Brain development in VCFS: a longitudinal study Stephan Eliez.
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Transcript of Brain development in VCFS: a longitudinal study Stephan Eliez.
Brain development in VCFS:a longitudinal study
Stephan Eliez
Outline
• Introduction and a few words on methods
• Impact of genetic factors and heart malformations
• How do early and maturational brain changes relate to psychosis
• Conclusion
Cortical volume changes in VCFS
Reduction of gray matter volume in 60 patients with VCFS compared to 80 typically developing individuals (6-40 y/old)
Measuring cortical changes
Ratio of “hidden cortex”
Local Gyrification Index 5
4
3
2
Quantify surface in circular region of interest (Schaer et al, IEEE Transactions on Medical Imaging, 2008)
Early
Sensitive to maturational
changes
Thickness Later
Gyrification in VCFS
Right
Left
Several regions of reduced surface
expansion,
which may explain the volume reduction
44 patients with VCFS, 53 typically developingCorrected for multiple comparisons using FDR<0.01
Gyrification within VCFS
Parental origin of the deletion
27 patients with maternal origin, 19 with paternal originUncorrected for multiple comparisons
Right lateral
Right medial Left medial
Left lateral
Gyrification within VCFS
Right lateral
Left lateral
18 with CHD (who underwent surgery), 17 withoutUncorrected for multiple comparisons
Defect of expansion along watershed territories suggests hypoperfusion during cortical development
Effect of congenital heart disease
Right medial
Left medial
Psychotic symptoms in VCFS
65 patients with 22q11DS
Gyrification within VCFS
44 patients (6-37yo)53 controls (6-37yo)
22 psychotic patients (10-37yo)22 matched controls
7 with hallucinations7 without
5 with delusion9 without
14 patients (12-16yo)
… on to the maturation of the cortex
2mm
4mm
https://surfer.nmr.mgh.harvard.edu/fswiki/LGI
The Geneva cohort
• 61 patients with VCFS (36F/25M) – Mean age 15.6 ± 8.9 (range: 6-37.4)– Average FSIQ 68.7 ± 12.0
• 80 matched controls (44F/36M) – Mean age 15.9 ± 8.4 (range: 6-39.7)– Average FSIQ 111.8 ± 12.8
Control VCFS
6 to 9 16 17
9 to 12 22 11
12 to 15 8 10
15 to 18 7 4
18 + 27 19
Cortical thickness changes
Right hemisphere
Cortical thickness changes
Trajectories of cortical thickness
Longitudinal measures of cortical changes over 3 years
Delayed thinning in preadolescents
(younger than 9 at T1)
Faster thinning in adolescents(older than 9 at T1)
32 patients younger than 18 at first time-point (T1) & 31 matched controls
Thickness changes in 22q11DS
Study-specific template, Covarying for gender and agecorrected for multiple comparisons using FDR<0.05
Thicker cortex in patients compared to control…
… but a faster thinning with age in patients
Uncorrected for multiple comparisons
Cortical thickness & schizophrenia
19 adult patients (6 with schizophrenia, 13 without) - 27 healthy adults
Conclusion
• Brain changes in VCFS are complex because they are caused by:– Early changes in cortical folding &– Later changes during cortical maturation
(dysmaturation)
• In addition, there is an important variability in inter-individual brain development resulting from genetic factors and environmental factors (e.g. heart malformation)
• Greater dysmaturation is associated with psychosis. This opens new avenues for prevention and treatment
Stephan Eliez Bronwyn GlaserMartin Debbané
Marie Schaer
Maude Schneider
Annalaura Lagioia
Mélanie Chabloz Michal Epstein
Catherine Pasca
Astrid Flahault Marie-Christine OttetCatherine Audrin
Thank you for your attention...
Additional thanks go to:– Participating parents and their families
– Connect 22 & Génération 22 family associations
– VCFS Educational Foundation– Service Médico-Pédagogique– The Swiss National Fund– Fondation Gertrude von Meissner
COMT in patients with 22q11DS
Cross-sectional: 29 Met / 28 Val
Yellow: thinner in Met compared to ValBlue: thinner in Val compared to Met
Yellow: faster thinning in Met than ValBlue: faster thinning in Val than Met
Longitudinal: 15 Met / 18 Val
Study 6 - Schaer, Debbané, Bach Cuadra, Ottet, Glaser, Thiran & Eliez, Deviant trajectories of cortical maturation in 22q11.2 deletion syndrome: a cross-sectional and longitudinal
study, in revision