Neuroanatomical Mechanism Of Cognitive Emotion Regulation In Patients With Panic Disorder:Multi-modal MRI Study

Cognitive strategies of emotion regulation in patients with panic disorderObjective:Until recently,there were few systematic studies on cognitive strategies of emotion regulation of patients with panic disorder(PD).Moreover,the effect of depressive symptoms on cognitive strategies of emotion regulation of PD patients was not excluded.In this study,the depressive components of patients with PD were strictly limited(HAMD score < 8),and the cognitive strategies of emotion regulation of patients with PD,patients with major depressive disorder(MDD)and healthy controls(HCs)were systematically analyzed.Methods:Fifty-three participants were recruited from the First Affiliated Hospital of Dalian Medical University in this study.Among them,26 patients met Diagnostic and Statistical Manual of Mental Disorders,Fourth edition(DSM-IV)criteria for PD,19 patients met DSM-IV criteria for MDD,and 27 HCs with no current or past Axis I psychiatric diagnosis.HAMA?HAMD?Panic Disorder Severity Scale(PDSS)and Cognitive Emotion Regulation Questionnaire(CERQ)were obtained from both patients and HCs to measure and evaluate the effects of different dimensions of emotion cognitive regulation strategies on anxiety,depression and the severity of PD.One way ANOVA was used to calculate different dimensions of the CERQ among PD group,depression group and healthy control group.Pearson correlation analysis was performed between the CERQ scores with statistical differences and PDSS?HAMA scores in PD group,and Pearson correlation analysis was conducted between the CERQ scores with statistical differences and HAMD scores in MDD group.Results:There were significant differences in positive focus,positive reappraisal,self blame,rumination and catastrophizing among three groups.(1)On adaptive coping strategies,PD patients shown obvious impairments of positive focus?positive reappraisal and putting into perspective compared to HCs.Positive reappraisal and putting into perspective were negatively correlated with the severity of PD(PDSS and HAMA scores).MDD group scored significantly lower on the positive reappraisal than HCs.(2)On non-adaptive coping strategies,PD group scored significantly higher on the catastrophizing than HCs.Catastrophizing was positively correlated with the severity of PD.While the MDD group scored significantly higher on self blame?rumination and catastrophizing than HCs,which were positively correlated with the severity of depression.(3)MDD group scored significantly higher on self blame?rumination than PD group.Conclusion:Both PD and MDD groups all demonstrated impariment of emotion regulations on both adaptive and non-adaptive coping strategies compared to the HCs.MDD group scored significantly higher on self blame?rumination than PD group.The depressive components of PD patients or the combination of depression might make PD patients pay attention to their negative emotions,which is not conducive for PD patients to get rid of negative emotionsAltered Resting-State Network Connectivity of Emotion Regulation Disorder in Patients with Panic DisorderObjective: Panic disorder(PD)is a prevalent anxiety disorder but its neurobiology is still poorly understood.Recently,it has been proposed that the pathophysiology of PD is related to abnormality of certain neural network.However,most studies investigating resting-state functional connectivity(FC)have relied on a priori restrictions on seed regions,which may bias observations.This study aimed to investigate the alterationsof intra-and inter-network FCs in the whole brain of the patients with PD using resting-state functional MRI.Methods: All participants were recruited from the First Affiliated Hospital of Dalian Medical University.Panic disorder was diagnosed by experienced psychiatrists on the basis of medical records and a Structured Clinical Interview for DSM-IV/Clinical Version(SCID-I/CV).rs-MRI was performed using a 3.0 T GE whole body imaging system(GE HDxt,USA).A voxel-wise data-driven method,independent component analysis,was performed on 26 PD patients and 27 healthy controls(HCs).We compared the differences in the intra-and inter-network FC between the two groups of subjects using Statistical Parametric Mapping with two-sample t-tests.A two-sample t test was used to test which pairs of resting-state networks(RSNs)showed significant differences(P<0.05)in the functional network connectivity(FNC)between the two groups.The mean z-values of the regions where the intra-network FC analysis showed significant FC alterations in patients with PD relative to HCs were extracted.Pearson's correlation analyses were conducted between regional mean z-values and scores of the PDSS ? HAMA and CERQ(including the positive focus?positive reappraisal?putting into perspective and catastrophizing).Results: Compared with HCs,PD patients exhibited decreased intra-network FCs in the right anterior cingulate cortex(ACC)of the anterior default mode network,the left precentral and postcentral gyrus of the sensorimotor network,the right lobule V/VI,the cerebellum vermis and the left lobule VI of the cerebellum network.The intra-network FC in the right ACCwerenegatively correlated with the PD symptom severity and catastrophizing score.None of the pairs of RSNs showed significant differences in the functional network connectivity between the two groups.Conclusion: These results suggest that the brain networks associated with the emotion regulation,the interoceptive awareness,the fear and somatosensory processing might play an important role in the pathophysiology of PD.The right ACC of the a DMN and the cerebellum vermis of the cerebellum network were negatively correlated with the PD symptom severity and catastrophizing score.Thus,the right ACC and the cerebellum vermis might be important network nodes of PD patients with emotion regulation disorder.Altered white matter Network Connectivityof Emotion Regulation Disorder in Patients with Panic DisorderObjective:In the last chapter,we found the disconnectivity of resting-state networks(RSNs)in PD using rs-f MRI independent components analysis.However,we could not demonstrated the location