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Jong-Hyun Jeong,1 Won-Myong Bahk,1 Young Sup Woo,1 Kyung-Uk Lee,1 Do Hoon Kim,2 Moon-Doo Kim,3 Won Kim,4 Jong-Chul Yang,5 Kwang Heun Lee6 1Department of Psychiatry, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 2Department of Psychiatry, Chuncheon Sacred Heart Hospital, Hallym University, Chuncheon, 3Department of Psychiatry, Jeju National University Hospital, Jeju, 4Department of Psychiatry, Stress Research Institute, Seoul Paik Hospital, College of Medicine, Inje University, Seoul, 5Department of Psychiatry, Chonbuk National University Medical School, Jeonju, 6Department of Psychiatry, College of Medicine, Dongguk University, Gyeongju, South Korea Objectives: The primary aim of this non-inferiority study was to investigate the clinical effectiveness and safety of generic escitalopram (Lexacure®) versus branded escitalopram (Lexapro®) for patients with major depressive disorder (MDD).Methods: The present study included 158 patients, who were randomized (1:1) to receive a flexible dose of generic escitalopram (n=78) or branded escitalopram (n=80) over a 6-week single-blind treatment period. The clinical benefits in the two groups were evaluated using the Montgomery–Åsberg Depression Rating Scale (MADRS), the 17-item Hamilton Depression Rating Scale (HDRS), the Clinical Global Impressions-Severity scale (CGI-S), and the Clinical Global Impressions-Improvement scale (CGI-I) at baseline, week 1, week 2, week 4, and week 6. The frequency of adverse events (AEs) was also assessed to determine safety at each follow-up visit.Results: During the 6-week study period, 30 patients (38.5%) from the generic escitalopram group and 28 patients (30.0%) from the branded escitalopram group dropped out of the study (P=0.727). The MADRS, HDRS, CGI-S, and CGI-I scores significantly decreased in both groups, and there were no significant differences between the groups. At week 6, 28 patients (57.1%) in the generic escitalopram group and 35 patients (67.3%) in the branded escitalopram group had responded to treatment (as indicated by a ≥50% decrease from the baseline MADRS score; P=0.126), and the remission rates (MADRS score: ≤10) were 42.9% (n=21) in generic escitalopram group and 53.8% (n=28) in the branded escitalopram group (P=0.135). The most frequently reported AEs were nausea (17.9%), sleepiness/somnolence (7.7%), weight gain (3.8%), and dry mouth (2.6%) in the generic escitalopram group and nausea (20.0%), sleepiness/somnolence (3.8%), weight gain (2.5%), and dry mouth (2.5%) in the branded escitalopram group.Conclusion: The present non-inferiority study demonstrated that generic escitalopram is a safe and an effective initial treatment for patients with MDD and may also be considered as an additional therapeutic option for this population. Keywords: depression, branded escitalopram, Lexapro®, generic escitalopram, Lexacure®

Jong-Hyun Jeong,1 Jeong Goo Lee,2,3 Moon-Doo Kim,4 Inki Sohn,5 Se-Hoon Shim,6 Hee Ryung Wang,1 Young Sup Woo,1 Duk-In Jon,7 Jeong Seok Seo,8 Young-Chul Shin,9 Kyung Joon Min,10 Bo-Hyun Yoon,11 Won-Myong Bahk1 1Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, 2Department of Psychiatry, Haeundae Paik Hospital, College of Medicine, Paik Institute for Clinical Research, Inje University, 3Department of Health Science and Technology, Graduate School of Inje University, Busan, 4Department of Psychiatry, Jeju National University Hospital, Jeju, 5Department of Psychiatry, Keyo Hospital, Keyo Medical Foundation, Uiwang, 6Department of Psychiatry, Soonchunhyang University Cheonan Hospital, College of Medicine, Soonchunhyang University, Cheonan, 7Department of Psychiatry, Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, 8Department of Psychiatry, Konkuk University Chungju Hospital, School of Medicine, Konkuk University, Chungju, 9Department of Psychiatry, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, 10Department of Psychiatry, Chung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul, 11Department of Psychiatry, Naju National Hospital, Naju, Korea Abstract: Our goal was to compare the recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2014 (KMAP-BP 2014) with other recently published guidelines for the treatment of bipolar disorder. We reviewed a total of four recently published global treatment guidelines and compared each treatment recommendation of the KMAP-BP 2014 with those in other guidelines. For the initial treatment of mania, there were no significant differences across treatment guidelines. All recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or the combination of an MS with an AAP as a first-line treatment strategy for mania. However, the KMAP-BP 2014 did not prefer monotherapy with MS or AAP for dysphoric/psychotic mania. Aripiprazole, olanzapine, quetiapine, and risperidone were the first-line AAPs in nearly all of the phases of bipolar disorder across the guidelines. Most guidelines advocated newer AAPs as first-line treatment options in all phases, and lamotrigine in 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, paliperidone, lurasidone, and long-acting injectable risperidone – became prominent. This comparison identifies that the treatment recommendations of the KMAP-BP 2014 are similar to those of other treatment guidelines and reflect current changes in prescription patterns for bipolar disorder based on accumulated research data. Further studies are needed to address several issues identified in our review. Keywords: bipolar disorder, pharmacotherapy, treatment algorithm, guideline comparison, KMAP-2014

