Self-Transcendence Mediates the Relationship between Early Trauma and Fatal Methods of Suicide Attempts

Background@#Early trauma is known to be a risk factor of suicide-related behavior. On the other hand, people who attempt suicide using a fatal method are reported to be more likely to complete suicide. In this study, we assumed that early trauma affects an individual's temperament and character and thereby increases the risk of a fatal method of suicide attempts. @*Methods@#We analyzed 92 people with a history of previous suicide attempts. We compared the Temperament and Character Inventory-Revised scores between the groups with and without early trauma, and between the groups with and without a history of suicide attempt using fatal methods through an analysis of covariance with age, sex, and presence of a psychiatric history as covariates. A mediation analysis was conducted of the relationship between early trauma and fatal methods of suicide attempt with self-transcendence as a mediator. @*Results@#Higher self-transcendence was reported in the fatal group (27.71 ± 13.78 vs. 20.97 ± 12.27, P = 0.010) and the early trauma group (28.05 ± 14.30 vs. 19.43 ± 10.73, P = 0.001), respectively. The mediation model showed that self-transcendence mediates the relationship between early trauma and fatal methods of suicide attempt. The 95% confidence intervals for the direct and indirect effect were (−0.559, 1.390) and (0.026, 0.947), respectively. @*Conclusion@#Self-transcendence may mediate the relationship between early trauma and fatal methods of suicide attempt. Self-transcendence may be associated with unhealthy defenses and suicidal behavior for self-punishment and may constitute a marker of higher suicide risk.

Association between the Arylalkylamine N-Acetyltransferase (AANAT) Gene and Seasonality in Patients with Bipolar Disorder

Objective@#Bipolar disorder (BD) is complex genetic disorder. Therefore, approaches using clinical phenotypes such as biological rhythm disruption could be an alternative. In this study, we explored the relationship between melatonin pathway genes with circadian and seasonal rhythms of BD. @*Methods@#We recruited clinically stable patients with BD (n=324). We measured the seasonal variation of mood and behavior (seasonality), and circadian preference, on a lifetime basis. We analyzed 34 variants in four genes (MTNR1a, MTNR1b, AANAT, ASMT) involved in the melatonin pathway. @*Results@#Four variants were nominally associated with seasonality and circadian preference. After multiple test corrections, the rs116879618 in AANAT remained significantly associated with seasonality (corrected p=0.0151). When analyzing additional variants of AANAT through imputation, the rs117849139, rs77121614 and rs28936679 (corrected p=0.0086, 0.0154, and 0.0092) also showed a significant association with seasonality. @*Conclusion@#This is the first study reporting the relationship between variants of AANAT and seasonality in patients with BD. Since AANAT controls the level of melatonin production in accordance with light and darkness, this study suggests that melatonin may be involved in the pathogenesis of BD, which frequently shows a seasonality of behaviors and symptom manifestations.

Self-Transcendence Mediates the Relationship between Early Trauma and Fatal Methods of Suicide Attempts

Background@#Early trauma is known to be a risk factor of suicide-related behavior. On the other hand, people who attempt suicide using a fatal method are reported to be more likely to complete suicide. In this study, we assumed that early trauma affects an individual's temperament and character and thereby increases the risk of a fatal method of suicide attempts. @*Methods@#We analyzed 92 people with a history of previous suicide attempts. We compared the Temperament and Character Inventory-Revised scores between the groups with and without early trauma, and between the groups with and without a history of suicide attempt using fatal methods through an analysis of covariance with age, sex, and presence of a psychiatric history as covariates. A mediation analysis was conducted of the relationship between early trauma and fatal methods of suicide attempt with self-transcendence as a mediator. @*Results@#Higher self-transcendence was reported in the fatal group (27.71 ± 13.78 vs. 20.97 ± 12.27, P = 0.010) and the early trauma group (28.05 ± 14.30 vs. 19.43 ± 10.73, P = 0.001), respectively. The mediation model showed that self-transcendence mediates the relationship between early trauma and fatal methods of suicide attempt. The 95% confidence intervals for the direct and indirect effect were (−0.559, 1.390) and (0.026, 0.947), respectively. @*Conclusion@#Self-transcendence may mediate the relationship between early trauma and fatal methods of suicide attempt. Self-transcendence may be associated with unhealthy defenses and suicidal behavior for self-punishment and may constitute a marker of higher suicide risk.