of the abnormal white matter fiber tracts resulting in the functional disconnectivity in PD patients.Until recently,the number of DTI studies on PD is relatively small.Some DTI studies used different methods to measure and analysis the white matter structure in PD,but their results were inconsistent.This chapter intends to analyze the integrity of white matter fiber tracts in PD patients by using the method of track-based spatial statistics(TBSS)and compared with the changes of brain functional network in PD in the last chapter.Thus,we can comprehensively study the brain network mechanism of emotional disorder in patients with PD.Methods: All participants were recruited from the First Affiliated Hospital of Dalian Medical University.Panic disorder was diagnosed by experienced psychiatrists on the basis ofmedical records and a Structured Clinical Interview for DSM-IV/Clinical Version(SCID-I/CV).rs-MRI was performed using a 3.0T GE whole body imaging system(GE HDxt,USA).Voxel-wise statistical analysis of the fractional anisotropy(FA)data of 26 PD patients and 27 HCs was performed using tract-based spatial statistics(TBSS),implemented in the FSL according to the standard procedure.Statistical analysis was performed voxel-by-voxel to detect regions with significant FA differences between the PD and HC groups by using non-parametric permutation tests with acorrection for multiple comparisons with the FSL Randomise program.Pearson correlation was performed to analyze the correlation between FA values and PDSS,HAMA and CERQ scores.Combined with the content of the last chapter,we tried to analyze the correlation between white matter disconnectivity and the functional disconnectivity of adjacent cerebral cortex.Results: Patients had reduced FA values than controls in the genu and body of corpus callosum(CC),bilateral anterior corona radiate,bilateral superior corona radiate and left external capsule.There were no clusters showing increased FA in patients compared with controls.In patients with PD,the PDSS scores were negatively correlated with the FA values of the bilateral anterior corona radiate,the body and genu of CC.The catastrophizing scores were negatively correlated with the FA values of the bilateral anterior corona radiate,the right superior corona radiate,the body and genu of CC.There was positive correlation between the positive reappraisal scores and the FA of the left external capsule.By comparing the TBSS results of this part with functional connectivity(FC)results of the last part,the FC values of the right anterior cingulate cortex(ACC)(Brodmann 32 area)were negatively correlated with the FA values of the adjacent right anterior corona radiate and thegenu of CC.The FC values of the left sensorimotor cortex(Brodmann3/4 area)were negatively correlated with the FA values of the adjacent left superior corona radiate and the body of the CC.Conclusion:An important network node of emotion regulation disorder in PD patients is the right ACC,while the range of white matter disconnection adjacent to it is more extensive,including both the projection fibers of prefrontal cortex(PFC)/ ACC and the association fibers between bilateral PFC / ACC.Paresthesia in PD patients is associated with a more complex topological network.The important node of disconnection is the left central posterior gyrus,and the adjacent projection fibers and the assocaciation fibers between the bilateral somatosensory cortex all exhibited disconnection.In addition,this study also found that there was disconnection in the left platen nucleus——cortex conduction pathway related to multi sensory integration in PD patients.Analysis of Cerebral Morphology and Blood Perfusion of Emotion Regulation Disorder in Patients with Panic DisorderObjective: Although recent neuroimaging studies have suggested that functional deficits in face perception are associated with panic disorder(PD),no study has examined the possible cortical thickness and perfusion abnormalities in patients with PD.The objective of this study is to investigate alterations in cortical thickness and regional cerebral blood flow(CBF)values between PD patients and health controls(HCs)using 3D T1-weighted MRI and 3D Arterial Spin Labeling(ASL)perfusion MRI.Methods: All participants were recruited from the First Affiliated Hospital of Dalian Medical University.Panic disorder was diagnosed by experienced psychiatrists on the basis ofmedical records and a Structured Clinical Interview for DSM-IV/Clinical Version(SCID-I/CV).3DBRAVO and 3DASL was performed using a 3.0T GE whole bodyimaging system(GE HDxt,USA).This study used an automated surface-based method(Cat12)to measure cortical thickness?Sulcal depth?Local gyrification index(LGI)and Fractal dimensionfor each subject.Z-score normalization for CBF maps were performed to generate the Z-score maps.Statistical comparisons were performed using statistical parametric mapping with two-sample t-tests.The cortical thickness?Sulcal depth?LGI?Fractal dimension and Z-scores of the regions where the statistical analysis showed significant differences in patients with PD relative to HCs were extracted.The one sample K-S test was performed to test the normality of these imaging parameters.Pearson's correlation analyses were conducted between these imaging parameters and scores of the PDSS?HAMA and CERQ(including the positive focus?positive reappraisal?putting into perspective and catastrophizing).Results: Compared with HCs,subjects with PD showed the impairment of the cortical thinningin the right fusiform(FG).A decreased Z-score and LGI in the right FG were also found after post hoc analysis.There was a significant positive correlation between the Z-score and the cortical thickness of the right FG.The cortical thickness,LGI and Z-score values of the right FG were negatively correlated with the PDSS?HAMA and catastrophizingscores.Z-score values of the right FG were positively correlated with thepositive reappraisal.Conclusion: These results provide further evidence for the significant role of the structural and functional deficit in the right FG in patients with PD.Due to the observed regional specificity,this finding bear important clinical implications for the potential treatment strategy.