Eun-Ho Kang

The Genetic Basis of Panic Disorder

Panic disorder is one of the chronic and disabling anxiety disorders. There has been evidence for either genetic heterogeneity or complex inheritance, with environmental factor interactions and multiple single genes, in panic disorders etiology. Linkage studies have implicated several chromosomal regions, but no research has replicated evidence for major genes involved in panic disorder. Researchers have suggested several neurotransmitter systems are related to panic disorder. However, to date no candidate gene association studies have established specific loci. Recently, researchers have emphasized genome-wide association studies. Results of two genome-wide association studies on panic disorder failed to show significant associations. Evidence exists for differences regarding gender and ethnicity in panic disorder. Increasing evidence suggests genes underlying panic disorder overlap, transcending current diagnostic boundaries. In addition, an anxious temperament and anxiety-related personality traits may represent intermediate phenotypes that predispose to panic disorder. Future research should focus on broad phenotypes, defined by comorbidity or intermediate phenotypes. Genome-wide association studies in large samples, studies of gene-gene and gene-environment interactions, and pharmacogenetic studies are needed.

Effect of Biofeedback-assisted Autogenic Training on Headache Activity and Mood States in Korean Female Migraine Patients

Biofeedback with or without combined autogenic training is known to be effective for the treatment of migraine. This study aimed to examine the effect of biofeedback treatment on headache activity, anxiety, and depression in Korean female patients with migraine headache. Patients were randomized into the treatment group (n=17) and monitoring group (n=15). Mood states including anxiety and depression, and psychophysiological variables such as mean skin temperature of the patients were compared with those of the normal controls (n=21). We found greater treatment response rate (defined as ≥50% reduction in headache index) in patients with biofeedback-assisted autogenic training than in monitoring group. The scores on the anxiety and depression scales in the patients receiving biofeedback-assisted autogenic training decreased after the biofeedback treatment. Moreover, the decrease in their anxiety levels was significantly related to the treatment outcome. This result suggests that the biofeedback-assisted autogenic training is effective for the treatment of migraine and its therapeutic effect is closely related to the improvement of the anxiety level.

Regional Brain Metabolism and Treatment Response in Panic Disorder Patients: An [18F]FDG-PET Study

Background: Panic disorder (PD) is a common and often chronic psychiatric condition that can lead to considerable disability in daily life. Using [18F]fluorodeoxyglucose-PET, we examined brain baseline glucose metabolism in PD patients in comparison with normal controls and the changes in glucose metabolism after 12 weeks of escitalopram treatment. Methods: Fifteen patients with PD were compared to 20 normal controls using [18F]FDG-PET at baseline and brain metabolism after 12 weeks of escitalopram treatment was compared to pretreatment in the patient group using voxel-based statistical analysis and post hoc region-of-interest analysis. Results: Patients with PD showed decreased metabolism in both the frontal, right temporal, and left posterior cingulate gyruses. After 12 weeks of escitalopram treatment, treatment responders showed metabolic increases in global neocortical areas as well as limbic areas whereas nonresponders did not. Conclusion: Abnormal neocortical function appears to be associated with the pathophysiology of PD and escitalopram exerts its therapeutic action by modulating brain activity at the level of the neocortex and limbic system, notably the amygdala and parahippocampal gyrus.

Platelet Serotonin Transporter Function and Heart Rate Variability in Patients with Panic Disorder

Many studies showed abnormal serotonin transporter (5-HTT) function and heart rate variability (HRV) in panic disorder patients. The present study investigated the relationship between HRV power spectral analysis findings and platelet serotonin uptake in panic disorder patients. Short-term HRV over 5 min and platelet serotonin transporter uptake parameters (Vmax and Km) were measured both in 45 patients with panic disorder and in 30 age-matched normal healthy control subjects. Low frequency power (LF) normalized unit (nu) and LF/high frequency power (HF) were significantly higher, whereas HF and HF nu were lower in the patient group than in the control group. Vmax and Km were all significantly lower (i.e., reflects decreased 5-HTT function) in patients with panic disorder than in normal controls. In the patient group, Km was negatively correlated with LF/HF and LF nu whereas no such correlations between them were found in the control group. By multivariate analysis based on multiple hierarchical linear regression, a low Km independently predicted an increased LF nu even after controlling for age, sex, and body mass index in the patient group. These results suggest that impaired 5-HTT function is closely related to dysregulation of autonomic nervous system in panic disorder.

