Impaired implicit emotion regulation in patients with panic disorder:An event-related potential study on affect labeling

BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance.However,there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators.AIM To study the neural mechanisms of implicit emotion regulation in PD with eventrelated potentials(ERP).METHODS A total of 25 PD patients and 20 healthy controls(HC)underwent clinical evaluations.The study utilized a case-control design with random sampling,selecting participants for the case group from March to December 2018.Participants performed an affect labeling task,using affect labeling as the experimental condition and gender labeling as the control condition.ERP and behavioral data were recorded to compare the late positive potential(LPP)within and between the groups.RESULTS Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling.In the HC group,late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease.Importantly,a significant group×condition interaction effect was observed.Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group.Furthermore,among PD patients under the affect labeling,the late LPP was negatively correlated with disease severity,symptom frequency,and intensity.CONCLUSION PD patients demonstrate abnormalities in implicit emotion regulation,hampering their ability to mobilize cognitive resources for downregulating negative emotions.The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity.

Glutamate decarboxylase 1 gene polymorphisms are associated with respiratory symptoms in panic disorder

BACKGROUND Genetic factors play an important role in the pathogenesis of panic disorder(PD).However,the effect of genetic variants on PD remains controversial.AIM To evaluate the associations between glutamate decarboxylase 1(GAD1)gene polymorphisms and PD risk and assess the effect of GAD1 gene polymorphisms on the severity of clinical symptoms in PD.METHODS We recruited 230 PD patients and 224 healthy controls in this study.All participants were assessed for anxiety and panic symptom severity using the Hamilton Anxiety Rating Scale(HAM-A)and Panic Disorder Severity Scale(PDSS).GAD1 gene polymorphisms(rs1978340 and rs3749034)were genotyped and assessed for allele frequencies.RESULTS There were no significant differences between cases and controls in the genotype distributions or allele frequencies of GAD1(rs1978340 and rs3749034).In addition,the effect of GAD1(rs1978340 and rs3749034)on PD severity was not significant.However,regarding respiratory symptoms,patients with the GAD1 rs1978340 A/A genotype had significantly higher scores than those with the A/G or G/G genotype.CONCLUSION Here,we showed that the A/A genotype of GAD1 rs1978340 was associated with increased severity of respiratory symptoms in patients with PD.

Pilot study of genome-wide DNA methylation and gene expression for treatment response to escitalopram in panic disorder

BACKGROUND Antidepressants,particularly selective serotonin reuptake inhibitors,are currently considered the first-line treatment for panic disorder(PD).However,little is known about the relationship between the biomarkers that may predict better treatment.AIM To compare genome-wide methylation and gene expression patterns between responsive and non-responsive patients with PD after 4 wk of escitalopram treatment.METHODS Thirty patients with PD were enrolled in this study(responders=13;nonresponders=17).All patients were assessed using the PD Severity Scale-Chinese version before and after treatment.The Illumina Infinium MethylationEPIC(850k)BeadChip for genome-wide methylation screening and mRNA sequencing was used in all patients with PD.RESULTS A total of 701 differentially methylated positions(DMPs)were found between responders and non-responders(|Δβ|≥0.06,q<0.05),and the hyper-and hypomethylated CpG sites were 511(72.9%)and 190(27.1%),respectively.Relative to non-responders,there were 59 differential transcripts,of which 20 were downregulated and 39 were upregulated(q<0.05).However,no differen tially expressed genes were identified by mRNA sequencing after correcting for multiple testing(|log2(FC)|>1,q>0.05).CONCLUSION This preliminary study showed that DMPs might be associated with the treatment response to escitalopram in PD;however,these DMPs need to be verified in large samples.

