| Objective:Functional connectivity between the dorsolateral prefrontal cortex(DLPFC)and subgenual anterior cingulate(sgACC)has been widely demonstrated to be associated with antidepressant efficacy,however,systematic studies based on magnetic source imaging are still scarce.This study would use magnetoencephalography(MEG)techniques to investigate resting-state functional connectivity of DLPFC-sgACC on baseline from full oscillations,theta,alpha,beta,and gamma oscillation,respectively:(1)to explore its predictive value on final clinical remission;(2)to explore its predictive value on early antidepressant efficacy.Methods:The patients were recruited from the Inpatient Department of Psychiatry at Nanjing Brain Hospital affiliated to Nanjing Medical University.The primary diagnosis of major depressive disorder was confirmed by an experienced psychiatrist at baseline according to the criteria of diagnostic and statistical manual of mental disorders,4th edition(DSM-IV),The matched healthy controls were also recruited.Assessed by the hamilton rating scale for depression(HAMD)and other scales,CTF 275-channel magnetoencephalography(MEG)was used to collect magnetic signals.The sgACC and left DLPFC(1DLPFC)and right DLPFC(rDLPFC)were selected as regions of interest to calculate the FC of DLPFC-sgACC in each oscillation(full oscillation,theta,alpha,beta,gamma).Meanwhile,a weekly assessment of the HAMD scale was performed to assess the efficacy without interfering with the patient's actual clinical treatment.The follow-up study will be divided into the following steps:(1)The functional connectivity of the dorsolateral prefrontal cortex and subgenual anterior cingulate is correlated with depressive symptoms?Two sample T test was used to compare the FC of the DLPFC-sgACC between the depression group and the healthy control group;? The correlation of the FC of DLPFC-sgACC in each oscillation with the total score of HAMD-17 and each factor score was analyzed by Pearson correlation;?The receiver operating characteristic curve(ROC)was used to analyze the diagnostic value of differential FC between depressive and control groups.(2)The functional connectivity of the dorsolateral prefrontal cortex and subgenual anterior cingulate help predict clinical remissionPatients receiving drug therapy and imaging scan was defined as the starting event,depressed patients received antidepressants and reach the HAMD-17 score ? 7 was defined as a positive outcome,if the patient did not reach the HAMD-17 total score? 7 and loss to follow-up was censoring data.From the beginning to the event-to-positive outcome or loss to follow-up was defined as survival time,and time dependent COX models were used to analyze the predictive effect of each FC on antidepressant efficacy.(3)The implication of functional connectivity of the dorsolateral prefrontal cortex and subgenual anterior cingulate in predicting early treatment responseThe response or nonresponse group was divided by the HAMD-6 reduction rate of 50%after 2 weeks of antidepressant treatment.? Two sample T test was used to compare the differences of FC between the depressed group and the control group;?one-way ANOVA with post-hoc test was conducted to compare the differences between the responders,nonresponders and healthy control;? Pearson correlation analysis was used to confirm the relationship between the HAMD-6 reduction rate and each FC;?The ROC curve analysis was performed for FC in distinguishing responders and nonresponders.Results:(1)The functional connectivity of the dorsolateral prefrontal cortex and subgenual anterior cingulate is correlated with depressive symptoms? Differences in functional connectivity of DLPFC-sgACC between depression and healthy controlsCompared with the anti-correlation of alpha-oscillation IDLPFC-sgACC connectivity in the control group,the depressed group showed a positive correlation and increased in intensity(t=3.98,P<0.001);Compared with the anti-correlation of beta-oscillation rDLPFC-sgACC