Hee Ryung Wang, Young Sup Woo, Tae-Youn Jun, Won-Myong Bahk Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea Objective: This study aimed to examine the sociodemographic and disease-related variables associated with the premature discontinuation of psychiatric outpatient treatment after discharge among patients with noncombat-related posttraumatic stress disorder. Methods: We retrospectively reviewed the medical records of patients who were discharged with a diagnosis of posttraumatic stress disorder. Results: Fifty-five percent of subjects (57/104) prematurely discontinued outpatient treatment within 6 months of discharge. Comparing sociodemographic variables between the 6-month non-follow-up group and 6-month follow-up group, there were no variables that differed between the two groups. However, comparing disease-related variables, the 6-month follow-up group showed a longer hospitalization duration and higher Global Assessment of Function score at discharge. The logistic regression analysis showed that a shorter duration of hospitalization predicted premature discontinuation of outpatient treatment within 6 months of discharge. Conclusion: The duration of psychiatric hospitalization for posttraumatic stress disorder appeared to influence the premature discontinuation of outpatient treatment after discharge. Keywords: posttraumatic stress disorder, discontinuation, compliance, predictor

Young Sup Woo,1 Jung Goo Lee,2,3 Jong-Hyun Jeong,1 Moon-Doo Kim,4 Inki Sohn,5 Se-Hoon Shim,6 Duk-In Jon,7 Jeong Seok Seo,8 Young-Chul Shin,9 Kyung Joon Min,10 Bo-Hyun Yoon,11 Won-Myong Bahk1 1Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 2Department of Psychiatry, Inje University Haeundae Paik Hospital, Busan, South Korea;3Paik Institute for Clinical Research, Inje Univeristy, Busan, South Korea; 4Department of Psychiatry, Jeju National University Hospital, Jeju, South Korea; 5Department of Psychiatry, Keyo Hospital, Keyo Medical Foundation, Uiwang, South Korea; 6Department of Psychiatry, Soonchunhyang University Cheonan Hospital, Soonchunhyang University, Cheonan, South Korea; 7Department of Psychiatry, Sacred Heart Hospital, Hallym University, Anyang, South Korea; 8Department of Psychiatry, School of Medicine, Konkuk University, Chungju, South Korea; 9Department of Psychiatry, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, South Korea; 10Department of Psychiatry, College of Medicine, Chung-Ang University, Seoul, South Korea; 11Department of Psychiatry, Naju National Hospital, Naju, South Korea Objective: To constitute the third revision of the guidelines for the treatment of bipolar disorder issued by the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP 2014). Methods: A 56-item questionnaire was used to obtain the consensus of experts regarding pharmacological treatment strategies for the various phases of bipolar disorder and for special populations. The review committee included 110 Korean psychiatrists and 38 experts for child and adolescent psychiatry. Of the committee members, 64 general psychiatrists and 23 child and adolescent psychiatrists responded to the survey. Results: The treatment of choice (TOC) for euphoric, mixed, and psychotic mania was the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP); the TOC for acute mild depression was monotherapy with MS or AAP; and the TOC for moderate or severe depression was MS plus AAP/antidepressant. The first-line maintenance treatment following mania or depression was MS monotherapy or MS plus AAP; the first-line treatment after mania was AAP monotherapy; and the first-line treatment after depression was lamotrigine (LTG) monotherapy, LTG plus MS/AAP, or MS plus AAP plus LTG. The first-line treatment strategy for mania in children and adolescents was MS plus AAP or AAP monotherapy. For geriatric bipolar patients, the TOC for mania was AAP/MS monotherapy, and the TOC for depression was AAP plus MS or AAP monotherapy. Conclusion: The expert consensus in the KMAP-BP 2014 differed from that in previous publications; most notably, the preference for AAP was increased in the treatment of acute mania, depression, and maintenance treatment. There was increased expert preference for the use of AAP and LTG. The major limitation of the present study is that it was based on the consensus of Korean experts rather than on experimental evidence. Keywords: pharmacological treatment, treatment guideline, expert consensus

