Relationship Between Default Mode Network Functional Connectivity And Cognitive Function In Children And Adolescents With First-episode Major Depressive Disorder

BackgroundMajor depressive disorder(MDD)is a common and debilitating mood disorder with the major clinical manifestations having pervasive and persistent low mood and/or losing interest and pleasure.Cognitive dysfunction is common in patients with MDD.Children and adolescent MDD is related to significantly high risk of suicide and is the leading cause of disability and morbidity.It is likely that Children and adolescent MDD has recurrent episodes of depression in adult life,leading to serious problem.Therefore,studying and fully understanding the etiology and pathogenesis of MDD among children and adolescents has tremendous clinical significance for the early diagnosis,treatment,and prognosis of MDD.In recent years,the continuous development of neuroimaging technology such as functional magnetic resonance imaging(fMRI)has made it possible to explore the structural and functional abnormalities in brain regions.Recent evidence indicates that MDD may alter the neurodevelopmental trajectories of the networks.At present,the default mode network(DMN)is receiving considerable research focus.The majority of researches on the DMN have tended to concentrate on adult MDD.There is evidence to suggest that patterns of functional connectivity(FCs)of DMN demonstrate a developmental change,undergoing a prolonged period of maturation.In fact,few studies have focused on FCs of DMN among children and adolescence with MDD and to date there was no consistent findings have been reported.It is necessary to figure out the FCs of DMN and the relationship between the abnormal FCs and cognitive function.Objective1 To investigate whether there is abnormal FCs of DMN in children and adolescents with MDD;2 To analyze the relationship between abnormal FCs of DMN and clinical features in children and adolescents with MDD;3 To figure out the relationship between the abnormal FCs of DMN and cognitive dysfunction in children and adolescents with MDD.MethodsThirty first-episode and drug-naive children and adolescent MDD patients were in line with “The Diagnostic and Statistical Manual of Mental Disorders”(4th edition,DSM-IV)diagnostic criteria.Twenty-nine age-,gender-and education matched adolescent healthy control(HC)participants were enrolled.Resting-state functional magnetic resonance images(rs-fMRI)were scanned.Using the Wisconsin Card Sorting Test(WCST)and connection test(TMT)for cognitive function testing and Hamilton Depression Scale(HAMD-17)for scoring clinical symptom.We utilized a seed-based analysis and selected the posterior cingulate cortex(PCC)and medial prefrontal cortex(MPFC)as regions of interest to investigate their functional connectivity(FC)with other regions of the brain.In addition,we examined relations between depression severity/duration,cognitive dysfunction and abnormal networks FCs.Results1 DMN-FCs ResultsWe discovered extensive abnormalities in the DMN FCs of children and adolescent MDD patients.Compared to HC,the dysregulation of brain regions included the cerebellum,temporal lobe,dorsal lateral prefrontal cortex(DLPFC),fusiform gyrus,anterior cingulate cortex(ACC)and so on.2 PCC-FCs ResultsThe children and adolescent MDD patients showed congruently decreased FCs of PCC.Compared to the HC group,the children and adolescent group had decreased FCs between the left PCC and right cerebelum,temporal gyrus(bilateral inferior temporal gyrus,bilateral middle temporal gyrus),bilateral middle occipiral gyrus,frontal gyrus(bilateral middle frontal gyrus,bilateral triangular inferior frontal gyrus),left inferior parietal gyrus.Left PCC had increase FCs with left orbital superior frontal gyrus.Right PCC had decreased FCs with right cerebelum,left fusiform,bilateral middle temporal gyrus,frontal gyrus(bilateral orbital inferior frontal gyrus,bilateral triangular inferior frontal gyrus,left DLPFC,right middle frontal gyrus),right superior parietal gyrus,left supplementary motor area3 MPFC-FCs ResultsThe children and adolescent MDD patients show both enhanced and reduced FCs of MPFC.The FC was reduced between the left MPFC and cerebelum,left fusiform,bilateral triangular inferior frontal gyrus,right middle temporal gyrus,bilateral middle frontal gyrus.The FC was enhanced between the left MPFC the occipital gyrus(left middle occipital gyrus,right superior occipital gyrus),right middle cingulum cortex,right postcentral gyrus and right superior parietal gyrus.The FC was reduced between the right MPFC and right orbital inferior frontal gyrus,right ACC,bilateral middle frontal gyrus.The FC was enhanced between the right MPFC the left cerebelum,bilateral middle occipital gyrus.4 Relationship between abnormal DMN FCs and clinical featuresImportantly,the abnormal DMN FCs was association with clinical variables(HAMD score and duration of depression since onset).Within the depressed group,the enhanced FC between the right precentral gyrus and right MPFC was positive correlations with HAMD scores.The reduced FC between the left middle temporal gyrus and left PCC and the enhanced FC between the right middle cingulum and right MPFC were positive correlations with the duration of depression since onset.5 Relationship between abnormal DMN FCs and cognitive dysfunctionThe abnormal cognitive function and abnormal FCs of DMN showed that the decrease FCs between the left PCC and right inferior temporal gyrus is positive correlations with the perseverative errors and negatively correlations with the number of correct answers.The decrease FCs between the right PCC and left middle temporal gyrus was positively related to the TMT-B completion time.The decrease FCs between the right PCC and middle frontal gyrus,the right MPFC and ACC were positively correlated with total time.The increase FCs between the right MPFC and right middle occipital gyrus was negative related to total time.Conclusions1 The current study showed that first-episode and medication-free children and adolescent MDD have abnormal FCs in the DMN.These findings are important in that they contribute to a more comprehensive understanding of the neurodevelopmental mechanisms of adolescent MDD.2 There is association between abnormal FCs of DMN and clinical characteristics in children and adolescents with MDD.The extensive abnormalities in the DMN FCs provides biological indicators that may help diagnosis.3 Cognitive function dysfunction may be relevant to the abnormal FCs of DMN in resting state of children and adolescent MDD.