Browsing by Author "Kubicki, Marek"

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    A preliminary choroid plexus volumetric study in individuals with psychosis
    (Wiley, 2023) Senay, Olcay; Seethaler, Magdalena; Makris, Nikos; Yeterian, Edward; Rushmore, Jarrett; Cho, Kang Ik K.; Rizzoni, Elizabeth; Heller, Carina; Pasternak, Ofer; Szczepankiewicz, Filip; Westin, Carl-Frederik; Losak, Jan; Ustohal, Libor; Tomandl, Josef; Vojtisek, Lubomir; Kudlicka, Peter; Kikinis, Zora; Holt, Daphne; Lewandowski, Kathryn E.; Lizano, Paulo; Keshavan, Matcheri S.; Öngür, Dost; Kasparek, Tomas; Breier, Alan; Shenton, Martha E.; Seitz-Holland, Johanna; Kubicki, Marek; Psychiatry, School of Medicine
    The choroid plexus (ChP) is part of the blood‐cerebrospinal fluid barrier, regulating brain homeostasis and the brain's response to peripheral events. Its upregulation and enlargement are considered essential in psychosis. However, the timing of the ChP enlargement has not been established. This study introduces a novel magnetic resonance imaging‐based segmentation method to examine ChP volumes in two cohorts of individuals with psychosis. The first sample consists of 41 individuals with early course psychosis (mean duration of illness = 1.78 years) and 30 healthy individuals. The second sample consists of 30 individuals with chronic psychosis (mean duration of illness = 7.96 years) and 34 healthy individuals. We utilized manual segmentation to measure ChP volumes. We applied ANCOVAs to compare normalized ChP volumes between groups and partial correlations to investigate the relationship between ChP, LV volumes, and clinical characteristics. Our segmentation demonstrated good reliability (.87). We further showed a significant ChP volume increase in early psychosis (left: p < .00010, right: p < .00010) and a significant positive correlation between higher ChP and higher LV volumes in chronic psychosis (left: r = .54, p = .0030, right: r = .68; p < .0010). Our study suggests that ChP enlargement may be a marker of acute response around disease onset. It might also play a modulatory role in the chronic enlargement of lateral ventricles, often reported in psychosis. Future longitudinal studies should investigate the dynamics of ChP enlargement as a promising marker for novel therapeutic strategies.
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    Cell type-specific manifestations of cortical thickness heterogeneity in schizophrenia
    (Springer Nature, 2022) Di Biase, Maria A.; Geaghan, Michael P.; Reay, William R.; Seidlitz, Jakob; Weickert, Cynthia Shannon; Pébay, Alice; Green, Melissa J.; Quidé, Yann; Atkins, Joshua R.; Coleman, Michael J.; Bouix, Sylvain; Knyazhanskaya, Evdokiya E.; Lyall, Amanda E.; Pasternak, Ofer; Kubicki, Marek; Rathi, Yogesh; Visco, Andrew; Gaunnac, Megan; Lv, Jinglei; Mesholam-Gately, Raquelle I.; Lewandowski, Kathryn E.; Holt, Daphne J.; Keshavan, Matcheri S.; Pantelis, Christos; Öngür, Dost; Breier, Alan; Cairns, Murray J.; Shenton, Martha E.; Zalesky, Andrew; Psychiatry, School of Medicine
    Brain morphology differs markedly between individuals with schizophrenia, but the cellular and genetic basis of this heterogeneity is poorly understood. Here, we sought to determine whether cortical thickness (CTh) heterogeneity in schizophrenia relates to interregional variation in distinct neural cell types, as inferred from established gene expression data and person-specific genomic variation. This study comprised 1849 participants in total, including a discovery (140 cases and 1267 controls) and a validation cohort (335 cases and 185 controls). To characterize CTh heterogeneity, normative ranges were established for 34 cortical regions and the extent of deviation from these ranges was measured for each individual with schizophrenia. CTh deviations were explained by interregional gene expression levels of five out of seven neural cell types examined: (1) astrocytes; (2) endothelial cells; (3) oligodendrocyte progenitor cells (OPCs); (4) excitatory neurons; and (5) inhibitory neurons. Regional alignment between CTh alterations with cell type transcriptional maps distinguished broad patient subtypes, which were validated against genomic data drawn from the same individuals. In a predominantly neuronal/endothelial subtype (22% of patients), CTh deviations covaried with polygenic risk for schizophrenia (sczPRS) calculated specifically from genes marking neuronal and endothelial cells (r = -0.40, p = 0.010). Whereas, in a predominantly glia/OPC subtype (43% of patients), CTh deviations covaried with sczPRS calculated from glia and OPC-linked genes (r = -0.30, p = 0.028). This multi-scale analysis of genomic, transcriptomic, and brain phenotypic data may indicate that CTh heterogeneity in schizophrenia relates to inter-individual variation in cell-type specific functions. Decomposing heterogeneity in relation to cortical cell types enables prioritization of schizophrenia subsets for future disease modeling efforts.