Longitudinal trajectories of cortical development in 22q11.2 copy number variants and typically developing controls.
Mol Psychiatry
; 27(10): 4181-4190, 2022 10.
Article
em En
| MEDLINE
| ID: mdl-35896619
ABSTRACT
Probing naturally-occurring, reciprocal genomic copy number variations (CNVs) may help us understand mechanisms that underlie deviations from typical brain development. Cross-sectional studies have identified prominent reductions in cortical surface area (SA) and increased cortical thickness (CT) in 22q11.2 deletion carriers (22qDel), with the opposite pattern in duplication carriers (22qDup), but the longitudinal trajectories of these anomalies-and their relationship to clinical symptomatology-are unknown. Here, we examined neuroanatomic changes within a longitudinal cohort of 261 22q11.2 CNV carriers and demographically-matched typically developing (TD) controls (84 22qDel, 34 22qDup, and 143 TD; mean age 18.35, ±10.67 years; 50.47% female). A total of 431 magnetic resonance imaging scans (164 22qDel, 59 22qDup, and 208 TD control scans; mean interscan interval = 20.27 months) were examined. Longitudinal FreeSurfer analysis pipelines were used to parcellate the cortex and calculate average CT and SA for each region. First, general additive mixed models (GAMMs) were used to identify regions with between-group differences in developmental trajectories. Secondly, we investigated whether these trajectories were associated with clinical outcomes. Developmental trajectories of CT were more protracted in 22qDel relative to TD and 22qDup. 22qDup failed to show normative age-related SA decreases. 22qDel individuals with psychosis spectrum symptoms showed two distinct periods of altered CT trajectories relative to 22qDel without psychotic symptoms. In contrast, 22q11.2 CNV carriers with autism spectrum diagnoses showed early alterations in SA trajectories. Collectively, these results provide new insights into altered neurodevelopment in 22q11.2 CNV carriers, which may shed light on neural mechanisms underlying distinct clinical outcomes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transtornos Psicóticos
/
Variações do Número de Cópias de DNA
Tipo de estudo:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Mol Psychiatry
Assunto da revista:
BIOLOGIA MOLECULAR
/
PSIQUIATRIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos