White matter development in 22q11.2 Deletion Syndrome Developmental - - PowerPoint PPT Presentation

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White matter development in 22q11.2 Deletion Syndrome Developmental - - PowerPoint PPT Presentation

Apr 06, 2023 162 likes •368 views

White matter development in 22q11.2 Deletion Syndrome Developmental Imaging and Psychopathology (DIP) lab, University of Geneva Jolle Bagautdinova - van der Molen 16-17.11.19 Introduction 3 Introduction The brain continues to mature

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White matter development in 22q11.2 Deletion Syndrome

Developmental Imaging and Psychopathology (DIP) lab, University of Geneva Joëlle Bagautdinova - van der Molen 16-17.11.19

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Introduction

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  • The brain continues to mature after birth and until adulthood
  • Brain development is determined by a combination of genetic and environmental

factors

Introduction

Birth Adulthood

More grey matter Less grey matter

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  • What is the brain made of?

White matter The « cables » of the brain Grey matter Includes neuronal bodies Mainly myelinated axons Neurone

Introduction

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  • What is the brain made of?

White matter The « cables » of the brain Grey matter Includes neuronal bodies Mainly myelinated axons Neurone

Introduction

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  • White matter development continues until adulthood
  • White matter development is mainly non-linear
  • Maturation peaks ranging from 20 to 40+ years

depending on the brain region

From Lebel and Beaulieu, 2011; Lebel et al., 2012

Age Age Age Age

White matter development in healthy individuals

White matter

Introduction

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  • Widespread alterations of white matter volume and microstructure

in 22q11.2DS

  • Lack of age-related changes in most white matter tracts

Introduction

Canu et al., 2015; Carletti et al., 2012; Davis et al., 2003; Scariati et al., 2016

Limitations

  • Limited sample sizes
  • Findings are based on cross-sectional studies
  • Discordant results

(for a review, see Scariati et al., 2016)

White matter in individuals with 22q11.2DS

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Introduction

White matter development in 22q11.2DS is largely unknown

?

White matter

Canu et al., 2015; Carletti et al., 2012; Davis et al., 2003; Scariati et al., 2016

  • Widespread alterations of white matter volume and microstructure

in 22q11.2DS

  • Lack of age-related changes in most white matter tracts

White matter in individuals with 22q11.2DS

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White matter development in 22q11.2DS

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Objective

Characterize the developmental trajectories of white matter microstructure in 22q11.2DS

  • Clarify the maturational profile of white matter microstructure related to a high genetic risk for

psychosis

  • Method: longitudinal (repeated measures) approach; mixed models regression

White matter development in 22q11.2DS

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Left lateral view Right lateral view

Main white matter tracts of the brain

White matter development in 22q11.2DS

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Female Male Total Controls

52 48 100

22q11.2DS

50 51 101

Total

102 99 201

  • From 5 to 35 years old
  • 1 - 3 time points (TPs)
  • ~ 3 years interval between TPs
  • n = 201
  • 302 scans

Age at scan Participants

Sample description

White matter development in 22q11.2DS

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Right cingulum (CCG) Age (years) RD p < 0.001

Radial Diffusivity

Right cingulum (CCG) p < 0.001 FA

Fractional Anisotropy

Age (years) Left cingulum (CCG) MD Age (years) p < 0.001

Mean Diffusivity Axial Diffusivity

AD p < 0.001 Age (years) Left superior longitudinal fasciculus (SLFT)

  • White matter development is affected in 22q11.2DS

Tracts with altered microstructure

White matter development in 22q11.2DS

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White matter development in 22q11.2DS

  • Multivariate approach to assess the impact or clinical risk factors on white matter maturation in 22q11.2DS
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White matter development in 22q11.2DS

  • Clinical risk factors have a significant impact on white matter development in 22q11.2DS

p = 0.03

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Take home message

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Take home message

  • RD reductions suggest excessive myelination
  • AD reductions suggest axonal disruptions, reduced tracts organisation or reduced axon diameter

RD reduction Hypermyelination

Healthy neuron

AD reduction Reduced tract organisation

Fiber bundle

AD reduction Reduced axonal diameter AD reduction Axonal damage

  • 22q11DS is associated with widespread alterations of white matter microstructure
  • Alterations point to a combination of neuropathological mechanisms in 22q11.2DS:
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  • Alterations are already visible early during development, pointing to pre-, perinatal or early

childhood altered maturation of white matter microstructure

  • Evidence for typical developmental rates (similar changes occurring 22q112DS and typically

developing controls)

  • Clinical risk factors for psyc

sychosi sis have an impact on white matter microstructure

  • 22q11DS is associated with widespread alterations of white matter microstructure
  • Alterations point to a combination of neuropathological mechanisms in 22q11.2DS:
  • RD reductions suggest excessive myelination
  • AD reductions suggest axonal disruptions, reduced tracts organisation or reduced axon diameter

Take home message

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Thank you!

Thank you for your attention!