Sympathetic nervous function and the effect of the catechol-O-methyltransferase Val158Met polymorphism in patients with panic disorder

BACKGROUND Sympathetic nervous function abnormalities have long been suggested to be a possible etiology of panic disorder (PD). Catechol-O-methyltransferase (COMT) affects sympathetic activities, and the COMT Val(158)Met polymorphism has been suggested to be related to PD. The authors examined the relationship between sympathetic nervous function and the COMT Val(158)Met polymorphism in PD patients. METHODS Fifty-eight patients [Val/Val (51.7%) and Met allele carriers (48.3%)] and 58 age-matched normal control subjects [Val/Val (56.9%) and Met allele carriers (43.1%)] were compared in terms of finger skin temperature, which is known to be a useful marker of sympathetic nervous function. RESULTS A significant COMT Val(158)Met polymorphismxdiagnosis interaction was found. Specifically, the met allele was found to be associated with a lower skin temperature in PD patients. CONCLUSION These results suggest that the COMT Met allele is related to the higher sympathetic nervous function observed in PD.

Long-term Escitalopram Treatment in Korean Patients with Panic Disorder: A Prospective, Naturalistic, Open-label, Multicenter Trial

Objective Panic disorder is characterized by recurrent panic attacks, persistent concerns about additional attacks, and worry about the implications of the attack or significant changes in behavior related to the attacks. We examined the efficacy of 24-week naturalistic, open-label escitalopram treatment in terms of the response and remission rates and functional disability in 119 adult Korean patients with panic disorder from 6 clinical centers in South Korea. Methods Clinical severity and functional impairment were assessed at baseline and at 4, 12, and 24 weeks after the treatment using the Panic Disorder Severity Scale and Sheehan Disability Scale. Ninety-six patients (80.7%) showed a treatment response, and 87 patients (73.1%) had attained remission after 24 weeks of escitalopram treatment. Results Continuous improvement in the Panic Disorder Severity Scale and Sheehan Disability Scale scores was found over the 24 weeks of treatment. Conclusion These findings suggest that escitalopram treatment is very effective for panic disorder in terms of both response and remission rates and that long-term pharmacotherapy with escitalopram continuously improved panic symptoms and functional disability in Korean patients with panic disorder.

Relationship between Personality and Insomnia in Panic Disorder Patients

Objective Panic disorder (PD) is frequently comorbid with insomnia, which could exacerbate panic symptoms and contribute to PD relapse. Research has suggested that characteristics are implicated in both PD and insomnia. However, there are no reports examining whether temperament and character affect insomnia in PD. Thus, we examined the relationship between insomnia and personality characteristics in PD patients. Methods Participants were 101 patients, recruited from 6 university hospitals in Korea, who met the DSM-IV-TR criteria for PD. We assessed sleep outcomes using the sleep items of 17-item Hamilton Depression Rating Scale (HAMD-17)(item 4=onset latency, item 5=middle awakening, and item 6=early awakening) and used the Cloningers Temperament and Character Inventory-Revised-Short to assess personality characteristics. To examine the relationship between personality and insomnia, we used analysis of variance with age, sex, and severity of depression (total HAMD scores minus sum of the three sleep items) as the covariates. Results There were no statistical differences (p>0.1) in demographic and clinical data between patients with and without insomnia. Initial insomnia (delayed sleep onset) correlated to a high score on the temperamental dimension of novelty seeking 3 (NS3)(F1,96=6.93, p=0.03). There were no statistical differences (p>0.1) in NS3 between patients with and without middle or terminal insomnia. Conclusion The present study suggests that higher NS3 is related to the development of initial insomnia in PD and that temperament and character should be considered when assessing sleep problems in PD patients.

