anterior, middle, posterior, and cerebellum regions, thereby identifying the spatial variation of glymphatic function in the two groups. We demonstrated that compared with HCs, larger CP and CSF volumes were found in SCA3 patients. More importantly, for DTI-ALPS index and BOLD-CSF coupling, these surrogate markers for glymphatic clearance were weaker in SCA3 patients. Furthermore, altered regional glymphatic functions were most prominent in midbrain, cerebellum and middle regions. Crucially, the altered midbrain, cerebellum, middle and global glymphatic functions were accompanied by the severity of ataxia and other SCA3 symptoms. Similar to other neurodegenerative disorders, the association between multiple glymphatic indexes and SCA3 symptoms suggested that waste clearance is disrupted in SCA3 patients, which shed light on the pathogenesis of this disease from a glymphatic lens. Our findings highlighted the dysregulated glymphatic function as a novel diagnostic marker for SCA3.

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“…The volumetric determination of the CP is a relatively new area of investigation, but is feasible with current MRI techniques. Changes have been described in complex pain syndrome 22 , anorexia nervosa 23 , multiple sclerosis 24 and most recently in major depression 25 and psychosis 26 . Mechanistically, stress leads in an animal model to changes in gene expression of the CP of receptors, which have been linked to MDD, including 5-HT2a, 5-HT2c, glucocorticoid, TNFα, IL1β, BDNF 27 as well as IL1 receptor 28 and the CRHreceptor 29 .…”

Section: Introductionmentioning

confidence: 99%

Brain Ventricle and Choroid Plexus Morphology as Predictor of Treatment Response: Findings from the EMBARC Study

Murck

Fava

Cusin³

et al. 2023

Preprint

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Recent observations suggest a role of the choroid plexus (CP) and cerebral ventricle volume (CV), to identify treatment resistance of major depressive disorder (MDD). We tested the hypothesis that these markers are associated with clinical improvement in subjects from the EMBARC study, as implied by a recent pilot study. The EMBARC study characterized biological markers in a randomized placebo-controlled trial of sertraline vs. placebo in patients with MDD. Association of baseline volumes of CV, CP and of the corpus callosum (CC) with treatment response after 4 weeks treatment were evaluated. 171 subjects (61 male, 110 female) completed the 4 week assessments; gender, site and age were taken into account for this analyses. As previously reported, no treatment effect of sertraline was observed, but prognostic markers for clinical improvement were identified. Responders (n = 54) had significantly smaller volumes of the CP and lateral ventricles, whereas the volume of mid-anterior and mid-posterior CC was significantly larger compared to non-responders (n = 117). A positive correlation between CV volume and CP volume was observed, whereas a negative correlation between CV volume and both central-anterior and central-posterior parts of the CC emerged. In an exploratory way correlations between enlarged VV and CP volume on the one hand and signs of metabolic syndrome, in particular triglyceride plasma concentrations, were observed. A primary abnormality of CP function in MDD may be associated with increased ventricles, compression of white matter volume, which may affect treatment response speed or outcome. Metabolic markers may mediate this relationship.

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A preliminary choroid plexus volumetric study in individuals with psychosis

Cited by 29 publications

References 96 publications

Histological examination of choroid plexus epithelia changes in schizophrenia

Histological examination of choroid plexus epithelia changes in schizophrenia

Regional Glymphatic Dysfunction is linked to Spinocerebellar Ataxia Type 3 pathophysiology

Brain Ventricle and Choroid Plexus Morphology as Predictor of Treatment Response: Findings from the EMBARC Study

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