Functional connectivity evidence for state-independent executive function deficits in patients with major depressive disorder.

Background: Persistent neurocognitive deficits are often associated with poor outcomes of major depressive disorder (MDD). Executive dysfunction is the most common cognitive deficit in MDD. However, it remains unclear which subcomponent of executive dysfunction is state-independent with distinct neural substrates.

Methods: A comprehensive neurocognitive test battery was used to assess four subcomponents of executive function (working memory, inhibition, shifting, and verbal fluency) in 95 MDD patients and 111 matched healthy controls (HCs). After 6 months of paroxetine treatment, 56 patients achieved clinical remission (rMDD) and completed the second-time neurocognitive test. Network-based statistics analysis was utilized to explore the changes in functional connectivity (FC).

Results: Compared with the HCs, all the four subcomponents of MDD patients were significantly impaired. After treatment, there was a significant improvement in working memory, inhibition, and verbal fluency in the rMDD group. And shifting and verbal fluency of the rMDD group remained impaired compared with the HCs. Fifteen functional connections were interrupted in the MDD group, and 11 connections remained in a disrupted state after treatment. Importantly, verbal fluency was negatively correlated with the disrupted FC between the right dorsal prefrontal cortex and the left inferior parietal lobule in patients with MDD and remitted MDD.

Limitations: The correlation analysis of the association between cognitive impairment and connectivity alterations precluded us from making causal inferences.

Conclusions: Verbal fluency is the potential state-independent cognitive deficit with distinct neural basis in patients with MDD.