Association between the Arylalkylamine N-Acetyltransferase (AANAT) Gene and Seasonality in Patients with Bipolar Disorder

Objective@#Bipolar disorder (BD) is complex genetic disorder. Therefore, approaches using clinical phenotypes such as biological rhythm disruption could be an alternative. In this study, we explored the relationship between melatonin pathway genes with circadian and seasonal rhythms of BD. @*Methods@#We recruited clinically stable patients with BD (n=324). We measured the seasonal variation of mood and behavior (seasonality), and circadian preference, on a lifetime basis. We analyzed 34 variants in four genes (MTNR1a, MTNR1b, AANAT, ASMT) involved in the melatonin pathway. @*Results@#Four variants were nominally associated with seasonality and circadian preference. After multiple test corrections, the rs116879618 in AANAT remained significantly associated with seasonality (corrected p=0.0151). When analyzing additional variants of AANAT through imputation, the rs117849139, rs77121614 and rs28936679 (corrected p=0.0086, 0.0154, and 0.0092) also showed a significant association with seasonality. @*Conclusion@#This is the first study reporting the relationship between variants of AANAT and seasonality in patients with BD. Since AANAT controls the level of melatonin production in accordance with light and darkness, this study suggests that melatonin may be involved in the pathogenesis of BD, which frequently shows a seasonality of behaviors and symptom manifestations.

Association between a Genetic Variant of CACNA1C and the Risk of Schizophrenia and Bipolar I Disorder Across Diagnostic Boundaries / 대한정신분열병학회지

OBJECTIVES: Genome-wide association studies (GWASs) and meta-analyses indicate that single-nucleotide polymorphisms (SNPs) in the a-1C subunit of the L-type voltage-dependent calcium channel (CACNA1C) gene increase the risk for schizophrenia and bipolar disorders (BDs). We investigated the association between the genetic variants on CACNA1C and schizophrenia and/or BDs in the Korean population. METHODS: A total of 582 patients with schizophrenia, 336 patients with BDs consisting of 179 bipolar I disorder (BD-I) and 157 bipolar II disorder (BD-II), and 502 healthy controls were recruited. Based on previous results from other populations, three SNPs (rs10848635, rs1006737, and rs4765905) were selected and genotype-wise association was evaluated using logistic regression analysis under additive, dominant and recessive genetic models. RESULTS: rs10848635 showed a significant association with schizophrenia (p=0.010), the combined schizophrenia and BD group (p=0.018), and the combined schizophrenia and BD-I group (p=0.011). The best fit model was dominant model for all of these phenotypes. The association remained significant after correction for multiple testing in schizophrenia and the combined schizophrenia and BD-I group. CONCLUSION: We identified a possible role of CACNA1C in the common susceptibility of schizophrenia and BD-I. However no association trend was observed for BD-II. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.

Feasibility of the Korean version of the Bipolar Depression Rating Scale in Adolescents with Early-Onset Bipolar Disorder

OBJECTIVE: This study explores the feasibility and psychometric properties of the Korean version of the Bipolar Depression Rating Scale (BDRS) in adolescents with Early-onset bipolar disorders. METHODS: Fifty-three participants (aged 13–18) with early-onset bipolar disorders (40 depressed and 18 euthymic, 5 patients were assessed at depressed state and reassessed after remission) were recruited. All participants were assessed using the BDRS, the Hamilton Depression Rating Scale (HAM-D), the Montgomery-Asperg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), and the Modified Overt Aggression scale (MOAS). RESULTS: BDRS exhibited good internal validity and significant correlations with the HAM-D and the MADRS. In item to scale correlations, all items on the BDRS were significantly correlated with the BDRS total scores except for ‘increased motor drive’ and ‘increased speech’, ‘depressed mood’ and ‘worthlessness’ showed the highest mean scores and endorsement rates. BDRS score of the depressed group was significantly higher compared with the euthymic group. Three factors (i.e., psychosomatic, mood, and mixed) were identified in the principal component analysis and hierarchical cluster analysis of the BDRS. CONCLUSION: In this study, we report that the Korean version of BDRS is a feasible and reliable tool for the assessment of depression in adolescents with Early-onset bipolar disorders.

