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The metric properties of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) were examined in 182 subjects treated with antipsychotics. Inter-rater reliability, test-retest reliability, and concurrent validity with other rating scales for EPS were high. Four factors were identified and the optimal diagnostic cut-off scores were obtained. These results suggest that the DIEPSS is a reliable and valid multidimensional rating scale.

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.

Objective Posttraumatic embitterment disorder (PTED) is characterized by states of “embitterment”, characteristically similar to “Hwa-byung”, which is a Korean culture-bound syndrome. The present study aimed to assess diagnostic relationships between PTED and Hwa-byung. Methods A total of 290 participants completed our survey. PTED and Hwa-byung were diagnosed using a diagnostic interview and scale. Scales for depression, suicide ideation, and anger were used for evaluation. Fisher's exact tests and Mann-Whitney U tests were performed to evaluate diagnostic overlap between PTED and Hwa-byung, and associations of scale scores for depression, suicide ideation, and anger between the PTED, Hwa-byung, and non-diagnosed groups. Associations of these scales between the depressive and non-depressive groups, and suicidal and non-suicidal groups were also evaluated. Results Among the participants, 1.7% of the sample fit the diagnostic criteria for PTED and 2.1% fit the criteria for Hwa-byung. No individual fit the criteria for both. Anger scores were significantly higher in the Hwa-byung group than in the non-diagnostic group. There were not any significant differences in anger scores between the PTED and non-diagnostic groups. Depression scores were significantly higher in the PTED than in the non-diagnostic groups. In contrast, no significant differences were observed between depression scores in the Hwa-byung and non-diagnostic groups. Conclusion These results suggest that PTED may be a disorder category that is distinct from Hwa-byung.

Both emotional and cognitive processes are involved in moral judgments. Ventromedial prefrontal lesions are related to impaired prosocial emotions and emotional dysregulation, and patients with these lesions exhibit increased utilitarian judgments of emotionally salient personal moral dilemmas. Bipolar patients experiencing manic episode also have impaired emotional regulation and behavioral control. We investigated the characteristics of moral judgment in manic and euthymic patients with bipolar disorder using the 50 hypothetical moral dilemma task (17 non-moral, 20 personal, and 13 impersonal). Our study included 27 manic bipolar patients, 26 euthymic bipolar patients, and 42 healthy controls. Subjects were instructed to determine whether or not each dilemma was morally acceptable, and their reaction times were recorded. Manic patients showed significantly greater utilitarian judgment than euthymic patients and normal controls for personal moral dilemmas. However, there were no significant between-group differences for the non-moral and impersonal moral dilemmas. Our results suggest that increased utilitarian judgments of personal moral dilemmas may be a state-related finding observed only in manic patients. This difference in moral judgment assessments may reflect the decision-making characteristics and underlying neurobiological mechanisms of bipolar disorder, especially during the manic state.

Backgrounds Seasonality, an individual trait of seasonal variations in mood and behavior, has received clinical attention for its association with mood disorders. This study aimed to explore the prevalence, specific manifestation, and associated individual and climatic factors of seasonality in the non-elderly adult population. Methods Five hundred fifty-two participants [male n =220; female n =332; mean age 34.92years, standard deviation (SD) 10.18] with no psychiatric history were recruited from the Seoul metropolitan area (37°33′58.87″N 126°58′40.63″E). Seasonality was evaluated using the Seasonal Pattern Assessment Questionnaire. Climatic variables used in analyses were averaged over recent 5years (from 2008 to 2013) on a monthly basis. Results The mean global seasonality score (GSS) was 5.53 (SD 3.91), and 16.2% ( n =89) of participants had seasonal affective disorder (SAD) or sub-SAD. The "feeling worst" month in most of the participants with significant seasonality were winter (41.6%) or summer (38.2%). Socio-demographic factors including age and sex were not related to the seasonality. Decreased sunlight amount and diurnal temperature range in a given and previous month, and increased humidity in a previous month showed significant associations with the percentage of participants with the worst mood. The most frequently reported symptom related to seasonality was ‘changes in energy level'. Specific manifestations were not significantly different between the winter type and the summer type. Conclusion The summer and winter type seasonality in the non-clinical adult population did not differ in terms of behavioral manifestations. Decreased sunlight amount, diurnal temperature range, and increased humidity appeared to be major climatic factors associated with seasonality.

