Sleep phase delay exacerbates treatment resistance in obsessive-compulsive disorder via elevated anterior cingulate...

Sleep phase delay (SPD) is a common comorbidity in patients with obsessive-compulsive disorder (OCD) and may affect the severity of OC symptoms and treatment response. This study aimed to explore the concentration of neurometabolites in the anterior cingulate cortex (ACC) of OCD patients with sleep phase delay, with a particular focus on the mediating role of ACC glutamate concentration to further understand the relationship between sleep phase delay and OCD.

94 participants (61 OCD patients and 33 healthy controls) underwent clinical assessments and imaging tests. Resting-state and functional-state magnetic resonance spectroscopy (MRS) was conducted to assess ACC neurochemical profiles. We compared clinical features and ACC neurometabolites among healthy controls, OCD patients with and without sleep phase delay. Mediation models were constructed to examine the mediating role of ACC glutamate.

Compared with OCD patients without sleep phase delay, OCD patients with sleep phase delay had higher PSQI scores, lower MEQ scores, higher Y-BOCS scores, and a higher proportion of treatment-resistant cases. In both resting-state and functional-state MRS, the concentrations of Glu and Glx in OCD patients with sleep phase delay were significantly higher than those in patients without sleep phase delay, but were not significantly different from those in healthy controls. Mediation analysis showed that resting-state Glu mediated the association between sleep phase delay treatment resistance in OCD.

Our findings indicate that glutamate concentration in the ACC serves as a key mediator in the relationship between delayed sleep phase and treatment resistance in OCD. Specifically, delayed sleep phase may exacerbate treatment resistance in OCD by elevating ACC glutamate levels, thereby identifying a novel neurobiological pathway.