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Changes in cortical thickness in the frontal lobes in schizophrenia are a result of thinning of pyramidal cell layers

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Abstract

Decreased cortical thickness and reduced activity as measured by fMRI in the grey matter of the subgenual cingulate cortex have been reported in schizophrenia and bipolar disorder, and cortical grey matter loss has been reliably reported in the frontal and temporal lobes in schizophrenia. The aim of this study was to examine the thickness of each of the six cortical layers in the subgenual cingulate cortex, five frontal lobe and four temporal lobe gyri. We examined two separate cohorts. Cohort 1 examines the subgenual cingulate cortex (SCC) in schizophrenia (n = 10), bipolar disorder (n = 15) and major depressive disorder (n = 20) against control subjects (n = 19). Cohort two examines frontal and temporal gyri in schizophrenia (n = 16), major depressive disorder (n = 6) against matched controls (n = 32). The cohorts were selected with identical clinical criteria, but underwent different tissue processing to contrast the effect of chemical treatment on tissue shrinkage. Measurements of layer I-VI thickness were taken from cresyl-violet- and haematoxylin-stained sections in cohort one and from cresyl-violet- and H&E-stained sections in cohort two. SCC cortical thickness decreased in male subjects with bipolar disorder (p = 0.048), and male schizophrenia cases showed a specific decrease in the absolute thickness of layer V (p = 0.003). Compared to controls, the relative thickness of layer V in the crown of the SCC decreased in schizophrenia (p < 0.001). A significant decrease in total cortical thickness was observed across the frontal lobe in schizophrenia (p < 0.0001), with specific pyramidal layer thinning in layers III (p = 0.0001) and V (p = 0.005). There was no effect of lateralization. No changes were noted in temporal lobe cortical thickness. This study demonstrates diminished pyramidal layer thickness resulting in decreased frontal lobe thickness in schizophrenia.

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Acknowledgments

The authors wish to thank Prof. Stephen Gentlemen and Dr. Federico Roncaroli for advice on anatomy and histology, Prof. Federico Turkheimer for advice on statistics, Miss Jayati Jain for help with illustrations and Dr. Dawn Duke and Dr. Rachel Marsh for help with data analysis. This work was supported by the Stanley Foundation and the tissue obtained from the Corsellis brain collection, funded by the Starr Foundation and West London Mental Health Trust R&D.

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Williams, M.R., Chaudhry, R., Perera, S. et al. Changes in cortical thickness in the frontal lobes in schizophrenia are a result of thinning of pyramidal cell layers. Eur Arch Psychiatry Clin Neurosci 263, 25–39 (2013). https://doi.org/10.1007/s00406-012-0325-8

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  • DOI: https://doi.org/10.1007/s00406-012-0325-8

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