This study aimed to investigate the overall prescription pattern for patients with bipolar disorders in Korea and its relevance to the practice guidelines. Prescription records from all patients with bipolar I and II disorders who have been admitted or who started the outpatient treatment during the year of 2009 in 10 academic setting hospitals were reviewed. A total of 1447 patients with bipolar I and II disorders were included in this study. Longitudinal prescription patterns of inpatients and outpatients were analyzed by episode types and compared with the clinical practice guideline algorithms. In all phases, polypharmacy was chosen as an initial treatment strategy (>80%). The combination of mood stabilizer and atypical antipsychotics was the most favored. Antipsychotics were prescribed in more than 80% of subjects across all phases. The rate of antidepressant use ranged from 15% to 40%, and it was more frequently used in acute treatment and bipolar II subjects. The concordance rate of prescriptions for manic inpatients to the guidelines was higher and relatively more consistent (43.8%-48.7%) compared with that for depressive inpatients (18.6%-46.9%). Polypharmacy was the most common reason for nonconcordance. In Korean psychiatric academic setting, polypharmacy and atypical antipsychotics were prominently favored in the treatment of bipolar disorder, even with the lack of evidence of its superiority. More evidence is needed to establish suitable treatment strategies. In particular, the treatment strategy for acute bipolar depression awaits more consensuses.

Background Time perception, which plays a fundamental role in decision-making and the evaluation of the environment, is also influenced by emotions. Patients with bipolar disorder have impairments in emotional processing as well as interval timing. We investigated the effects of emotional stimuli on time estimation and reproduction in manic and euthymic bipolar patients compared with healthy controls. Methods We recruited 22 manic bipolar patients, 24 euthymic bipolar patients and 24 healthy controls. Each subject performed time estimation and reproduction tasks using standardized affective pictures that were classified into 4 stimulus groups according to valence and level of arousal and presented for durations of 2, 4, and 6 s. We analyzed temporal performance on these tasks using transformed data expressed as a proportion of the target period. Results The interactions between arousal and valence were different in manic patients compared with euthymic patients and healthy controls in both time estimation and reproduction tasks. Manic patients showed no effect of positive valence low arousal stimuli in the time estimation task compared to euthymic patients and healthy controls. In the time reproduction task, the effect of emotional stimuli was reversed in manic patients compared to euthymic patients and healthy controls. Significant correlations between the severity of manic symptoms or illness severity and average temporal performance scores were found in manic patients. Conclusion Our results suggest that altered emotion-related time judgments may be a state-dependent phenomenon observed in manic patients only. This difference in time perception for emotional stimuli may be related to the underlying neurobiological mechanisms of the manic state.

Objective: We discuss the rationale behind staging systems described specifically for bipolar disorders. Current applications, future directions and research gaps in clinical staging models for bipolar disorders are outlined. Method: We reviewed the literature pertaining to bipolar disorders, focusing on the first episode onwards. We systematically searched data on staging models for bipolar disorders and allied studies that could inform the concept of staging. Results: We report on several dimensions that are relevant to staging concepts in bipolar disorder. We consider whether staging offers a refinement to current diagnoses by reviewing clinical studies of treatment and functioning and the potential utility of neurocognitive, neuroimaging and peripheral biomarkers. Conclusion: Most studies to date indicate that globally defined late-stage patients have a worse overall prognosis and poorer response to standard treatment, consistent with patterns for end-stage medical disorders. We believe it is possible at this juncture to speak broadly of 'early'- and 'late'-stage bipolar disorder. Next steps require further collaborative efforts to consider the details of preillness onset and intermediary stages, and how many additional stages are optimal.

Objective Ethnic, social and cultural factors contribute to axis I comorbid conditions in bipolar disorder (BPD). Korea has strict laws against illicit drugs and a relatively permissive prevailing attitude toward alcohol. The present study aimed to explore the lifetime axis I comorbidity rate in patients with BPD in Korea. Methods Clinically stable patients with bipolar I (n=222) and bipolar II (n=194) disorders were recruited from four tertiary medical centers in Korea. The subjects׳ diagnoses and axis I comorbid conditions were evaluated using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) and the Korean version of the Diagnostic Interview for Genetic Studies (K-DIGS). The lifetime prevalence of anxiety disorders, substance use disorders and eating disorders was explored. The prevalence of these axis I comorbid conditions was compared with data from prior studies in other countries and to data concerning the general Korean population. Results A total of 45.1% of all subjects had at least one axis I comorbid condition. Anxiety disorders (30.2%) were the most common comorbidity, followed by alcohol use disorders (16.8%). Males with BPD showed a higher rate of alcohol dependence compared to the general male population and females with BPD showed a greater risk of having alcohol use disorder compared to the general female population. The rate of drug use disorder was extremely low (1.7%), and only one subject had an illicit-drug-related problem. Limitation Cross-sectional studies. Conclusion Comorbid conditions of Korean patients with BPD showed a distinct pattern, which is associated with the ethnic, social and cultural characteristics in Korea.

