Baseline connectome modular abnormalities in the childhood phase of a longitudinal study on individuals with chromosome 22q11.2 deletion syndrome

Liang Zhan, Lisanne M. Jenkins, Aifeng Zhang, Giorgio Conte, Angus Forbes, Danielle J Harvey, Kathleen Angkustsiri, Naomi J. Goodrich-Hunsaker, Courtney Durdle, Aaron Lee, Cynthia Schumann, Owen Carmichael, Kristopher Kalish, Alex D. Leow, Tony J Simon

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Occurring in at least 1 in 3,000 live births, chromosome 22q11.2 deletion syndrome (22q11DS) produces a complex phenotype that includes a constellation of medical complications such as congenital cardiac defects, immune deficiency, velopharyngeal dysfunction, and characteristic facial dysmorphic features. There is also an increased incidence of psychiatric diagnosis, especially intellectual disability and ADHD in childhood, lifelong anxiety, and a strikingly high rate of schizophrenia spectrum disorders, which occur in around 30% of adults with 22q11DS. Using innovative computational connectomics, we studied how 22q11DS affects high-level network signatures of hierarchical modularity and its intrinsic geometry in 55 children with confirmed 22q11DS and 27 Typically Developing (TD) children. Results identified 3 subgroups within our 22q11DS sample using a K-means clustering approach based on several midline structural measures-of-interests. Each subgroup exhibited distinct patterns of connectome abnormalities. Subtype 1, containing individuals with generally healthy-looking brains, exhibited no significant differences in either modularity or intrinsic geometry when compared with TD. By contrast, the more anomalous 22q11DS Subtypes 2 and 3 brains revealed significant modular differences in the right hemisphere, while Subtype 3 (the most anomalous anatomy) further exhibited significantly abnormal connectome intrinsic geometry in the form of left-right temporal disintegration. Taken together, our findings supported an overall picture of (a) anterior-posteriorly differential interlobar frontotemporal/frontoparietal dysconnectivity in Subtypes 2 and 3 and (b) differential intralobar dysconnectivity in Subtype 3. Our ongoing studies are focusing on whether these subtypes and their connnectome signatures might be valid biomarkers for predicting the degree of psychosis-proneness risk found in 22q11DS.

Original languageEnglish (US)
JournalHuman Brain Mapping
DOIs
StateAccepted/In press - 2017

Fingerprint

Connectome
DiGeorge Syndrome
Chromosome Deletion
Longitudinal Studies
Brain
Live Birth
Mental Disorders
Intellectual Disability
Psychotic Disorders
Cluster Analysis
Anatomy
Schizophrenia
Anxiety
Biomarkers
Phenotype

Keywords

  • 22q11DS
  • Brain connectome
  • Diffusion MRI
  • Intrinsic geometry
  • Modularity

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology

Cite this

Baseline connectome modular abnormalities in the childhood phase of a longitudinal study on individuals with chromosome 22q11.2 deletion syndrome. / Zhan, Liang; Jenkins, Lisanne M.; Zhang, Aifeng; Conte, Giorgio; Forbes, Angus; Harvey, Danielle J; Angkustsiri, Kathleen; Goodrich-Hunsaker, Naomi J.; Durdle, Courtney; Lee, Aaron; Schumann, Cynthia; Carmichael, Owen; Kalish, Kristopher; Leow, Alex D.; Simon, Tony J.

In: Human Brain Mapping, 2017.

Research output: Contribution to journalArticle

Zhan, Liang ; Jenkins, Lisanne M. ; Zhang, Aifeng ; Conte, Giorgio ; Forbes, Angus ; Harvey, Danielle J ; Angkustsiri, Kathleen ; Goodrich-Hunsaker, Naomi J. ; Durdle, Courtney ; Lee, Aaron ; Schumann, Cynthia ; Carmichael, Owen ; Kalish, Kristopher ; Leow, Alex D. ; Simon, Tony J. / Baseline connectome modular abnormalities in the childhood phase of a longitudinal study on individuals with chromosome 22q11.2 deletion syndrome. In: Human Brain Mapping. 2017.
@article{0e51fc3ddf3e42bb8fac922042139477,
title = "Baseline connectome modular abnormalities in the childhood phase of a longitudinal study on individuals with chromosome 22q11.2 deletion syndrome",
abstract = "Occurring in at least 1 in 3,000 live births, chromosome 22q11.2 deletion syndrome (22q11DS) produces a complex phenotype that includes a constellation of medical complications such as congenital cardiac defects, immune deficiency, velopharyngeal dysfunction, and characteristic facial dysmorphic features. There is also an increased incidence of psychiatric diagnosis, especially intellectual disability and ADHD in childhood, lifelong anxiety, and a strikingly high rate of schizophrenia spectrum disorders, which occur in around 30{\%} of adults with 22q11DS. Using innovative computational connectomics, we studied how 22q11DS affects high-level network signatures of hierarchical modularity and its intrinsic geometry in 55 children with confirmed 22q11DS and 27 Typically Developing (TD) children. Results identified 3 subgroups within our 22q11DS sample using a K-means clustering approach based on several midline structural measures-of-interests. Each subgroup exhibited distinct patterns of connectome abnormalities. Subtype 1, containing individuals with generally healthy-looking brains, exhibited no significant differences in either modularity or intrinsic geometry when compared with TD. By contrast, the more anomalous 22q11DS Subtypes 2 and 3 brains revealed significant modular differences in the right hemisphere, while Subtype 3 (the most anomalous anatomy) further exhibited significantly abnormal connectome intrinsic geometry in the form of left-right temporal disintegration. Taken together, our findings supported an overall picture of (a) anterior-posteriorly differential interlobar frontotemporal/frontoparietal dysconnectivity in Subtypes 2 and 3 and (b) differential intralobar dysconnectivity in Subtype 3. Our ongoing studies are focusing on whether these subtypes and their connnectome signatures might be valid biomarkers for predicting the degree of psychosis-proneness risk found in 22q11DS.",
keywords = "22q11DS, Brain connectome, Diffusion MRI, Intrinsic geometry, Modularity",
author = "Liang Zhan and Jenkins, {Lisanne M.} and Aifeng Zhang and Giorgio Conte and Angus Forbes and Harvey, {Danielle J} and Kathleen Angkustsiri and Goodrich-Hunsaker, {Naomi J.} and Courtney Durdle and Aaron Lee and Cynthia Schumann and Owen Carmichael and Kristopher Kalish and Leow, {Alex D.} and Simon, {Tony J}",
year = "2017",
doi = "10.1002/hbm.23838",
language = "English (US)",
journal = "Human Brain Mapping",
issn = "1065-9471",
publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - Baseline connectome modular abnormalities in the childhood phase of a longitudinal study on individuals with chromosome 22q11.2 deletion syndrome