connectivity in the control group,the depressed group showed a positive correlation but decreased in intensity(t=2.561,P=0.012).? Correlation between DLPFC-sgACC and HAMD-17 scoresThe theta-oscillation 1DLPFC-sgACC was positively correlated with sleep factor score(r=0.36,P=0.027);the alpha-oscillation IDLPFC-sgACC was positively correlated with this duration(r=0.3816,P=O.018)and tended to be negatively correlated with the total HAMD-17 score(r=-0.276,P=0.055);the beta-oscillation 1DLPFC-sgACC was negatively correlated with the retardation factor score(r=-0.38,P=0.02).? The Diagnostic Value of DLPFC-sgACC connectivity for MDDROC analysis suggested that the alpha-oscillation 1DLPFC-sgACC(AUC=0.746,P<0.001,sensitivity 87.8%,specificity 64.3%),beta-oscillation rDLPFC-sgACC(AUC=0.664,P=0.017,sensitivity 55.1%,specificity 78.6%)connections help identify depression and healthy controls.The combination of the two FC made it more valuable in diagnosing MDD(AUC=0.8,P<0.001,sensitivity 85.7%,specificity 67.9%).(2)The functional connectivity of the dorsolateral prefrontal cortex and subgenual anterior cingulate help predict clinical remissionThe alpha-oscillation IDLPFC-sgACC connectivity at baseline could be used as an independent predictor of clinical remission(HR 1.858,95%Cl 1.013-3.408,P=0.045).(3)The implication of functional connectivity of the dorsolateral prefrontal cortex and subgenual anterior cingulate in predicting early treatment response? Differences of DLPFC-sgACC connectivity between depression and healthy controlsCompared with the anti-correlation of alpha-oscillation IDLPFC-sgACC connectivity in the control group,the depressed group showed a positive correlation and increased in intensity(t=-3.451,P=0.001);compared with the anti-correlation of beta-oscillation rDLPFC-sgACC connectivity in the control group,the depressed group showed a positive correlation but decreased in intensity(t=-3.221,P=0.002).? Differences of DLPFC-sgACC connectivity between responders and nonrespondersCompared with theta-oscillation anti-correlation of rDLPFC-sgACC in responders,the nonresponders showed a positive correlation and the intensity was increased(t=2.239,P=0.031);compared to the beta-oscillation anti-correlation of rDLPFC-sgACC in responders,the nonresponders showed a positive correlation and increased intensity(t=2.126,P=0.04);compared with the beta-oscillation anti-correlation of 1DLPFC-sgACC in responders,the nonresponders showed a positive correlation but decreased intensity(t= 4.35,P=0.0001,Bonferroni corrected).? The correlation between the 1DLPFC-sgACC connectivity and HAMD-6 reduction rateBeta-oscillation 1DLPFC-sgACC(i=-0.48,P=0.006),rDLPFC-sgACC(r=-0.54,P=0.002)connections were negatively correlated with 2-week HAMD-6 score reduction rates? Diagnostic Value of DLPFC-sgACC connectivity for Early Treatment efficacayROC analysis revealed beta-oscillation IDLPFC-sgACC(AUC=0.863,P= 0.0001,sensitivity 61.9%,specificity 94.1%),rDLPFC-sgACC(AUC=0.692,P= 0.044,sensitivity 81%,specificity 52.9%)connectivities helped to identify whether 2-week antidepressant treatment would be effective or not.The combination of two FC would have a higher diagnostic value for early antidepressant efficacy(AUC = 0.868,P=0.0001,sensitivity 70.6%,specificity 90.5%).Conclusion:The functional connectivity of IDLPFC-sgACC in alpha oscillation and rDLPFC-sgACC in beta oscillation would be valuale for clinical diagnosis of major depressive disorder.Furthermore,the functional connectivity of 1DLPFC-sgACC in alpha and beta oscillation,rDLPFC-sgACC in beta oscillation were significantly associated with the efficacy of antidepressant efficacy.In detail,the higher alpha-oscillation functional connectivity of 1DLPFC-sgACC at baseline would predict the more probability of reaching remission;meanwhile,the higher beta-oscillation functional connectivity of the IDLPFC-sgACC and rDLPFC-sgACC would suggest a poorer early antidepressant efficacy. |
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