Background Suicide attempters treated in emergency rooms were studied in order to understand the motives behind this behavior. Disparities between the etiological contributions to suicidal ideation, intention, and action were examined in order to characterize motives in these categories. Methods Suicide attempters who visited the emergency departments of seven university hospitals were analyzed. Attempts leading to mortality were excluded from the analysis. Participants were assessed using semi-structured questionnaires, the results of which were noted on their medical records. These were analyzed retrospectively. Results Attempter self-report assessment revealed that participants chose external sources of stress (75.4%) and psychiatric symptoms (19.1%) as their main reasons for attempting suicide. However, assessments by interviewers indicated that stressors contributed to suicide attempts to a lesser degree (52.8%) while psychiatric symptoms were more etiologically relevant (36.6%). Compared to those with stressors that was identified as causal in both self-report and clinician assessed evaluation, the participants—regardless of their self-report evaluation—who identified with causal psychiatric symptoms by psychiatrist had more severe and intense suicidal ideation and more determined suicidal intention. Limitations We collected samples from only university hospitals, resulting in selection bias. In addition, we did not use psychiatric scales to evaluate the participants׳ symptoms. Conclusions Stress was the greatest motive for attempting suicide, affirmed in both self-report and clinician assessed evaluation. A fair proportion of people were objectively identified as being motivated by psychiatric symptoms, yet were unaware of what they suffered from. Furthermore, suicide severity, intensity, and suicidal intention were stronger in psychiatrically driven cases.

Objective The aim of this study was to investigate the overgeneralization of autobiographical memory (AM) in bipolar disorder (BD) and assess its association with multiple cognitive domains. Method Twenty-eight clinically stable bipolar I patients and an equal number of age- and gender-matched healthy controls (HC) were included. All participants were examined using the autobiographical memory test (AMT) and the neuropsychological battery including the general intelligence, attention, verbal memory, verbal fluency, visual memory, and executive functions domain. Demographic, clinical, and test variables were compared between BD and HC groups. Correlation analyses of AMT scores with cognitive functions were performed within each group, controlling for demographic and clinical variables. Results Total and negative scores of AMT were significantly lower in BD patients compared to HC individuals. AMT scores were significantly correlated with WAIS similarities, WCST perseverative errors, and WCST categories completed in BD, whereas AMT scores were correlated with verbal memory and verbal fluency in HC. Conclusion Our findings suggest that overgeneral AM is a characteristic of BD and is related to executive function. Future studies should investigate the benefit of additional treatment focusing on overgeneral AM in BD.

A task force report presents 12 recommendations for antidepressant use in bipolar disorder rated by at least 80% of International Society for Bipolar Disorders experts as essential or important. Objective The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. Method An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. Results There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. Conclusions Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Episodes of bipolar disorder are defined as depressive or manic, but depressive and manic symptoms can combine in the same episode. Coexistence or rapid alternation of depressive and manic symptoms in the same episode may indicate a more severe form of bipolar disorder and may pose diagnostic and treatment challenges. However, definitions of mixed states, especially those with prominent depression, are not well established.The authors performed literature searches for bipolar disorder, multivariate analyses, and the appearance of the terms "mixed" in any field; references selected from the articles found after the search were combined after a series of conferences among the authors.The authors reviewed the evolution of the concept of mixed states and examined the symptom structure of mixed states studied as predominantly manic, predominantly depressive, and across both manic and depressive episodes, showing essentially parallel structures of mixed states based on manic or depressive episodes. The authors analyzed the relationships between mixed states and a severely recurrent course of illness in bipolar disorder, with early onset and increased co-occurring anxiety-, stress-, and substance-related disorders, and they used this information to derive proposed diagnostic criteria for research or clinical use.The definitions and properties of mixed states have generated controversy, but the stability of their characteristics over a range of clinical definitions and diagnostic methods shows that the concept of mixed states is robust. Distinct characteristics related to the course of illness emerge at relatively modest opposite polarity symptom levels in depressive or manic episodes.

Clozapine affects the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in the brain, which plays an important role in its antipsychotic action. However, previous findings are inconsistent, and related molecular mechanisms require further clarification.Time- and dose-dependent effects of clozapine on the ERK1/2 pathway and its regulatory mechanism were investigated in rat frontal cortex.At 15, 30, 60, and 120 min after intraperitoneal injection of clozapine (5, 10, and 20 mg/kg), changes in ERK1/2, its upstream canonical kinases (Raf1 and mitogen-activated protein kinase kinase 1/2 [MEK1/2]), and its downstream molecule (p90 ribosomal S6 kinase [p90RSK]) were investigated in rat frontal cortex. At 15 min, p-Raf1, p-MEK1/2, p-ERK1/2, and p-p90RSK all increased dose-dependently. At 30 min, p-ERK1/2 and p-p90RSK showed no significant changes, while dose-dependent increases in p-Raf1 and p-MEK1/2 were found. At 60 and 120 min, although p-ERK1/2 and p-p90RSK decreased, increases in p-Raf1 and p-MEK1/2 were maintained. A clozapine-induced reduction in ERK1/2 phosphorylation was evident at both tyrosine and threonine residues, suggesting the involvement of dual specificity phosphatases (DUSPs; mitogen-activated protein kinase phosphatases [MKPs]). mRNA expression of seven Dusps that can dephosphorylate ERK1/2 were examined; Mkp-1 (Dusp1) mRNA increased following clozapine treatment. Moreover, MKP-1 protein and phosphatase activity increased, and binding of MKP-1 to ERK1/2 was also upregulated by clozapine administration.In rat frontal cortex, clozapine regulates ERK1/2 phosphorylation via MKP-1, which induces uncoupling between Raf1-MEK1/2 and ERK1/2-p90RSK activity. These findings suggest an important role of MKP-1 in the mechanism of action of clozapine.

