No difference in extra-axial cerebrospinal fluid volumes across neurodevelopmental and psychiatric conditions in later childhood and adolescence

Abstract

Background While autism spectrum disorder has been associated with various organizational and developmental aberrations in the brain, an increase in extra-axial cerebrospinal fluid volume has recently garnered attention. A series of studies indicate that an increased volume between the ages of 6 months and 4 years was both predictive of the autism diagnosis and symptom severity regardless of genetic risk for the condition. However, there remains a minimal understanding regarding the specificity of an increased volume of extra-axial cerebrospinal fluid to autism. Methods In the present study, we explored extra-axial cerebrospinal fluid volumes in children and adolescents ages 5–21 years with various neurodevelopmental and psychiatric conditions. We hypothesized that an elevated extra-axial cerebrospinal fluid volume would be found in autism compared with typical development and the other diagnostic group. We tested this hypothesis by employing a cross-sectional dataset of 446 individuals (85 autistic, 60 typically developing, and 301 other diagnosis). An analysis of covariance was used to examine differences in extra-axial cerebrospinal fluid volumes between these groups as well as a group by age interaction in extra-axial cerebrospinal fluid volumes. Results Inconsistent with our hypothesis, we found no group differences in extra-axial cerebrospinal fluid volume in this cohort. However, in replication of previous work, a doubling of extra-axial cerebrospinal fluid volume across adolescence was found. Further investigation into the relationship between extra-axial cerebrospinal fluid volume and cortical thickness suggested that this increase in extra-axial cerebrospinal fluid volume may be driven by a decrease in cortical thickness. Furthermore, an exploratory analysis found no relationship between extra-axial cerebrospinal fluid volume and sleep disturbances. Conclusions These results indicate that an increased volume of extra-axial cerebrospinal fluid may be limited to autistic individuals younger than 5 years. Additionally, extra-axial cerebrospinal fluid volume does not differ between autistic, neurotypical, and other psychiatric conditions after age 4.

Increased extra-axial cerebrospinal fluid and benign external hydrocephalus in early autism

“…2). Indeed, two large studies have recently reported that EA-CSF volumes of ASD children above the age of four do not differ significantly from those of controls 19,20 . Taken together, these findings suggest that excessive EA-CSF volumes and EA-CSF/TBV ratios in the sub-group described above are a transient characteristic that appears during early development and disappears later in childhood as the children mature.…”

“…It was suggested that this increased EA-CSF/TBV ratio may indicate a unique etiology of ASD. Two large follow-up studies examining older ASD children did not find any differences in EA-CSF volumes in ASD children 4-years-old and older 19,20 , suggesting that EA-CSF differences are transient and normalize during later childhood.…”

“…The copyright holder for this preprint this version posted January 6, 2024. ; https://doi.org/10.1101/2024.01.04.574160 doi: bioRxiv preprint participant, annotators used the itk-SNAP software (www.itksnap.org), to visually inspect the CSF labeling and manually correct it. Ventricles were manually removed and only extra-axial CSF voxels above the anterior-posterior commissure horizontal plane were included in the final analysis as also performed by previous studies 16,[18][19][20] . Total brain volumes were estimated by two annotators (Radiology interns) who were blind to the children's diagnoses (Fig.…”