Effects of BDNF Val66Met Polymorphism on White Matter Microalterations of the Corpus Callosum in Patients with Panic Disorder in Korean Populations

Objective@#The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism is suggested to be associated with the pathophysiology of anxiety disorders, including panic disorder (PD). Although the fronto-limbic white matter (WM) microstructures have been investigated, the corpus callosum (CC) has not yet been studied regarding its relationship with BDNF Val66Met polymorphism in PD. @*Methods@#Ninety-five PD patients were enrolled. The Neuroticism, the Anxiety Sensitivity Inventory-Revised, Panic Disorder Severity Scale, and Beck Depression Inventory-II (BDI-II) were administered. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the CC regions using Tract-Based Spatial Statistics. @*Results@#The GG genotype in BDNF Val66Met polymorphism has significantly higher fractional anisotropy (FA) values of the body and splenium of the CC, neuroticism and depressive symptom scale scores than the non-GG genotype in PD. The FA values of the body of the CC in the two groups were significantly different independent of age, sex, neuroticism, and BDI-II. @*Conclusion@#Our findings demonstrate that the BDNF Val66Met polymorphism is associated with WM connectivity of the body and splenium of the CC, and may be related to neuroticism and depressive symptoms in PD. Additionally, the CC connectivity according to BDNF polymorphism may play a role in the pathophysiology of PD.

Clinical Characteristics of Female Panic Disorder Patients with Abortion History

OBJECTIVES: The objective of this study is to investigate differences in clinical characteristics between female panic disorder (PD) patients with abortion history (PD+A) and without abortion history (PD−A).METHODS: We examined data from 341 female patients diagnosed with PD. We divided the patients with PD into PD+A (82 patients) and PD−A (259 patients) to compare demographic and clinical characteristics. The following instruments were applied : stress coping strategies, NEO-neuroticism, the Anxiety Sensitivity Index-Revised (ASI-R), the Albany Panic and Phobia Questionnaire (APPQ), the Beck Depression Inventory, the Beck Anxiety Inventory (BAI) and the Sheehan Disability Scale.RESULTS: Compared to the PD−A, the PD+A group showed no significant difference in coping strategies. However, significantly higher scores in neuroticism, the ASI-R, the APPQ and the BAI were observed. In terms of health-related disability, the PD+A group did not show significant difference.CONCLUSIONS: Our results suggest that the PD+A group may differ from the PD−A group in trait markers such as neuroticism and anxiety sensitivity, and abortion history may be associated with panic-related symptom severity. Our study suggests that further consideration is needed on such clinical characteristics in PD patients with abortion history.

Comparison of Fornix and Stria Terminalis Connectivity among First-Episode Schizophrenia, Chronic Schizophrenia and Healthy Controls

OBJECTIVES: Disrupted integrities of the fornix and stria terminalis have been suggested in schizophrenia. However, very few studies have focused on the fornix and stria terminalis comparing first-episode schizophrenia (FESZ), chronic schizophrenia (CS), and healthy controls (HCs) with the application of diffusion-tensor imaging (DTI) technique. The objective of this study is to compare the connectivity of the fornix and stria terminalis among FESZ, CS, and HCs. METHODS: We included the 44 FESZ patients, 39 CS patients and 20 HCs in this study. Voxel-wise statistical analysis of the fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics to analyze the connectivity of fornix and stria terminalis. In addition, the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were used to evaluate clinical symptom severities. RESULTS: There were no significant differences between the FESZ, CS, and HCs in age, sex, education years. The SAPS and SANS scores of the schizophrenia groups showed no significant differences. FA values of the right fornix cres/stria terminalis in the CS group were significantly lower than those in FESZ and HCs. There were no significant differences of FA values of the right fornix cres/stria terminalis between the FESZ and the HCs. Pearson correlation analyses revealed that significant correlation between FA values of the right fornix cres/stria terminalies of the the FESZ group and positive, negative symptom scales, and FA values of the right fornix cres/stria terminalis of the CS group and negative symptom scales. CONCLUSIONS: This study shows that FA values of the fornix and stria terminalis in the CS were lower than in the FESZ and the HCs. These results suggest that the fornix and stria terminalis can play a role in pathophysiology of schizophrenia. Thus current study can broaden our understanding of the pathophysiology of schizophrenia.

