Shared and Anxiety-Specific Pediatric Psychopathology Dimensions Manifest Distributed Neural Correlates.
Anxiety
Disruptive behavior
Intrinsic brain connectivity
Irritability
Joint canonical correlation and independent component analysis
Youth
Journal
Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264
Informations de publication
Date de publication:
15 03 2021
15 03 2021
Historique:
received:
13
03
2020
revised:
16
10
2020
accepted:
27
10
2020
pubmed:
3
1
2021
medline:
24
4
2021
entrez:
2
1
2021
Statut:
ppublish
Résumé
Imaging research has not yet delivered reliable psychiatric biomarkers. One challenge, particularly among youth, is high comorbidity. This challenge might be met through canonical correlation analysis designed to model mutual dependencies between symptom dimensions and neural measures. We mapped the multivariate associations that intrinsic functional connectivity manifests with pediatric symptoms of anxiety, irritability, and attention-deficit/hyperactivity disorder (ADHD) as common, impactful, co-occurring problems. We evaluate the replicability of such latent dimensions in an independent sample. We obtained ratings of anxiety, irritability, and ADHD, and 10 minutes of resting-state functional magnetic resonance imaging data, from two independent cohorts. Both cohorts (discovery: n = 182; replication: n = 326) included treatment-seeking youth with anxiety disorders, with disruptive mood dysregulation disorder, with ADHD, or without psychopathology. Functional connectivity was modeled as partial correlations among 216 brain areas. Using canonical correlation analysis and independent component analysis jointly we sought maximally correlated, maximally interpretable latent dimensions of brain connectivity and clinical symptoms. We identified seven canonical variates in the discovery and five in the replication cohort. Of these canonical variates, three exhibited similarities across datasets: two variates consistently captured shared aspects of irritability, ADHD, and anxiety, while the third was specific to anxiety. Across cohorts, canonical variates did not relate to specific resting-state networks but comprised edges interconnecting established networks within and across both hemispheres. Findings revealed two replicable types of clinical variates, one related to multiple symptom dimensions and a second relatively specific to anxiety. Both types involved a multitude of broadly distributed, weak brain connections as opposed to strong connections encompassing known resting-state networks.
Sections du résumé
BACKGROUND
Imaging research has not yet delivered reliable psychiatric biomarkers. One challenge, particularly among youth, is high comorbidity. This challenge might be met through canonical correlation analysis designed to model mutual dependencies between symptom dimensions and neural measures. We mapped the multivariate associations that intrinsic functional connectivity manifests with pediatric symptoms of anxiety, irritability, and attention-deficit/hyperactivity disorder (ADHD) as common, impactful, co-occurring problems. We evaluate the replicability of such latent dimensions in an independent sample.
METHODS
We obtained ratings of anxiety, irritability, and ADHD, and 10 minutes of resting-state functional magnetic resonance imaging data, from two independent cohorts. Both cohorts (discovery: n = 182; replication: n = 326) included treatment-seeking youth with anxiety disorders, with disruptive mood dysregulation disorder, with ADHD, or without psychopathology. Functional connectivity was modeled as partial correlations among 216 brain areas. Using canonical correlation analysis and independent component analysis jointly we sought maximally correlated, maximally interpretable latent dimensions of brain connectivity and clinical symptoms.
RESULTS
We identified seven canonical variates in the discovery and five in the replication cohort. Of these canonical variates, three exhibited similarities across datasets: two variates consistently captured shared aspects of irritability, ADHD, and anxiety, while the third was specific to anxiety. Across cohorts, canonical variates did not relate to specific resting-state networks but comprised edges interconnecting established networks within and across both hemispheres.
CONCLUSIONS
Findings revealed two replicable types of clinical variates, one related to multiple symptom dimensions and a second relatively specific to anxiety. Both types involved a multitude of broadly distributed, weak brain connections as opposed to strong connections encompassing known resting-state networks.
Identifiants
pubmed: 33386133
pii: S0006-3223(20)32043-6
doi: 10.1016/j.biopsych.2020.10.018
pmc: PMC7889729
mid: NIHMS1645094
pii:
doi:
Banques de données
ClinicalTrials.gov
['NCT02531893', 'NCT00025935', 'NCT00018057']
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
579-587Subventions
Organisme : Intramural NIH HHS
ID : ZIA MH002778
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA MH002782
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA MH002786
Pays : United States
Informations de copyright
Published by Elsevier Inc.
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