In Vivo Evidence of Reduced Integrity of the Gray–White Matter Boundary in Autism Spectrum Disorder

Abstract Autism spectrum disorder is a highly prevalent and highly heritable neurodevelopmental condition, but studies have mostly taken traditional categorical diagnosis approach (yes/no for autism spectrum disorder). In contrast, an emerging notion suggests a continuum model of autism spectrum disorder with a normal distribution of autistic tendencies in the general population, where a full diagnosis is at the severe tail of the distribution. We set out to investigate such a viewpoint by investigating the interaction of polygenic risk scores for autism spectrum disorder and Age2 on neuroimaging measures (cortical thickness and white matter connectivity) in a general population (n = 391, with age ranging from 3 to 21 years from the Pediatric Imaging, Neurocognition and Genetics study). We observed that children with higher polygenic risk for autism spectrum disorder exhibited greater cortical thickness for a large age span starting from 3 years up to ∼14 years in several cortical regions localized in bilateral precentral gyri and the left hemispheric postcentral gyrus and precuneus. In an independent case–control dataset from the Autism Brain Imaging Data Exchange (n = 560), we observed a similar pattern: children with autism spectrum disorder exhibited greater cortical thickness starting from 6 years onwards till ∼14 years in wide-spread cortical regions including (the ones identified using the general population). We also observed statistically significant regional overlap between the two maps, suggesting that some of the cortical abnormalities associated with autism spectrum disorder overlapped with brain changes associated with genetic vulnerability for autism spectrum disorder in healthy individuals. Lastly, we observed that white matter connectivity between the frontal and parietal regions showed significant association with polygenic risk for autism spectrum disorder, indicating that not only the brain structure, but the white matter connectivity might also show a predisposition for the risk of autism spectrum disorder. Our findings showed that the fronto-parietal thickness and connectivity are dimensionally related to genetic risk for autism spectrum disorder in general population and are also part of the cortical abnormalities associated with autism spectrum disorder. This highlights the necessity of considering continuum models in studying the aetiology of autism spectrum disorder using polygenic risk scores and multimodal neuroimaging.

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Early white matter development is abnormal in tuberous sclerosis complex patients who develop autism spectrum disorder

Journal of Neurodevelopmental Disorders ◽

10.1186/s11689-019-9293-x ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 10

Author(s):

Anna K. Prohl ◽

◽

Benoit Scherrer ◽

Xavier Tomas-Fernandez ◽

Peter E. Davis ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

White Matter ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Neural Circuits ◽

Diffusion Tensor ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Fiber Bundles ◽

The Brain

Abstract Background Autism spectrum disorder (ASD) is prevalent in tuberous sclerosis complex (TSC), occurring in approximately 50% of patients, and is hypothesized to be caused by disruption of neural circuits early in life. Tubers, or benign hamartomas distributed stochastically throughout the brain, are the most conspicuous of TSC neuropathology, but have not been consistently associated with ASD. Widespread neuropathology of the white matter, including deficits in myelination, neuronal migration, and axon formation, exist and may underlie ASD in TSC. We sought to identify the neural circuits associated with ASD in TSC by identifying white matter microstructural deficits in a prospectively recruited, longitudinally studied cohort of TSC infants. Methods TSC infants were recruited within their first year of life and longitudinally imaged at time of recruitment, 12 months of age, and at 24 months of age. Autism was diagnosed at 24 months of age with the ADOS-2. There were 108 subjects (62 TSC-ASD, 55% male; 46 TSC+ASD, 52% male) with at least one MRI and a 24-month ADOS, for a total of 187 MRI scans analyzed (109 TSC-ASD; 78 TSC+ASD). Diffusion tensor imaging properties of multiple white matter fiber bundles were sampled using a region of interest approach. Linear mixed effects modeling was performed to test the hypothesis that infants who develop ASD exhibit poor white matter microstructural integrity over the first 2 years of life compared to those who do not develop ASD. Results Subjects with TSC and ASD exhibited reduced fractional anisotropy in 9 of 17 white matter regions, sampled from the arcuate fasciculus, cingulum, corpus callosum, anterior limbs of the internal capsule, and the sagittal stratum, over the first 2 years of life compared to TSC subjects without ASD. Mean diffusivity trajectories did not differ between groups. Conclusions Underconnectivity across multiple white matter fiber bundles develops over the first 2 years of life in subjects with TSC and ASD. Future studies examining brain-behavior relationships are needed to determine how variation in the brain structure is associated with ASD symptoms.

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Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes

Molecular Autism ◽

10.1186/s13229-020-00323-8 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

Lucia Janickova ◽

Karin Farah Rechberger ◽

Lucas Wey ◽

Beat Schwaller

Keyword(s):

Autism Spectrum Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Risk Gene

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Paternal age contribution to brain white matter aberrations in autism spectrum disorder

Psychiatry and Clinical Neurosciences ◽

10.1111/pcn.12909 ◽

2019 ◽

Vol 73 (10) ◽

pp. 649-659 ◽

Cited By ~ 4

Author(s):

Walid Yassin ◽

Masaki Kojima ◽

Keiho Owada ◽

Hitoshi Kuwabara ◽

Wataru Gonoi ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

White Matter ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Paternal Age ◽

Brain White Matter

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Social performance–based interventions promote gains in social knowledge in the absence of explicit training for youth with autism spectrum disorder

Bulletin of the Menninger Clinic ◽

10.1521/bumc.2019.83.3.301 ◽

2019 ◽

Vol 83 (3) ◽

pp. 301-325 ◽

Cited By ~ 2

Author(s):

Bianca M. Marro ◽

Erin Kang ◽

Kathryn M. Hauschild ◽

Karys M. Normansell ◽

Tamara M. Abu-Ramadan ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Social Engagement ◽

Social Performance ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Social Knowledge ◽

Community Based ◽

Social Skills Interventions ◽

Explicit Training

Youth with autism spectrum disorder (ASD) experience deficits in social knowledge. It has long been theorized that these youth must learn these skills explicitly, and social skills interventions (SSIs) have followed suit. Recently, performance-based SSIs have emerged, which promote in vivo opportunities for social engagement without explicit instruction. Effects of performance-based SSIs on social knowledge have not been examined. This study employs two discrete samples (one lab-based, one community-based) of youth with ASD to examine the effects of performance-based interventions on social knowledge. Results largely support the efficacy and effectiveness of improving social knowledge by performance-based interventions without explicit teaching. This indicates that youth with ASD may be able to learn these aspects of social cognition implicitly, rather than exclusively explicitly. The results of the current study also suggest that SSI content, dosage, and intensity may relate to these outcomes, which are important considerations in clinical practice and future studies.

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