Brain morphometry in 22q11.2 deletion syndrome: an exploration of differences in cortical thickness, surface area, and their contribution to cortical volume

Abstract

22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans, with a heterogenous clinical presentation including medical, behavioural and psychiatric conditions. Previous neuroimaging studies examining the neuroanatomical underpinnings of 22q11.2DS show alterations in cortical volume (CV), cortical thickness (CT) and surface area (SA). The aim of this study was to identify (1) the spatially distributed networks of differences in CT and SA in 22q11.2DS compared to controls, (2) their unique and spatial overlap, as well as (3) their relative contribution to observed differences in CV. Structural MRI scans were obtained from 62 individuals with 22q11.2DS and 57 age-and-gender-matched controls (aged 6–31). Using FreeSurfer, we examined differences in vertex-wise estimates of CV, CT and SA at each vertex, and compared the frequencies of vertices with a unique or overlapping difference for each morphometric feature. Our findings indicate that CT and SA make both common and unique contributions to volumetric differences in 22q11.2DS, and in some areas, their strong opposite effects mask differences in CV. By identifying the neuroanatomic variability in 22q11.2DS, and the separate contributions of CT and SA, we can start exploring the shared and distinct mechanisms that mediate neuropsychiatric symptoms across disorders, e.g. 22q11.2DS-related ASD and/or psychosis/schizophrenia.

Altered cortical thickness development in 22q11.2 deletion syndrome and association with psychotic symptoms

“…Widely decreased SA in 22q11DS compared to controls found in our analyses is in line with previous studies reporting reduced SA in 22q11DS using parcellation [ 15 ] and vertex-wise cross-sectional approaches [ 14 , 16 , 17 ]. For a detailed discussion of SA findings, see Supplementary Discussion .…”

“…Syndromic individuals are typically identified very early during development and can therefore be followed up starting from childhood, providing a unique opportunity to gain insight into the neurodevelopmental mechanisms preceding the onset of psychosis. On a neuroanatomical level, studies have generally reported widespread increased CT in 22q11DS and focal decreases in posterior cingulate and superior temporal gyri (STG) compared to healthy controls [ 14 – 16 ], a finding that was recently confirmed in a large multisite study [ 17 ]. However, the developmental trajectory of CT in 22q11DS remains unclear [ 18 ], as some reported faster thinning [ 19 ], while others found slower thinning [ 16 , 20 ], a lack of thinning [ 15 ] or no difference in thinning [ 17 ] in 22q11DS compared to controls.…”

“…On a neuroanatomical level, studies have generally reported widespread increased CT in 22q11DS and focal decreases in posterior cingulate and superior temporal gyri (STG) compared to healthy controls [ 14 – 16 ], a finding that was recently confirmed in a large multisite study [ 17 ]. However, the developmental trajectory of CT in 22q11DS remains unclear [ 18 ], as some reported faster thinning [ 19 ], while others found slower thinning [ 16 , 20 ], a lack of thinning [ 15 ] or no difference in thinning [ 17 ] in 22q11DS compared to controls. A large-scale longitudinal study investigating gray matter development with a fine-grained temporal and topological resolution is thus needed to clarify neuroanatomical development in 22q11DS.…”

“…Another potentially important, yet understudied component of brain structure is surface area (SA). Studies have shown reduced SA in 22q11DS [ 14 , 16 , 17 ] and idiopathic schizophrenia [ 25 , 26 ], as well as steeper cross-sectional decline over age in 22q11DS [ 16 ]. No alterations were found when comparing individuals with 22q11DS with and without psychotic symptoms [ 15 , 17 ].…”

Variability and magnitude of brain volume abnormalities in disruptive behavior disorders, antisocial personality disorder, and psychopathy - a meta-analysis

“…To date, genetic and neurodevelopmental mechanisms of antisocial behavior remain poorly understood, though GWAS have begun to identify some potential contributory factors (25)(26)(27). One factor which may play a role in variability is relative contribution to brain volume of surface area and cortical thickness, which have been shown to have separable genetic underpinnings (28) and which contribute to the neurodevelopment of volume in autism in unique ways (29,30). The group differences in mean volumes in whole brain, intracranial volume, total gray matter, and amygdala are broadly consistent with previous structural MRI literature in groups of antisocial youth and adults.…”