Disrupted Intrinsic Functional Connectivity Of The Cognitive Control Network Underlies Disease Severity And Executive Dysfunction In First-episode,Treatment-naive Adolescent Depression

Objective:Previous neuroimaging studies have showed that imbalanced functional integration of distributed large-scale brain networks is associated with pathophysiological characteristics of major depressive disorder(MDD).However,the association between network integrative disturbances and clinical features and cognitive functions remains largely unclear in adolescent MDD.This study investigated the neural correlates of abnormal functional connectivity networks with clinical and executive characteristics in adolescent MDD.Methods:1.Twenty-eight first-episode,treatment-naive adolescents with MDD were recruited from the Department of Mental Health at the First Affiliated Hospital,College of Medicine,Zhejiang University from September 2014 to December 2016.Twenty-four demographics-matched healthy controls(HCs)were recruited from the local community.2.In the current study,each participant underwent a battery of clinical and neuropsychological tests.Specifically,the severity of mood symptoms for each participant was assessed using two scales:the 17-item Hamilton Depression Rating Scale(HAMD)and the 17-item Children’s Depression Rating Scale-Revised(CDRS-R).IVThe CDRS-R was based on reports from the participants and their parents.For neuropsychological assessments,the Wisconsin Card Sorting Test(WCST),Continuous Performance Test(CPT),Trail-making test(TMT)and Stroop Color Word Test(SCWT)were used.3.Both groups underwent functional magnetic resonance imaging(fMRI).A seed-based resting-state functional connectivity(RSFC)approach was used to depict connectivity patterns of the cognitive control network(CCN;seed ＝ the bilateral dorsolateral prefrontal cortex,DLPFC),affective network(AN;seed = the bilateral subgenual anterior cingulate cortex,sgACC)and default mode network(DMN;seed =the bilateral precuneus,PCUN),whose between-group differences were correlated with clinical variables and executive functions in the patients.Results:1.Our neuropsychological tests revealed that adolescents with MDD spent more time on the Stroop B(t=3.33,P<0.01),Stroop C(t=2.826,P<0.01),which measured selective attention/processing speed and behavioral inhibition,respectively.2.The functional connectivity analysis revealed characteristic alterations for the three studied networks in the MDD adolescents,as characterized by lower CCN functional connectivity with the right temporal,the bilateral middle cingulate gyri,right inferior frontal gyrus(IFG)and insula,higher AN functional connectivity with the left fusiform gyrus、cerebellum posterior lobe、lingual gyrus、right superior temporal gyrus and right middle temporal gyrus,and lower DMN functional connectivity with the cerebellum and right insula.3.In the adolescent MDD group,the HAMD scores were negatively correlated with the RSFC between the left DLPFC and the right IFG and the RSFC between the right sgACC and the left cerebellum posterior lobe.For neuropsychological measures,the RSFC between the right DLPFC and the bilateral mild cingulate gyrus was negatively correlated with the SCWT B and SCWT C scores.Conclusions:1.Adolescents with MDD showed disrupted executive function and aberrant RSFC of CCN,AN and DMN.2.Abnormal function of the CCN was related to disease severity and executive dysfunction.These results might have revealed the pathophysiology of adolescent MDD and guide the selection of appropriate interventions to help improve long-term outcomes for individuals with the illness.