Young Sup Woo, Hee Ryung Wang, Won-Myong Bahk Department of Psychiatry, Yeouido St Mary's Hospital, The Catholic University of Korea, Seoul, Korea Abstract: Lurasidone is a benzisothiazol derivative and an atypical antipsychotic approved by the US Food and Drug Administration for the acute treatment of adults with schizophrenia (October 2010) and bipolar 1 depression (June 2013). Lurasidone has a strong antagonistic property at the D2, serotonin (5-HT)2A, and 5-HT7 receptors, and partial agonistic property at the 5-HT1A receptor. Lurasidone also has lower binding affinity for the α2C and 5-HT2C receptor. Lurasidone is rapidly absorbed (time to maximum plasma concentration: 1–3 hours), metabolized mainly by CYP3A4 and eliminated by hepatic metabolism. In two large, well-designed, 6-week trials in adult patients with bipolar 1 depression, lurasidone monotherapy and adjunctive therapy with mood stabilizers were significantly more effective than placebo at improving depressive symptoms assessed using the Montgomery–Åsberg Depression Rating Scale total score. In both trials, lurasidone also reduced the Clinical Global Impression–Bipolar Severity depression score to a greater extent than placebo. In these two trials, discontinuation rates due to adverse events in the lurasidone group were small (

Seung Oh Bae,1 Moon Doo Kim,2 Jung Goo Lee,3 Jeong-Suk Seo,4 Seung-Hee Won,5 Young Sup Woo,6 Jeong-Ho Seok,7 Won Kim,8 Se Joo Kim,7 Kyung Joon Min,9 Duk-In Jon,10 Young Chul Shin,11 Won Myong Bahk,6 Bo-Hyun Yoon121Hangang Mental Clinic, Kimpo, 2Department of Psychiatry, School of Medicine, Jeju National University, Jeju, 3Department of Psychiatry, College of Medicine, Inje University Haeundae Paik Hospital and Paik Institute for Clinical Research, Busan, 4Department of Psychiatry, College of Medicine, Konkuk University, Chungju, 5Department of Psychiatry, College of Medicine, Kyungpook National University, Daegu, 6Department of Psychiatry, Yeouido St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 7Department of Psychiatry, Yonsei University, College of Medicine, Seoul, 8Department of Psychiatry, College of Medicine, Inje University, Seoul, 9Department of Psychiatry, College of Medicine, Chung-Ang University, Seoul, 10Department of Psychiatry, College of Medicine, Hallym University, Anyang, 11Department of Psychiatry, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, 12Naju National Hospital, Naju, KoreaBackground: The purpose of this study was to assess the prevalence of bipolar spectrum disorder (BSD) in the general Korean population.Methods: A sample of college students (n = 1026) was stratified to reflect geographical differences accurately in Korean college students. The Korean version of the Mood Disorder Questionnaire (K-MDQ) was administered and an epidemiological survey carried out between November 2006 and February 2007. BSD was defined as a score of at least seven K-MDQ symptoms that co-occurred and resulted in minimal or more functional impairment.Results: The prevalence of BSD was 18.6% (95% confidence interval [CI] 16.2–21.0) in total, being 19.8% (95% CI 16.3–23.2) in men and 17.5% (95% CI 14.2–20.8) in women. The prevalence of BSD was more common in rural dwellers than in urban dwellers (P = 0.008, chi-square test). Univariate and multivariate regression models showed that rural residence was a significant factor associated with BSD. There were significant relationships between BSD and gender, age, and socioeconomic status.Conclusion: The prevalence of BSD found in the present study is higher than that reported by other epidemiological studies in Korea and in international studies.Keywords: general population, bipolar disorder, epidemiological study, Mood Disorder Questionnaire

