Hwa-Young Lee

Increased levels of plasma glial-derived neurotrophic factor in children with attention deficit hyperactivity disorder

Abstract Background: Recent evidence suggests that neurotrophic growth factor systems, including brain-derived neurotrophic factor, might be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Glial cell line-derived neurotrophic factor (GDNF) is from the transforming growth factor-β family and is abundantly expressed in the central nervous system, where it plays a role in the development and function of hippocampal cells. To date, no association studies have been done between ADHD and GDNF. Thus, here we investigate the hypothesis that there are differences in plasma GDNF levels between children with ADHD and healthy controls. Methods: Plasma GDNF levels were measured in 86 drug-naïve children with ADHD and 128 healthy children. The severity of ADHD symptoms was determined by scores on the Korean ADHD Rating Scale (K-ARS) in patients and healthy controls. Results: The median plasma GDNF levels in ADHD patients was 74.0 (IQR: 23.4–280.1) pg/ml versus 24.6 (IQR: 14.5–87.3) pg/ml in healthy controls; thus the median plasma GDNF levels in ADHD patients were significantly higher than in healthy controls (Mann–Whitney U-test, P < 0.01). Plasma GDNF levels were correlated positively with K-ARS subscale scores (inattention, hyperactivity–impulsivity and total), determined by Spearmans correlation test in ADHD patients and healthy controls (r = 0.371, P < 0.01; r = 0.331, P < 0.01; and r = 0.379, P < 0.01, respectively). Conclusions: These findings suggest increased plasma GDNF levels in untreated ADHD patients. In addition, plasma GDNF levels had a significant positive correlation with inattention, hyperactivity–impulsivity and K-ARS total scores in ADHD patients and healthy controls. Further studies are required to determine the source and role of circulating GDNF in ADHD.

Changes in Dpysl2 expression are associated with prenatally stressed rat offspring and susceptibility to schizophrenia in humans.

Exposure to stress during critical periods of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. In the present study, a repeated-variable stress paradigm was applied to pregnant rats during the last week of gestation, which is analogous to the second trimester of brain development in humans. Behavioral and proteomic analyses were conducted in prenatally-stressed (PNS) adult offspring and non-stressed (NS) adult controls. In the behavioral tests, grooming behavior in the social interaction test, line-crossing behavior in the open field test, and swimming behavior in the forced swimming test were decreased in the PNS group. Western blot analysis and immunohistochemical analysis revealed that the expression of dihydropyrimidinase-like 2 (Dpysl2) or collapsin response mediator protein 2 (Crmp2) was downregulated in the prefrontal cortex and hippocampus of rats in the PNS group. Subsequently, single-nucleotide polymorphisms (SNPs) of the human dihydropyrimidinase-like 2 (DPYSL2) gene were analyzed in a population. Two functional SNPs (rs9886448 in the promoter region and rs2289593 in the exon region) were associated with susceptibility to schizophrenia. The present findings demonstrated that the downregulation of genes such as Dpysl2 and Dypsl3 in a rat model of prenatal stress may affect subsequent behavioral changes and that polymorphisms of the DPYSL2 gene in humans may be associated with the development of schizophrenia. Taken together with previous studies investigating the association between the DPYSL2 gene and schizophrenia, the present findings may contribute additional evidence regarding developmental theories of the pathophysiology of schizophrenia.

Knowledge and Attitude of 851 Nursing Personnel toward Depression in General Hospitals of Korea

Our study aimed to examine the knowledge and attitude of nursing personnel toward depression in general hospitals of Korea. A total of 851 nursing personnel enrolled at four university-affiliated general hospitals completed self-report questionnaires. Chi-square tests were used to compare the knowledge and attitude of registered or assistant nurses toward depression. In addition, binary logistic regression analysis was used to adjust for the following confounders: age-group and workplace. Registered and assistant nurses differed in their knowledge and attitude toward depression. The proportion of rational and/or correct responses were higher in registered nurses than assistant nurses for the following: constellation of depressive symptoms defined by DSM-IV (adjusted odds ratio [aOR], 3.876; P<0.001); suicide risk in depression recovery (aOR, 3.223; P=0.001) and psychological stress as a cause of depression (aOR, 4.370; P<0.001); the relationship between chronic physical disease and depression (aOR, 8.984; P<0.001); and other items. Our results suggest that in terms of the biological model of depression, the understanding of registered nurses is greater than that of assistant nurses. Moreover, specific psychiatric education programs for nursing personnel need to be developed in Korea. Our findings can contribute to the development of a general hospital-based model for early detection of depression in patients with chronic medical diseases. Graphical Abstract