Clinical Characteristics of Female Panic Disorder with Early Sexual Abuse History

OBJECTIVES: The objective of this study is to investigate differences of clinical characteristics between a healthy female control group and female panic disorder (PD) patients with early sexual abuse history (PD+S) and without early sexual abuse history (PD-S). METHODS: We examined data from 83 patients diagnosed with PD and 20 healthy control subjects. We divided the patients with PD into PD+S (32 patients) and PD-S (51 patients) to compare demographic and clinical characteristics. The following instruments were applied: the Stress coping strategies, the Beck Depression Inventory (BDI) , the Panic Disorder Severity Scale, the Anxiety Sensitivity Index-Revised (ASI-R), the Albany Panic and Phobia Questionnaire (APPQ) and the NEO-neuroticism. RESULTS: Compared to the PD-S, the PD+S group showed higher scores in neuroticism and the APPQ. And, in the PD+S group, the scores of neuroticism were correlated with the ASI-R and APPQ subscale scores and the APPQ total scores were associated with the scores of BDI. CONCLUSIONS: This study shows that female PD+S patients have higher scores in neuroticism and the APPQ than the PD-S group, and these factors are associated with the panic-related symptoms severity. It emphasizes the need of specific strategies considering the childhood abuse history such as early sexual abuse in clinical approach among patients with PD.

Association between COMT and 5-HTTLPR Polymorphisms in Korean Patients with Panic Disorder : A Replication Study

OBJECTIVES: We investigated whether the catechol-O-methyltransferase (COMT) and serotonin related gene polymorphisms may be associated with agoraphobia in patients with panic disorder in Korea. METHODS: The COMT gene (rs4680), 5-hydroxytryptamine (serotonin) transporter linked polymorphic region (5-HTTLPR) gene (rs25531), serotonin receptor 1A (HTR1A) gene (rs6295) genotypes were analyzed in 406 patients with panic disorder and age-sex matched 206 healthy controls. Patients with panic disorder were dichotomized by the presence of agoraphobia. The following instruments were applied : the Beck Depression Inventory, the Beck Anxiety Inventory, the Panic Disorder Severity Scale. RESULTS: There was a significant difference in the distribution of 5-HTTLPR genotype between panic patients with agoraphobia and without agoraphobia (p = 0.024). That is, the panic patients with agoraphobia had a significant excess of the less active 5-HTTLPR allele (S allele). (p = 0.039) Also, we replicated previous western reports which indicated a significant difference in the distribution of COMT genotype between the patients with panic disorder and the healthy controls (p = 0.040). However, no significant associations of agoraphobia or panic disorder with HTR1A gene polymorphisms were found. CONCLUSIONS: This result supports that the COMT polymorphisms may be associated with panic disorder and suggests that the 5-HTTLPR polymorphisms may play a role in the pathogenesis of agoraphobia in the Korean patients with panic disorder.

Impact of Mindfulness-Based Cognitive Therapy on Intolerance of Uncertainty in Patients with Panic Disorder

OBJECTIVE: Intolerance of uncertainty (IU) is a transdiagnostic construct in various anxiety and depressive disorders. However, the relationship between IU and panic symptom severity is not yet fully understood. We examined the relationship between IU, panic, and depressive symptoms during mindfulness-based cognitive therapy (MBCT) in patients with panic disorder. METHODS: We screened 83 patients with panic disorder and subsequently enrolled 69 of them in the present study. Patients participating in MBCT for panic disorder were evaluated at baseline and at 8 weeks using the Intolerance of Uncertainty Scale (IUS), Panic Disorder Severity Scale-Self Report (PDSS-SR), and Beck Depression Inventory (BDI). RESULTS: There was a significant decrease in scores on the IUS (p<0.001), PDSS (p<0.001), and BDI (p<0.001) following MBCT for panic disorder. Pre-treatment IUS scores significantly correlated with pre-treatment PDSS (p=0.003) and BDI (p=0.003) scores. We also found a significant association between the reduction in IU and PDSS after controlling for the reduction in the BDI score (p<0.001). CONCLUSION: IU may play a critical role in the diagnosis and treatment of panic disorder. MBCT is effective in lowering IU in patients with panic disorder.

Serotonin Transporter and COMT Polymorphisms as Independent Predictors of Health-related Quality of Life in Patients with Panic Disorder

There is growing evidence of poor health-related quality of life (HRQOL) in patients with panic disorder (PD). However, little is known about the factors affecting HRQOL in patients with PD. The authors examined whether 5-HTTLPR tri-allelic approach and Cathechol-O-methyltransferase (COMT) Val(158)Met polymorphism can predict HRQOL in patients with PD controlling for sociodemographic factors and disorder-related symptom levels. The sample consisted of 179 patients with PD consecutively recruited from an outpatient clinic and age- and gender ratio-matched 110 healthy controls. The SF-36 was used to assess multiple domains of HRQOL. Hierarchical multiple regression analysis was performed to determine the independent effect of the 5-HTTLPR and COMT Val(158)Met on the SF-36 in panic patients. Patients with PD showed lowered HRQOL in all sub-domains of the SF-36 compared to healthy controls. The 5-HTTLPR independently and additively accounted for 2.2% of variation (6.7% of inherited variance) of perceived general health and the COMT Val(158)Met independently and additively accounted for 1.5% of variation (5.0% of inherited variance) of role limitation due to emotional problems in patient group. The present study suggests that specific genetic polymorphisms are associated with certain domains of HRQOL and provides a new insight on exploring the factors that predict HRQOL in patients with PD.