The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009. This third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunction with the previous publications.The recommendations for the management of acute mania remain largely unchanged. Lithium, valproate, and several atypical antipsychotic agents continue to be first-line treatments for acute mania. Monotherapy with asenapine, paliperidone extended release (ER), and divalproex ER, as well as adjunctive asenapine, have been added as first-line options.For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, as well as olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. Lurasidone monotherapy and the combination of lurasidone or lamotrigine plus lithium or divalproex have been added as a second-line options. Ziprasidone alone or as adjunctive therapy, and adjunctive levetiracetam have been added as not-recommended options for the treatment of bipolar depression. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone long-acting injection, and adjunctive ziprasidone continue to be first-line options for maintenance treatment of bipolar disorder. Asenapine alone or as adjunctive therapy have been added as third-line options.

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.

Patients with bipolar disorders (BD) show a broad range of neurocognitive impairments. We compared the patterns of neuropsychological performance in depressed and euthymic patients with BD, and explored the state-dependent cognitive markers of bipolar depression.The study participants included 32 BD patients (15 depressed and 17 euthymic) and 42 healthy controls. All of the subjects completed tests that assessed attention, psychomotor speed, verbal and visual memory, and executive functions. Between-group neuropsychological performance differences were examined. Multidimensional scaling (MDS) was used to compare the patterns of cognitive variables in euthymic and depressed BD patients.Compared to the euthymic BD patients and healthy controls, the depressed BD patients performed lower in verbal memory and executive functions. No significant differences were found between the three groups in attention, psychomotor speed, and visual memory. The depressed BD patients showed a lower level of association between psychomotor speed and the time to initial concept formation than the healthy controls and euthymic BD patients. In contrast, the correlation between word association and verbal memory was stronger in the depressed group than either the control or euthymic groups.The depressed BD patients showed greater impairments in verbal memory and executive functions than the euthymic BD patients. In addition, our study identified a differential pattern of correlations between the cognitive domains of euthymic and depressed BD patients, which suggests the potential role of verbal memory and executive functions as cognitive markers of BD.

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.

Objectives Effective, long-term therapy for bipolar disorders is a critical goal of mental health care, but achieving this goal is complicated by numerous factors in real clinical settings. The aim of this study was to investigate dropout patterns and their associated factors in patients with bipolar disorders. Methods The study participants were 275 patients with DSM-IV bipolar disorders, receiving planned maintenance treatment among patients at the Mood Disorders Clinic of Seoul National University Bundang Hospital between January 2005 and December 2007. The rates of dropout in patients were prospectively examined for 3 years. The factors affecting the dropouts were analyzed using a Cox regression model. Results The dropout rates were 10.9%, 20.4%, 24.7%, 33.8%, 44.0%, and 50.2% at 1, 3, 6, 12, 24, and 36 months after treatment entry, respectively. The dropout rates increased rapidly during the first three months and slowed after 12 months. Past psychotic symptoms (HR 0.523, 95% CI 0.339–0.807), longer illness duration (HR 0.975, 95% CI 0.955–0.966), past psychiatric diagnoses (bipolar disorder, HR 0.242, 95% CI 0.120–0.490; other axis I disorders 0.434, 95% CI 0.268–0.701), and a past history of dropouts (HR 1.746, 95% CI 1.028–2.965) significantly influenced the time to dropout in bipolar patients. The main reasons for dropout were ‘denial of therapeutic need’ (34.8%) and ‘lack of treatment efficacy’ (23.2%). Dropout from the maintenance phase of treatment was mainly attributed to the patients' poor understanding of the effects of their treatment. Conclusion A high early dropout rate for subjects with bipolar disorders was observed in this study, suggesting an increased risk for insufficient maintenance treatment. These results may support the role of psychoeducational approaches in enhancing adherence to treatment, as well as social approaches to improving public awareness. Following the early evaluation of a patient's concept of bipolar disorders, individualized psychoeducational strategies are necessary to improve the long-term outcomes for subjects with bipolar disorders.