Reliability and validity of the Korean version of the Scale for the Assessment of Thought, Language, and Communication

BACKGROUND Our study aimed to assess the inter-rater and test-retest reliability, as well as concurrent and convergent validity, of the Korean version of the Scale for the Assessment of Thought, Language, and Communication (TLC scale). METHODS The factor solutions and psychometric properties of the Korean version of the TLC scale were evaluated among 167 schizophrenia inpatients (study subjects) at two sites in South Korea. Using Pearsons correlation, the concurrent and convergent validities of each of the factor solutions were represented by the correlations with the scores on the Clinical Language Disorder Rating Scale, Brief Psychiatric Rating Scale, Young Mania Rating Scale, and Calgary Depression Scale. Using receiver operating characteristics curves, the optimal cut-off score for the Korean version of the TLC scale to distinguish between study subjects with and without disorganized speech, was identified. RESULTS The results showed that the Korean version of the TLC scale has a three-factor solution: fluent disorganization, speech emptiness, and speech peculiarity. In addition, the interrater reliability of the Korean version of the TLC scale was moderately good (intraclass correlation coefficient = 0.51) and its test-retest reliability was very good (Pearsons correlation coefficient = 0.94). For detecting the current presence of disorganized speech, the optimal cut-off total score on the TLC scale was proposed to be 8 points (sensitivity = 88.1%; specificity = 82.9%). LIMITATIONS Psychometric tools covering cognitive functions were not used in our study. CONCLUSIONS The Korean version of the TLC scale is a promising psychometric method for examining formal thought disorder (FTD) and disorganized speech in schizophrenia patients.

Influence of Panax ginseng on the offspring of adult rats exposed to prenatal stress

The exposure of pregnant females to stress during a critical period of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. Schizophrenia is a group of common mental disorders of unclear origin, affecting approximately 1% of the global population, showing a generally young age at onset. In the present study, a repeated variable stress paradigm was applied to pregnant rats during the final week of gestation. The effects of an extract of Panax ginseng C.A. Meyer (PG) on rats exposed to prenatal stress (PNS) were investigated in terms of behavioral activity and protein expression analyses. In the behavioral tests, grooming behavior in a social interaction test, line-crossing behavior in an open-field test and swimming activity in a forced-swim test were decreased in the rats exposed to PNS compared with the non-stressed offspring; the changes in behavioral activity were reversed upon oral treatment with PG (300 mg/kg). Subsequently, western blot analysis and immunohistochemical analyses of the prefrontal cortex and hippocampus revealed that the downregulation of several neurodevelopmental genes which occurred following exposure to PNS was reversed upon treatment with PG. The current findings demonstrate that the downregulation of several genes following exposure to PNS may affect subsequent behavioral changes, and that these phenomena are reversed following treatment with PG during pregnancy. Our results suggest that oral treatment with PG reduces the incidence of psychiatric disorders, such as schizophrenia.

Prolactin and macroprolactin levels in psychiatric patients receiving atypical antipsychotics: A preliminary study

The aims of this study were to clarify whether atypical antipsychotics can elevate serum levels of both macroprolactin and prolactin, and whether the macroprolactin levels differ according to the type of atypical antipsychotic being taken. In total, 245 subjects were enrolled consecutively in 6 hospitals. Serum prolactin and macroprolactin levels were measured at a single time point during maintenance antipsychotic monotherapy. The mean total serum prolactin levels including macroprolactin were 11.91, 20.73, 16.41, 50.83, 12.84, and 59.1ng/mL for patients taking aripiprazole, blonanserin, olanzapine, paliperidone, quetiapine, and risperidone, respectively, while those for macroprolactin were 1.71, 3.86, 3.73, 7.28, 2.77, and 8.0ng/mL. The total prolactin and macroprolactin levels were significantly higher among those taking paliperidone and risperidone than among those taking any of the other antipsychotics (p<0.01). Moreover, there was a strong positive correlation between serum levels of prolactin and macroprolactin. Sexual dysfunction was reported in 35.5% (87/245) of the total subjects. However, the total prolactin level did not differ significantly between subjects with and without sexual dysfunction except gynecomastia. These findings suggest that treatment with risperidone and paliperidone can induce hyperprolactinemia and macroprolactinemia in psychiatric patients.

