When Defense Becomes Compulsion: An Evolutionary and Circuit Framework for Obsessive-Compulsive Disorder

AI Summary

OCD reflects pathological dysregulation of neural systems that normally support adaptive defence, reframing compulsions as maladaptive defensive responses.
Defensive control is organised into threat appraisal, action selection and execution, and post defence safety assessment, each with distinct circuit dysfunctions.
Stage-specific mechanisms include heightened cue salience, intolerance of uncertainty and corticostriatal habit biases, plus impaired safety learning preventing completion signals.

TL;DR (AI Generated)

Integrating evidence from human studies with circuit-level findings from rodent studies, we organize defensive control into three sequential but interacting stages: threat appraisal, defensive action selection and execution, and post-defense safety assessment.

Following defensive action, impaired outcome evaluation and safety-state updating may prevent successful actions from generating stable signals of safety or completion, allowing defensive responding to persist despite objective threat reduction.

By organizing OCD-related circuitry according to when it contributes to defensive processing rather than solely where abnormalities occur, this framework integrates threat-based, corticostriatal, habit, and safety-learning accounts into a process-based model of how adaptive defense may transition into persistent compulsive behavior.

Basic summary

Neurosci Biobehav Rev. 2026 Nov 7:107084. doi: 10.1016/j.neubiorev.2026.107084. Online ahead of print.

ABSTRACT

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive behaviors that are frequently organized around preventing potential harm. Although existing neurobiological models have focused on abnormalities in cortico-striato-thalamo-cortical circuits, habit formation, and cognitive control, they provide a less complete explanation for why compulsions preferentially take the form of precautionary actions. Here, we propose an evolutionary and circuit-level framework in which compulsive behavior is understood as a pathological dysregulation of neural systems that normally support adaptive defense. Integrating evidence from human studies with circuit-level findings from rodent studies, we organize defensive control into three sequential but interacting stages: threat appraisal, defensive action selection and execution, and post-defense safety assessment. During threat appraisal, abnormalities in sensory salience, threat valuation, contextual gating, and interoceptive processing may increase the salience or threat value of ambiguous cues. During action selection and execution, intolerance of uncertainty, impaired behavioral flexibility, corticostriatal dysfunction, and negative reinforcement may bias behavior toward premature and repetitive threat-reducing actions that can become increasingly habitual. Following defensive action, impaired outcome evaluation and safety-state updating may prevent successful actions from generating stable signals of safety or completion, allowing defensive responding to persist despite objective threat reduction. By organizing OCD-related circuitry according to when it contributes to defensive processing rather than solely where abnormalities occur, this framework integrates threat-based, corticostriatal, habit, and safety-learning accounts into a process-based model of how adaptive defense may transition into persistent compulsive behavior. This framework may help map stage-specific dysfunction onto symptom heterogeneity and guide more targeted interventions.

PMID:42998778 | DOI:10.1016/j.neubiorev.2026.107084

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