Jong-Hyun Jeong,1 Won-Myong Bahk,1 Young Sup Woo,1 Ho-Jun Seo,1 Seung-Chul Hong,1 Duk-In Jon,2 Kyung Joon Min,3 Bo-Hyun Yoon41Department of Psychiatry, College of Medicine, The Catholic of University of Korea, Seoul, 2Department of Psychiatry, College of Medicine, Hallym University, Anyang, 3Department of Neuropsychiatry, College of Medicine, Chung-Ang University, Seoul, 4Naju National Hospital, Naju, KoreaPurpose: To evaluate and compare the therapeutic efficacy of quetiapine in bipolar I and II depression patients in the clinical setting.Patients and methods: This was an 8-week, multicenter, open-label, observational study for bipolar depression. The dosage of quetiapine was flexible, and concomitant medications were permitted on clinician's judgments. A total of 1097 patients were enrolled, and 764 bipolar depression patients who exhibited good therapeutic compliance (>75% compliance rate) were analyzed.Results: Clinical Global Impression – Bipolar scale and Montgomery–Asberg Depression Rating Scale scores were significantly improved at weeks four and eight compared with the baseline scores. At the end of the 8-week study, the response rate was 58.9%, and the remission rate was 42.1%. However, there were no significant differences in the response and remission rates between bipolar I and II disorder (BD-I and BD-II) patients (response rate 60.1% versus 56.3%; remission rate 44.5% versus 37.0%). Montgomery–Asberg Depression Rating Scale score at baseline (β = 0.612, P < 0.001), duration of current episode (β = −0.152, P = 0.001), and presence of remission on previous episode (β = 0.111, P = 0.012) were significantly associated with improvements in depressive symptoms. Fatigue (16.0%), somnolence (14.9%), and manic/hypomanic switching (0.6% at week four, 0.3% at week eight) were observed throughout the study period.Conclusion: The results of this study suggest that quetiapine improves depressive symptoms in BD-I and BD-II patients with a minimal incidence of manic switching. The therapeutic efficacy of quetiapine increased with time. Quetiapine could be an effective and safe modality for the treatment of BD-I and BD-II.Keywords: bipolar depression, quetiapine, therapeutic efficacy, observational study

Objective: : The present study was performed to investigate the validity and reliability of the Korean version of the THINC-it tool (THINC-it-K) in adult patients with major depressive disorder (MDD)., Methods: : Subjects aged 19-65 years with recurrent MDD experiencing moderate to severe major depressive episode (n = 44) were evaluated and compared to age and sex matched healthy controls (n = 44). Subjects completed the THINC-it-K which includes variants of the Identification Task (IDN) using Choice Reaction Time, One-Back Test, Digit Symbol Substitution Test, Trail Making Test-Part B, and the Perceived Deficits Questionnaire for Depression-5-item (PDQ-5-D)., Results: : A total of 75.0% of patients with MDD exhibited cognitive performance 1 standard deviation or below. The differences in Spotter ( p = 0.001), Codebreaker ( p = 0.001), PDQ-5-D ( p ＜ 0.001) and objective THINC-it-K composite score ( p = 0.002) were significant between the two groups. Concurrent validity of the THINC-it-K based on a calculated composite score was good (r = 0.856, p ＜ 0.001), and ranges for each component tests were from 0.076 (IDN) to 0.928 (PDQ-5-D)., Conclusion: : The THINC-it-K exhibits good reliability and validity in adults with MDD. It could be a useful tool for the measurement of cognitive deficits in persons with MDD and should be implemented in clinical practice.

Purpose: As science and technology advance, older people's ability to use smart devices in their daily living is becoming more demanding. This study addresses the increasing use of smartphones by the older adults, who often struggle with technology due to lack of competence. We developed an educational app tailored for older adults users and compare its effectiveness with existing educational videos., Methods: An app was created based on the learning characteristics of the older adults, using the ADDIE model, and compared with traditional video education. It involved six participants aged 65 or older, and convenience sampling method was used, evaluating the app and video through usability assessments and eye tracking. Quantitative and qualitative analyzes were conducted with focus groups under the researcher's control., Results: The app received higher usability scores than the video in content, motivation, and interaction. Eye tracking showed users paid more consistent attention to the app., Conclusion: The smartphone app facilitates learning for the older adults without the constraints of time and place, improving their quality of life and technology skills. Eye tracking can be instrumental in future app development for this demographic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Woo, Shin and Park.)

