Association of Serotonin Transporter Gene (5-HTTLPR/rs25531) Polymorphism with Comorbidities of Panic Disorder.

INTRODUCTION: Panic disorder (PD) has many comorbidities such as depression, bipolar disorder (BPD), and agoraphobia (AG). PD is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Recently, a tri-allelic serotonin transporter (5-HTTLPR/rs25531) polymorphism was reported to be more sensitive to personality traits compared to the bi-allelic 5-HTTLPR polymorphism. We hypothesized that the 5-HTTLPR/rs25531 polymorphism may lead to a pathological anxious state depending on the presence or absence of a comorbidity in PD. METHODS: In this study, we investigated the relationship between comorbidities in PD and tri-allelic 5-HTTLPR polymorphisms. A total of 515 patients with PD (148 males, 367 females) were genotyped, and the Revised NEO Personality Inventory as well as anxiety-related psychological tests were administered. Depression, BPD, and AG were diagnosed as comorbidities. RESULTS: For the tri-allele 5-HTTLPR genotype, a significant interaction effect was found between openness to experience and comorbid depression. Examination of the interaction between AG and the tri-allelic 5-HTTLPR genotype revealed that L' allele carriers are associated with higher trait anxiety than the S'S' genotype group in PD without AG. CONCLUSION: Some anxiety and personality traits can be characterized by the tri-allelic gene effect of 5-HTTLPR. These results suggest that tri-allelic 5-HTTLPR genotypes have genetic effects on the presence of comorbidities of PD.

Auditory change-related cerebral responses and personality traits.

The rapid detection of changes in sensory information is an essential process for survival. Individual humans are thought to have their own intrinsic preattentive responsiveness to sensory changes. Here we sought to determine the relationship between auditory change-related responses and personality traits, using event-related potentials. A change-related response peaking at approximately 120 ms (Change-N1) was elicited by an abrupt decrease in sound pressure (10 dB) from the baseline (60 dB) of a continuous sound. Sixty-three healthy volunteers (14 females and 49 males) were recruited and were assessed by the Temperament and Character Inventory (TCI) for personality traits. We investigated the relationship between Change-N1 values (amplitude and latency) and each TCI dimension. The Change-N1 amplitude was positively correlated with harm avoidance scores and negatively correlated with the self-directedness scores, but not with other TCI dimensions. Since these two TCI dimensions are associated with anxiety disorders and depression, it is possible that the change-related response is affected by personality traits, particularly anxiety- or depression-related traits.

Anger tendency may be associated with duration of illness in panic disorder.

BACKGROUND: Several studies have reported an increased tendency towards anger in patients with panic disorder (PD). If this propensity for anger arises from the pathological process of PD, it may be associated with the duration of the illness. The present study therefore examined the relationship between duration of PD and the personality tendency to experience anger in PD patients. METHODS: Participants were 413 patients (132 men and 281 women; age = 38.7 years) with PD. Diagnoses were confirmed using the Mini-International Neuropsychiatric Interview. Illness duration ranged from less than a year to 51 years. After participants completed the Revised NEO Personality Inventory, we examined the association between illness duration and the Angry Hostility and Impulsiveness subscale scores. In the analysis, participants were divided into two groups by duration of illness (long group, n = 186 and short group, n = 200) using the median value (9 years) as a cut-off because of the skewed distribution of the duration. Patients with an illness duration of 9 years (n = 27) were excluded from the comparison. RESULTS: The duration of illness was significantly correlated with the Angry Hostility score (p = 0.002) after controlling for age. Scores were significantly higher in the long group than in the short group (p = 0.04). No significant association was observed between Impulsiveness scores and duration of illness. CONCLUSION: The present study suggests that longer PD duration is related to a stronger tendency to experience anger.

Gender-specific association between the COMT Val158Met polymorphism and openness to experience in panic disorder patients.

BACKGROUND: Because major depression and panic disorder are both more prevalent among females and since several lines of evidence suggest that genetic factors might influence an individual's vulnerability to panic disorder, gene-gender interactions are being examined in such psychiatric disorders and mental traits. A number of studies have suggested that specific genes, e.g. catechol-O-methyltransferase (COMT), might lead to distinct clinical characteristics of panic disorder. METHOD: We compared gender-specific personality-related psychological factors of 470 individuals with panic disorder and 458 healthy controls in terms of their COMT Val158Met polymorphism and their scores on the Revised NEO Personality Inventory (NEO PI-R) and State-Trait Anxiety Inventory (STAI) with a 1-way analysis of covariance. RESULTS: In the male panic disorder patients, the NEO PI-R score for openness to experience was significantly lower in the Met/Met carrier group, whereas there was no such association among the female panic disorder patients or the male or female control groups. CONCLUSION: The gender-specific effect of the COMT genotype suggests that the COMT Val/Met genotype may influence a personality trait, openness to experience, in males with panic disorder.

Gene×gene×gender interaction of BDNF and COMT genotypes associated with panic disorder.