Neuroinflammation is associated with the pathophysiology of various neurodegenerative diseases. Emerging evidence indicates that imipramine, a tricyclic antidepressant commonly used in depressive disorders, exhibits neuroprotective activity partly through anti-inflammatory effects. However, the molecular mechanisms underlying imipramine-mediated anti-inflammatory response are poorly understood. In this study, rat primary cultured astrocytes were used to elucidate the effect of the imipramine on TNFα-induced inflammatory responses. The results clearly demonstrated that imipramine reduced TNFα-induced CXCL1 expression through suppression of NF-κB-dependent CXCL1 promoter activity in primary astrocytes. In addition, we found that imipramine suppressed TNFα-induced phosphorylation of inhibitor of κBα (IκBα) and p65/RelA nuclear factor-κB (NF-κB), as well as the nuclear translocation of p65/RelA in primary cultured astrocytes. Chemotaxis assay demonstrated that astrocyte-derived CXCL1 contributed to migration of BV2 microglial cells toward astrocytes. This response was significantly blocked by treatment of astrocytes with imipramine or NF-κB inhibitor BAY11-7082. This study indicates that the antidepressant imipramine inhibits TNFα-induced CXCL1 expression via down-regulation of NF-κB signaling pathway in astrocytes and suggests that imipramine has a potential as an anti-inflammatory drug.

Differences and similarities in microstructural white matter alterations between bipolar I and bipolar II disorder were investigated. Twelve patients with bipolar I disorder, 12 patients with bipolar II disorder and 22 healthy controls underwent diffusion tensor imaging. Fractional anisotropy (FA) and mean apparent diffusion coefficient (ADC) maps were compared between groups using voxel-based whole brain analyses. Both bipolar I and II groups had a FA decrease in the corpus callosum, cingulate and right prefrontal regions, and a ADC increase in the medial frontal, anterior cingulate, insular and temporal regions, compared to controls. The bipolar I group had a FA decrease in the right temporal white matter and a ADC increase in the frontal, temporal, parietal and thalamic regions, compared to the bipolar II group. The results suggest disrupted integrity of commissural fibers and white matter in the anterior paralimbic structures in bipolar disorder. Relative sparing of the dorsal system and long association fibers may differentiate bipolar II from I disorder.

Recent evidence has suggested that deficits in glial plasticity contribute to the pathophysiology of depressive disorders. The present study explored early growth response 1 (EGR-1) transcriptional regulation of imipramine-induced glial cell line-derived neurotrophic factor (GDNF) expression in astrocytes. After we observed the induction of GDNF mRNA expression in rat astrocytes in response to imipramine, deletion mutant studies showed that the proximal region between − 493 and − 114 of the GDNF promoter, which contains three binding sites for EGR-1, was essential for maximal imipramine-induced activation of GDNF promoter. The dose-dependent upregulation of EGR-1 by imipramine, the activation of GDNF by the over-expression of EGR-1 without imipramine and the reduction in the imipramine-induced GDNF mRNA expression after silencing of endogenous EGR-1 demonstrated that EGR-1 is upregulated by imipramine to activate the GDNF promoter. Furthermore, imipramine-induced GDNF mRNA expression was strongly attenuated in primary astrocytes from Egr-1−/− mice, and the immunoreactivity to an anti-GDNF antibody in glial fibrillary acidic protein-positive cells was lower in imipramine-treated astrocytes from Egr-1−/− mice than in those from Egr-1+/− mice. To determine whether mitogen-activated protein kinases (MAPKs) were associated with imipramine-induced EGR-1 expression, we examined the induction of MAPK phosphorylation in response to imipramine. Pretreatment of rat primary astrocytes with the MAPK kinase inhibitor U0126 or the JNK inhibitor SP600125 strongly inhibited imipramine-stimulated EGR-1 expression. In conclusion, we found that imipramine induction of EGR-1 upregulated GDNF in astrocytes in a dose-dependent manner. This upregulation may occur through the MEK/ERK and JNK MAPK pathways, which suggests a new therapeutic mechanism of action for depressive disorders.