Mirtazapine versus venlafaxine for the treatment of somatic symptoms associated with major depressive disorder: A randomized, open-labeled trial

Somatic symptoms are often important in the treatment of major depressive disorder (MDD). The aim of this open-labeled trial was to examine the efficacy of mirtazapine for the treatment of MDD with clinically significant somatic symptoms, as compared with venlafaxine. A total of 126 patients with MDD (score >/=18 on the Hamilton Rating Scale for Depression-17) were included in both the intent-to-treat (n=73 in the mirtazapine group and n=53 in the venlafaxine group) and completer analysis (n=51 and n=37, respectively). After treatment, both treatment groups showed similar improvements in depressive symptoms. Repeated measures analysis of variance for the intent-to-treat population revealed that there were no significant differences in mean change of the Symptom Check List-90-Revised (SCL-90-R) somatization subscores between the two groups. For completers, there was a significant timextreatment interaction in the SCL-90-R somatization subscores, but the differences between the two groups at endpoint did not reach statistical significance in post-hoc analysis. In conclusion, this study suggests that overall efficacies of mirtazapine and venlafaxine are similar for the treatment of overall symptoms in MDD, and both drugs may be useful for the treatment of somatic symptoms in MDD patients.

β-adrenoceptor affinity as a biological predictor of treatment response to paroxetine in patients with acute panic disorder

BACKGROUND Few studies have reported on the functional differences of the beta-adrenoceptor between treatment responders and non-responders in panic disorder (PD). The aim of this study was to compare the nature of the beta-adrenoceptor function and clinical variables between treatment responders and non-responders to paroxetine treatment in acute PD patients. METHOD Paroxetine was administered to all of the panic patients for 12 weeks. The lymphocyte beta-adrenoceptor density (Bmax), affinity (1/Kd), and sensitivity (cAMP ratio) were measured in 22 untreated outpatients with acute PD and 22 age, sex and BMI matched control subjects. Psychological assessments were conducted using the HAM-A, and HAM-D, STAI-S and STAI-T, Anxiety sensitivity index (ASI), and Acute panic inventory (API). RESULTS A significantly higher Kd was observed in the panic patients before treatment as compared with the control subjects, but there was no significant difference in Kd between the panic patients and control subjects after the treatment. Among the 22 patients, the 11 treatment responders (50%) showed a significantly higher Kd and lower mean scores of HAM-D, STAI-S, STAI-T, and ASI at baseline, compared with the non-responders. Logistic regression revealed that the pretreatment Kd and HAM-D were significantly reliable predictors for treatment response (p<0.05). CONCLUSION The beta-adrenoceptor affinity (1/Kd) was decreased and adaptively normalized after treatment with paroxetine in the acute panic patients. In addition, a low pretreatment beta-adrenoceptor affinity (1/Kd) was found to predict the treatment response and can be suggested as a biological predictor of treatment response in acute PD.

Panic disorder and health-related quality of life: The predictive roles of anxiety sensitivity and trait anxiety

Panic disorder (PD) is a very common anxiety disorder and is often a chronic disabling condition. However, little is known about the factors that predict health-related quality of life (HRQOL) other than sociodemographic factors and illness-related symptomatology that explain HRQOL in only small to modest degrees. This study explored whether anxiety-related individual traits including anxiety sensitivity and trait anxiety can predict independently HRQOL in panic patients. Patients with panic disorder with or without agoraphobia (N=230) who met the diagnostic criteria in the Structured Clinical Interview for DSM-IV were recruited. Stepwise regression analysis was performed to determine the factors that predict HRQOL in panic disorder. HRQOL was assessed by the 36-item Short-Form Health Survey (SF-36). Anxiety sensitivity was an independent predictor of bodily pain and social functioning whereas trait anxiety independently predicted all of the eight domains of the SF-36. Our data suggests that the assessment of symptomatology as well as individual anxiety-related trait should be included in the evaluation of HRQOL in panic patients.