Neural systems for social cognition: gray matter volume abnormalities in boys at high genetic risk of autism symptoms, and a comparison with idiopathic autism spectrum disorder

Abstract

Klinefelter syndrome (47, XXY) is associated with several physical, cognitive, and behavioral consequences. In terms of social development, there is an increased risk of autism symptomatology. However, it remains unclear how social deficits are related to abnormal brain development and to what degree underlying mechanisms of social dysfunction in 47, XXY are similar to, or different from, those in idiopathic autism (ASD). This study was aimed at investigating the neural architecture of brain structures related to social information processing in boys with 47, XXY, also in comparison with boys with idiopathic ASD. MRI scans of 16 boys with 47, XXY, 16 with ASD, and 16 nonclinical, male controls were analyzed using voxel-based morphometry (VBM). A region of interest mask containing the superior temporal cortex, amygdala, orbitofrontal cortex (OFC), insular cortex, and medial frontal cortex was used. The Social Responsiveness Scale (SRS) was used to assess degree of autism spectrum symptoms. The 47, XXY group could not be distinguished from the ASD group on mean SRS scores, and their scores were significantly higher than in controls. VBM showed that boys with 47, XXY have significant gray matter volume reductions in the left and right insula, and the left OFC, compared with controls and boys with ASD. Additionally, boys with 47, XXY had significantly less gray matter in the right superior temporal gyrus than controls. These results imply social challenges associated with 47, XXY may be rooted in neural anatomy, and autism symptoms in boys with 47, XXY and boys with ASD might have, at least partially, different underlying etiologies.

Systematic review and meta‐analysis of the association of Autism Spectrum Disorder in visually or hearing impaired children

“…Sensory integration is a key weakness for those with ASD and so a lack of visual or auditory cues would decrease their ability to recognise and integrate verbal and visual cues to help them develop a social picture . Currently evidence suggests that the superior temporal sulcus is atypical in ASD where there is sensory integration of both visual and auditory information and forms a key component of the social brain . The lack of input to the superior temporal sulcus via primary visual or auditory cortex is in line with current evidence that supports a significant role for the superior temporal sulcus in the pathophysiology of ASD.…”

Advances in the Interdisciplinary Care of Children with Klinefelter Syndrome

“…67,101 Recent important studies comparing autism symptoms and neuroanatomy in XXY to a group with idiopathic autism demonstrated that although behavioral questionnaires indicated similar autism symptoms between the groups, there were significant neuroanatomical differences in XXY compared to idiopathic ASD, suggesting that autism symptoms in the respective groups may have, at least partially, different etiologies. 103 Taken together, these studies support that ASD is an important clinical consideration in KS.…”

“…83 Most studies have focused on describing autism symptoms which have identified features such as decreased social attention, decreased empathic skills, difficulty interpreting facial expressions, and social communication difficulties. 67,101–103 Studies that have included direct diagnostic assessment for autism spectrum disorders (ASD) are more limited, and report a rate of 27% in a Dutch cohort (n=51) using a standardized diagnostic autism interview called the ADI-R, 93 and a rate of 10% in an American cohort (n=20) using a battery including the ADI-R and direct assessment via the Autism Diagnostic Observation Scales (ADOS). 5 Two other studies that evaluated rates of previous clinical ASD diagnosis in their cohort with KS also reported approximately 10% with ASD.…”

Psychological functioning, brain morphology, and functional neuroimaging in Klinefelter syndrome

“…A search of the literature revealed 14 studies reporting measures of total brain volume in KS with a comparison to a male control group (Bryant et al, 2011;DeLisi et al, 2005;Giedd et al, 2007;Goddard et al, 2016;Lentini et al, 2013;Mankiw et al, 2017;Nadig et al, 2018;Patwardhan et al, 2000;Patwardhan et al, 2002;Raznahan et al, 2016;Reardon et al, 2016;Rezaie et al, 2009; This article is protected by copyright. All rights reserved.…”

“…Local volumetric differences are primarily found in the ventral (e.g. medial temporal) and central (subcortical) parts of the brain (Bryant et al, 2011;DeLisi et al, 2005;Giedd et al, 2007;Goddard et al, 2016;Lentini et al, 2013;Mankiw et al, 2017;Nadig et al, 2018;Patwardhan et al, 2000;Patwardhan et al, 2002;Raznahan et al, 2016;Reardon et al, 2016;Shen et al, 2004;Skakkebaek et al, 2013), and these local differences alone predict status (i.e. KS or male control) in 96.9 % of cases (Skakkebaek et al, 2013).…”