Longitudinal Development of Thalamocortical Functional Connectivity in 22q11.2 Deletion Syndrome
Year: 2023
Type: article
Study design: Observational Study
Abstract: 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: 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: 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: 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.
Authors: Charles H. Schleifer, Kathleen P. O’Hora, Maria Jalbrzikowski, Elizabeth Bondy, Leila Kushan-Wells, Amy Lin, Lucina Q. Uddin, Carrie E. Bearden
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,480
Awards: 3/9 Dissecting the effects of genomic variants on neurobehavioral dimensions in CNVs enriched for neuropsychiatric disorders, Mapping functional brain connectivity, neurodevelopment, and imaging-genetic associations in individuals with genetic and clinical risk factors for neuropsychiatric illness, G5581563115, Neurodevelopment and Psychosis in the 22q11.2 Deletion Syndrome, G8212269863, G8425615888, Training Grant in Neurobehavioral Genetics, Neurodevelopment and Psychosis in the 22q11.2 Copy Number Variants, Predicting psychosis risk in youth using a novel structural neuroimaging score that measures deviation from normative development. Can we bring it to communities using portable, low-field MRI?
OpenAlex ID: W4386648118