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a "breakthrough therapy" for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin's potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT 2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials [DB-RCTs]) trials exploring psilocybin's impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over six months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.

This study presents a comprehensive exploration of topic modeling methods tailored for large language model (LLM) using data obtained from Web of Science and LexisNexis from June 1, 2020, to December 31, 2023. The data collection process involved queries focusing on LLMs, including "Large language model," "LLM," and "ChatGPT." Various topic modeling approaches were evaluated based on performance metrics, including diversity and coherence. latent Dirichlet allocation (LDA), nonnegative matrix factorization (NMF), combined topic models (CTM), and bidirectional encoder representations from Transformers topic (BERTopic) were employed for performance evaluation. Evaluation metrics were computed across platforms, with BERTopic demonstrating superior performance in diversity and coherence across both LexisNexis and Web of Science. The experiment result reveals that news articles maintain a balanced coverage across various topics and mainly focus on efforts to utilize LLM in specialized domains. Conversely, research papers are more concise and concentrated on the technology itself, emphasizing technical aspects. Through the insights gained in this study, it becomes possible to investigate the future path and the challenges that LLMs should tackle. Additionally, they could offer considerable value to enterprises that utilize LLMs to deliver services., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study determined the threshold for recurrent depressive episodes that predicted conversion from major depressive disorder (MDD) to bipolar disorder (BD)., Methods: We retrospectively reviewed the medical records of 296 patients diagnosed with MDD for a minimum of 5 years in two university hospitals. We examined their the Diagnostic and Statistical Manual of Mental Disorders, 5th edition diagnoses and detailed clinical information at the initial admission and yearly assessments after discharge to establish the threshold for recurrent depressive episodes indicating a risk of diagnostic conversion from MDD to BD. Optimal cut-offs were derived using receiver operating characteristic (ROC) curves., Results: ROC curve analysis revealed that more than four recurrent depressive episodes was indicative of potential diagnostic conversion from MDD to BD (area under the curve, 0.604; sensitivity, 0.353; specificity, 0.855; positive predictive value, 0.421; negative predictive value, 0.816)., Conclusion: These findings suggest that the best predictor of conversion from MDD to BD is more than four recurrent depressive episodes. Our findings have the potential to enhance diagnostic accuracy and treatment efficiency. To validate our results, longitudinal prospective studies are necessary.

Background: We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment., Methods: Seventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit., Results: The overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM., Limitations: The small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times., Conclusion: The results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: We aimed to identify the expectations and preferences for medication and medical decision-making in patients with major psychiatric disorders., Methods: A survey was conducted among patients with major psychiatric disorders who visited psychiatric outpatient clinics at 15 hospitals between 2016 and 2018 in Korea. The survey consisted of 12 questions about demographic variables and opinions on their expectations for medication, important medical decision-makers, and preferred drug type. The most preferred value in each category in the total population was identified, and differences in the preference ratio of each item among the disease groups were compared., Results: A total of 707 participants were surveyed. In the total population, patients reported high efficacy (44.01%±21.44%) as the main wish for medication, themselves (37.39%±22.57%) and a doctor (35.27%±22.88%) as the main decision makers, and tablet/capsule (36.16%±30.69%) as the preferred type of drug. In the depressive disorders group, the preference ratio of high efficacy was significantly lower, and the preference ratio of a small amount was significantly higher than that of the psychotic disorder and bipolar disorder groups. The preference ratio of a doctor as an important decision maker in the bipolar disorder group was higher compared to the other groups., Conclusion: This study revealed the preference for medications and showed differences among patients with psychiatric disorders. Providing personalized medicine that considers a patient's preference for the drug may contribute to the improvement of drug compliance and outcomes.