Psychological predictors of bipolarity in panic disorder

BACKGROUND Panic disorders frequently occur with affective disorders,particularly bipolar disorder.Patients with panic disorder and bipolar disorder are more likely to present with severe symptoms,such as high rates of suicidal behavior,poor symptomatic and functional recovery,and poor drug responses.AIM To investigate the psychological characteristics of panic disorder patients related to bipolarity.METHODS A total of 254 patients(136 men and 118 women,mean age=33.48±3.2 years)who were diagnosed with panic disorder were included in the study.Panic disorder with bipolarity(BP+)was defined as a score of≥7 on the Korean version of the Mood Disorder Questionnaire(K-MDQ),and a score lower than 7 was considered as a panic disorder without bipolarity(BP-).Self-report questionnaires were analyzed to examine their association with bipolarity.Psychological tests used in the study were the Mood Disorder Questionnaire(MDQ),Panic Disorder Severity Scale,Beck Depression Inventory,State-Trait Anxiety Inventory(STAI),Temperament and Character Inventory(TCI),and Minnesota Multiphasic Personality Inventory(MMPI).Statistical analyses were performed to evaluate the correlation between bipolarity of panic disorder patients and various psychological test results indicative of psychological characteristics.RESULTS Patients with a K-MDQ score of 7 or more were considered to have a history of manic or hypomanic episodes(BP+group,n=128),while patients with K-MDQ scores below 7 were defined as those without bipolarity(BP-group,n=126).The BP+group were more likely to be unmarried(single 56.2%vs 44.4%,P=0.008)and younger(30.78±0.59 vs 37.11±3.21,P<0.001).Additionally,the BP+group had significantly higher scores on psychological assessment scales,such as the hypochondriasis,psychopathic deviate,masculinity-femininity,psychasthenia,schizophrenia,and hypomania(Ma)in MMPI,and novelty seeking,harm avoidance and self-transcendence in TCI,and STAI(state and trait)compared to the BP-group.In logistic regression analysis,depression in MMPI,selfdirectedness in TCI,and age were negatively associated with MDQ score,meanwhile,Ma in MMPI and STAI(trait)were positively associated with MDQ score.CONCLUSION The result of this study suggests that almost 50%of patients with panic disorder are likely to have hypomanic or manic symptoms,and certain psychological factors are associated bipolarity in panic disorder.

Increased functional connectivity of amygdala subregions in patients with drug-naïve panic disorder and without comorbidities

Background:Amygdala plays an important role in the neurobiological basis of panic disorder(PD),and the amygdala contains different subregions,which may play different roles in PD.The aim of the present study was to examine whether there are common or distinct patterns of functional connectivity of the amygdala subregions in PD using resting-state functional magnetic resonance imaging and to explore the relationship between the abnormal spontaneous functional connectivity patterns of the regions of interest(ROIs)and the clinical symptoms of PD patients.Methods:Fifty-three drug-naïve,non-comorbid PD patients and 70 healthy controls(HCs)were recruited.Seed-based resting-state functional connectivity(rsFC)analyses were conducted using the bilateral amygdalae and its subregions as the ROI seed.Two samples t test was performed for the seed-based Fisher's z-transformed correlation maps.The relationship between the abnormal spontaneous functional connectivity patterns of the ROIs and the clinical symptoms of PD patients was investigated by Pearson correlation analysis.Results:PD patients showed increased rsFC of the bilateral amygdalae and almost all the amygdala subregions with the precuneus/posterior cingulate gyrus compared with the HC group(left amygdala[lAMY]:t=4.84,P<0.001;right amygdala[rAMY]:t=4.55,P<0.001;left centromedial amygdala[lCMA]:t=3.87,P<0.001;right centromedial amygdala[rCMA]:t=3.82,P=0.002;left laterobasal amygdala[lBLA]:t=4.33,P<0.001;right laterobasal amygdala[rBLA]:t=4.97,P<0.001;left superficial amygdala[lSFA]:t=3.26,P=0.006).The rsFC of the lBLA with the left angular gyrus/inferior parietal lobule remarkably increased in the PD group(t=3.70,P=0.003).And most of the altered rsFCs were located in the default mode network(DMN).A significant positive correlation was observed between the severity of anxiety and the rsFC between the lSFA and the left precuneus in PD patients(r=0.285,P=0.039).Conclusions:Our research suggested that the increased rsFC of amygdala subregions with DMN plays an important role in the pathogenesis of PD.Future studies may further explore whether the rsFC of amygdala subregions,especially with the regions in DMN,can be used as a biological marker of PD.