Background The present study was designed to investigate whether bipolar II disorder (BP-II) has different characteristics from bipolar I disorder (BP-I), not only in manic severity but also in clinical features, prior course, comorbidity, and family history, sufficiently enough to provide its nosological separation from BP-I. Methods Comprehensive clinical evaluation was performed based on information available from ordinary clinical settings. Seventy-one BP-I and 34 BP-II patients were assessed using the Diagnostic Interview for Genetic Studies, Korean version. Psychiatric assessment for first-degree relatives ( n = 374) of the probands was performed using the modified version of the Family History-Research Diagnostic Criteria. Results The frequency of depressive episodes was higher in BP-II ( p = 0.009) compared to BP-I. Further, seasonality ( p = 0.035) and rapid-cycling course ( p = 0.062) were more common in BP-II. Regarding manic expression, ‘elated mood’ was predominant in BP-II whereas ‘elated mood’ and ‘irritable mood’ were equally prevalent in BP-I. With regard to depressive symptoms, psychomotor agitation, guilty feeling, and suicidal ideation were more frequently observed in BP-II. BP-II patients exhibited a higher trend of lifetime co-occurrence of an axis I diagnosis ( p = 0.09), and a significantly higher incidence of phobia and eating disorder. The overall occurrence rate of psychiatric illness in first-degree relatives was 15.4% in BP-I and 26.5% in BP-II ( p = 0.01). Major depression ( p = 0.005) and substance-related disorder ( p = 0.051) were more prevalent in relatives of BP-II probands. Conclusion Distinctive characteristics of BP-II were identified in the current study and could be adopted to facilitate the differential diagnosis of BP-I and BP-II in ordinary clinical settings.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder in 2005, with a 2007 update. This second update, in conjunction with the International Society for Bipolar Disorders (ISBD), reviews new evidence and is designed to be used in conjunction with the previous publications. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate, and several atypical antipsychotics continue to be first-line treatments for acute mania. Tamoxifen is now suggested as a third-line augmentation option. The combination of olanzapine and carbamazepine is not recommended. For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. New data support the use of adjunctive modafinil as a second-line option, but also indicate that aripiprazole should not be used as monotherapy for bipolar depression. Lithium, lamotrigine, valproate, and olanzapine continue to be first-line options for maintenance treatment of bipolar disorder. New data support the use of quetiapine monotherapy and adjunctive therapy for the prevention of manic and depressive events, aripiprazole monotherapy for the prevention of manic events, and risperidone long-acting injection monotherapy and adjunctive therapy, and adjunctive ziprasidone for the prevention of mood events. Bipolar II disorder is frequently overlooked in treatment guidelines, but has an important clinical impact on patients' lives. This update provides an expanded look at bipolar II disorder.

To investigate white matter abnormalities in patients with obsessive-compulsive disorder and to clarify the relationship between discrete white matter alterations and obsessive-compulsive symptom dimensions, the fractional anisotropy obtained from 25 male patients and 25 matched normal controls were analyzed. The patients had a significantly lower fractional anisotropy in the left anterior cingulate white matter than the controls. When stratified by clinical symptom dimensions, patients with a predominant aggressive/checking symptom dimension exhibited a significantly lower fractional anisotropy in the left anterior cingulate white matter, whereas patients with a predominant contamination/cleaning symptom dimension showed a significantly higher fractional anisotropy in the bilateral prefrontal white matter. Our findings provide evidence that obsessive-compulsive disorder may be a heterogeneous disease with distinct white matter changes.

ObjectiveaaThe current study explored the relationship between the polarity of the first episode and the timing of eventual diagnosis of bipolar I disorder, and associated clinical implications. MethodsaaTwelve years of clinical data from the medical records of 258 inpatients meeting DSM-III-R or DSM-IV criteria for bipolar I disorder were analyzed. Subjects were divided into two groups according to the polarity of the first episode: those with depressive polarity (FE-D), and those with manic polarity (FE-M). Comparisons were made between the two groups on variables associated with the timing of diagnosis and related outcomes. ResultsaaIn population with bipolar I disorder, a significant longer time lapse from the first major mood episode to the confirmed diagnosis was associated with the FE-D group compared to the FE-M group [5.6 (±6.1) vs. 2.5 (±5.5) years, p

Despite the high prevalence and clinical significance of bipolar II disorder (BD II), the underlying pathophysiology is not well explored in previous studies. The purpose of the current study was to investigate brain gray matter abnormalities in BD II. High resolution magnetic resonance brain images from 23 BD II patients, 23 sex- and age-matched patients with bipolar I disorder (BD I) and 23 healthy controls were acquired and processed according to the optimized voxel-based morphometry protocol. The processed gray matter tissue volumes were compared among the three groups. Both the BD II and BD I group showed gray matter deficits in the ventromedial prefrontal regions, compared to controls. The BD I group had widespread gray matter reductions in the bilateral frontal, temporal, parietal and parahippocampal cortices, compared to controls. However, gray matter reductions in these regions were not found in the BD II group. With a less conservative statistical threshold, the BD II group showed additional gray matter deficits in the anterior limbic cortices. Our data suggest that gray matter deficits in the ventromedial prefrontal and anterior limbic cortices are common in both BD II and BD I. On the other hand, different pattern of gray matter abnormalities between BD II and BD I found in this study supports that two subtypes may have different neurobiological characteristics.

