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      Morphometry and gyrification in bipolar disorder and schizophrenia: A comparative MRI study

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          Highlights

          • Increased right globus pallidus is a consistent marker in schizophrenia (SCZ).

          • Left supramarginal gyrification increases in bipolar disorder (BPD) in contrast with SCZ.

          • Gyrification analysis may help distinguish early phases of BPD and SCZ.

          Abstract

          Schizophrenia is believed to be a neurodevelopmental disease with high heritability. Differential diagnosis is often challenging, especially in early phases, namely with other psychotic disorders or even mood disorders. such as bipolar disorder with psychotic symptoms. Key pathophysiological changes separating these two classical psychoses remain poorly understood, and current evidence favors a more dimensional than categorical differentiation between schizophrenia and bipolar disorder. While established biomarkers like cortical thickness and grey matter volume are heavily influenced by post-onset changes and thus provide limited possibility of accessing early pathologies, gyrification is assumed to be more specifically determined by genetic and early developmental factors. The aim of our study was to compare both classical and novel morphometric features in these two archetypal psychiatric disorders. We included 20 schizophrenia patients, 20 bipolar disorder patients and 20 age- and gender-matched healthy controls. Data analyses were performed with CAT12/SPM12 applying general linear models for four morphometric measures: gyrification and cortical thickness (surface-based morphometry), and whole-brain grey matter/grey matter volume (voxel-based morphometry - VBM). Group effects were tested using age and gender as covariates (and total intracranial volume for VBM). Voxel-based morphometry analysis revealed a schizophrenia vs. control group effect on regional grey matter volume ( p < 0.05, familywise error correction) in the right globus pallidus. There was no group effect on white matter volume when correcting for multiple comparisons neither on cortical thickness. Gyrification changes in clinical samples were found in the left supramarginal gyrus (BA40) – increased and reduced gyrification, respectively, in BPD and SCZ patients - and in the right inferior frontal gyrus (BA47), with a reduction in gyrification of the SCZ group when compared with controls. The joint analysis of different morphometric features, namely measures such as gyrification, provides a promising strategy for the elucidation of distinct phenotypes in psychiatric disorders. Different morphological change patterns, highlighting specific disease trajectories, could potentially generate neuroimaging-derived biomarkers, helping to discriminate schizophrenia from bipolar disorder in early phases, such as first-episode psychosis patients.

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          Most cited references57

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          Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group

          Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen’s d=−0.293; P=1.71 × 10−21), left fusiform gyrus (d=−0.288; P=8.25 × 10−21) and left rostral middle frontal cortex (d=−0.276; P=2.99 × 10−19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.
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            A surface-based approach to quantify local cortical gyrification.

            The high complexity of cortical convolutions in humans is very challenging both for engineers to measure and compare it, and for biologists and physicians to understand it. In this paper, we propose a surface-based method for the quantification of cortical gyrification. Our method uses accurate 3-D cortical reconstruction and computes local measurements of gyrification at thousands of points over the whole cortical surface. The potential of our method to identify and localize precisely gyral abnormalities is illustrated by a clinical study on a group of children affected by 22q11 Deletion Syndrome, compared to control individuals.
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              Schizophrenia as a disorder of neurodevelopment.

              A combination of genetic susceptibility and environmental perturbations appear to be necessary for the expression of schizophrenia. In addition, the pathogenesis of the disease is hypothesized to be neurodevelopmental in nature based on reports of an excess of adverse events during the pre- and perinatal periods, the presence of cognitive and behavioral signs during childhood and adolescence, and the lack of evidence of a neurodegenerative process in most individuals with schizophrenia. Recent studies of neurodevelopmental mechanisms strongly suggest that no single gene or factor is responsible for driving a highly complex biological process. Together, these findings suggest that combinatorial genetic and environmental factors, which disturb a normal developmental course early in life, result in molecular and histogenic responses that cumulatively lead to different developmental trajectories and the clinical phenotype recognized as schizophrenia.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                19 February 2020
                2020
                19 February 2020
                : 26
                : 102220
                Affiliations
                [a ]Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Portugal
                [b ]Institute of Psychological Medicine, Faculty of Medicine, University of Coimbra, Portugal
                [c ]Department of Psychiatry, Centro Hospitalar e Universitário de Coimbra, Portugal
                [d ]Institute of Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Portugal
                [e ]Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Faculty of Medicine, University of Coimbra, Portugal
                Author notes
                [* ]Corresponding author at: CIBIT, ICNAS-Instituto de Ciências Nucleares Aplicadas à Saúde, Pólo das Ciências da Saúde, Universidade de Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. mcbranco@ 123456fmed.uc.pt
                [1]

                Both authors contributed equally to this work.

                Article
                S2213-1582(20)30057-7 102220
                10.1016/j.nicl.2020.102220
                7063231
                32146321
                55cf05ee-96e8-45c6-aae8-0c2740ce7224
                © 2020 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 19 October 2019
                : 20 January 2020
                : 17 February 2020
                Categories
                Regular Article

                schizophrenia,bipolar disorder,gyrification,morphometry
                schizophrenia, bipolar disorder, gyrification, morphometry

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