The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP): Changes in preferred treatment strategies and medications over 16 years and five editions.

OBJECTIVES: The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) is based on expert consensus and has been revised five times since 2002. This study evaluated the changes in treatment strategies advocated by the KMAP-BP over time. METHODS: The five editions of the KMAP-BP were reviewed, and the recommendations of the KMAP-BP were compared with those of other bipolar disorder (BP) treatment guidelines. RESULTS: The most preferred option for the initial treatment of mania was a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP). Either MS or AAP monotherapy was also considered a first-line strategy for mania, but not for all types of episodes, including mixed/psychotic mania. In general, although lithium and valproic acid were commonly recommended, valproic acid has been increasingly preferred for all phases of BP. The most notable changes over time included the increasing preference for AAPs for all phases of BP, and lamotrigine for the depressive and maintenance phases. The use of antidepressants for BP has gradually decreased, but still represents a first-line option for severe and psychotic depression. CONCLUSIONS: In general, the recommended strategies of the KMAP-BP were similar to those of other guidelines, but differed in terms of the emphasis on rapid effectiveness, which is often desirable in actual clinical situations. The major limitation of the KMAP-BP is that it is a consensus-based rather than an evidence-based tool. Nevertheless, it may confer advantages in actual clinical practice.

Character strengths as protective factors against depression and suicidality among male and female employees.

BACKGROUND: So far, studies on workplace mental health have only focused on work-related environmental risk factors, disregarding both protective and individual factors of employees. Therefore, we aimed to identify character strengths that act as protective factors against depressive moods and suicidality in Korean employees. METHODS: In total, 84 male and 151 female employees (aged 19-50 years) reported their sociodemographic characteristics; depressive symptoms, as measured by the Beck Depression Inventory-II; suicidality, as measured by the Korean version of the MINI International Neuropsychiatric Interview suicidality module; and character strengths, as measured by the 24 Character Strength Alphas on the Values in Action Survey-72. We conducted a hierarchical logistic regression, in which depressive mood and suicidality served as the categorical outcome variables. RESULTS: In females, scores on the "curiosity" (B = 1.107, Wald = 10.207, odds ratio = 3.026, p = .001) and "love" (B = .862, Wald = 5.767, odds ratio = 2.367, p = .016) sub scales of the 24 Character Strength Alphas on the Values in Action Survey-72 were statistically significant predictors of having depressive mood. Additionally, females' scores on "judgment" (B = - 1.405, Wald = 5.663, odds ratio = .245, p = .017) and "kindness" (B = - 1.456, Wald = 6.486, odds ratio = .233, p = .011) were protective factors against suicidality. In males, the "love" (B = 1.746, Wald = 4.279, odds ratio = 5.729, p = .039) score was a predictor of having depressive mood, while "teamwork" (B = - 2.204, Wald = 4.666, odds ratio = .110, p = .031) and "creativity" (B = - 1.384, Wald = 4.202, odds ratio = .251, p = .040) scores were protective factors against having depressive mood and suicidality, respectively. CONCLUSIONS: We suggest that focusing on "judgement" and "kindness" in female employees, and "teamwork" and "creativity" in male employees, and engaging in activities that use these strengths at the workplace can be protective factors against depression and suicidality. Future research should focus on developing interventions to promote these character strengths among employees at the workplace.

Clinical assessment of bipolar depression: validity, factor structure and psychometric properties of the Korean version of the Bipolar Depression Rating Scale (BDRS).