The rapid progress in treatments for bipolar disorder makes it necessary to revise the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) published in 2002. This study was performed to timely revise KMAP-BP 2002. A questionnaire comprising 37 questions and 645 treatment options was developed for surveying the opinions of Korean experts. We classified the opinions into three categories: first-, second-, and third-line treatments. Fifty-three (75.7%) of the 70 selected experts answered the questionnaire. For an acute manic episode, the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP) was the preferred first-line treatment. Most experts recommended divalproex and lithium as MSs, and olanzapine, quetiapine, and risperidone as AAPs. For moderately to severely depressed bipolar patients, MS monotherapy and a combination of an MS and an antidepressant (AD) were considered to be preferred treatments respectively. A combination of an MS and an AD was the preferred strategy in severe nonpsychotic depression. Most ADs were rated as second-line drugs. Overall, the preference for lamotrigine and AAPs was higher than in KMAP-BP 2002. The algorithm was developed mainly using consensus among experts supplemented with findings of recent clinical trials to ensure that our algorithm was both up to date and balanced. These results suggest that the medication strategies of KMAP-BP are changing rapidly, reflecting recent studies and clinical experiences.

Objective To investigate the efficacy of a u-healthcare service using Zigbee and mobile phone for elderly patients with diabetes mellitus or heart diseases. Materials and methods From July to October, 2005, 29 patients were enrolled in our study. Two selected u-healthcare items, ECG and blood glucose measurement, were monitored. Twenty patients were provided with ZigBee built-in blood glucometer and mobile phones, and were instructed on using a web service where the measured blood glucose could be transmitted directly to the web and be administrated. Nine patients participated in ECG monitoring, by using a wireless, transmittable ECG recording instrument equipped with ZigBee protocol attached to their chest. Daily average transmission frequency, rate of transmission loss, and error reasons were analyzed. In addition, the patients were asked to score their degree of satisfaction about the sensors and u-healthcare services. Results The mean transmission frequencies were 2.1 times/day in blood glucose monitoring and 6.1 times/day in ECG. The patients’ satisfaction scores of the blood glucometer and service used in this research were 8.59 and 9.01 of 10 points, respectively. The mean satisfaction scores about ECG sensor and ECG monitoring services were 5.79 and 7.29, respectively. Discussion Despite the many problems still encountered such as technological problems related to sensors and some problems like battery replacement, we could transfer the data of glucometer and ECG sensors to web-server via ZigBee protocol. Authors think the ZigBee could be one of components of wireless u-healthcare systems in the future due to its advantages of lower power consumption.

We compared the severity of subjective and objective symptomatology of akathisia between the acute and chronic subtypes of neuroleptic-induced akathisia. Sixty-one schizophrenic subjects were evaluated. Multivariate analysis revealed that motor manifestations and distress of akathisia were less severe in chronic akathisia than in acute akathisia. The severity of subjective restlessness was not significantly different between the two groups. In conclusion, there were differences in the severity of symptoms and signs between the acute and chronic subtypes of akathisia, suggesting that the severity of the subjective and objective components of akathisia may be differentially affected by the duration of akathisia.

Two image datasets (one thick section dataset and another volumetric dataset) were typically reconstructed from each single CT projection data. The volumetric dataset was stored in a mini-PACS with 271-Gb online and 680-Gb nearline storage and routed to radiologists’ workstations, whereas the thick section dataset was stored in the main PACS. Over a 5-month sample period, 278 Gb of CT data (8976 examinations) was stored in the main PACS, and 738 Gb of volumetric datasets (6193 examinations) was stored in the mini-PACS. The volumetric datasets formed 32.8% of total data for all modalities (2.20 Tb) in the main PACS and mini-PACS combined. At the end of this period, the volumetric datasets of 1892 and 5162 examinations were kept online and nearline, respectively. Mini-PACS offers an effective method of archiving every volumetric dataset and delivering it to radiologists.

Schizophrenia and obsessive-compulsive disorder (OCD) are assumed to be neurodevelopmental disorders. To examine the cortical patterns in the two disorders, three-dimensional fractal dimension (FD) of skeletonized cerebral cortical surface was estimated from magnetic resonance (MR) images of 50 patients with schizophrenia, 45 patients with OCD and 26 healthy normal controls. The schizophrenic group had a significantly smaller mean FD than OCD group, and the OCD group than normal controls. The FD revealed a significant interaction effect of group-by-hemisphere, and the FD asymmetry index distinguished the schizophrenic group from normal controls. In logistic regression models, the FD and CSF volume correctly classified 95.6% of the schizophrenics from the controls and 88.0% of the patients with OCD from the controls. In the control and schizophrenic groups, the FD was not associated with any of tissue volume measures. In the OCD group, however, the FD was significantly correlated with gray matter tissue volume and intracranial volume (ICV). The results of the present study suggest that three-dimensional FD of cortical surface may be a sensitive indicator for investigation of the structural brain abnormalities in mental disorders, especially those developmentally disturbed. Further studies to explore regional FD changes in mental disorders and clinical implications of the FD including diagnostic value should be performed in the future.