Objective: : Attention-deficit/hyperactivity disorder (ADHD) is prevalent in adults, and psychiatric comorbidities are common in adults with ADHD. We aimed to examine the prevalence of adult ADHD with several common psychiatric conditions in a community sample in Korea and the association between adult ADHD and risk of psychiatric comorbidities., Methods: : This study used a cross-sectional survey design. We provided supplementary and optional self-report questionnaires, including the Korean version of the World Health Organization Adult ADHD Self-Report Scale (ASRS) short screening scale, Patient Health Questionnaire-9 for screening for depression, Alcohol Use Disorders Identification Test alcohol consumption questions, and the Korean version of the Mood Disorders Questionnaire, to Korean adults who visited one of six centers of a large private healthcare company for the National General Health Examination., Results: : A total of 17,799 subjects included in this study, and 430 (2.4%) were positive on the ASRS screen. ADHD was significantly associated with the 19-30-year-old age group (odds ratio [OR] = 3.938), lower income (OR = 1.298), depression (OR = 11.563), and bipolar disorder (OR = 3.162)., Conclusion: : Adult ADHD was highly associated with depression and bipolar disorder, suggesting that clinicians should carefully evaluate and treat such psychiatric disorders in adults with ADHD symptoms.

Coronavirus disease 2019 (COVID-19) has multiple negative impacts on the psychiatric health of both those previously infected and not infected with severe acute respiratory syndrome coronavirus 2. Moreover, the negative impacts of COVID-19 are closely associated with geographical region, culture, medical system, and ethnic background. We summarized the evidence of the impact of COVID-19 on the psychiatric health of the Korean population. This narrative review included thirteen research articles, which investigated the impact of COVID-19 on the psychiatric health of Koreans. COVID-19 survivors were reported to have a 2.4 times greater risk of developing psychiatric disorders compared to members of a control group, and anxiety and stress-related disorders were the most common newly diagnosed psychiatric illnesses. Studies also reported that COVID-19 survivors had a 3.33-fold higher prevalence of insomnia, a 2.72-fold higher prevalence of mild cognitive impairment, and a 3.09-fold higher prevalence of dementia compared to the control group. In addition, more than four studies have highlighted that the medical staff members, including nurses and medical students, exhibit a greater negative psychiatric impact of COVID-19. However, none of the articles investigated the biological pathophysiology or mechanism linking COVID-19 and the risk of diverse psychiatric disorders. Moreover, none of the studies were actual prospective studies. Thus, longitudinal studies are needed to more clearly elucidate the effect of COVID-19 on the psychiatric health of the Korean population. Lastly, studies focusing on preventing and treating COVID-19-associated psychiatric problems are needed to provide a benefit in real clinical settings.

With the increasing use of virtual reality (VR) devices, interest in reducing their negative effects, such as VR sickness, is also increasing. This study used electroencephalography (EEG) to investigate participants' VR sickness recovery time after watching a VR video. We tested 40 participants in advance using a motion sickness susceptibility questionnaire (MSSQ). We classified the participants into two groups (sensitive group/non-sensitive group) depending on their MSSQ scores. We used a simulator sickness questionnaire (SSQ) and EEG to evaluate VR sickness. The SSQ score increased significantly after watching the VR sickness-inducing video (VR video) in both groups (p < 0.001). The recovery time based on the SSQ was 11.3 ± 6.6 min for the sensitive group and 9.1 ± 5.2 min for the non-sensitive group. The difference in recovery time between the two groups was not significant (p > 0.05). EEG results showed that recovery time took an average of 11.5 ± 7.1 min in both groups. The EEG data showed that the delta wave increased significantly across all brain areas (p < 0.01). There was no statistical difference between groups in recovering VR sickness depending on individual characteristics. However, we confirmed that subjective and objective VR recovery required at least 11.5 min. This finding can inform recommendations regarding the VR sickness recovery times., (© 2023 The Authors.)

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) with other recently published guidelines for treating bipolar disorder. We reviewed a total of six recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2022 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 in a same degree for mania. However, the KMAP-BP 2022 recommended MS + AAP combination therapy for psychotic mania, mixed mania and psychotic depression as treatment of choice. Aripiprazole, quetiapine and olanzapine were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Some guideline suggested olanzapine is a second-line options during maintenance treatment, related to concern about long-term tolerability. Most guidelines advocated newer AAPs (asenapine, cariprazine, long-acting injectable risperidone, and aripiprazole once monthly) 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. KMAP-BP 2022 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 2022, predominantly in the treatment of psychotic mania, mixed mania and psychotic depression.