Associations between Smartphone Addiction Proneness and Psychopathology

OBJECTIVES: This study aims to investigate possible associations between proneness toward smartphone addiction and certain psychopathological variables to evaluate the psychopathological meaning of smartphone addiction. METHODS: Questionnaires were assigned to 755 adults between September and November 2012. We used the Korean Smartphone Addiction Proneness Scale (SAPS), the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), the Obsessive-Compulsive Inventory-Revised (OCI-R), and the Barratt Impulsivity Scale-11 (BIS-11). Subjects were classified into two groups according to the scores of the SAPS ; the addiction proneness group and the normal-user group. RESULTS: The addiction proneness group had significantly higher scores than the normal-user group in the BDI, BAI, OCI-R, and BIS-11. The scores of the SAPS were positively correlated with the scores of the BDI, BAI, OCI-R, and BIS-11. Using logistic regression analysis, smartphone addiction proneness showed a significant association with BIS-11. CONCLUSIONS: The results of this study suggest that smartphone addiction proneness may be associated with depression, anxiety, obsessive-compulsive symptoms, and impulsivity. Furthermore, impulsivity could be a vulnerability marker for smartphone addiction proneness.

The Effects of 5-HTR1A Polymorphism on Cingulum Connectivity in Patients with Panic Disorder

OBJECTIVE: Serotonin-1A receptors (5-HTR1A) is suggested to be involved in the etiology of several psychiatric disorders including panic disorder (PD). A few imaging studies have suggested the alterations of the cingulum bundle in PD. The objective of this study is to examine the structural changes of cingulum related to the 5-HTR1A polymorphism rs6295 in the patients with PD. METHODS: Thirty-two right-handed patients with PD [11 men, 21 women; 40.34+/-13.17 (mean+/-SD) age] who met the diagnostic criteria in Structured Clinical Interview for DSM-IV were examined by means of MRI at 3 Tesla. We divided the patients with PD into CC genotype group and non CC genotype group (GG/CG genotype group) of the 5-HTR1A rs6295 polymorphism to compare the cingulum white matter connectivity. RESULTS: Tract-based spatial statistics showed significantly increased fractional anisotropy (FA) values in cingulate gyrus process of left cingulum in 5-HTR1A CC genotype compared to GG/CG genotype in PD. Significant positive correlations were shown between the Albany Panic and Phobia Questionnaire (APPQ) interoceptive fear subscale scores, the Anxiety Sensitivity Inventory-Revised fear of publicly observable anxiety reaction subscale scores and FA values of cingulate gyrus process of left cingulum in 5-HTR1A rs6295 GG/CG genotype group. In CC genotype group, APPQ total, APPQ agoraphobia subscale and APPQ social phobia subscale scores also showed significant positive correlations with FA values of hippocampal process of right cingulum. CONCLUSION: This preliminary study suggests that 5-HTR1A polymorphism may be associated with the cingulum white matter connectivity in PD.

Factors Associated with Treatment Outcomes in Mindfulness-Based Cognitive Therapy for Panic Disorder

PURPOSE: Although the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) for panic disorder (PD) has been studied previously, data on the predictors of treatment outcomes in MBCT for PD are scarce. MATERIALS AND METHODS: Eighty patients with PD were screened to analyze treatment outcomes such as MBCT completion, treatment response, and remission after undergoing MBCT for PD. Sociodemographic characteristics, comorbid personality disorders, and baseline medication doses were examined. The study administered the Panic Disorder Severity Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale and Anxiety Sensitivity Inventory-Revised to patients at baseline and at eight weeks. RESULTS: Sixty-five participants were enrolled in the present study. Comorbid personality disorder was significantly associated with MBCT non-completion. We found that anxiety sensitivity (AS) improvement after an eight week MBCT program was a statistically significant factor associated with treatment response. Using logistic regression analysis, AS improvement after MBCT showed significant association with PD remission after MBCT. CONCLUSION: Comorbid personality disorders of participants could be a potential predictor of MBCT non-completion. Furthermore, AS improvement after MBCT may predict treatment response and remission after MBCT for PD. However, better designed studies with a larger number of patients are needed to confirm our findings.