BACKGROUND: The Bipolar Depression Rating Scale (BDRS) is a scale for assessment of the clinical characteristics of bipolar depression. The primary aims of this study were to describe the development of the Korean version of the BDRS (K-BDRS) and to establish more firmly its psychometric properties in terms of reliability and validity. METHODS: The study included 141 patients (62 male and 79 female) who had been diagnosed with bipolar disorder, were currently experiencing symptoms of depression, and were interviewed using the K-BDRS. Other measures included the Montgomery and Asberg Depression Scale (MADRS), the 17-item Hamilton Depression Scale (HAMD), and the Young Mania Rating Scale (YMRS). Additionally, the internal consistency, concurrent validity, inter-rater reliability, and test-retest reliability of the K-BDRS were evaluated. RESULTS: The Cronbach's α-coefficient for the K-BDRS was 0.866, the K-BDRS exhibited strong correlations with the HAMD (r = 0.788) and MADRS (r = 0.877), and the mixed symptoms score of the K-BDRS was significantly correlated with the YMRS (r = 0.611). An exploratory factor analysis revealed three factors that corresponded to psychological depressive symptoms, somatic depressive symptoms, and mixed symptoms. CONCLUSIONS: The present findings suggest that the K-BDRS has good psychometric properties and is a valid and reliable tool for assessing depressive symptoms in patients with bipolar disorder.

One-year rehospitalization rates of patients with first-episode bipolar mania receiving lithium or valproate and adjunctive atypical antipsychotics.

AIM: We compared the 1-year rehospitalization rates of first-episode bipolar manic patients who were discharged while being treated with lithium or valproate in combination with an atypical antipsychotic. METHODS: We investigated the rehospitalization status of first-episode bipolar manic patients who were discharged between 1 January 2003 and 31 December 2010 while they were taking lithium or valproate in combination with aripiprazole, olanzapine, quetiapine, or risperidone. Rehospitalization rates during a 1-year period after discharge were compared between the group receiving lithium plus an atypical antipsychotic and the group receiving valproate plus an atypical antipsychotic using the Kaplan-Meier method. A Cox regression model was used to analyze covariates hypothesized to affect time to rehospitalization. RESULTS: The rehospitalization rate was 17.3% during the 1-year follow-up period. We found significant differences in the rehospitalization rates of patients in the lithium (23.1%) and the valproate (13.3%) groups using the Kaplan-Meier formula. According to Cox proportional hazards regression analysis, higher Clinical Global Impression-Bipolar Version-Severity score at discharge (P = 0.005) and lithium treatment (P = 0.055) contributed to the risk of rehospitalization. CONCLUSION: Treatment with valproate and an atypical antipsychotic can be more effective than treatment with lithium and an atypical antipsychotic in preventing rehospitalization during the 1 year after hospitalization due to a first manic episode in patients with bipolar I disorder. Higher Clinical Global Impression-Bipolar Version-Severity scores at discharge also negatively affected rehospitalization rates.

A 6-month exercise intervention clinical trial in women: effects of physical activity on multi-omics biomarkers and health during the first wave of COVID-19 in Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) was first reported in December 2019 and the first case in Korea was confirmed on January 20, 2020. Due to the absence of therapeutic agents and vaccines, the Korean government implemented social distancing on February 29, 2020. This study aimed to examine the effect of physical activity (PA) on health through changes in multi-omics biomarkers with a 6-month of exercise intervention during the first wave of COVID-19 in Korea. METHODS: Twenty-seven healthy middle-aged women were recruited and 14 subjects completed the exercise intervention. The mean age (± SD) was 46.3 (± 5.33) and the mean BMI (± SD) was 24.9 (± 3.88). A total of three blood and stool samples were collected at enrollment, after period 1, and after period 2 (3-month intervals). The amount of PA was measured with an accelerometer and by questionnaire. Clinical variables were used, including blood pressure, grip strength, flexibility, and blood glucose levels and lipid markers obtained from laboratory tests. The concentration of blood metabolites was measured by targeted metabolomics. Fecal microbiome data were obtained by 16 S rRNA gene amplicon sequencing. RESULTS: During the second half period (period 2), Coronavirus disease 2019 occurred and spread out in Korea, and PA decreased compared with the first half period (period 1) (185.9 ± 168.73 min/week to 102.5 ± 82.30 min/week; p = 0.0101). Blood pressure, hemoglobin A1c (HbA1c), and low-density lipoprotein cholesterol (LDL-C) decreased in period 1 (p < 0.05) and tended to increase again during period 2 (p < 0.05). Forty metabolites were changed significantly during period 1 (FDR p < 0.05), and we found that 6 of them were correlated with changes in blood pressure, HbA1c, and LDL-C via network analysis. CONCLUSIONS: Our results may suggest that exercise improves health through changes in biomarkers at multi-omics levels. However, reduced PA due to COVID-19 can adversely affect health, emphasizing the necessity for sustained exercise and support for home-based fitness to maintain health. TRIAL REGISTRATION: The trial is retrospectively registered on ClinicalTrials.gov (NCT05927675; June 30, 2023).

