The role of stress in the pathogenesis and maintenance of obsessive-compulsive disorder

Abstract

Individuals with OCD often identify psychosocial stress as a factor that exacerbates their symptoms, and many trace the onset of symptoms to a stressful period of life or a discrete traumatic incident. However, the pathophysiological relationship between stress and OCD remains poorly characterized: it is unclear whether trauma or stress is an independent cause of OCD symptoms, a triggering factor that interacts with a preexisting diathesis, or simply a nonspecific factor that can exacerbate OCD along with other aspects of psychiatric symptomatology. Nonetheless, preclinical research has demonstrated that stress has conspicuous effects on corticostriatal and limbic circuitry. Specifically, stress can lead to neuronal atrophy in frontal cortices (particularly the medial prefrontal cortex), the dorsomedial striatum (caudate), and the hippocampus. Stress can also result in neuronal hypertrophy in the dorsolateral striatum (putamen) and amygdala. These neurobiological effects mirror reported neural abnormalities in OCD and may contribute to an imbalance between goal-directed and habitual behavior, an imbalance that is implicated in the pathogenesis and expression of OCD symptomatology. The modulation of corticostriatal and limbic circuits by stress and the resultant imbalance between habit and goal-directed learning and behavior offers a framework for investigating how stress may exacerbate or trigger OCD symptomatology.

Keywords: Corticostriatal-Limbic Circuitry; Goal-Directed; Habit; OCD; Stress.

Figure 1.

Excessive stress adversely affects goal-directed control and enhances habit learning and behavior. This may be partly explained by the demonstrated effects of stress on limbic and cortico-striatal circuitry. More specifically, stress can result in the atrophy of brain regions associated with goal-directed control, shown here in red—the frontal cortex (particularly the medial and orbital frontal regions), hippocampus, and caudate—while also causing hypertrophy in regions associated with habit, shown here in green—the amygdala and putamen. Moreover, stress can disrupt functional connectivity between these various regions. Dysregulation of limbic and cortico-striatal circuitry has repeatedly been demonstrated in OCD. These abnormalities may be related to the neurocognitive impairments implicated in the pathogenesis and maintenance of OCD, including the acquisition, arbitration, and expression of goal-directed and habitual behaviors. Given the likely association between excessive stress and OCD, the adverse effects of stress on corticostriatal-limbic circuitry and the associated disruption in the balance between goal-directed control and habit may play a causal role in the pathogenesis and maintenance of OCD, at least for some patients.