Prefrontal dysfunction and neurotransmitter imbalances underlying cognitive fusion in first-episode drug-naïve...

This study aimed to investigate the neural correlates of cognitive fusion (CF) in drug-naïve patients with obsessive-compulsive disorder (OCD) and to explore the potential involvement of neurotransmitter systems in these abnormalities.

Following quality control, 54 first-episode, drug-naïve OCD patients and 56 matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) scanning. The amplitude of low-frequency fluctuations (ALFF) and functional connectivity analyses were performed to examine differences in brain activity between the groups. Clinical assessments, including the Yale-Brown Obsessive Compulsive Scale, Beck Anxiety Inventory, Beck Depression Inventory, and CF questionnaire, were administered to measure the severity of obsessive-compulsive, anxiety, and depressive symptoms, as well as CF levels. Mediation and correlation analyses were conducted to explore the relationships between brain activity, CF, and OCD symptoms. Additionally, spatial correlation analyses were conducted to investigate the relationship between neural abnormalities and neurotransmitter systems.

OCD patients exhibited elevated ALFF in prefrontal regions. Crucially, the activity of the left dorsolateral superior frontal gyrus (SFGdl) mediated 45.11 % of CF's effect on obsessive-compulsive symptoms (indirect effect = 0.060, 95 %CI = [0.005,0.133]). Moreover, neurochemical analysis revealed significant negative correlations between regional ALFF in the left SFGdl and neurotransmitter systems, including dopamine, acetylcholine, and glutamate.

Our findings suggest that CF is associated with altered brain activity in prefrontal regions, which may contribute to the cognitive and emotional dysfunction observed in OCD. The negative correlations between these neural abnormalities and neurotransmitter systems provide further insight into the neurochemical mechanisms underlying OCD. These results offer novel perspectives on the pathophysiology of OCD and highlight potential targets for future therapeutic interventions.