[Show abstract][Hide abstract] ABSTRACT: Decreases in astrocyte density and in glial fibrillary acid protein (GFAP) mRNA in the anterior cingulate cortex have been reported changed in mood and affective disorders. Our study examines the relative density and frequency of fibrillary and gemistocytic astrocytes in the white matter of the subgenual cingulate cortex in 11 schizophrenia, 16 bipolar disorder, 20 major depression and 20 normal control cases. Serial coronal sections were stained with H&E for anatomical guidance and GFAP immunohistochemistry for astrocyte identification. Astrocyte density was measured using systematic anatomical distinctions and randomised counting methods previously reported. Astrocytes were classified as fibrillary or gemistocytic based on staining and morphometric criteria and were measured in the crown and base of the gyral white matter. Fibrillary astrocytes were decreased in the base of the cingulate white matter in schizophrenia (p = 0.046), with no change in the density of gemistocytic astrocytes. There was no change in density of gemistocytic astrocytes. This suggests that the previously reported decrease in astrocytes in schizophrenia in the subgenual cingulate is accounted for only by a change in fibrillary astrocytes. With recent findings suggesting fibrillary astrocytes regulate synaptic glutamate this morphological change may relate to disregulation of function of the subgenual cingulate cortex.
European Archives of Psychiatry and Clinical Neuroscience 12/2013; 264(4). DOI:10.1007/s00406-013-0482-4 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The nucleus basalis has not been examined in detail in severe mental illness. Several studies have demonstrated decreases in glia and glial markers in the cerebral cortex in schizophrenia, familial bipolar disorder and recurrent depression. Changes in neocortical neuron size and shape have also been reported. The nucleus basalis is a collection of large cholinergic neurons in the basal forebrain receiving information from the midbrain and limbic system, projecting to the cortex and involved with attention, learning and memory, and receives regulation from serotonergic inputs. Forty-one cases aged 41-60 years with schizophrenia or major depressive disorder with age-matched controls were collected. Formalin-fixed paraffin-embedded coronal nucleus basalis sections were histologically stained for oligodendrocyte identification with cresyl-haematoxylin counterstain, for neuroarchitecture with differentiated cresyl violet stain and astrocytes were detected by glial fibrillary acid protein immunohistochemistry. Cell density and neuroarchitecture were measured using Image Pro Plus. There were larger NB oval neuron soma in the combined schizophrenia and major depression disorder groups (p = 0.038), with no significant change between controls and schizophrenia and major depression disorder separately. There is a significant reduction in oligodendrocyte density (p = 0.038) in the nucleus basalis in schizophrenia. The ratio of gemistocytic to fibrillary astrocytes showed a greater proportion of the former in schizophrenia (18.1 %) and major depressive disorder (39.9 %) than in controls (7.9 %). These results suggest glial cell abnormalities in the nucleus basalis in schizophrenia possibly leading to cortical-limbic disturbance and subcortical dysfunction.
European Archives of Psychiatry and Clinical Neuroscience 12/2012; 263(6). DOI:10.1007/s00406-012-0387-7 · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Decreases in glial cell density and in GFAP mRNA in the anterior cingulate cortex have been reported in schizophrenia, bipolar disorder and major depressive disorder. Our study examines astrocyte and oligodendrocyte density in the white and grey matter of the subgenual cingulate cortex, and at the midline of the genu of the corpus callosum, in schizophrenia, bipolar disorder, depression and normal control cases. Serial coronal sections were stained with H and E for anatomical guidance, cresyl haematoxylin for oligodendrocyte identification and GFAP immunohistochemistry for astrocyte identification. Oligodendrocyte and astrocyte density was measured using systematic anatomical distinctions and randomised counting methods. A significant decrease in astrocyte density was observed in schizophrenia compared with normal controls in the cingulate grey matter, cingulate white matter and the midline of the corpus callosum (p = 0.025). Bipolar disorder and depression cases showed no significant changes in astrocyte density. Oligodendrocytes did not show any changes between diagnostic groups. In subgenual cingulate cortex, the ratio of oligodendrocytes to astrocytes was decreased between the controls and the three disease groups, suggesting a specific glial cell type specific change in schizophrenia.
European Archives of Psychiatry and Clinical Neuroscience 06/2012; 263(1). DOI:10.1007/s00406-012-0328-5 · 3.53 Impact Factor
[Show abstract][Hide abstract] 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.
European Archives of Psychiatry and Clinical Neuroscience 05/2012; 263(1). DOI:10.1007/s00406-012-0325-8 · 3.53 Impact Factor