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

Merage Ghane; Lucas Trambaiolli; Michele A Bertocci; Freddyson J Martinez-Rivera; Henry W Chase; Tyler Brady; Alex Skeba; Simona Graur; Lisa Bonar; Satish Iyengar; Gregory J Quirk; Steven A Rasmussen; Suzanne N Haber; Mary L Phillips

doi:10.1016/j.biopsych.2023.12.027

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

Biol Psychiatry. 2024 Feb 7:S0006-3223(24)00078-7. doi: 10.1016/j.biopsych.2023.12.027. Online ahead of print.

Affiliations

¹ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA. Electronic address: ghaneezabadim@upmc.edu.
² Department of Psychiatry, McLean Hospital, Harvard Medical School, Boston, MA.
³ Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.
⁴ 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).
⁵ Department of Statistics, University of Pittsburgh, Pittsburgh, PA, NY.
⁶ School of Medicine, University of Puerto Rico, San Juan, PR.
⁷ Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI.
⁸ Department of Psychiatry, McLean Hospital, Harvard Medical School, Boston, MA; School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY.

PMID: 38336216
DOI: 10.1016/j.biopsych.2023.12.027

Abstract

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: 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: 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: 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.

Keywords: BLA; Harm Avoidance; OCD; Persistent Avoidance; dACC; resting-state functional connectivity.