Developing a scoring guide for the Appraisal of Guidelines for Research and Evaluation II instrument in Korea: a modified Delphi consensus process.

Korea has a relatively short history in the development and use of clinical practice guidelines (CPGs). Additionally, it has been difficult to employ the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument due to the lack of consensus and the presence of differences in Korean medical settings and in the Korean socio-cultural environment. An AGREE II scoring guide was therefore developed to reduce differences among evaluators using the same tool. In consideration of the importance of using a quantitative measure of satisfaction with the elements described in the AGREE II manual, a final draft was developed through a Delphi consensus process. Ninety-two draft scoring guides for anchor points 1, 3, 5, and 7 (full score) in 23 items were developed. Consensus was defined as agreement among at least 70% of the raters. Agreement on 88 draft scoring guidelines was reached in the first Delphi round, and agreement for the remaining four was achieved in the second round. The development of an AGREE II scoring guide in this study is expected to contribute to improving the CPG environment.

The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD): Changes in Preferred Treatment Strategies and Medications over 20 Years and Five Editions.

BACKGROUND: The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) is an expert consensus guideline for depressive disorder created in 2002, and since then, four revisions (2006, 2012, 2017, 2021) have been published. In this study, changes in the content of the KMAP-DD survey and recommendations for each period were examined. METHODS: The development process of the KMAP-DD was composed of two stages. First, opinions from experts with abundant clinical experience were gathered through surveys. Next, a final guideline was prepared through discussion within the working committee regarding the suitability of the results with reference to recent clinical studies or other guidelines. RESULTS: In mild depressive symptoms, antidepressant (AD) monotherapy was preferred, but when severe depression or when psychotic features were present, a combination of AD and atypical antipsychotics (AD + AAP) was preferred. AD monotherapy was preferred in most clinical subtypes. AD monotherapy was preferred for mild depressive symptoms, and AD + AAP was preferred for severe depression and depression with psychotic features in children, adolescents, and the elderly. CONCLUSIONS: This study identified the changes in the KMAP-DD treatment strategies and drug preferences in each period over the past 20 years. This work is expected to aid clinicians in establishing effective treatment strategies.

Effects of Methylphenidate on Somatic Symptoms and Brain Functional Connectivity in Adolescents with Attention Deficit Hyperactivity Disorder: A Pilot Study.

Objective: This study aimed to evaluate whether somatic symptoms in adolescents with attention deficit hyperactivity disorder (ADHD) are associated with a dissociative pattern of functional connectivity (FC) within the default mode network (DMN) and whether methylphenidate administration can improve clinical and somatic symptoms. We also evaluated whether the improvement of somatic symptoms is associated with increased FC within the DMN in response to methylphenidate treatment. Methods: Fifteen male adolescents with somatic symptoms of ADHD and 15 male adolescents with ADHD without somatic symptoms were included. At baseline and after 6 months of methylphenidate treatment, all adolescents were asked to complete questionnaires for the Korean version of the Dupaul's ADHD rating scale, the symptom checklist-90- revised-somatization subscales, the Beck Depression Inventory, and the Beck Anxiety Inventory. Additionally, a resting- state functional magnetic resonance imaging scan was conducted. Results: Methylphenidate treatment improved clinical and somatic symptoms in adolescents with ADHD. In addition, it increased brain FC within the DMN from the posterior cingulate cortex (posterior DMN) to the middle prefrontal cortex (anterior DMN). The improvement of somatic symptoms was associated with FC within the DMN from the posterior cingulate cortex to the middle prefrontal cortex in ADHD adolescents with somatic symptoms. Conclusion: Methylphenidate increased brain FC between the anterior and posterior DMN. The improvement of somatic symptoms in adolescents with ADHD was associated with FC within the DMN. The DMN in adolescents with ADHD seems to be associated with the severity of the clinical and somatic symptoms of ADHD.

