Seockhoon Chung

The association of nocturnal hypoxemia with arterial stiffness and endothelial dysfunction in male patients with obstructive sleep apnea syndrome.

Background: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular complications, and atherosclerosis is considered to mediate this association. Arterial stiffness and endothelial dysfunction are widely accepted as early markers of atherosclerosis. Objectives: The purpose of this study was to investigate the influence of sleep apnea on arterial stiffness and endothelial dysfunction. Methods: We enrolled 83 OSAS patients including 39 with mild to moderate degree (apnea hypopnea index, AHI ≧5, AHI <30) and 44 with severe degree sleep apnea (AHI ≧30) and 29 normal control subjects (AHI <5). After finishing polysomnography, carotid-femoral pulse wave velocity (cfPWV) and flow-mediated dilation (FMD) were measured using noninvasive devices. Results: In patients with severe degree of OSAS, cfPWV was significantly higher than mild to moderate degree of OSAS or normal control subjects. Also, the severe OSAS group showed lower FMD than the normal control group (all p < 0.01). The cfPWV was significantly correlated with FMD (r = –0.26, p < 0.01). Age (β = 0.33, p < 0.01) and percentage of time below 90% O2 saturation (β = 0.34, p < 0.01) were the significant variables to determine cfPWV (adjusted R2 = 21%, p < 0.01) in multivariate analysis, and the lowest O2 saturation was a significant determinant for FMD (β = 0.25, adjusted R2 = 6%, p < 0.01). Conclusions: Nocturnal hypoxemia may alter arterial elasticity and endothelial function in OSAS patients, and those impairments could increase the risk of cardiovascular complications.

A Structural Model of Stress, Motivation, and Academic Performance in Medical Students

Objective The purpose of the present study was 1) to identify factors that may influence academic stress in medical students and 2) to investigate the causal relationships among these variables with path analysis. Methods One hundred sixty medical students participated in the present study. Psychological parameters were assessed with the Medical Stress Scale, Minnesota Multiphasic Personality Inventory, Hamilton Depression Scale, Beck Depression Inventory, and Academic Motivation Scale. Linear regression and path analysis were used to examine the relationships among variables. Results Significant correlations were noted between several factors and Medical Stress scores. Specifically, Hamilton Depression Scale scores (β=0.26, p=0.03) and amotivation (β=0.20, p=0.01) and extrinsically identified regulation (β=0.27, p<0.01) response categories on the Academic Motivation Scale had independent and significant influences on Medical Stress Scale scores. A path analysis model indicated that stress, motivation, and academic performance formed a triangular feedback loop. Moreover, depression was associated with both stress and motivation, and personality was associated with motivation. Conclusion The triangular feedback-loop structure in the present study indicated that actions that promote motivation benefit from interventions against stress and depression. Moreover, stress management increases motivation in students. Therefore, strategies designed to reduce academic pressures in medical students should consider these factors. Additional studies should focus on the relationship between motivation and depression.

Association among aggressiveness, neurocognitive function, and the Val66Met polymorphism of brain-derived neurotrophic factor gene in male schizophrenic patients.

BACKGROUND The aim of this study was to investigate the association among aggressive behavior, neuropsychological function, and the Val66Met functional polymorphism of brain-derived neurotrophic factor (BDNF) gene in male schizophrenic patients. METHODS We examined 51 male patients with schizophrenia who had committed homicide (ie, H-SCZ), 50 male patients with schizophrenia who had not committed homicide (ie, NH-SCZ), and 50 healthy male controls. Patients were evaluated using the Positive and Negative Syndrome Scale, Life History of Aggression, and the Overt Aggression Scale. In addition, patients were given neurocognitive function tests, including Korean-Wechsler Adult Intelligence Scale short form, the Korean version of the Rey Memory Test, the Stroop Test, and the Wisconsin Card Sorting Test. The Val66Met polymorphism of the BDNF gene was also genotyped in all schizophrenic patients. RESULTS We observed no significant difference between patients in the H-SCZ and NH-SCZ groups, with regard to Positive and Negative Syndrome Scale scores. Total Life History of Aggression (P < .01) and Overt Aggression Scale scores for the most severe episode (P < .01) or for the previous month (P < .05) were higher in the H-SCZ group than in the NH-SCZ group. There were no significant differences in the genotype distribution or allelic frequency of the Val66Met polymorphism between the schizophrenic groups. In addition, we observed no significant differences between H-SCZ and NH-SCZ groups with regard to performance on neuropsychological tests. The Met allele of the Val66Met polymorphism was associated with poor intelligence quotient, memory quotient), learning, and delayed recall in the H-SCZ group. However, genotype did not seem to influence neurocognitive function in schizophrenic patients who had committed homicide. CONCLUSIONS The neurocognitive tests used in our study were unable to distinguish between violent and nonviolent schizophrenic patients. Furthermore, the Val66Met polymorphism was not associated with aggressiveness in patients with schizophrenia.

Insomnia and sleepiness in Parkinson disease: associations with symptoms and comorbidities.

