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

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.

The traumagenic neurodevelopmental model of psychosis revisited

“…Gray matter volume loss is observed in widespread areas of the frontal/prefrontal regions in psychosis, including middle frontal gyrus, inferior frontal regions, anterior cingulate, and orbitofrontal and dorsolateral prefrontal cortices [74][75][76][77]. A recent study of child abuse, in which individuals diagnosed with psychotic disorders had significantly higher rates of sexual abuse, physical abuse, emotional abuse and physical neglect [78], reported that prefrontal cortical volume loss was significantly correlated with sexual abuse, but not with other forms of abuse or neglect.…”

“…Reduced in all subfields [73,102] Reduced in all subfields 69,70] Reductions in middle frontal gyrus, inferior frontal regions, anterior cingulate, and orbitofrontal and dorsolateral prefrontal cortices [74][75][76][77] Volume loss correlated with sexual abuse and with various aspects of cognitive dysfunction [78,[149][150][151] GR mRNA expression Decreased, including dorsolateral prefrontal regions [71][72][73] Decrease in GR mRNA expression in dorsolateral prefrontal cortex [79,80] Dendritic pathology in pyramidal cells Apical dendritic retraction and debranching [68] Reduced dendritic spine density in dorsolateral prefrontal cortex; reduced density, size and shape in anterior cingulate the HPA axis. Among the component processes involved are: initially increased diurnal levels of cortisol, which may later change to reduced levels; increased reactivity to both the administration of cortisol and exposure to stress; and increased hypothalamic production of corticotrophin-releasing hormone (CRH) [41,42].…”

Association of a risk allele of ANK3 with cognitive performance and cortical thickness in patients with first-episode psychosis

“…66 Furthermore, it has been shown that cortical thinning in the frontal lobes of these patients is due to thinning of pyramidal cell layers. 67 Testing prospectively at multiple time points could verify if the risk allele is associated with progressive cortical thinning over time. However, Ankyrin G plays an important role in early development, 26 which could implicate developmental rather than progressive effects on cortical thickness.…”

Schizophrenia: brain morphology and treatment aspects

“…Williams et al [7] investigated neuronal cell density and found decreased pyramidal layer thickness resulting in decreased frontal lobe thickness in schizophrenia patients. They additionally report decreased astrocyte density in the subgenual cingulated cortex and callosal genu for their sample [8], which extends neurobiological hypotheses on the dysfunction of astrocytes in maintaining synaptic stability.…”