Lower cortical gyrification and connectivity in major depressive disorder associated with cognition deficits and...

This study aimed to compare the local gyrification index (LGI) between first-episode drug-naive major depressive disorder (MDD) patients and healthy controls (HC), to investigate associated alterations in functional connectivity (FC) and effective connectivity (EC), and to examine the relationships of neuroimaging alterations to cognitive performances and to neurotransmitter profiles.

Structural and resting-state functional magnetic resonance imaging were acquired from 159 MDD patients and 141 HC. LGI was calculated using FreeSurfer software. Seed-based FC and EC analyses were performed in regions showing significant group differences in LGI to explore the associated functional alterations. Neuropsychological tests for cognitive function included attention, working memory, processing speed, and executive function. Spatial correlation analysis was performed between LGI alterations and neurotransmitter receptor/transporter density maps.

Compared to HC, MDD patients showed significantly lower LGI in bilateral anterior cingulate cortex (ACC), left medial orbitofrontal cortex (mOFC), left inferior parietal cortex, and right lateral occipital cortex; lower FC between left mOFC and left superior frontal gyrus, and lower EC from left caudal ACC to right middle frontal gyrus. Lower LGI correlated with impaired cognitive performance in attention, working memory, and processing speed in MDD. Spatial patterns of altered LGI were positively correlated with distributions of serotonin transporter, dopamine transporter, acetylcholine transporter, and histamine receptor.

In MDD, impaired LGI in critical regions of the default mode network and occipital cortex is linked to prefrontal network functional dysconnectivity and to cognitive deficits. The spatial relationship of impaired LGI to specific neurotransmitter systems throws light on neurodevelopmental aspects of MDD pathophysiology.