Reduced sleep efficiency leads to cognitive dysfunction in major depressive disorder via disrupting fronto-visual circuit functional connectivity

BACKGROUND: Reduced sleep efficiency (SE) is common in Major Depressive Disorder (MDD) and correlates with cognitive deficits. However, the underlying neurobiological mechanisms remain inadequately explained. METHODS: Resting-state functional magnetic resonance imaging, event-related potentials (P3a and P3b), and polysomnography data were collected from 102 MDD patients into Low SE group (SE < 90%, n = 54) and Normal SE group (SE ≥ 90%, n = 48). Brain function was evaluated using amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC). Analyses included group comparisons, correlations, and mediation models. RESULTS: Compared to the Normal SE patients, the Low SE patients showed prolonged P3a and P3b latencies, reduced ALFF in the right cuneus and left precuneus, increased ALFF in the right nucleus accumbens, and attenuated FC between the right cuneus and right orbital part of the inferior frontal gyrus and between the right cuneus and left medial superior frontal gyrus. Correlation analyses further revealed negative associations between P3a/P3b latencies and SE. The FC between the right cuneus and right orbital part of the inferior frontal gyrus was positively associated with SE, but was negatively associated with P3a/P3b latencies. Importantly, mediation analysis revealed that within the tested model, this FC statistically fully mediated the association between SE and P3a latency and partially mediated the association between SE and P3b latency. CONCLUSION: Our findings suggest that reduced SE may cause cognitive dysfunction in MDD via disrupting the fronto-visual circuit connectivity, which may expose this circuit as a promising potential therapeutic target for ameliorating sleep-related cognitive deficits in patients with MDD.