Abstract
Investigation of brain changes in functional connectivity and functional network topology from receiving 8-week selective serotonin reuptake inhibitor (SSRI) treatments is conducted in 12 unmedicated adolescents with major depressive disorder (MDD) by using wavelet-filtered resting-state functional magnetic resonance imaging (fMRI). Changes are observed in frontal-limbic, temporal, and default mode networks. In particular, topological analysis shows, at the global scale and in the 0.12–0.25 Hz band, that the normalized clustering coefficient and smallworldness of brain networks decreased after treatment. Regional changes in clustering coefficient and efficiency were observed in the bilateral caudal middle frontal gyrus, rostral middle frontal gyrus, superior temporal gyrus, left pars triangularis, putamen, and right superior frontal gyrus. Furthermore, changes of nodal centrality and changes of connectivity associated with these frontal and temporal regions confirm the global topological alternations. Moreover, frequency dependence is observed from FDR-controlled subnetworks for the limbic-cortical connectivity change. In the high-frequency band, the altered connections involve mostly frontal regions, while the altered connections in the low-frequency bands spread to parietal and temporal areas. Due to the limitation of small sample sizes and lack of placebo control, these preliminary findings require confirmation with future work using larger samples. Confirmation of biomarkers associated with treatment could suggest potential avenues for clinical applications such as tracking treatment response and neurobiologically informed treatment optimization.
Highlights
Major depressive disorder (MDD) is a highly debilitating condition that can result in tragic outcomes such as chronic disability and suicide
This study aims to discover treatment-related changes in brain functional network topology and whole-brain connectivity for 12 unmedicated adolescents with MDD before and after receiving an 8-week selective serotonin reuptake inhibitor (SSRI) medication treatment
The increased clustering coefficient and smallworldness indicate that core network topology has changed toward a small world network that is commonly observed from human brain networks
Summary
Major depressive disorder (MDD) is a highly debilitating condition that can result in tragic outcomes such as chronic disability and suicide. The onset of depression is frequent during the adolescent period [1], a time notable for significant brain development and physical and social changes [2,3]. According to the World Health Organization (WHO), more than 10% of adolescents are affected by MDD in the US [4,5]. Early onset MDD has been shown to increase the risk of developing adult depression [6]. Current evidence-based treatments including antidepressant medication and cognitive behavioral therapy are only successful in reducing depression in about half to two-thirds of cases [7].
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