The purpose of the present study was to examine the developmental patterns of Cloninger's biogenetic character traits in subjects with borderline personality disorder (BPD). Study subjects met Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised; DSM-III-R) criteria for BPD without comorbid axis I or II disorders, as determined by the Diagnostic Interview for Borderlines-Revised, Structured Clinical Interview for the DSM-III-R, and Diagnostic Interview for Personality Disorders. The BPD subjects and age- and sex-matched healthy comparison subjects were initially interviewed for Cloninger's biogenetic characters and re-interviewed at an interval of 1 year for the following 3 years. There were significant differences in the developmental patterns of self-directedness, cooperativeness, and self-transcendence between BPD and healthy comparison subjects (significant group by time interaction: repeated measures manova, F = 17.3, d.f. = 3,240, P

Working memory (WM) deficit in schizophrenic patients has been well established. Still, underlying biological substrate of the impairment is not clear. Among neurotransmitter hypotheses of schizophrenia, N-methyl-D-aspartate (NMDA) receptor model is mostly supported, considering that NMDA receptor antagonist can elicit both psychosis and cognitive impairment observed in schizophrenic patients. In current study, to test the neuropsychological and the electrophysiological effects of NMDA receptor in WM, event-related potentials (ERPs) of Sternberg's short-term memory scanning task (SMST) were analyzed in 10 healthy subjects under intravenous administration of a subanesthetic dose of ketamine (0.65 mg/kg/h) or placebo (normal saline). Late positive component (LPC) of ERP was hypothesized to reflect later stage of WM. Brief Psychiatric Rating Scale score was significantly increased (t=-5.75, df=9, P

We describe a method for the statistical parametric mapping of low resolution electromagnetic tomography (LORETA) using high-density electroencephalography (EEG) and individual magnetic resonance images (MRI) to investigate the characteristics of the mismatch negativity (MMN) generators in schizophrenia. LORETA, using a realistic head model of the boundary element method derived from the individual anatomy, estimated the current density maps from the scalp topography of the 128-channel EEG. From the current density maps that covered the whole cortical gray matter (up to 20,000 points), volumetric current density images were reconstructed. Intensity normalization of the smoothed current density images was used to reduce the confounding effect of subject specific global activity. After transforming each image into a standard stereotaxic space, we carried out statistical parametric mapping of the normalized current density images. We applied this method to the source localization of MMN in schizophrenia. The MMN generators, produced by a deviant tone of 1,200 Hz (5% of 1,600 trials) under the standard tone of 1,000 Hz, 80 dB binaural stimuli with 300 msec of inter-stimulus interval, were measured in 14 right-handed schizophrenic subjects and 14 age-, gender-, and handedness-matched controls. We found that the schizophrenic group exhibited significant current density reductions of MMN in the left superior temporal gyrus and the left inferior parietal gyrus (P < 0. 0005). This study is the first voxel-by-voxel statistical mapping of current density using individual MRI and high-density EEG. Hum. Brain Mapping 17:168–178, 2002. © 2002 Wiley-Liss, Inc.

There have been no studies systematically investigating relationships between biogenetic temperament dimensions and patterns of brain glucose metabolism. Nineteen healthy subjects were evaluated regarding the biogenetic temperament using Cloninger's Temperament and Character Inventory (TCI). In addition, [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) was used to measure regional brain glucose metabolism. Voxel-based correlation analysis was used to test correlations between regional brain glucose metabolism and scores on the TCI. We identified that each temperament dimension, such as Novelty Seeking, Harm Avoidance, and Reward Dependence, was significantly correlated with specific brain regions. The majority of correlations were observed in the areas of paralimbic regions and temporal lobes. The current study provides evidence linking each biogenetic temperament dimension with specific brain areas and provides a promising base for future personality research.

·Young-Sun Lee, PhD·In-Hee Cho, MD·Myung-Min Choi, PhD·Myoung-Ho Hyun, PhD Offices of Research Planning and Health Services Research, National Evidence-based Healthcare Collaborating Agency, Department of Psychiatry, Seoul National University College of Medicine, Office of Planning & Evaluation, Korea Youth Counseling & Welfare Institute, Seoul, Department of Psychiatry, Inje University College of Medicine, Busan, Division of Mental Health Policy, Ministry of Health & Welfare, Department of Psychiatry, Sungkyunkwan University School of Medicine, Seoul, Department of Psychiatry, Jeju National University School of Medicine, Jeju, Department of Psychiatry, The Catholic University of Korea School of Medicine, Seoul, Goyang Community Mental Health Center, Goyang, Department of Psychiatry, Kangwon National University School of Medicine, Chuncheon, Office of Students and Parents Research, Korean Educational Development Institute, Department of Preventive Medicine, The Catholic University of Korea School of Medicine, Students Health Management Division, Ministry of Education, Science and Technology, Central Church of Korea Evangelical Holiness Church, Seoul, Department of Nursing, Inje University, Busan, Office of Counseling & Welfare, Korea Youth Counseling & Welfare Institute, Department of Psychology, Ewha Womans University, Seoul, Department of Psychiatry, Gil Hospital, Gachon University, Incheon, Department of Social Welfare, Baekseok University, Cheonan, Department of