STUDY OBJECTIVES Insomnia and daytime sleepiness are common complaints in Parkinson disease (PD), but the main causes remain unclear. We examined the potential impact of both motor and non-motor symptoms of PD on sleep problems. METHODS Patients with PD (n = 128) were assessed using the Insomnia Severity Index, Epworth Sleepiness Scale, Unified Parkinson Disease Rating Scale, Beck Depression Inventory, Fatigue Severity Scale, Survey of Autonomic Symptoms, and the 39-item Parkinson Disease Questionnaire. A subset of subjects (n = 38, 30%) also completed nocturnal polysomnography and a multiple sleep latency test (MSLT). RESULTS Multivariate stepwise logistic regression models revealed that subjective insomnia was independently associated with depressed mood (odds ratio [OR] = 1.79; 95% confidence interval (CI) [1.01-3.19]), autonomic symptoms (1.77 [1.08-2.90]), fatigue (1.19 [1.02-1.38]), and age (0.61 [0.39-0.96]). Subjective daytime sleepiness was associated with dosage of dopaminergic medication (1.74 [1.08-2.80]) and fatigue (1.14 [1.02-1.28]). On polysomnography, longer sleep latency correlated with autonomic symptoms (rho = 0.40, p = 0.01) and part I (non-motor symptoms) of the Unified PD Rating Scale (rho = 0.38, p = 0.02). Decreased sleep efficiency correlated with autonomic symptoms (rho = -0.42, p < 0.0001). However, no significant difference emerged on polysomnography and MSLTs between patients with or without insomnia or daytime sleepiness. Higher rates of apneic events did predict shorter sleep latencies on the MSLTs. CONCLUSIONS Non-motor symptoms appear to be associated with subjective insomnia, whereas fatigue and dopaminergic medication are associated with subjective daytime sleepiness. Objective sleep laboratory data provided little insight into complaints of insomnia and sleepiness, though obstructive sleep apnea predicted worsened sleepiness when measured objectively.

Gender-specific association of the brain-derived neurotrophic factor gene with attention-deficit/hyperactivity disorder.

Objective Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder with a strong genetic component. Brain-derived neurotrophic factor (BDNF), which participates in the differentiation and survival of dopaminergic and noradrenergic neurons, could play a role in ADHD development. We aimed to explore the relationships between ADHD and BDNF gene polymorphism. Methods We conducted a case-control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test on 151 trios, and compared the results of a continuous performance test (CPT) according to the genotype of the three single nucleotide polymorphisms (rs11030101, rs6265, rs16917204) in the BDNF gene. Results In the case-control analysis, the AA genotype of the BDNF rs11030101 polymorphism was significantly associated with ADHD only in girls (p=0.024, odds ratio=3.00). The T-G-G haplotype was significantly less frequent (p=0.005) and A-G-G was more frequent (p=0.048) in girls with ADHD than in control girls (global p=0.027). A multivariate analysis of variance for commission errors on the CPT showed a significant main effect for the rs11030101 genotype (p=0.026) and an interaction effect of the rs11030101 genotype and gender (p=0.032) in ADHD probands. Conclusion These results provide preliminary evidence for a gender-specific association between BDNF and ADHD in the Korean population.

Effects of Age on the Clinical Features of Men with Obstructive Sleep Apnea Syndrome

Background: There is little information on the differences in polysomnographic findings in obstructive sleep apnea syndrome (OSAS) between elderly and young or middle-aged adults. Objectives: The aim of this study was to elucidate the clinical characteristics of elderly patients compared to young or middle-aged patients with OSAS. Methods: A total of 757 male patients who were found to have OSAS (apnea-hypopnea index, AHI ≥ 5) were enrolled. After nocturnal polysomnography, patients also completed the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Results: The patients were divided into three groups: ages 20–44 (n = 254), ages 45–64 (n = 373), and ages 65–86 (n = 130). Body mass index (BMI) and the proportion of overweight patients (BMI ≥25) were lower in the elderly group (ages 65–84) than in the other age groups (all p < 0.01). However, in the elderly group, there was a significant correlation between AHI and BMI (r = 0.28, p < 0.01), and BMI was a significant determinant of AHI (β = 0.30, p < 0.01). In addition, the elderly group showed a high percentage of apneas among apneas and hypopneas ( p = 0.02) and increased duration of apnea-hypopnea (p < 0.01) compared to the other age groups. Conclusions: Despite the occurrence of OSAS in the elderly with low BMI, the influence of body weight on the severity of OSAS was still significant in elderly patients. Age-related high collapsibility of the upper airways could explain the higher percentage of apneas and longer duration of apnea-hypopnea in the elderly compared to young or middle-aged patients with OSAS.

