Sleep spindles and schizophrenia: interactions between white matter, thalamus, and cortex
MetadataShow full item record
BACKGROUND: Sleep deprivation is one of the first symptoms to manifest in schizophrenia patients. An important proponent for both sleep and cognition, sleep spindles have been investigated to understand the connection between sleep and schizophrenia. This thesis aims to conduct a meta-analysis on this topic to conglomerate previous research and come to a definitive conclusion on how sleep and schizophrenia interact. Multiple studies have reported associations between sleep, schizophrenia, and the thalamus. Novel methods have allowed researchers to segment the thalamus into 25 different nuclei. Therefore, this thesis will also attempt to validate these findings and use new segmentation software to investigate which specific nuclei affect schizophrenia. This thesis also extends this thalamic investigation to explore white matter tracts related to the thalamus. Using both arms of this study, we aim to further understand the complex relationship between brain structure, sleep, and schizophrenia. METHODS: The meta-analysis portion of this thesis pooled fifteen studies for a total of 321 patients and 323 healthy controls. The patient population was made up of first-episode psychosis (FEP), family high-risk (FHR), and schizophrenia (SZ) populations. R Studio was utilized to run a meta-analysis on sleep spindle density (SSD) values pulled from each study. This dataset was also used for meta-regressions and funnel plots. The imaging aspect of this thesis pulled subjects from two separate Boston studies for a total of 54 early course patients (EC) and 27 healthy controls (HC). A brain editing software, FreeSurfer, was used to quality control and segment the thalamus. This segmentation provided volumes for each nuclei. A free-water imaging pipeline was used to process diffusion weighted images so that free-water (FW) and corrected fractional anisotropy (FAt) could be collected. These values were run through Tract-Based Spatial Statistics (TBSS) to standardize scans and identify white matter regions of interest. RESULTS: This thesis reports an effect size of -1.24 between HC and the collective subject groups with a confidence interval of -1.63 to -.84. Via meta-regression, we report that illness duration, publication year, and spindle frequency gap (SFG) all are associated with sleep spindles. The thalamic volumetric analysis showed that four nuclei differed between EC and HC and two nuclei differed between EC and FH. The imaging aspect of this thesis discovered no significant FAt findings comparing volume to population, though heat maps revealed a trend where FHR and EC had lower FAt than HC. For FW analysis, we found a similar trend where FHR and EC had higher FW than HC. CONCLUSION: Using both analyses, this thesis connected sleep spindles, schizophrenia, and brain structure. We illuminated consistent reports of schizophrenia populations having lower sleep spindle density compared to healthy controls. This thesis reports a difference in thalamic nuclei volumes between both HC and FHR versus EC as well as FAt and FW differences between both FHR and EC and HC.