[article]
| Titre : |
Evidence of neurocognitive and resting state functional connectivity differences in carriers of NRXN1 deletions |
| Type de document : |
texte imprimé |
| Auteurs : |
Jacqueline FITZGERALD, Auteur ; Ciara J. MOLLOY, Auteur ; Thomas DINNEEN, Auteur ; Niamh E. FEERICK, Auteur ; Matthew O'SULLIVAN, Auteur ; Richard O'CONAILL, Auteur ; Maryam AL-SHEHHI, Auteur ; Richard REILLY, Auteur ; Sally Ann LYNCH, Auteur ; Eleisa A. HERON, Auteur ; Clare KELLY, Auteur ; Sanbing SHEN, Auteur ; Louise GALLAGHER, Auteur |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Humans Female Male Magnetic Resonance Imaging Adult Young Adult Calcium-Binding Proteins/genetics Diffusion Tensor Imaging Brain/diagnostic imaging/physiopathology Neural Cell Adhesion Molecules/genetics Adolescent Cell Adhesion Molecules, Neuronal/genetics Cognition/physiology Neuropsychological Tests Gene Deletion Neural Pathways/diagnostic imaging/physiopathology Executive Function/physiology Cognition Copy number variant NRXN1 deletion Neuroimaging the study was obtained from St. James’s Hospital/Tallaght University Hospital Research Ethics Committee (REC reference: 2015/03/01). Participants over 18 years provided written consent and parental written consent was provided for those under 18 years. Consent for publication: All authors who contributed to the article have approved the submitted version. Competing interests: The authors declare no competing interests. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: NRXN1 deletion (NRXN1 del) is a rare copy number variant associated with several neurodevelopmental, neuropsychiatric, and cognitive outcomes. The NRXN1 gene encodes for a pre-synaptic cell adhesion molecule that is important for synapse formation, regulation and neurotransmission. We used a gene-first approach to investigate neurocognitive and brain phenotypes in NRXN1 del carriers. METHODS: Forty-two participants (21 NRXN1 del carriers and 21 neurotypical age and sex-matched comparisons) completed IQ assessments, and a neurocognitive battery, including, executive function, attention, and social cognition tasks. Magnetic resonance imaging (MRI) data, including T1-weighted anatomical scans, resting state functional MRI and diffusion tensor imaging, were acquired in 36 participants (17 NRXN1 del carriers and 19 comparisons). RESULTS: NRXN1 del carriers had lower mean IQ and poorer spatial working memory performance compared to comparisons (p ≤ 0.05). Neuroimaging results revealed group differences in visual and ventral attention resting state networks (p < 0.05). Network-based statistical analysis showed a significant effect of group status for 28/115 connections, with poorer segregation between visual and default networks in NRXN1 del carriers relative to comparisons. No differences in brain structural volume or cortical thickness, or diffusion measures of white matter structural architecture were observed between groups. CONCLUSIONS: This exploratory study provides evidence for neurocognitive impacts and brain functional differences related to underlying synaptic mechanisms. Brain functional differences in NRXN1 del carriers may support altered excitation/inhibition dynamics within the brain. Gene-first approaches may establish brain-based translational markers to identify neurobiologically informed subgroups within neurodevelopmental and neuropsychiatric conditions, and ultimately transdiagnostic therapeutic strategies. |
| En ligne : |
https://dx.doi.org/10.1186/s11689-025-09625-5 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 |
in Journal of Neurodevelopmental Disorders > 17 (2025)
[article] Evidence of neurocognitive and resting state functional connectivity differences in carriers of NRXN1 deletions [texte imprimé] / Jacqueline FITZGERALD, Auteur ; Ciara J. MOLLOY, Auteur ; Thomas DINNEEN, Auteur ; Niamh E. FEERICK, Auteur ; Matthew O'SULLIVAN, Auteur ; Richard O'CONAILL, Auteur ; Maryam AL-SHEHHI, Auteur ; Richard REILLY, Auteur ; Sally Ann LYNCH, Auteur ; Eleisa A. HERON, Auteur ; Clare KELLY, Auteur ; Sanbing SHEN, Auteur ; Louise GALLAGHER, Auteur. Langues : Anglais ( eng) in Journal of Neurodevelopmental Disorders > 17 (2025)
| Mots-clés : |
Humans Female Male Magnetic Resonance Imaging Adult Young Adult Calcium-Binding Proteins/genetics Diffusion Tensor Imaging Brain/diagnostic imaging/physiopathology Neural Cell Adhesion Molecules/genetics Adolescent Cell Adhesion Molecules, Neuronal/genetics Cognition/physiology Neuropsychological Tests Gene Deletion Neural Pathways/diagnostic imaging/physiopathology Executive Function/physiology Cognition Copy number variant NRXN1 deletion Neuroimaging the study was obtained from St. James’s Hospital/Tallaght University Hospital Research Ethics Committee (REC reference: 2015/03/01). Participants over 18 years provided written consent and parental written consent was provided for those under 18 years. Consent for publication: All authors who contributed to the article have approved the submitted version. Competing interests: The authors declare no competing interests. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: NRXN1 deletion (NRXN1 del) is a rare copy number variant associated with several neurodevelopmental, neuropsychiatric, and cognitive outcomes. The NRXN1 gene encodes for a pre-synaptic cell adhesion molecule that is important for synapse formation, regulation and neurotransmission. We used a gene-first approach to investigate neurocognitive and brain phenotypes in NRXN1 del carriers. METHODS: Forty-two participants (21 NRXN1 del carriers and 21 neurotypical age and sex-matched comparisons) completed IQ assessments, and a neurocognitive battery, including, executive function, attention, and social cognition tasks. Magnetic resonance imaging (MRI) data, including T1-weighted anatomical scans, resting state functional MRI and diffusion tensor imaging, were acquired in 36 participants (17 NRXN1 del carriers and 19 comparisons). RESULTS: NRXN1 del carriers had lower mean IQ and poorer spatial working memory performance compared to comparisons (p ≤ 0.05). Neuroimaging results revealed group differences in visual and ventral attention resting state networks (p < 0.05). Network-based statistical analysis showed a significant effect of group status for 28/115 connections, with poorer segregation between visual and default networks in NRXN1 del carriers relative to comparisons. No differences in brain structural volume or cortical thickness, or diffusion measures of white matter structural architecture were observed between groups. CONCLUSIONS: This exploratory study provides evidence for neurocognitive impacts and brain functional differences related to underlying synaptic mechanisms. Brain functional differences in NRXN1 del carriers may support altered excitation/inhibition dynamics within the brain. Gene-first approaches may establish brain-based translational markers to identify neurobiologically informed subgroups within neurodevelopmental and neuropsychiatric conditions, and ultimately transdiagnostic therapeutic strategies. |
| En ligne : |
https://dx.doi.org/10.1186/s11689-025-09625-5 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 |
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