A Study of the Current State of the Mental Health Service Delivery System Using the Focused-Group Interview / 신경정신의학

OBJECTIVES: To use focus-group interviews (FGI) to determine the current state of the Korean mental health service delivery system, inter-agency patient links, and identify associated problems. METHODS: The FGI were conducted by seven workers from psychiatric rehabilitation centers and community mental health centers and seven social workers from mental health hospitals. RESULTS: Within the mental health service delivery system, disconnection of the community network after discharge is considered a serious problem. The following improvement proposals are suggested : 1) the control tower should govern the community network after discharge, 2) consider insurance costs during activation of hospital links, and 3) expand information sharing related to community social facilities. With regard to non-voluntary admission and long-term hospitalization, most focus group members considered the revolving-door phenomenon to be more serious than non-voluntary admission. In order to prevent unnecessary long-term hospitalization, the FGI results indicated that the government should proactively intervene in the admission/discharge process. In addition, the following improvement proposals were suggested : 1) functional activation of the mental health review board via the reinforcement of workers' expertise, 2) expansion of local mental health centers, and 3) undertake institutional changes related to the family-related issue of preferring hospitalization over a stay at a secure facility. CONCLUSION: For the government to improve the efficiency of the mental health service delivery system, it is necessary to improve institutional linkages, expand mental health infrastructure, and develop an integrated management system.

The Relationship between Personality, Sense of Efficacy, and Stress in Korean Teachers

Several studies have linked teachers' personality characteristics and sense of efficacy to stress. However, investigating the relationship between these three constructs in this context was limited. This study aims to investigate the relationship between personality, sense of efficacy and perceived stress among Korean teachers. A total of 137 teachers working in elementary, middle, and high schools located in Seoul, South Korea were recruited for the study. The participants were administered Temperament and Character Inventory, Teacher's Sense of Efficacy Scale (TSES), and Perceived Stress Scale. The TSES was negatively correlated with harm avoidance and positively correlated with persistence, self-directedness, cooperativeness, and self-transcendence. Perceived stress was positively correlated with harm avoidance and negatively correlated with persistence and self-directedness. The path analysis showed that harm avoidance directly predicted perceived stress (β=0.37, 95% CI=0.21–0.53, p=0.002), and self-directedness and persistence predicted one's sense of efficacy (β=0.18, 95% CI=0.01–0.39 and β=0.31, 95% CI=0.10–0.47), which predicted perceived stress (β=-0.21, 95% CI=-0.39 to -0.02). The results of the present study indicate that harm avoidance might be associated with stress-proneness, while persistence, self-directedness, and sense of efficacy might act as protective resources against stress in Korean teachers.

A Comparative Study of Permissive Attitudes Toward Suicide : An Analysis of Cross-National Survey in South Korea, Japan, and the United States

OBJECTIVES: There were previous studies which indicated that attitude toward suicide is able to influence the suicide outcome in both individual and group levels. In regard to the highest suicide rate in Korea, our study aims to explore the influence that attitude toward suicide has on suicide by comparing the national attitude towards suicide with a representative sample of the general population. METHODS: The target population was 20- to 59-year-old adults from South Korea, Japan, and the United States. The panel data were divided according to gender, age, and residential area of individuals, and an email with a hyperlink to our web survey was sent to the randomly selected participants in each stratum. To measure the perceptual differences about suicide in different cultures, this study adopted the Attitudes Toward Suicide questionnaire. RESULTS: A total of 2247 subjects in three countries participated in this study. According to results from factor analysis, there were different structure of factors and included items within factors in the three countries : five factors with nineteen items in South Korea, five factors with nineteen items in the United States, and five factors with twenty-five items in Japan. With regard to permissive attitude toward suicide, the mean value of permissiveness was not significantly different among countries, but permissiveness according to education level, gender, and marital status was different in each country. CONCLUSIONS: This study is the first nationwide comparative study about attitude toward suicide with a representative sample. Our findings suggest that permissive attitude toward suicide influence the suicide phenomenon in each country ; however, its impact is not a mean score of permissiveness, but the detailed difference by various demographics.

