Dataset Information

Linking Cortical and Connectional Pathology in Schizophrenia.

ABSTRACT: Schizophrenia is associated with cortical thickness (CT) deficits and breakdown in white matter microstructure. Whether these pathological processes are related remains unclear. We used multimodal neuroimaging to investigate the relationship between regional cortical thinning and breakdown in adjacent infracortical white matter as a function of age and illness duration. Structural magnetic resonance and diffusion images were acquired in 218 schizophrenia patients and 167 age-matched healthy controls to map CT and fractional anisotropy in regionally adjacent infracortical white matter at various cortical depths. We found a robust and reproducible relationship between thickness and anisotropy deficits, which were inversely correlated across cortical regions (r = -.5, P < .0001): the most anisotropic infracortical white matter was found adjacent to regions with extensive cortical thinning. This pattern was evident in early (20 y: r = -.3, P = .005) and middle life (30 y: r = -.4, P = .004, 40 y: r = -.3, P = .04), but not beyond 50 years (P > .05). Frontal pathology contributed most to this pattern, with cortical thinning in patients compared to controls at all ages (P < .05); in contrast to initially elevated frontal white matter anisotropy in patients at 30 years, followed by rapid white matter decline with age (rate of annual decline; patients: 0.0012, controls 0.0006, P < .001). Our findings point to pathological dependencies between gray and white matter in a large sample of schizophrenia patients. We argue that elevated frontal anisotropy reflects regionally-specific, compensatory responses to cortical thinning, which are eventually overwhelmed with increasing illness duration.

SUBMITTER: Di Biase MA

PROVIDER: S-EPMC6581130 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Linking Cortical and Connectional Pathology in Schizophrenia.

Di Biase Maria Angelique MA Cropley Vanessa L VL Cocchi Luca L Fornito Alexander A Calamante Fernando F Ganella Eleni P EP Pantelis Christos C Zalesky Andrew A

Schizophrenia bulletin 20190601 4

Schizophrenia is associated with cortical thickness (CT) deficits and breakdown in white matter microstructure. Whether these pathological processes are related remains unclear. We used multimodal neuroimaging to investigate the relationship between regional cortical thinning and breakdown in adjacent infracortical white matter as a function of age and illness duration. Structural magnetic resonance and diffusion images were acquired in 218 schizophrenia patients and 167 age-matched healthy cont ...[more]

PMID: 30215783

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Project description:Prior studies have demonstrated reduced dendritic spine density in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia. However, it remains unclear how generalizable this finding is in schizophrenia and if it is seen in bipolar disorder, a historically distinct psychiatric condition.To assess whether spine loss is present in the DLPFC of individuals with schizophrenia and individuals with bipolar disorder.This study used postmortem human brain tissue from individuals with schizophrenia (n=14), individuals with bipolar disorder (n=9), and unaffected control participants (n=19). Tissue samples containing the DLPFC (Brodmann area 46) were Golgi-stained, and basilar dendrites of pyramidal cells in the deep half of layer III were reconstructed.The number of spines per dendrite, spine density, and dendrite length were compared across groups. We also assessed for the potential effects of clinical and demographic variables on dendritic parameters.The mean (SD) spine density was significantly reduced (ie, by 10.5%) in individuals with bipolar disorder (0.28 [0.04] spines/?m) compared with control participants (0.31 [0.05] spines/?m) (P=.02). In individuals with schizophrenia, the mean (SD) spine density was also reduced (by 6.5%; 0.29 [0.03] spines/?m) but just missed significance when compared with control participants (P=.06). There was a significant reduction in the mean (SD) number of spines per dendrite in both individuals with schizophrenia (72.8 [24.9] spines per dendrite) and individuals with bipolar disorder (68.9 [12.9] spines per dendrite) compared with controls (92.8 [31.1] spines per dendrite) (individuals with schizophrenia vs controls: 21.6% reduction [P=.003]; individuals with bipolar disorder vs controls: 25.8% reduction [P=.005]). In addition, both individuals with schizophrenia and individuals with bipolar disorder had a reduced mean (SD) dendrite length (246.5 [67.4] and 245.6 [29.8] ?m, respectively) compared with controls (301.8 [75.1] ?m) (individuals with schizophrenia vs controls: 18.3% reduction [P=.005]; individuals with bipolar disorder vs controls: 18.6% reduction [P=.005]).Dendritic spine loss in the DLPFC was seen in both individuals with schizophrenia and individuals with bipolar disorder, suggesting that the 2 disorders may share some common pathophysiological features.

Dataset Information

Linking Cortical and Connectional Pathology in Schizophrenia.

Publications

Linking Cortical and Connectional Pathology in Schizophrenia.

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