Novelty-seeking and avoidant coping strategies are associated with academic stress in Korean medical students

High levels of stress and depression in medical students is raising concern. In this study, we sought to identify coping strategies and other factors influencing academic stress in medical students. We enrolled 157 students from the University of Ulsan College of Medicine, Korea, in November, 2010. We used the Medical Stress Scale, Temperament and Character Inventory, Hamilton Depression Scale, Beck Depression Inventory, and Coping Response Inventory to assess psychological parameters. We used Pearsons correlation and linear regression analyses to analyze the data. Novelty-seeking, self-directedness, cooperativeness, coping strategy, and depression scale scores all correlated significantly with stress level. Linear regression analysis indicated that students who are novelty-seeking, likely to use avoidant coping strategies, and unlikely to use active-cognitive and active-behavioral strategies tend to have higher stress levels. Reduction of stress in medical students may be achieved through evaluation of coping strategies and personality features and use of interventions to promote active coping strategies.

A 12-week, naturalistic switch study of the efficacy and tolerability of aripiprazole in stable outpatients with schizophrenia or schizoaffective disorder.

The objectives of this 12-week multicenter open-label switching study were to evaluate the overall clinical efficacy, safety, and tolerability of aripiprazole in stable patients with schizophrenia or schizoaffective disorder, and to assess, in a naturalistic setting, whether such patients experience symptom worsening when switched from D2 receptor antagonists to aripiprazole (a D2 receptor partial agonist). Patients with schizophrenia or schizoaffective disorder in a symptomatically stable state were randomized to aripiprazole or standard-of-care antipsychotics. The Clinical Global Impression (CGI), Positive and Negative Syndrome Scale, and Investigators Assessment Questionnaire were used monthly. The Udvalg for Kliniske Undersogelser side-effect rating scale scores and treatment emergent adverse events were recorded to assess the safety and tolerability of switching to aripiprazole from other antipsychotics. A total of 292 patients were randomly assigned to receive aripiprazole (N = 245) or non-aripiprazole antipsychotics (N = 47). Mean CGI-Improvement score at 12 weeks was 3.56±1.29 (95% confidence interval: 3.39–3.73) in the aripiprazole group, indicating that aripiprazole was effective in treating schizophrenic patients. Aripiprazole treatment resulted in improvement from baseline on all efficacy outcome measures, including Positive and Negative Syndrome Scale total, positive, negative, and general subscale, and CGI-Severity scores. In addition, after aripiprazole treatment, the remission rate was increased from 43.9% at baseline to 51.7% at 12 weeks. The proportion of patients with symptom worsening at 12 weeks was low (12.4%). Both Investigators Assessment Questionnaire and Udvalg for Kliniske Undersogelser scores showed that there were fewer prolactin-related adverse events in the aripiprazole group than in the standard-of-care antipsychotics group (P<0.05). There were no significant between-group differences in time to failure to maintain remission and time to dropout. In the naturalistic setting, symptomatically stable outpatients with schizophrenia who were switched to aripiprazole showed clinically meaningful treatment benefits. The majority of patients was successfully switched from other antipsychotics without serious symptom exacerbation or adverse events over a course of 12 weeks.

Neurotrophin-3 gene, intelligence, and selective attention deficit in a Korean sample with attention-deficit/hyperactivity disorder

OBJECTIVE Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder with a strong genetic component. Neurotrophin-3 (NTF3), which participates in the differentiation and survival of dopaminergic and noradrenergic neurons, has been identified as a factor in the development of ADHD. We investigated the relationships between ADHD and NTF3 gene polymorphism. METHODS We conducted a case-control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test (TDT) on 151 trios, and compared the intelligence quotient (IQ) and a continuous performance test (CPT) according to the genotype of two single-nucleotide polymorphisms (SNPs) (rs6332 and rs6489630) in the NTF3 gene. RESULTS In the case-control and family-based analyses, NTF3 was not significantly associated with ADHD. However, in the ADHD probands, the subjects with AA genotype in the rs6332 SNP had significantly higher mean T-scores for commission errors on the CPT than did those with the AG genotypes (p=0.045). The mean IQ of the ADHD probands who had the CC genotype of the rs6489630 SNP were higher compared with those who had the CT or TT genotype (p=0.035). The mean T-score for response time on the CPT was higher in the subjects with TT genotype in the rs6489630 SNP compared to those with the CC or CT genotype, even after adjusting for the effect of IQ (p=0.021). CONCLUSIONS These results provide preliminary evidence of an association between NTF3 and the intelligence and selective attention deficit in the Korean population.

Microsatellite marker in gamma - aminobutyric acid - a receptor beta 3 subunit gene and autism spectrum disorders in Korean trios.

This study aimed to identify the association between gamma-aminobutyric acid-A (GABA-A) receptor subunit β3 (GABRB3) gene and autism spectrum disorders (ASD) in Korea. Fifty-eight children with ASD [47 boys (81.0%), 5.5 ± 4.1 years old], 46 family trios, and 86 healthy control subjects [71 males (82.6%), 33.6 ± 9.3 years old] were recruited. Transmission disequilibrium test revealed that, 183 bp long allele in GABRB3 gene was preferentially transmitted in families with ASD (p = 0.025), whereas a population-based case-control study, however, showed no association between ASD and GABRB3 microsatellite polymorphism. Our data provide preliminary evidence that GABRB3 gene is associated with ASD in Korea.