Abstract
Background Schizophrenia is often described as a disorder of dysconnectivity, with disruptions in neural connectivity reported on the cellular microscale as well as the global macroscale level of brain organization. How these effects on these two scales are related is poorly understood. Methods First (part I of this study), we collated data on layer 3 pyramidal spine density of the healthy brain from the literature and cross-analyzed these data with new data on macroscale connectivity as derived from diffusion imaging. Second (part II of this study), we examined how alterations in regional spine density in schizophrenia are related to changes in white matter connectivity. Data on group differences in spine density were collated from histology reports in the literature and examined in a meta-regression analysis in context of alterations in macroscale white matter connectivity as derived from diffusion imaging data of a (separately acquired) group of 61 patients and 55 matched control subjects. Results Densely connected areas of the healthy human cortex were shown to overlap with areas that display high pyramidal complexity, with pyramidal neurons that are more spinous (p =.0027) compared with pyramidal neurons in areas of low macroscale connectivity. Cross-scale meta-regression analysis showed a significant association between regional variation in level of disease-related spine density reduction in schizophrenia and regional level of decrease in macroscale connectivity (two data sets examined, p =.0028 and p =.0011). Conclusions Our study presents evidence that regional disruptions in microscale neuronal connectivity in schizophrenia go hand in hand with changes in macroscale brain connectivity.
| Original language | English |
|---|---|
| Pages (from-to) | 293-301 |
| Number of pages | 9 |
| Journal | Biological Psychiatry |
| Volume | 80 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 15 Aug 2016 |
| Externally published | Yes |
Funding
This work was supported by the Netherlands Organisation for Scientific Research (Nederlandse Organisatie voor Wetenschappelijk Onderzoek) Innovational Research Incentives Scheme Veni grant (Grant No. 451-12-001 to MPvdH). The funding agency did not have any influence on the data acquisition, analysis, or report of the data. Human neuroimaging data (for part I of this study) was provided by the Human Connectome Project, WU-Minn Human Connectome Project Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; Grant No. 1U54MH091657) funded by the 16 National Institutes of Health Institutes and Centers that support the National Institutes of Health Blueprint for Neuroscience Research and by the McDonnell Center for Systems Neuroscience at Washington University. We thank Ruben Schmidt for helping out with the statistical analysis. The authors report no biomedical financial interests or potential conflicts of interest. Appendix A
Keywords
- Connectivity
- Connectome
- Diffusion imaging
- MRI
- Schizophrenia
- Spine density