ORCID Profile
0000-0001-6090-4974
Current Organisation
UCSF Medical Center
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Publisher: Springer Science and Business Media LLC
Date: 26-07-2022
DOI: 10.1038/S41398-022-02057-Y
Abstract: In iduals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P in iduals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P in iduals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or ergence of neuroanatomical profiles between in iduals. Second, using a normative modelling approach, to assess the ‘normativeness’ of neuroanatomical profiles in in iduals at CHR-P. CHR-P in iduals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical ergence in global SA, CT and SV profiles in CHR-P in iduals compared with HC. Normative PBSI analysis identified 11 CHR-P in iduals (0.70%) with marked deviation ( .5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater ergence in neuroanatomical profiles at an in idual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.BIOPSYCH.2022.02.959
Abstract: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre erinatal periods may be reflected in in idual variations in cortical surface area later in life. Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 in iduals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre erinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2023
DOI: 10.1038/S41380-023-02221-W
Abstract: Converging evidence suggests that schizophrenia (SZ) with primary, enduring negative symptoms (i.e., Deficit SZ (DSZ)) represents a distinct entity within the SZ spectrum while the neurobiological underpinnings remain undetermined. In the largest dataset of DSZ and Non-Deficit (NDSZ), we conducted a meta-analysis of data from 1560 in iduals (168 DSZ, 373 NDSZ, 1019 Healthy Controls (HC)) and a mega-analysis of a subs led data from 944 in iduals (115 DSZ, 254 NDSZ, 575 HC) collected across 9 worldwide research centers of the ENIGMA SZ Working Group (8 in the mega-analysis), to clarify whether they differ in terms of cortical morphology. In the meta-analysis, sites computed effect sizes for differences in cortical thickness and surface area between SZ and control groups using a harmonized pipeline. In the mega-analysis, cortical values of in iduals with schizophrenia and control participants were analyzed across sites using mixed-model ANCOVAs. The meta-analysis of cortical thickness showed a converging pattern of widespread thinner cortex in fronto-parietal regions of the left hemisphere in both DSZ and NDSZ, when compared to HC. However, DSZ have more pronounced thickness abnormalities than NDSZ, mostly involving the right fronto-parietal cortices. As for surface area, NDSZ showed differences in fronto-parietal-temporo-occipital cortices as compared to HC, and in temporo-occipital cortices as compared to DSZ. Although DSZ and NDSZ show widespread overlapping regions of thinner cortex as compared to HC, cortical thinning seems to better typify DSZ, being more extensive and bilateral, while surface area alterations are more evident in NDSZ. Our findings demonstrate for the first time that DSZ and NDSZ are characterized by different neuroimaging phenotypes, supporting a nosological distinction between DSZ and NDSZ and point toward the separate disease hypothesis.
Location: United States of America
Location: United States of America
Location: United States of America
No related grants have been discovered for Daniel Mathalon.