title: The effects of antidepressant treatment on resting-state functional brain networks in patients with major depressive disorder.
abstract: Although most knowledge regarding antidepressant effects is at the receptor level, the neurophysiological correlates of these neurochemical changes remain poorly understood. Such an understanding could benefit from elucidation of antidepressant effects at the level of neural circuits, which would be crucial in identifying biomarkers for monitoring treatment efficacy of antidepressants. In this study, we recruited 20 first-episode drug-naive major depressive disorder (MDD) patients and performed resting-state functional magnetic resonance imaging (MRI) scans before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor-escitalopram. Twenty healthy controls (HCs) were also scanned twice with an 8-week interval. Whole-brain connectivity was analyzed using a graph-theory approach-functional connectivity strength (FCS). The analysis of covariance of FCS was used to determine treatment-related changes. We observed significant group-by-time interaction on FCS in the bilateral dorsomedial prefrontal cortex and bilateral hippocampi. Post hoc analyses revealed that the FCS values in the bilateral dorsomedial prefrontal cortex were significantly higher in the MDD patients compared to HCs at baseline and were significantly reduced after treatment; conversely, the FCS values in the bilateral hippocampi were significantly lower in the patients at baseline and were significantly increased after treatment. Importantly, FCS reduction in the dorsomedial prefrontal cortex was significantly correlated with symptomatic improvement. Together, these findings provided evidence that this commonly used antidepressant can selectively modulate the intrinsic network connectivity associated with the medial prefrontal-limbic system, thus significantly adding to our understanding of antidepressant effects at a circuit level and suggesting potential imaging-based biomarkers for treatment evaluation in MDD.
authors.affiliation: Peking University Sixth Hospital, Beijing, China; Ministry of Health Key Laboratory of Mental Health, Beijing, China; Institute of Mental Health, Peking University, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Mingrui
authors.initials: M
authors.lastname: Xia
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zeng
authors.forename: Yunai
authors.initials: Y
authors.lastname: Su
authors.forename: Wenji
authors.initials: W
authors.lastname: Dai
authors.forename: Qinge
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Jin
authors.forename: Philip B
authors.initials: PB
authors.lastname: Mitchell
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.forename: Tianmei
authors.initials: T
authors.lastname: Si
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D001931:Brain Mapping; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D015203:Reproducibility of Results; D012146:Rest; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors
keywords: antidepressant; connectomics; depression; graph theory; resting-state fMRI