AU - Zhan, Liang

AU - Jenkins, Lisanne M.

AU - Zhang, Aifeng

AU - Conte, Giorgio

AU - Forbes, Angus

AU - Harvey, Danielle J

AU - Angkustsiri, Kathleen

AU - Goodrich-Hunsaker, Naomi J.

AU - Durdle, Courtney

AU - Lee, Aaron

AU - Schumann, Cynthia

AU - Carmichael, Owen

AU - Kalish, Kristopher

AU - Leow, Alex D.

AU - Simon, Tony J

PY - 2017

Y1 - 2017

N2 - Occurring in at least 1 in 3,000 live births, chromosome 22q11.2 deletion syndrome (22q11DS) produces a complex phenotype that includes a constellation of medical complications such as congenital cardiac defects, immune deficiency, velopharyngeal dysfunction, and characteristic facial dysmorphic features. There is also an increased incidence of psychiatric diagnosis, especially intellectual disability and ADHD in childhood, lifelong anxiety, and a strikingly high rate of schizophrenia spectrum disorders, which occur in around 30% of adults with 22q11DS. Using innovative computational connectomics, we studied how 22q11DS affects high-level network signatures of hierarchical modularity and its intrinsic geometry in 55 children with confirmed 22q11DS and 27 Typically Developing (TD) children. Results identified 3 subgroups within our 22q11DS sample using a K-means clustering approach based on several midline structural measures-of-interests. Each subgroup exhibited distinct patterns of connectome abnormalities. Subtype 1, containing individuals with generally healthy-looking brains, exhibited no significant differences in either modularity or intrinsic geometry when compared with TD. By contrast, the more anomalous 22q11DS Subtypes 2 and 3 brains revealed significant modular differences in the right hemisphere, while Subtype 3 (the most anomalous anatomy) further exhibited significantly abnormal connectome intrinsic geometry in the form of left-right temporal disintegration. Taken together, our findings supported an overall picture of (a) anterior-posteriorly differential interlobar frontotemporal/frontoparietal dysconnectivity in Subtypes 2 and 3 and (b) differential intralobar dysconnectivity in Subtype 3. Our ongoing studies are focusing on whether these subtypes and their connnectome signatures might be valid biomarkers for predicting the degree of psychosis-proneness risk found in 22q11DS.

AB - Occurring in at least 1 in 3,000 live births, chromosome 22q11.2 deletion syndrome (22q11DS) produces a complex phenotype that includes a constellation of medical complications such as congenital cardiac defects, immune deficiency, velopharyngeal dysfunction, and characteristic facial dysmorphic features. There is also an increased incidence of psychiatric diagnosis, especially intellectual disability and ADHD in childhood, lifelong anxiety, and a strikingly high rate of schizophrenia spectrum disorders, which occur in around 30% of adults with 22q11DS. Using innovative computational connectomics, we studied how 22q11DS affects high-level network signatures of hierarchical modularity and its intrinsic geometry in 55 children with confirmed 22q11DS and 27 Typically Developing (TD) children. Results identified 3 subgroups within our 22q11DS sample using a K-means clustering approach based on several midline structural measures-of-interests. Each subgroup exhibited distinct patterns of connectome abnormalities. Subtype 1, containing individuals with generally healthy-looking brains, exhibited no significant differences in either modularity or intrinsic geometry when compared with TD. By contrast, the more anomalous 22q11DS Subtypes 2 and 3 brains revealed significant modular differences in the right hemisphere, while Subtype 3 (the most anomalous anatomy) further exhibited significantly abnormal connectome intrinsic geometry in the form of left-right temporal disintegration. Taken together, our findings supported an overall picture of (a) anterior-posteriorly differential interlobar frontotemporal/frontoparietal dysconnectivity in Subtypes 2 and 3 and (b) differential intralobar dysconnectivity in Subtype 3. Our ongoing studies are focusing on whether these subtypes and their connnectome signatures might be valid biomarkers for predicting the degree of psychosis-proneness risk found in 22q11DS.

KW - 22q11DS

KW - Brain connectome

KW - Diffusion MRI

KW - Intrinsic geometry

KW - Modularity

UR - http://www.scopus.com/inward/record.url?scp=85030648778&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030648778&partnerID=8YFLogxK

U2 - 10.1002/hbm.23838

DO - 10.1002/hbm.23838

M3 - Article

JO - Human Brain Mapping

JF - Human Brain Mapping

SN - 1065-9471

ER -