title: Impaired Bottom-Up Effective Connectivity Between Amygdala and Subgenual Anterior Cingulate Cortex in Unmedicated Adolescents with Major Depression: Results from a Dynamic Causal Modeling Analysis.
abstract: Major depressive disorder (MDD) is a significant contributor to lifetime disability and frequently emerges in adolescence, yet little is known about the neural mechanisms of MDD in adolescents. Dynamic causal modeling (DCM) analysis is an innovative tool that can shed light on neural network abnormalities. A DCM analysis was conducted to test several frontolimbic effective connectivity models in 27 adolescents with MDD and 21 healthy adolescents. The best neural model for each person was identified using Bayesian model selection. The findings revealed that the two adolescent groups fit similar optimal neural models. The best across-groups model was then used to infer upon both within-group and between-group tests of intrinsic and modulation parameters of the network connections. First, for model validation, within-group tests revealed robust evidence for bottom-up connectivity, but less evidence for strong top-down connectivity in both groups. Second, we tested for differences between groups on the validated parameters of the best model. This revealed that adolescents with MDD had significantly weaker bottom-up connectivity in one pathway, from amygdala to sgACC (p=0.008), than healthy controls. This study provides the first examination of effective connectivity using DCM within neural circuitry implicated in emotion processing in adolescents with MDD. These findings aid in advancing understanding the neurobiology of early-onset MDD during adolescence and have implications for future research investigating how effective connectivity changes across contexts, with development, over the course of the disease, and after intervention.
authors.affiliation: 1 Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Musgrove
authors.affiliation: 1 Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Eberly
authors.affiliation: 2 Department of Psychology, College of Liberal Arts, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Klimes-Dougan
authors.affiliation: 3 Cognitive Science Department, Informatics Institute, Middle East Technical University , Ankara, Turkey .
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Basgoze
authors.affiliation: 4 Institute of Child Development, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Thomas
authors.affiliation: 5 Department of Psychiatry, School of Medicine, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Bryon A
authors.initials: BA
authors.lastname: Mueller
authors.affiliation: 5 Department of Psychiatry, School of Medicine, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Alaa
authors.initials: A
authors.lastname: Houri
authors.affiliation: 5 Department of Psychiatry, School of Medicine, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Kelvin O
authors.initials: KO
authors.lastname: Lim
authors.affiliation: 5 Department of Psychiatry, School of Medicine, University of Minnesota , Minneapolis, Minnesota.
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Cullen
mesh_terms: D000293:Adolescent; D000679:Amygdala / Q000473:pathology*; D001499:Bayes Theorem; D001931:Brain Mapping / Q000379:methods*; D002648:Child; D003198:Computer Simulation; D003865:Major Depressive Disorder / Q000378:metabolism / Q000473:pathology*; D004644:Emotions / Q000502:physiology; D005149:Facial Expression; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000378:metabolism; D055815:Young Adult
keywords: adolescent; depression; dynamic causal modeling; effective connectivity; emotion; functional connectivity