The effect of initial antidepressant type on treatment adherence in outpatients with new onset depression.

BACKGROUND: Continuous use of antidepressants can relieve depressive symptoms and prevent recurrence in people with depression; however, many studies have reported low drug compliance rates. This study aimed to investigate the relationship between the type of initial antidepressants and treatment adherence in outpatients with new onset depression. METHODS: This was a retrospective cohort study using National Health Insurance claim data for services provided in 2012. We examined data from 142,336 individuals aged 18 years or older, who were continuously enrolled in treatment after a new episode of depression, and had initiated antidepressant treatment. A new diagnosis of depression, is defined as a first reported diagnosis of depression in the preceding five years. Adherence was operationally defined as the antidepressant being dispensed to the patient at least 80% of the time during the first three- and six-month treatment periods. To investigate the relationship between the initial type of antidepressants and treatment adherence, we estimated adjusted odds ratios and 95% confidence intervals using logistic regression analysis, adjusting for socio-demographic and health care utilization characteristics. RESULTS: A statistically significant association was found between initial antidepressant type and adherence in the first three- and six-month treatment periods for employed and self-employed patients newly diagnosed with major depression. In addition, patients with starting prescriptions for tricyclic antidepressants had significantly lower adherence compared to selective serotonin reuptake inhibitors. LIMITATIONS: This study used national insurance data; therefore, only variables on the claim form were available, and psychological and environmental factors were not considered. CONCLUSIONS: This was the first study to demonstrate the relationship between initial antidepressant type and treatment adherence among Korean outpatients with new onset depression.

The Korean Medication Algorithm Project for Depressive Disorder 2021: Comparisons with Other Treatment Guidelines.

The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) first was published in 2002, and has been revised four times, in 2006, 2012, 2017, and 2021. In this review, we compared recommendations from the recently revised KMAP-DD 2021 to four global clinical practice guidelines (CPGs) for depression published after 2010. The recommendations from the KMAP-DD 2021 were similar to those from other CPGs, although there were some differences. The KMAP-DD 2021 reflected social culture and the healthcare system in Korea and recent evidence about pharmacotherapy for depression, as did other recently published evidence-based guidelines. Despite some intrinsic limitations as an expert consensus-based guideline, the KMAP-DD 2021 can be helpful for Korean psychiatrists making decisions in clinical settings by complementing previously published evidence-based guidelines, especially for some clinical situations lacking evidence from rigorously designed clinical trials.

Relationship between painful physical symptoms and severity of depressive symptomatology and suicidality.

We examined the prevalence of painful physical symptoms in patients with major depressive disorder (MDD), clinical correlations therewith, and associations between painful symptoms and depression severity, quality of life, and suicidality, in a clinical sample in Korea. A total of 414 psychiatric outpatients at least 18years of age, with a primary diagnosis of MDD based on the DSM-IV-TR, were enrolled at the discretion of their treating psychiatrist. Patients were assessed for the presence or absence of painful physical symptoms (PPS+ and PPS-, respectively), defined by a total score ≥5 on the pain subscale (PS) of the Depression and Somatic Symptoms Scale (DSSS). DSSS and the Clinical Global Impressions-Severity of Illness scale (CGI-S) determined depression severity, and the EuroQoL Questionnaire-5 dimensions (EQ-5D) determined perceived quality of life. Questions about suicidality during current depressive episode were also asked to the participants. Overall, 30.4% of patients were classified as PPS+. PPS+ patients were older, less educated, less frequently unmarried, and more frequently widowed/divorced/separated compared to PPS- patients. PPS+ patients showed a significantly greater depression severity (CGI-S mean difference 0.92; 95% CI=0.68 to 1.16; DSSS mean difference 18.39; 95% CI=16.28 to 20.50), a significantly lower quality of life (EQ-5D VAS mean difference -18.15; 95% CI=-22.68 to -13.62), and significantly higher suicidal ideation (OR 1.73; 95% CI 1.04-2.86) during the current depressive episode. This study suggests that assessment of depressive patients should include detailed questions about painful physical symptoms, and treatment of MDD should involve management targeting painful physical symptoms as well as emotional and non-painful physical symptoms.

