Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study

Julio E. Villalón-Reina, Kenia Martínez, Xiaoping Qu, Christopher R.K. Ching, Talia M. Nir, Deydeep Kothapalli, Conor Corbin, Daqiang Sun, Amy Lin, Jennifer K. Forsyth, Leila Kushan, Ariana Vajdi, Maria Jalbrzikowski, Laura Hansen, Rachel K. Jonas, Therese van Amelsvoort, Geor Bakker, Wendy R. Kates, Kevin M. Antshel, Wanda FremontLinda E. Campbell, Kathryn L. McCabe, Eileen Daly, Maria Gudbrandsen, Clodagh M. Murphy, Declan Murphy, Michael Craig, Beverly Emanuel, Donna M. McDonald-McGinn, Jacob A.S. Vorstman, Ania M. Fiksinski, Sanne Koops, Kosha Ruparel, David Roalf, Raquel E. Gur, J. Eric Schmitt, Tony J. Simon, Naomi J. Goodrich-Hunsaker, Courtney A. Durdle, Joanne L. Doherty, Adam C. Cunningham, Marianne van den Bree, David E.J. Linden, Michael Owen, Hayley Moss, Sinead Kelly, Gary Donohoe, Kieran C. Murphy, Celso Arango, Neda Jahanshad, Paul M. Thompson, Carrie E. Bearden

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

22q11.2 deletion syndrome (22q11DS)—a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22—is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6–52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen’s d’s ranging from −0.9 to −1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.

Original languageEnglish (US)
JournalMolecular Psychiatry
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

DiGeorge Syndrome
Diffusion Tensor Imaging
Internal Capsule
Diffusion Magnetic Resonance Imaging
Corpus Callosum
Anisotropy
Subthalamus
Chromosome Deletion
Neurogenesis
Brain Diseases
White Matter
Psychotic Disorders
Extremities
Animal Models
Radiation
Neurons

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Villalón-Reina, J. E., Martínez, K., Qu, X., Ching, C. R. K., Nir, T. M., Kothapalli, D., ... Bearden, C. E. (Accepted/In press). Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study. Molecular Psychiatry. https://doi.org/10.1038/s41380-019-0450-0

Altered white matter microstructure in 22q11.2 deletion syndrome : a multisite diffusion tensor imaging study. / Villalón-Reina, Julio E.; Martínez, Kenia; Qu, Xiaoping; Ching, Christopher R.K.; Nir, Talia M.; Kothapalli, Deydeep; Corbin, Conor; Sun, Daqiang; Lin, Amy; Forsyth, Jennifer K.; Kushan, Leila; Vajdi, Ariana; Jalbrzikowski, Maria; Hansen, Laura; Jonas, Rachel K.; van Amelsvoort, Therese; Bakker, Geor; Kates, Wendy R.; Antshel, Kevin M.; Fremont, Wanda; Campbell, Linda E.; McCabe, Kathryn L.; Daly, Eileen; Gudbrandsen, Maria; Murphy, Clodagh M.; Murphy, Declan; Craig, Michael; Emanuel, Beverly; McDonald-McGinn, Donna M.; Vorstman, Jacob A.S.; Fiksinski, Ania M.; Koops, Sanne; Ruparel, Kosha; Roalf, David; Gur, Raquel E.; Eric Schmitt, J.; Simon, Tony J.; Goodrich-Hunsaker, Naomi J.; Durdle, Courtney A.; Doherty, Joanne L.; Cunningham, Adam C.; van den Bree, Marianne; Linden, David E.J.; Owen, Michael; Moss, Hayley; Kelly, Sinead; Donohoe, Gary; Murphy, Kieran C.; Arango, Celso; Jahanshad, Neda; Thompson, Paul M.; Bearden, Carrie E.

In: Molecular Psychiatry, 01.01.2019.