Genetic and gender differences are among the factors that have a role in the etiology of panic disorder (PD). It is thought that PD is related to neurotransmitter pathways, such as brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT), both of which are involved in the regulation of the monoamine mechanism. We examined the interactions of BDNF, COMT and gender differences in terms of personality characteristics in PD. The subjects were 470 patients (178 men, 292 women) with a DSM-IV diagnosis of PD, and 458 healthy controls (195 men, 263 women). The subjects were further clinically characterized using the Revised NEO Personality Inventory (NEO-PI-R) and State-Trait Anxiety Inventory (STAI). COMT Val158Met polymorphisms (rs4680) and BDNF Val66Met (rs6265) polymorphisms were genotyped using allelic discrimination by a real-time PCR assay. A multivariate analysis of covariance (MANCOVA) was performed with STAI and NEO-PI-R scores as the dependent factor, gender and genotyping groups (BDNF and COMT) as fixed factors, and the covariate of age in the PD and healthy control groups. Post hoc MANCOVA tests were conducted to evaluate COMT × BDNF interactions. An interaction of BDNF × COMT × gender was confirmed in the PD group by MANCOVA on STAI scores and NEO-PI-R Neuroticism and Extraversion scores, whereas no association of such interactions was observed in the healthy controls. The anxiety sensitivity of the COMT Met+BDNF Val/Val carriers was higher than that of the COMT Val/Val+BDNF Val/Val carriers by post hoc MANCOVA. A significant BDNF × COMT × gender interaction was observed in the PD patients but not in the controls. Our findings partly demonstrated the involvement of a gene × gene × gender interaction in the pathogenesis of PD.

The Association of BDNF Val66Met Polymorphism With Trait Anxiety in Panic Disorder.

Recent studies indicate that early-onset panic disorder (PD) may show distinct clinical characteristics. The authors compared patients with early-onset PD, patients with late-onset PD, and healthy control subjects in terms of brain-derived neurotrophic factor (BDNF), the Val66Met polymorphism, State-Trait Anxiety Inventory (STAI) scores, and the Revised NEO Personality Inventory. In patients with early-onset PD, the STAI-T score was high in the Met/Met group, whereas the STAI-T score of the Val/Val group tended to be higher for healthy control subjects. The conflicting effect of the BDNF genotype between patients with early-onset PD and healthy control subjects suggests that the BDNF Met/Met genotype may increase trait anxiety in early-onset PD.

Prevalence of bipolar disorder in panic disorder patients in the Japanese population.

BACKGROUND: We examined the rate of bipolar I (BPD-I) and bipolar II disorders (BPD-II) in panic disorder (PD) patients, and compared clinical and psychological variables between PD patients with and without bipolar disorders (BPD). METHODS: Participants were 649 Japanese patients with PD (215 men and 434 women, 38.49 ± 10.40 years) at outpatient clinics for anxiety disorders. Constructive interviews using the Mini-International Neuropsychiatric Interview (MINI) were conducted to confirm the diagnosis of PD, agoraphobia, and BPD, as well as the presence and severity of suicide risk in each subject. Clinical records were also reviewed to confirm the diagnosis of PD and BPD. Participants then completed several questionnaires, including the State Trait Anxiety Inventory-Trait scale, the Anxiety Sensitivity Index, and the Revised Neuroticism-Extraversion- Openness Personality Inventory (NEO-PI-R). RESULTS: We found that 22.34% of the PD patients had BPD (BPD-I: 5.24%, BPD-II: 17.10%). PD patients with BPD-I showed higher prevalence and severity of suicide risk, trait anxiety, anxiety sensitivity, and neuroticism, and lower agreeableness (subscales of the NEO-PI-R) than those with BPD-II and those without BPD. LIMITATION: First, we could not investigate the order of the onset of PD and BPD. Second, BPD patients without PD were not studied as another control group for PD patients with BPD. CONCLUSION: PD patients had high prevalence of BPD. Both PD patients with BPD-I and those with BPD-II had high severity of suicide risk, trait anxiety, anxiety sensitivity, neuroticism, and agreeableness, though these characteristics were more prominent in patients with BPD-I.

A genome-wide CNV association study on panic disorder in a Japanese population.

Family and twin studies have indicated that genetic factors have an important role in panic disorder (PD), whereas its pathogenesis has remained elusive. We conducted a genome-wide copy number variation (CNV) association study to elucidate the involvement of structural variants in the etiology of PD. The participants were 2055 genetically unrelated Japanese people (535 PD cases and 1520 controls). CNVs were detected using Genome-Wide Human SNP array 6.0, determined by Birdsuite and confirmed by PennCNV. They were classified as rare CNVs (found in <1% of the total sample) or common CNVs (found in ≥5%). PLINK was used to perform global burden analysis for rare CNVs and association analysis for common CNVs. The sample yielded 2039 rare CNVs and 79 common CNVs. Significant increases in the rare CNV burden in PD cases were not found. Common duplications in 16p11.2 showed Bonferroni-corrected P-values <0.05. Individuals with PD did not exhibit an increased genome-wide rare CNV burden. Common duplications were associated with PD and found in the pericentromeric region of 16p11.2, which had been reported to be rich in low copy repeats and to harbor developmental disorders, neuropsychiatric disorders and dysmorphic features.

Axial type self-bearing motor for axial flow blood pump.

An axial self-bearing motor is proposed which can drive an axial blood pump without physical contact. It is a functional combination of the bi-directional disc motor and the axial active magnetic bearing, where it actively controls single degree-of-freedom motion, while other motions such as lateral vibration are passively stable. For application to a blood pump, the proposed self-bearing motor has the advantages of simple structure and small size. Through the finite element method (FEM) analysis and the experimental test, its good feasibility is verified. Finally, the axial flow pump is fabricated using the developed magnetically suspended motor. The pump test is carried out and the results are discussed in detail.