Factors Affecting Stigma Resistance in Patients with Bipolar Disorder / 신경정신의학

OBJECTIVES: Stigma resistance is an individual capacity to fight the stigma of mental illness and is an issue of ongoing research regarding the stigma. The aim of this study was to evaluate predictors of stigma resistance in patients with bipolar disorder. METHODS: Demographic, clinical, and psychosocial data were collected from 102 bipolar patients in a university mental hospital. Stigma resistance was measured using a subscale of the Internalized Stigma of Mental Illness Scale. Patients completed self-reported questionnaires including items on self-esteem, hopelessness, social support, and social conflict. RESULTS: Stigma resistance showed positive association with functioning, self-esteem, and social support, and showed negative association with depressive symptoms, hopelessness, and social conflict. In multivariate analysis, stigma resistance was predicted by sex, education, and self-esteem. Self-esteem was the strongest predictive factor of stigma resistance. CONCLUSION: In accordance with previous studies, self-esteem was a central role of predicting stigma resistance. A program for improving self-esteem and its related psychosocial factors will be helpful to enhancing stigma resistance in bipolar patients.

Tardive Dyskinesia and Tardive Dystonia with Second-Generation Antipsychotics in Bipolar Disorder Patients Unexposed to First-Generation Antipsychotics

OBJECTIVES: Second-generation antipsychotics (SGAs) are frequently used in the treatment of bipolar disorder. However, there is still no consensus on their risk of tardive movement syndromes especially for first-generation antipsychotics (FGAs)-naive patients. This study aimed to investigate the prevalence and associated factors of SGAs-related tardive dyskinesia and tardive dystonia in patients with bipolar disorder, in a naturalistic out-patient clinical setting. METHODS: The authors assessed 78 non-elderly patients with bipolar (n = 71) or schizoaffective disorder (n = 7) who received SGAs with a combined use of mood stabilizers for more than three months without previous exposure to FGAs. Multiple direct assessments were performed and hospital records longer than one recent year describing any observed tardive movement symptoms were also reviewed. RESULTS: The prevalence rates of tardive dyskinesia and tardive dystonia were 7.7% and 6.4%, respectively. These patients were being treated with ziprasidone, risperidone, olanzapine, quetiapine, or paliperidone at the time of the onset of the movement symptoms. Tardive dyskinesia was mostly observed in the orolingual area, and tardive dystonia was most frequently detected in oromandibular area. A past history of acute dystonia was significantly associated with presence of both tardive movement syndromes. CONCLUSIONS: Our findings suggest that SGAs-related tardive movement syndromes occur in a substantial portion of bipolar disorder patients. Acute dystonia, a reported risk factor of tardive movement syndromes in the era of FGAs is confirmed as a risk factor of both tardive dyskinesia and tardive dystonia that were induced-by SGAs.

Neuropsychological and Behavioral Profiles in Attention-Deficit Hyperactivity Disorder Children of Parents with a History of Mood Disorders: A Pilot Study