Research output: Contribution to journalArticle

Villalón-Reina, JE, Martínez, K, Qu, X, Ching, CRK, Nir, TM, Kothapalli, D, Corbin, C, Sun, D, Lin, A, Forsyth, JK, Kushan, L, Vajdi, A, Jalbrzikowski, M, Hansen, L, Jonas, RK, van Amelsvoort, T, Bakker, G, Kates, WR, Antshel, KM, Fremont, W, Campbell, LE, McCabe, KL, Daly, E, Gudbrandsen, M, Murphy, CM, Murphy, D, Craig, M, Emanuel, B, McDonald-McGinn, DM, Vorstman, JAS, Fiksinski, AM, Koops, S, Ruparel, K, Roalf, D, Gur, RE, Eric Schmitt, J, Simon, TJ, Goodrich-Hunsaker, NJ, Durdle, CA, Doherty, JL, Cunningham, AC, van den Bree, M, Linden, DEJ, Owen, M, Moss, H, Kelly, S, Donohoe, G, Murphy, KC, Arango, C, Jahanshad, N, Thompson, PM & Bearden, CE 2019, 'Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study', Molecular Psychiatry. https://doi.org/10.1038/s41380-019-0450-0
Villalón-Reina, Julio E. ; Martínez, Kenia ; Qu, Xiaoping ; Ching, Christopher R.K. ; Nir, Talia M. ; Kothapalli, Deydeep ; Corbin, Conor ; Sun, Daqiang ; Lin, Amy ; Forsyth, Jennifer K. ; Kushan, Leila ; Vajdi, Ariana ; Jalbrzikowski, Maria ; Hansen, Laura ; Jonas, Rachel K. ; van Amelsvoort, Therese ; Bakker, Geor ; Kates, Wendy R. ; Antshel, Kevin M. ; Fremont, Wanda ; Campbell, Linda E. ; McCabe, Kathryn L. ; Daly, Eileen ; Gudbrandsen, Maria ; Murphy, Clodagh M. ; Murphy, Declan ; Craig, Michael ; Emanuel, Beverly ; McDonald-McGinn, Donna M. ; Vorstman, Jacob A.S. ; Fiksinski, Ania M. ; Koops, Sanne ; Ruparel, Kosha ; Roalf, David ; Gur, Raquel E. ; Eric Schmitt, J. ; Simon, Tony J. ; Goodrich-Hunsaker, Naomi J. ; Durdle, Courtney A. ; Doherty, Joanne L. ; Cunningham, Adam C. ; van den Bree, Marianne ; Linden, David E.J. ; Owen, Michael ; Moss, Hayley ; Kelly, Sinead ; Donohoe, Gary ; Murphy, Kieran C. ; Arango, Celso ; Jahanshad, Neda ; Thompson, Paul M. ; Bearden, Carrie E. / Altered white matter microstructure in 22q11.2 deletion syndrome : a multisite diffusion tensor imaging study. In: Molecular Psychiatry. 2019.
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abstract = "22q11.2 deletion syndrome (22q11DS)—a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22—is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6–52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen’s d’s ranging from −0.9 to −1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.",
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T1 - Altered white matter microstructure in 22q11.2 deletion syndrome

T2 - a multisite diffusion tensor imaging study

AU - Villalón-Reina, Julio E.

AU - Martínez, Kenia

AU - Qu, Xiaoping

AU - Ching, Christopher R.K.

AU - Nir, Talia M.

AU - Kothapalli, Deydeep

AU - Corbin, Conor

AU - Sun, Daqiang

AU - Lin, Amy

AU - Forsyth, Jennifer K.

AU - Kushan, Leila

AU - Vajdi, Ariana

AU - Jalbrzikowski, Maria

AU - Hansen, Laura

AU - Jonas, Rachel K.

AU - van Amelsvoort, Therese

AU - Bakker, Geor

AU - Kates, Wendy R.

AU - Antshel, Kevin M.

AU - Fremont, Wanda

AU - Campbell, Linda E.

AU - McCabe, Kathryn L.

AU - Daly, Eileen

AU - Gudbrandsen, Maria

AU - Murphy, Clodagh M.

AU - Murphy, Declan

AU - Craig, Michael

AU - Emanuel, Beverly

AU - McDonald-McGinn, Donna M.

AU - Vorstman, Jacob A.S.

AU - Fiksinski, Ania M.

AU - Koops, Sanne

AU - Ruparel, Kosha

AU - Roalf, David

AU - Gur, Raquel E.

AU - Eric Schmitt, J.

AU - Simon, Tony J.

AU - Goodrich-Hunsaker, Naomi J.

AU - Durdle, Courtney A.

AU - Doherty, Joanne L.

AU - Cunningham, Adam C.

AU - van den Bree, Marianne

AU - Linden, David E.J.

AU - Owen, Michael

AU - Moss, Hayley

AU - Kelly, Sinead

AU - Donohoe, Gary

AU - Murphy, Kieran C.

AU - Arango, Celso

AU - Jahanshad, Neda

AU - Thompson, Paul M.

AU - Bearden, Carrie E.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 22q11.2 deletion syndrome (22q11DS)—a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22—is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6–52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen’s d’s ranging from −0.9 to −1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.

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