Specific patterns of endogenous functional connectivity are associated with harm avoidance in OCD.

BLA Harm Avoidance OCD Persistent Avoidance dACC resting-state functional connectivity

Journal

Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264

Informations de publication

Date de publication:
07 Feb 2024
Historique:
received: 07 07 2023
revised: 11 11 2023
accepted: 06 12 2023
medline: 10 2 2024
pubmed: 10 2 2024
entrez: 9 2 2024
Statut: aheadofprint

Résumé

Individuals with OCD show persistent-avoidance behaviors, often in the absence of actual threat. Quality-of-life costs and heterogeneity support the need for novel brain-behavior intervention targets. Informed by mechanistic and anatomic studies of persistent-avoidance in rodents and non-human primates, our goal was to test whether connections within a hypothesized persistent-avoidance related network predicted OCD-related harm-avoidance (HA), a trait measure of persistent-avoidance. We hypothesized that 1)HA, not OCD diagnosis, would be associated with altered endogenous connectivity in at least one connection in the network; 2)HA-specific findings would be robust to comorbid symptoms; and 3)reliable findings would replicate in an holdout testing subsample. Using resting-state fcMRI, cross-validated elastic-net for feature selection and Poisson generalized linear models, we tested which connections significantly predicted HA in our training subsample(n=73;71.8% Female;nHC=36,nOCD=37); robustness to comorbidities; and replicability in a testing subsample(n=30;56.7% Female;nHC=15,nOCD=15). Stronger inverse connectivity between right dorsal anterior cingulate and right basolateral-amygdala (R_dACC-R_BLA) and stronger positive connectivity between right ventral anterior insula and left ventral-striatum (R_vaIns-L_VS) were associated with greater HA across groups. Network connections did not discriminate OCD diagnosis or predict HA-correlated traits, suggesting sensitivity to trait HA. The dACC-BLA relationship was robust to controlling for comorbidities and medication in individuals with OCD and was also predictive of HA in our testing subsample. Stronger inverse dACC-BLA connectivity was robustly and reliably associated with HA across groups and in OCD. Results support the relevance of a cross-species persistent-avoidance-related network to OCD, with implications for precision-based approaches and treatment.

Sections du résumé

BACKGROUND BACKGROUND
Individuals with OCD show persistent-avoidance behaviors, often in the absence of actual threat. Quality-of-life costs and heterogeneity support the need for novel brain-behavior intervention targets. Informed by mechanistic and anatomic studies of persistent-avoidance in rodents and non-human primates, our goal was to test whether connections within a hypothesized persistent-avoidance related network predicted OCD-related harm-avoidance (HA), a trait measure of persistent-avoidance. We hypothesized that 1)HA, not OCD diagnosis, would be associated with altered endogenous connectivity in at least one connection in the network; 2)HA-specific findings would be robust to comorbid symptoms; and 3)reliable findings would replicate in an holdout testing subsample.
METHODS METHODS
Using resting-state fcMRI, cross-validated elastic-net for feature selection and Poisson generalized linear models, we tested which connections significantly predicted HA in our training subsample(n=73;71.8% Female;nHC=36,nOCD=37); robustness to comorbidities; and replicability in a testing subsample(n=30;56.7% Female;nHC=15,nOCD=15).
RESULTS RESULTS
Stronger inverse connectivity between right dorsal anterior cingulate and right basolateral-amygdala (R_dACC-R_BLA) and stronger positive connectivity between right ventral anterior insula and left ventral-striatum (R_vaIns-L_VS) were associated with greater HA across groups. Network connections did not discriminate OCD diagnosis or predict HA-correlated traits, suggesting sensitivity to trait HA. The dACC-BLA relationship was robust to controlling for comorbidities and medication in individuals with OCD and was also predictive of HA in our testing subsample.
CONCLUSION CONCLUSIONS
Stronger inverse dACC-BLA connectivity was robustly and reliably associated with HA across groups and in OCD. Results support the relevance of a cross-species persistent-avoidance-related network to OCD, with implications for precision-based approaches and treatment.

Identifiants

pubmed: 38336216
pii: S0006-3223(24)00078-7
doi: 10.1016/j.biopsych.2023.12.027
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Merage Ghane (M)

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA. Electronic address: ghaneezabadim@upmc.edu.

Lucas Trambaiolli (L)

Department of Psychiatry, McLean Hospital, Harvard Medical School, Boston, MA.

Michele A Bertocci (MA)

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Freddyson J Martinez-Rivera (FJ)

Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine Mount Sinai, New York, NY (FJM currently at Department of Neuroscience, University of Florida, Gainesville, FL).

Henry W Chase (HW)

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Tyler Brady (T)

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Alex Skeba (A)

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Simona Graur (S)

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Lisa Bonar (L)

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Satish Iyengar (S)

Department of Statistics, University of Pittsburgh, Pittsburgh, PA, NY.

Gregory J Quirk (GJ)

School of Medicine, University of Puerto Rico, San Juan, PR.

Steven A Rasmussen (SA)

Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI.

Suzanne N Haber (SN)

Department of Psychiatry, McLean Hospital, Harvard Medical School, Boston, MA; School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY.

Mary L Phillips (ML)

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Classifications MeSH