A polymorphism in DMT1 is associated with lead-related hypertensive status

Divalent metal transporter 1 (DMT1) is an iron transporting membrane protein important for dietary iron uptake and as a carrier of other metals, such as zinc, copper, and lead. This study evaluated the possible association of DMT1 with clinical variables in a lead-exposed population. We investigated three single nucleotide polymorphisms (SNPs) (1303C/A, 1254T/C and IVS4+44C/A) of DMT1 in 662 male lead-exposed workers from Korea using polymerase chain reaction-restriction fragment length polymorphism. Among the three SNPs, the frequencies of IVS4+44C/A were significantly different between normotensive and hypertensive subjects. This suggests that a polymorphism in DMT1 is associated with increased risk of lead-related hypertensive status in a Korean male population.

Genetic relationship between an endothelin 1 gene polymorphism and lead-related high blood pressure

This study investigated the effect of an endothelin 1 (EDN1) T-1370G polymorphism on blood lead levels and lead-related blood pressure (LBP) of male Korean workers who had exposure to lead. A cross sectional study involving 771 male lead-exposed workers from Korea was conducted. High resolution melting analysis was used to differentiate the genotypes of the polymorphism. Association of clinical characteristics with genotypes as modifiers was estimated after adjusting for age, smoking status, drinking status, and job duration. Genotype and allele frequencies of the polymorphism were found to be associated with LBP. Blood lead levels were not associated with genotype or allele frequencies. Based on these results, it was concluded that G allele carrier (GG or GG+TG) and G allele of EDN1 polymorphism might be a risk factor of lead-related high blood pressure.

A polymorphism in AGT and AGTR1 gene is associated with lead-related high blood pressure

We investigated the association of polymorphisms in two renin-angiotensin system-related genes, expressed as angiotensinogen (AGT) and angiotensin II type 1 receptor (AGTR1), with blood lead levels and lead-related blood pressure in lead-exposed male workers in Korea. A cross-sectional study involving 808 lead-exposed male workers in Korea was conducted using a restriction fragment length polymorphism-based strategy to differentiate the various genotypes of polymorphisms in the AGT and AGTR1 genes. The association of clinical characteristics with genotypes as modifiers was estimated after adjustment for age, smoking status, drinking status, body mass index and job duration of each subject. Genotype and allele frequencies of the M235T polymorphism in AGT were associated with lead-related high blood pressure status. Moreover, blood lead levels were associated with allele frequencies of the AGT M235T polymorphism. These results suggested that the M/M genotype and M allele of AGT are risk factors for lead-related high blood pressure.

Factors Associated with Emotional Exhaustion in South Korean Nurses: A Cross-Sectional Study

Objective We examined associations between emotional exhaustion and selected sociodemographic and psychological factors among nurses in inpatient and outpatient nursing units at a university hospital in South Korea. Methods The participants were 386 nurses who completed the Maslach Burnout Inventory, a measure of emotional exhaustion. Psychological characteristics were evaluated, including hardiness, self-esteem, experience of trauma, resilience, perceived stress, and social support. Correlation analyses examined the relationships between emotional exhaustion with sociodemographic, occupational, and psychological characteristics. Linear regression was used to evaluate the associations between emotional exhaustion and the assessed characteristics. Results Higher emotional exhaustion scores were associated with greater depression, anxiety, traumatic experience, and perceived stress. Exhaustion was inversely associated with hardiness, self-esteem, resilience, and quality of life. The regression analysis indicated that gender, marriage, resilience, depression, perceived stress, and secondary traumatic stress were significantly associated with emotional exhaustion. Conclusion This study showed that psychological characteristics, such as resilience, depression, and secondary traumatic experiences, may cause emotional exhaustion. Understanding the needs of people with distinct demographic and psychological characteristics offers valuable direction for the development of intervention programs to prevent burnout among nurses.