OBJECTIVE: We aimed to investigate the neurocognitive and behavioral endophenotypes of premorbid mood disorder. We compared intelligence, neuropsychological functioning, and behavioral problems among three groups: 1) a high-risk group [attention-deficit hyperactivity disorder (ADHD) children of parents with a history of a mood disorder], 2) a low-risk group (ADHD children of parents without a history of a mood disorder), and 3) normal comparison subjects. METHODS: We used the Korean Educational Development Institute Wechsler Intelligence Scale for Children-Revised (KEDI-WISC-R), the Stroop Color Word Interference Test (Stroop), the Wisconsin Card Sorting Test (WCST), and the Rey-Osterrieth Complex Figure Test (RCFT) as neurocognitive measures, and we used the Child Behavior Checklist (CBCL) as a behavioral measure. Performance on these neuropsychological tests and score on the CBCL of 18 high-risk children were compared to those of 20 low-risk children and 24 healthy children. We also assessed the children's current mood state and familial functioning to control for the confounding effects of these variables. RESULTS: Compared to low-risk and healthy children, high-risk children were impaired on the Picture Completion and Stroop Word subtest and showed higher scores on the CBCL subscales representing internalizing symptoms. These significant group differences persisted even after adjustment for the children's current mood state and familial functioning. CONCLUSION: Neuropsychological deficits in the offspring of parents with a mood disorder may be associated with the current mood state rather than with innate characteristics, while their internalizing symptoms may partially stem from innate characteristics that are endophenotypes of a premorbid mood disorder.

National Evidence-based Collaborating Agency (NECA) Round-table Conference Consensus Statement: multidisciplinary responses to suicide, the first ranked cause of death in adolescents

The National Evidence-based Collaborating Agency (NECA) holds the NECA Round-table Conference that not only disseminates objective and systematic information on topics of social concern in public health care but also organizes discussions on core issues under dispute in the literature through panels composed of multidisciplinary experts. Accordingly, the Round-table Conference was composed of multidisciplinary experts including medical specialists in the areas of psychiatry and preventive medicine, psychiatric and mental health nursing, psychologists, social welfare experts, consultation experts, religious leaders, and government officials from the Ministry of Education, Science and Technology, and Ministry of Health and Welfare. The Round-table Conference, tasked with analysis of the actual status and causes of, and search for solutions for suicide in adolescents, has reached consensus on the current status, trend, risk factors and prevention factors, problems and issues in prevention and coping strategies, effective prevention and coping strategies and areas of research needed for the future. The Round-table Conference commented on the actual status and gravity of suicides in adolescents, and came to the agreement that mental health issues including stress from interpersonal relationships and depression are the key risk factors of suicide. It was further agreed that problems in the measures being implemented for each of the areas include lack of manpower and funding, and inadequate organic association and cooperation among relevant institutions. They also agreed that development of a government-initiated suicide prevention program for adolescents, association among relevant experts, and development, and management of practical guidelines that are of broad and practical use are important. Furthermore, the panels were in agreement that the mass media must comply with the recommended level of coverage in reporting of suicide as adolescents are greatly influenced by provocative mass media reports due to their strong impulsive dispositions.

Subclinical Hypothyroidism in Patients with Bipolar Disorders Managed by Lithium or Valproic Acid

OBJECTIVES: To investigate the pattern of subclinical hypothyroidism (SCH) in patients with bipolar disorders managed by lithium or valproic acid. METHODS: The study participants were 106 patients with DSM-IV bipolar disorders receiving planned maintenance treatment at the Mood Disorders Clinic of Seoul National University Bundang Hospital (aged between 17 and 64, mean duration of follow-up = 875.65 days). Using the bipolar disorder registry, thyroid function data were analyzed to assess the frequency of and the risk factors for SCH in patients managed by lithium (n = 64) or valproic acid (n = 42) for more than 5 months. RESULTS: Overall frequencies of SCH were 20.3% (13/64) in the lithium group, 14.3% (6/42) in the valproic acid group, and between the two groups there is no difference (p = 0.43). No differences were observed in the potential risk factors for SCH between the two groups including age, sex, subtype of bipolar disorder, baseline TSH, and concomitant antipsychotic use. In cases with SCH, thyroid-stimulating hormone (TSH) showed a tendency to increase at 3 month after the initiation of lithium or valproic acid. A gradual increase in the number of patients showing SCH was found within the first 3 years of medication. CONCLUSIONS: With regular monitoring and careful assessment, there was no difference in the risk of SCH between lithium and valproic acid maintenance. The risk of mood stabilizer-associated SCH may gradually increase within 3 years following the commencement of medication, thereby mandating close monitoring for the first 3 years of treatment. Further studies with large sample size would be needed to confirm these findings.

