Subcortical Brain Morphometry Differences between Adults with Autism Spectrum Disorder and Schizophrenia

Abstract

Autism spectrum disorder (ASD) and schizophrenia (SZ) are neuropsychiatric disorders that overlap in symptoms associated with social-cognitive impairment. Subcortical structures play a significant role in cognitive and social-emotional behaviors and their abnormalities are associated with neuropsychiatric conditions. This exploratory study utilized ABIDE II/COBRE MRI and corresponding phenotypic datasets to compare subcortical volumes of adults with ASD (n = 29), SZ (n = 51) and age and gender matched neurotypicals (NT). We examined the association between subcortical volumes and select behavioral measures to determine whether core symptomatology of disorders could be explained by subcortical association patterns. We observed volume differences in ASD (viz., left pallidum, left thalamus, left accumbens, right amygdala) but not in SZ compared to their respective NT controls, reflecting morphometric changes specific to one of the disorder groups. However, left hippocampus and amygdala volumes were implicated in both disorders. A disorder-specific negative correlation (r = -0.39, p = 0.038) was found between left-amygdala and scores on the Social Responsiveness Scale (SRS) Social-Cognition in ASD, and a positive association (r = 0.29, p = 0.039) between full scale IQ (FIQ) and right caudate in SZ. Significant correlations between behavior measures and subcortical volumes were observed in NT groups (ASD-NT range; r = -0.53 to -0.52, p = 0.002 to 0.004, SZ-NT range; r = -0.41 to -0.32, p = 0.007 to 0.021) that were non-significant in the disorder groups. The overlap of subcortical volumes implicated in ASD and SZ may reflect common neurological mechanisms. Furthermore, the difference in correlation patterns between disorder and NT groups may suggest dysfunctional connectivity with cascading effects unique to each disorder and a potential role for IQ in mediating behavior and brain circuits.

Keywords: FIQ; MRI; amygdala; autism; caudate; hippocampus; schizophrenia; social skills; subcortical.

Figure 1

Mean ± standard deviation for non-normalized volumetric measures (in mm³) of total gray matter, subcortical gray matter, cortical white matter and CSF for the disorder groups and their respective neurotypical groups (ASD [n = 29] and ASD-NT [n = 29]; SZ [n = 51] and SZ-NT [n = 51]). Statistical significance of group differences is indicated numerically. Red circle: ASD, blue circle: ASD-NT, red triangle: SZ, blue triangle: SZ-NT.

Figure 2

Mean ± standard deviation for eTIV-normalized volumetric measures of subcortical structures in disorder groups and their respective neurotypical groups (ASD [n = 29] and ASD-NT [n = 29]; SZ [n = 51] and SZ-NT [n = 51]). Statistical significance is indicated numerically. Red circle: ASD, blue circle: ASD-NT, red triangle: SZ, blue triangle: SZ-NT.

Figure 3

Correlation plots in ASD. (Left): correlation between normalized left amygdala volume and SRS-social cognition score in ASD (r = −0.39, p = 0.038) and ASD-NT (r= −0.30, p = 0.117). (Middle): correlation between normalized left amygdala volume and FIQ score in ASD (r = 0.08, p = 0.668) and ASD-NT (r= −0.53, p = 0.002). (Right): correlation between normalized right amygdala volume and FIQ score in ASD (r = −0.11, p = 0.552) and ASD-NT (r = −0.52, p = 0.004). Solid-lines: regression-line (red = ASD, blue = ASD-NT); dashed-lines indicate the 95% confidence intervals for respective regression lines.

Figure 4

Schizophrenia correlation plots. (Left): correlation between normalized left caudate volume and FIQ in SZ (r = 0.26, p = 0.061) and SZ-NT (r = −0.33, p = 0.018). (Right): correlation between normalized right caudate volume and FIQ score in SZ (r = 0.29, p = 0.039) and SZ-NT (r = −0.41, p = 0.003). Solid-lines: regression-line (red = SZ, blue = SZ-NT); dashed-lines indicate the 95% confidence intervals for respective regression lines.