Korean Medication Algorithm for Depressive Disorder 2021, Fourth Revision: An Executive Summary.

OBJECTIVE: In the 19 years since the Korean College of Neuropsychopharmacology and the Korean Society for Affective Disorders developed the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) in 2002, four revisions have been conducted. METHODS: To increase survey efficiency in this revision, to cover the general clinical practice, and to compare the results with previous KMAP-DD series, the overall structure of the questionnaire was maintained. The six sections of the questionnaire were as follows: 1) pharmacological treatment strategies for major depressive disorder (MDD) with/without psychotic features; 2) pharmacological treatment strategies for persistent depressive disorder and other depressive disorder subtypes; 3) consensus for treatment-resistant depression; 4) the choice of an antidepressant in the context of safety, adverse effects, and comorbid physical illnesses; 5) treatment strategies for special populations (children/adolescents, elderly, and women); and 6) non-pharmacological biological therapies. Recommended first-, second-, and third-line strategies were derived statistically. RESULTS: There has been little change in the four years since KMAP-DD 2017 due to the lack of newly introduced drug or treatment strategies. However, shortened waiting time between the initial and subsequent treatments, increased preference for atypical antipsychotics (AAPs), especially aripiprazole, and combination strategies with AAPs yield an active and somewhat aggressive treatment trend in Korea. CONCLUSION: We expect KMAP-DD to provide clinicians with useful information about the specific strategies and medications appropriate for treating patients with MDD by bridging the gap between clinical real practice and the evidence-based world.

The effect of dopamine partial agonists on the nicotine dependency in patients with schizophrenia.

OBJECTIVE: We compared the effects of haloperidol and three atypical antipsychotics (risperidone, olanzapine, and aripiprazole) on nicotine dependence in schizophrenic patients. METHODS: One hundred and thirty nine schizophrenic patients, who began using antipsychotic medication, were assessed for severity of nicotine dependence and for cigarette craving at baseline and following 8 weeks of treatment using the Fagerström Tolerance Questionnaire (FTQ) and a Likert-style, seven point, visual-analogue rating scale. RESULTS: Nicotine dependence increased in the haloperidol group, but not in atypical antipsychotics groups. Patients treated with aripiprazole showed a reduction both in nicotine dependence and cigarette craving. CONCLUSIONS: The effects of aripiprazole, a partial agonist of the dopamine D2 receptor, may reduce the severity of nicotine dependence in schizophrenic patients.

Risperidone in the treatment of mixed state bipolar patients: results from a 24-week, multicenter, open-label study in Korea.

AIMS: The goal of the present study was to evaluate the efficacy of risperidone combined with mood stabilizers for treating bipolar mixed state. METHODS: The present study was a 24-week, open-label, combination, prospective investigation of the efficacy of risperidone in combination with mood stabilizers. Risperidone (1-6 mg/day) was given in combination with mood stabilizers in flexible doses according to clinical response and tolerability for 114 patients in mixed or manic episode. RESULTS: Forty-four patients met our criteria for mixed state bipolar disorder and 70 met the criteria for pure mania. Mean age for the subjects was 39.0 +/- 11.0 years and 55.3% were female. The combination of risperidone with mood stabilizers significantly improved the scores on the Young Mania Rating Scale (YMRS), 17-item Hamilton Rating Scale for Depression (HAMD), 18-item Brief Psychiatric Rating Scale (BPRS), Global Assessment Scale (GAS), and Clinical Global Impression Scale for use in bipolar illness Severity (CGI-BP) at 24 weeks (P < 0.0001). Analysis of the YMRS, BPRS, GAS, and CGI-BP scores showed significant improvement in both the manic and mixed groups. The rate of response in YMRS scores was 84.2% (n = 96) and the rate of YMRS remission was 77.2% (n = 88) at week 24 in the total population. Seventy-four patients met both YMRS < or = 12 and HAMD < or = 7 at week 24 (64.9%). Risperidone was well tolerated, and adverse events were mostly mild. CONCLUSION: The combination of risperidone with mood stabilizers was an effective and safe treatment for manic symptoms and coexisting depressive symptoms of bipolar disorder.

