Longitudinal Development of Thalamocortical Functional Connectivity in 22q11.2 Deletion Syndrome.

Autism Copy number variant Neurodevelopment Psychosis Thalamus fMRI

Journal

Biological psychiatry. Cognitive neuroscience and neuroimaging
ISSN: 2451-9030
Titre abrégé: Biol Psychiatry Cogn Neurosci Neuroimaging
Pays: United States
ID NLM: 101671285

Informations de publication

Date de publication:
12 Sep 2023
Historique:
received: 28 07 2023
revised: 15 08 2023
accepted: 04 09 2023
pubmed: 15 9 2023
medline: 15 9 2023
entrez: 14 9 2023
Statut: aheadofprint

Résumé

The 22q11.2 deletion syndrome (22qDel) is a genetic copy number variant that strongly increases risk for schizophrenia and other neurodevelopmental disorders. Disrupted functional connectivity between the thalamus and the somatomotor/frontoparietal cortex has been implicated in cross-sectional studies of 22qDel, idiopathic schizophrenia, and youths at clinical high risk for psychosis. Here, we used a novel functional atlas approach to investigate longitudinal age-related changes in network-specific thalamocortical functional connectivity (TCC) in participants with 22qDel and typically developing (TD) control participants. TCC was calculated for 9 functional networks derived from resting-state functional magnetic resonance imaging scans collected from 65 participants with 22qDel (63.1% female) and 69 demographically matched TD control participants (49.3% female) ages 6 to 23 years. Analyses included 86 longitudinal follow-up scans. Nonlinear age trajectories were characterized with generalized additive mixed models. In participants with 22qDel, TCC in the frontoparietal network increased until approximately age 13, while somatomotor TCC and cingulo-opercular TCC decreased from age 6 to 23. In contrast, no significant relationships between TCC and age were found in TD control participants. Somatomotor connectivity was significantly higher in participants with 22qDel than in TD control participants in childhood, but lower in late adolescence. Frontoparietal TCC showed the opposite pattern. 22qDel is associated with aberrant development of functional network connectivity between the thalamus and cortex. Younger individuals with 22qDel have lower frontoparietal connectivity and higher somatomotor connectivity than control individuals, but this phenotype may normalize or partially reverse by early adulthood. Altered maturation of this circuitry may underlie elevated neuropsychiatric disease risk in this syndrome.

Sections du résumé

BACKGROUND BACKGROUND
The 22q11.2 deletion syndrome (22qDel) is a genetic copy number variant that strongly increases risk for schizophrenia and other neurodevelopmental disorders. Disrupted functional connectivity between the thalamus and the somatomotor/frontoparietal cortex has been implicated in cross-sectional studies of 22qDel, idiopathic schizophrenia, and youths at clinical high risk for psychosis. Here, we used a novel functional atlas approach to investigate longitudinal age-related changes in network-specific thalamocortical functional connectivity (TCC) in participants with 22qDel and typically developing (TD) control participants.
METHODS METHODS
TCC was calculated for 9 functional networks derived from resting-state functional magnetic resonance imaging scans collected from 65 participants with 22qDel (63.1% female) and 69 demographically matched TD control participants (49.3% female) ages 6 to 23 years. Analyses included 86 longitudinal follow-up scans. Nonlinear age trajectories were characterized with generalized additive mixed models.
RESULTS RESULTS
In participants with 22qDel, TCC in the frontoparietal network increased until approximately age 13, while somatomotor TCC and cingulo-opercular TCC decreased from age 6 to 23. In contrast, no significant relationships between TCC and age were found in TD control participants. Somatomotor connectivity was significantly higher in participants with 22qDel than in TD control participants in childhood, but lower in late adolescence. Frontoparietal TCC showed the opposite pattern.
CONCLUSIONS CONCLUSIONS
22qDel is associated with aberrant development of functional network connectivity between the thalamus and cortex. Younger individuals with 22qDel have lower frontoparietal connectivity and higher somatomotor connectivity than control individuals, but this phenotype may normalize or partially reverse by early adulthood. Altered maturation of this circuitry may underlie elevated neuropsychiatric disease risk in this syndrome.

Identifiants

DOI: 10.1016/j.bpsc.2023.09.001 PMID: 37709253
pubmed: 37709253
pii: S2451-9022(23)00239-2
doi: 10.1016/j.bpsc.2023.09.001
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Auteurs

Charles H Schleifer (CH)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California. Electronic address: cschleifer@mednet.ucla.edu.

Kathleen P O'Hora (KP)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.

Maria Jalbrzikowski (M)

Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts.

Elizabeth Bondy (E)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.

Leila Kushan-Wells (L)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.

Amy Lin (A)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California.

Lucina Q Uddin (LQ)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California; Department of Psychology, University of California, Los Angeles, Los Angeles, California.

Carrie E Bearden (CE)

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California; Department of Psychology, University of California, Los Angeles, Los Angeles, California. Electronic address: cbearden@mednet.ucla.edu.

Classifications MeSH