Effects of Combined Treatments of Lithium and Valproate on the Phosphorylation of ERK1/2 and Transcriptional Activity of ELK1 and C-FOS in PC12 Cells

OBJECTIVES: Mechanisms of clinical synergistic effects, induced by co-treatments of lithium and valproate, are unclear. Extracellular signal-regulated kinase (ERK) has been suggested to play important roles in mechanisms of the action of mood stabilizers. In this study, effects of co-treatments of lithium and valproate on the ERK1/2 signal pathway and its down-stream transcription factors, ELK1 and C-FOS, were investigated in vitro. METHODS: PC12 cells, human pheochromocytoma cells, were treated with lithium chloride (30 mM), valproate (1 mM) or lithium chloride + valproate. The phosphorylation of ERK1/2 was analyzed with immunoblot analysis. Transcriptional activities of ELK1 and C-FOS were analyzed with reporter gene assay. RESULTS: Single treatment of lithium and valproate increased the phosphorylation of ERK and transcriptional activities of ELK1 and C-FOS, respectively. Combined treatments of lithium and valproate induced more robust increase in the phosphorylation of ERK1/2 and transcriptional activities of ELK1 and C-FOS, compared to those in response to single treatment of lithium or valproate. CONCLUSIONS: Co-treatments of lithium and valproate induced synergistic increase in the phosphorylation of ERK1/2 and transcriptional activities of its down-stream transcription factors, ELK1 and C-FOS, compared to effects of single treatment. The findings might suggest potentiating effects of lithium and valproate augmentation treatment strategy.

Seoul National University Bundang Hospital's Electronic System for Total Care / 대한의료정보학회지

OBJECTIVES: Seoul National University Bundang Hospital, which is the first Stage 7 hospital outside of North America, has adopted and utilized an innovative and emerging information technology system to improve the efficiency and quality of patient care. The objective of this paper is to briefly introduce the major components of the SNUBH information system and to describe our progress toward a next-generation hospital information system (HIS). METHODS: SNUBH opened in 2003 as a fully digital hospital by successfully launching a new HIS named BESTCare, "Bundang hospital Electronic System for Total Care". Subsequently, the system has been continuously improved with new applications, including close-loop medication administration (CLMA), clinical data warehouse (CDW), health information exchange (HIE), and disaster recovery (DR), which have resulted in the achievement of Stage 7 status. RESULTS: The BESTCare system is an integrated system for a university hospital setting. BESTCare is mainly composed of three application domains: the core applications, an information infrastructure, and channel domains. The most critical and unique applications of the system, such as the electronic medical record (EMR), computerized physician order entry (CPOE), clinical decision support system (CDSS), CLMA, CDW, HIE, and DR applications, are described in detail. CONCLUSIONS: Beyond our achievement of Stage 7 hospital status, we are currently developing a next-generation HIS with new goals of implementing infrastructure that is flexible and innovative, implementing a patient-centered system, and strengthening the IT capability to maximize the hospital value.

Seoul National University Bundang Hospital's Electronic System for Total Care / 대한의료정보학회지

OBJECTIVES: Seoul National University Bundang Hospital, which is the first Stage 7 hospital outside of North America, has adopted and utilized an innovative and emerging information technology system to improve the efficiency and quality of patient care. The objective of this paper is to briefly introduce the major components of the SNUBH information system and to describe our progress toward a next-generation hospital information system (HIS). METHODS: SNUBH opened in 2003 as a fully digital hospital by successfully launching a new HIS named BESTCare, "Bundang hospital Electronic System for Total Care". Subsequently, the system has been continuously improved with new applications, including close-loop medication administration (CLMA), clinical data warehouse (CDW), health information exchange (HIE), and disaster recovery (DR), which have resulted in the achievement of Stage 7 status. RESULTS: The BESTCare system is an integrated system for a university hospital setting. BESTCare is mainly composed of three application domains: the core applications, an information infrastructure, and channel domains. The most critical and unique applications of the system, such as the electronic medical record (EMR), computerized physician order entry (CPOE), clinical decision support system (CDSS), CLMA, CDW, HIE, and DR applications, are described in detail. CONCLUSIONS: Beyond our achievement of Stage 7 hospital status, we are currently developing a next-generation HIS with new goals of implementing infrastructure that is flexible and innovative, implementing a patient-centered system, and strengthening the IT capability to maximize the hospital value.