The Influence of Current Mood States on Screening Accuracy of the Mood Disorder Questionnaire.

OBJECTIVE: In this study we investigated whether current mood states of patients with bipolar disorder have an influence on the screening accuracy of the Mood Disorder Questionnaire (MDQ). METHODS: A total of 452 patients with mood disorder (including 192 with major depressive disorder and 260 with bipolar disorder completed the Korean version of the MDQ. Patients with bipolar disorder were subdivided into three groups (bipolar depressed only, bipolar euthymic only, bipolar manic/hypomanic only) according to current mood states. The screening accuracy of the MDQ including sensitivity, specificity and area under the curve (AUC) of receiver operating characteristic (ROC) curves were evaluated according to current mood states. RESULTS: The optimal cutoff of MDQ was 5 in this study sample. Sensitivity and specificity were not significantly different according to current mood states. Significant differences in AUCs of four independent ROC curves were not found (ROC 1st curve included all bipolar patients; ROC 2nd curve included only bipolar depressed patients; ROC 3rd curve included only bipolar manic/hypomanic patients; ROC 4th curve included only bipolar euthymic patients). CONCLUSION: The study results showed that current mood states (either euthymic state, depressed or manic/hypomanic) did not significantly influence the screening accuracy of the MDQ suggesting that the MDQ could be a useful screening instrument for detecting bipolar disorder in clinical practice regardless of the current mood symptoms of subjects.

Effects of Amisulpride Adjunctive Therapy on Working Memory and Brain Metabolism in the Frontal Cortex of Patients with Schizophrenia: A Preliminary Positron Emission Tomography/Computerized Tomography Investigation.

OBJECTIVE: Dopamine plays a significant role in working memory by acting as a key neuromodulator between brain networks. Additionally, treatment of patients with schizophrenia using amisulpride, a pure dopamine class 2/3 receptor antagonist, improves their clinical symptoms with fewer side effects. We hypothesized that patients with schizophrenia treated with amisulpride and aripiprazole show increased working memory and glucose metabolism compared with those treated with cognitive behavioral therapy (CBT) and aripiprazole instead. METHODS: Sixteen patients with schizophrenia (eight in the amisulpride group [aripiprazole+amisulpride] and eight in the CBT group [aripiprazole+CBT]) and 15 age- and sex-matched healthy control subjects were recruited for a 12-week-long prospective trial. An [18F]-fluorodeoxyglucose-positron emission tomography/computerized tomography scanner was used to acquire the images. RESULTS: After 12 weeks of treatment, the amisulpride group showed greater improvement in the Letter-Number Span scores than the CBT group. Additionally, although brain metabolism in the left middle frontal gyrus, left occipital lingual gyrus, and right inferior parietal lobe was increased in all patients with schizophrenia, the amisulpride group exhibited a greater increase in metabolism in both the right superior frontal gyrus and right frontal precentral gyrus than the CBT group. CONCLUSION: This study suggests that a small dose of amisulpride improves the general psychopathology, working memory performance, and brain glucose metabolism of patients with schizophrenia treated with aripiprazole.

Korean Medication Algorithm for Bipolar Disorder 2018: Comparisons with Other Treatment Guidelines.

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2018 (KMAP-BP 2018) with other recently published guidelines for treating bipolar disorder. We reviewed a total of five recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2018 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy for mania. However, the KMAP-BP 2018 did not prefer monotherapy with MS or AAP for psychotic mania. Quetiapine, olanzapine and aripiprazole were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Most guidelines advocated newer AAPs as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. As research evidence accumulated over time, recommendations of newer AAPs (such as asenapine, cariprazine, paliperidone, lurasidine, long-acting injectable risperidone and aripiprazole once monthly) became prominent. KMAP-BP 2018 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2018, predominantly in the treatment of psychotic mania and severe depression. Further studies were needed to address several issues identified in our review.

The prevalence and diagnostic classification of mixed features in patients with major depressive episodes: A multicenter study based on the DSM-5.