QT wave dispersion in patients with panic disorder

Objective QT dispersion （QTd）, defined as the maximal inter-lead difference in QT intervals on 12 leads of the surface electrocardiogram （ECG）, reflects the regional heterogeneity of ventricular repolarization and has been suggested as an important marker for risk of arrhythmia in addition to the QT interval. Some investigators proposed that it might be a predisposing factor for arrhythmic events and sudden death. Thus, we aimed to investigate whether QTd differs in patients with panic disorder from that in healthy controls. Methods In 40 panic disorder patients and 40 healthy controls, Qmax, Qmin, and QTd values were measured. In addition, the Hamilton depression rating scale and the panic agoraphobia scale were scored for both patients and healthy volunteers. Results Qmax and Qmin values in the panic disorder patients were significantly higher than those in healthy controls. The mean corrected QTd was significantly greater in the patients than in the controls. One-way analysis of covariance （ANCOVA; using left atrial size, age and heart rate as covariates） also corrected the significant difference. In addition, ANCOVA revealed a significant main effect for the diagnosis, indicating a significantly higher QTd for patients compared with controls. Conclusion QTd might be associated with panic disorder. Future studies in larger samples evaluating the effects of treatment are required.

Increased P wave duration in patients with depression or anxiety disorder

BACKGROUND： Activation of the sympathetic nervous system plays an important role in regulating cardiovascular actions. P wave parameters can provide general information on central cardiovascular autonomic regulatory responses, which are altered in patients with anxiety disorders and depression. In particular, there are no reports addressing changes in P wave duration and dispersion. OBJECTIVE： To compare the differences in P wave duration and P wave dispersion between patients with anxiety disorders and depression, because patients with anxiety disorders and depression develop abnormal electrocardiograms. DESIGN, TIME AND SETTING： A non-randomized concurrent controlled study was performed. Patients with depression and general anxiety disorders were admitted at the psychiatry outpatient clinics of the Medical Faculty of Duezce University of Turkey between May 2005 and October 2006. PARTICIPANTS： A total of 71 consecutive patients with depression and anxiety disorders, as well as 50 physically and mentally healthy age- and gender-matched controls were selected. METHODS： Electrocardiogram records were obtained at the time of admission to the outpatient clinics. MAIN OUTCOME MEASURES： P wave duration and P wave dispersion were measured. RESULTS： Both the maximum （Prnax） and minimum （Pmin） P wave duration were greater in patients with psychiatric disorders than in healthy controls. Pmax was significantly greater in patients with depression or anxiety disorders （Bonferroni test, P 〈 0.017）. The P wave dispersion was similar between patients and controls （P 〉 0.017）. P waves were similar between panic patients and other anxiety patients. Beck depression results were positively correlated with Prawn and Prnax （r= 0.374, 0.302, P = 0.013, 0.049, respectively）, and not associated with P wave dispersion （P 〉 0.05）. CONCLUSION： Psychiatric disorders are associated with increases in Prnax, but not with P wave dispersion. The P wave changes were associated with the degree of depression.

Optical neuroimaging:advancing transcranial magnetic stimulation treatments of psychiatric disorders

Transcranial magnetic stimulation(TMS)has been established as an important and effective treatment for various psychiatric disorders.However,its effectiveness has likely been limited due to the dearth of neuronavigational tools for targeting purposes,unclear ideal stimulation parameters,and a lack of knowledge regarding the physiological response of the brain to TMS in each psychiatric condition.Modern optical imaging modalities,such as functional near-infrared spectroscopy and diffuse optical tomography,are promising tools for the study of TMS optimization and functional targeting in psychiatric disorders.They possess a unique combination of high spatial and temporal resolutions,portability,real-time capability,and relatively low costs.In this mini-review,we discuss the advent of optical imaging techniques and their innovative use in several psychiatric conditions including depression,panic disorder,phobias,and eating disorders.With further investment and research in the development of these optical imaging approaches,their potential will be paramount for the advancement of TMS treatment protocols in psychiatry.