Verbal and Visual Memory Impairments in Bipolar I and II Disorder

OBJECTIVE: To compare verbal and visual memory performances between patients with bipolar I disorder (BD I) and patients with bipolar II disorder (BD II) and to determine whether memory deficits were mediated by impaired organizational strategies. METHODS: Performances on the Korean-California Verbal Learning Test (K-CVLT) and the Rey-Osterrieth Complex Figure Test (ROCF) in 37 patients with BD I, 46 patients with BD II and 42 healthy subjects were compared. Mediating effects of impaired organization strategies on poor delayed recall was tested by comparing direct and mediated models using multiple regression analysis. RESULTS: Both patients groups recalled fewer words and figure components and showed lower Semantic Clustering compared to controls. Verbal memory impairment was partly mediated by difficulties in Semantic Clustering in both subtypes, whereas the mediating effect of Organization deficit on the visual memory impairment was present only in BD I. In all mediated models, group differences in delayed recall remained significant. CONCLUSION: Our findings suggest that memory impairment may be one of the fundamental cognitive deficits in bipolar disorders and that executive dysfunctions can exert an additional influence on memory impairments.

A new synthetic chalcone derivative, 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139), suppresses the Toll-like receptor 4-mediated inflammatory response through inhibition of the Akt/NF-kappaB pathway in BV2 microglial cells

Microglial cells are the resident innate immune cells that sense pathogens and tissue injury in the central nervous system (CNS). Microglial activation is critical for neuroinflammatory responses. The synthetic compound 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139) is a novel chalcone-derived compound. In this study, we investigated the effects of DK-139 on Toll-like receptor 4 (TLR4)-mediated inflammatory responses in BV2 microglial cells. DK-139 inhibited lipopolysaccharide (LPS)-induced TLR4 activity, as determined using a cell-based assay. DK-139 blocked LPS-induced phosphorylation of IkappaB and p65/RelA NF-kappaB, resulting in inhibition of the nuclear translocation and trans-acting activity of NF-kappaB in BV2 microglial cells. We also found that DK-139 reduced the expression of NF-kappaB target genes, such as those for COX-2, iNOS, and IL-1beta, in LPS-stimulated BV2 microglial cells. Interestingly, DK-139 blocked LPS-induced Akt phosphorylation. Inhibition of Akt abrogated LPS-induced phosphorylation of p65/RelA, while overexpression of dominant-active p110CAAX enhanced p65/RelA phosphorylation as well as iNOS and COX2 expression. These results suggest that DK-139 exerts an anti-inflammatory effect on microglial cells by inhibiting the Akt/IkappaB kinase (IKK)/NF-kappaB signaling pathway.

Designing Clinical Studies and Keeping Research Ethics

Data from clinical studies are needed for psychiatrists to make quick and scientific decisions based on the best available evidence in clinical settings. Various methods of clinical studies are useful for clinicians to have reliable answers to unmet clinical needs. Although randomized controlled trials may provide high-quality information about major issues, well-designed, naturalistic and observational studies often give us unbiased explanation for real-world phenomena. Adequate selection of clinical variables and appropriate number of participants are key factors of well-designed clinical studies. Statistical methods can add an extra dimension to initial design of clinical studies. Given ethical issues in clinical studies on psychiatric disorders, special regards should be paid to participants' ability to provide informed consents. New strategies of clinical studies need to be developed to meet clinical needs and protect the rights and welfare of study participants.