RESUMO
Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.
RESUMO
Este estudio comparó el rendimiento de las adquisiciones tempranas de 18F-florbetapir PET/TC con el de 18F-FDG PET/TC. Métodos: Se incluyó a 12 pacientes que se sometieron a PET/TC con 18F-FDG y una PET/TC con 18F-florbetapir en dos tiempos (exploración temprana de 1 a 6 min y exploración tardía de 50 min). La PET/TC fue analizada visualmente por 3médicos de medicina nuclear con diferente experiencia utilizando una escala de 4puntos (0=sin reducción, 1=leve, 2=moderada, 3=reducción severa) para 18F-florbetapir en fase temprana y 18F-FDG imágenes en 10 regiones corticales (frontal bilateral, temporal, parietal, occipital, cingulado/precúneo posterior) y fase tardía de 18F-florbetapir en las mismas regiones corticales utilizando una escala de 3puntos (0=normal, 1=anormal con placas menores, 2=anormal con placas importantes). Usamos SPM12 para el análisis semicuantitativo aplicando un análisis de correlación basado en ROI (considerando precúneo como región objetivo y normalizado para la unión global media), un análisis de covarianza tomando precúneo como objetivo y una comparación de DMN global (red de modo predeterminado). resultados: La concordancia entre lectores fue alta (kappa de Cohen 0,762 para 18F-FDG, 0,775 para 18F-florbetapir en la fase temprana y 0,794 para la fase tardía). Las puntuaciones visuales regionales de la fase temprana y la 18F-FDG se correlacionaron significativamente (ρ=0,867). También el análisis basado en el ROI, el análisis visual cerebral global y la comparación de DMN revelaron resultados concordantes, especialmente en parietal y precúneo (p <0,001). Conclusiones: Las exploraciones de fase temprana de 18F-florbetapir se correlacionan significativamente en imágenes cuantitativas y visuales con las exploraciones de 18F-FDG-PET/TC, lo que sugiere que se podría usar un marcadore de amiloide en lugar de 18F-FDG (AU)
This study compared the performance of 18F-florbetapir PET/CT early acquisitions to 18F-FDG PET/CT. Methods: We included 12 patients who underwent 18F-FDG PET/CT and a dual-time 18F-florbetapir PET/CT (1-6minutes early-scan and 50minutes late-scan). PET/CT were analyzed visually by 3nuclear medicine physicians with different experience using a four-point scale (0=no reduction, 1=slight, 2=moderate, 3=severe reduction) for 18F-florbetapir early-phase and 18F-FDG images in 10 cortical regions (bilateral frontal, temporal, parietal, occipital, posterior cingulate/precuneus), and 18F-florbetapir late-phase in the same cortical regions using a three-point scale (0=normal, 1=abnormal with minor plaques, 2=abnormal with major plaques). We used SPM12 for semiquantitative analysis applying a ROI-based correlation analysis (considering precuneus as target region and normalized for the mean global binding), a covariance-analysis taking precuneus as target and a comparison of global DMN (default mode network). esults: Inter-reader agreement was high (Cohen's kappa 0.762 for 18F-FDG, 0.775 for 18F-florbetapir early-phase and 0.794 for late-phase). Regional visual scores of early-phase and 18F-FDG were significantly correlated (ρ=0.867). Also ROI-based analysis, global brain visual analysis and DMN comparison revealed concordant results, especially at parietal and precuneus(p<0.001). Conclusions: 18F-florbetapir early-phase scans significantly correlate on quantitative and visual images with 18F-FDG-PET/CT scans, suggesting that amyloid tracer could be used instead of 18F-FDG (AU)