OBJECTIVES: The purpose of this study was to evaluate the prevalence of mixed features using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and to examine how patients with mixed states would be classified using the DSM-5. METHODS: In total, 12 hospitals participated in this study, and data on the demographic characteristics and clinical diagnoses of patients treated between October 2013 and September 2016 were obtained. We reviewed the data for opposite-polarity symptoms according to the DSM-5 criteria and the research-based diagnostic criteria. RESULTS: Of the 859 patients included in the final analysis, the prevalence of mixed features in patients with major depressive episodes based on the DSM-5 remained low. Patients with major depressive disorder were more likely to be classified as experiencing anxious distress and/or a cluster-B personality disorder in mixed state patients not diagnosed with DSM-5 mixed features, whereas more mixed state patients with bipolar disorder were diagnosed with mixed features using the DSM-5. CONCLUSIONS: The prevalence of mixed features did not increase significantly when the DSM-5 was used, and patients with mixed states were more likely to be classified as having anxious distress and/or a cluster-B personality disorder in addition to mixed features.

Craving for alcohol and food during treatment for alcohol dependence: modulation by T allele of 1519T>C GABAAalpha6.

BACKGROUND: Craving for alcohol and food has been studied in association with alcohol dependence and eating disorders, respectively. One subclass of the gamma-aminobutyric acid (GABA) receptor, 1519T>C GABA(A)alpha6 has been reported to be associated with both alcohol dependence and weight gain. In this study, we hypothesized that patients being treated for alcohol dependence would report decreased craving for alcohol, but an increased craving for food during a 4-week treatment period. We further hypothesized that the T allele of the 1519T>C GABA(A)alpha6 gene would modulate the extent of changes in craving for alcohol and food. METHODS: This study included 98 male inpatients being treated for alcohol dependence. A 7-point visual analog scale was applied to evaluate relative levels of alcohol and food craving at baseline and again 4 weeks later. Body weight was also checked at the same periods. Genotyping of the 1519T>C SNP in GABA(A)alpha6 was carried out by restriction fragment length polymorphism. RESULTS: There were significant changes in craving for alcohol and food in all patients with alcohol dependence. During the treatment period, body weight increased in all patients with alcohol dependence. Changes in alcohol and food craving in T-allele carriers (CT + TT) of 1519T>C GABA(A)alpha6 were greater than those observed in CC homozygotes. In T-allele carriers, body weight significantly increased and the changes in weight showed a negative correlation with the change in the craving for alcohol and a positive correlation with the changes in craving for food. DISCUSSION: The current results suggest that in T-allele carriers the change in craving for alcohol during treatment for alcohol dependence is negatively associated with changes in craving for food. The T allele of the 1519T>C GABA(A)alpha6 gene may be one of the modulating factors associated with changes in craving for alcohol and food during treatment of patients with alcohol dependence.

Theta-phase gamma-amplitude coupling as a neurophysiological marker in neuroleptic-naïve schizophrenia.

Theta-phase gamma-amplitude coupling (TGC) was used as an evidence-based tool to reflect the dysfunctional cortico-thalamic interaction in patients with schizophrenia. The aim of the present study was to evaluate the diagnostic utility of TGC. The subjects included 90 patients with schizophrenia and 90 healthy controls. We compared the TGC results between the groups using an analysis of covariance (ANCOVA) to adjust for age and sex and receiver operator characteristic (ROC) curve analyses to examine the discrimination ability of delta to gamma frequency bands and TGC. Patients with schizophrenia showed a significant increase in the resting-state TGC at all 19 electrodes. The analysis of the ROC curves for each frequency band exhibited relatively low classification accuracies for the delta, theta, slow alpha, fast alpha, and beta power. The TGC generated the most accurate results among the electroencephalography (EEG) measures, with an overall classification accuracy of 92.5%. The resting-state TGC value was increased in patients with schizophrenia compared to that in healthy controls and had a higher discriminating ability than the other parameters. These findings may be related to the compensatory hyper-arousal patterns of the dysfunctional default-mode network (DMN) in schizophrenia. Therefore, resting-state TGC is a promising neurophysiological marker of schizophrenia.