Objective: The Functioning Assessment Short Test (FAST) is a relatively specific test for bipolar disorders designed to assess the main functioning problems experienced by patients. This brief instrument includes 24 items assessing impairment or disability in 6 domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. It has already been translated into standardized versions in several languages. The aim of this study is to measure the validity and reliability of the Korean version of FAST (K-FAST)., Methods: A total of 209 bipolar disorder patients were recruited from 14 centers in Korea. K-FAST, Young Mania Rating Scale (YMRS), Bipolar Depression Rating Scale (BDRS), Global Assessment of Functioning (GAF) and the World Health Organization Quality of Life Assessment Instrument Brief Form (WHOQOL-BREF) were administered, and psychometric analysis of the K-FAST was conducted., Results: The internal consistency (Cronbach's alpha) of the K-FAST was 0.95. Test-retest reliability analysis showed a strong correlation between the two measures assessed at a 1-week interval (ICC = 0.97; p < 0.001). The K-FAST exhibited significant correlations with GAF (r = -0.771), WHOQOL-BREF (r = -0.326), YMRS (r = 0.509) and BDRS (r = 0.598). A strong negative correlation with GAF pointed to a reasonable degree of concurrent validity. Although the exploratory factor analysis showed four factors, the confirmatory factor analysis of questionnaires had a good fit for a six factors model (CFI = 0.925; TLI = 0.912; RMSEA = 0.078)., Conclusion: The K-FAST has good psychometric properties, good internal consistency, and can be applicable and acceptable to the Korean context.

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.

Objective: We investigated the differences in suicidality between young people and older adults with depression over the course of 12-week naturalistic treatment with antidepressants., Methods: A total of 565 patients who had moderate to severe depression (Hamilton Depression Rating Scale [HAM-D] score ≥14) and significant suicidal ideation (Beck Scale for Suicide Ideation [SSI-B] score ≥6) were recruited from 18 hospitals. Participants were classified into two groups: the younger group (13-24 years of age, n=82) and the older group (≥25 years of age, n=483). Total scores over time on the SSI-B, HAM-D, and Hamilton Anxiety Rating Scale (HAM-A) were assessed and compared between the two groups., Results: At baseline, the younger group had lower HAM-D scores (21.0 vs. 22.2; p=0.028) but higher SSI-B scores (19.4 vs. 15.6; p<0.001) compared with the older group. The overall 12-week proportion of patients with resolved suicidality was 44.1% in the younger group and 69.2% in the older group. Although the improvement in the HAM-D and HAM-A scores did not differ between the groups, suicidal ideation in the younger group remained more severe than in the older group throughout the treatment. The ratio of the subjects who achieved HAM-D remission or response but did not achieve SSI-B remission was significantly higher in the younger group than in the older group., Conclusion: These data suggest that in depressed youths, suicide risk is a serious concern throughout the course of depression even when favorable treatment outcomes are obtained.

Objective: We revised the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP), first published in 2002 and revised in 2006, 2010, 2014, and 2018, to reflect recent progress in the treatment of bipolar disorder., Methods: The questionnaires consisted of 56 items for adult patients and 7 items for child/adolescent patients, and were used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of bipolar disorder. The review committee included 87 Korean psychiatrists and 40 child and adolescent psychiatry experts., Results: For treatment of manic episodes, a combination of a mood stabilizer (MS) and atypical antipsychotics (AAP), or monotherapy with MS or AAP were recommended as first-line treatments. Combinations of MS and AAP, or AAP and lamotrigine (LMT) were recommended as first-line treatments for depressive episodes regardless of the severity. Monotherapy with MS, AAP, or LMT were also first-line treatments for mild to moderate depressive episodes. For mixed features, a combination of MS and AAP, or monotherapy with AAP or MS were recommended as first-line treatments, and a combination of AAP and LMT, or MS and LMT were the first-line treatments for depressive mixed state., Conclusion: The recommendations of the KMAP-BP 2022 have changed from the previous version, to reflect the evolution of the social culture and healthcare system in Korea and recent evidence regarding pharmacotherapy of bipolar disorder. The KMAP-BP 2022 provides clinicians with a wealth of information regarding appropriate strategies to treat patients with bipolar disorder.

Comorbid psychiatric disorders in adults with ADHD are important because these comorbidities might complicate the diagnosis of ADHD and also worsen the prognosis. However, the prevalence of comorbid psychiatric disorders in adult ADHD varies according to the diagnostic tools used and the characteristics of target populations. The purpose of this review was to describe the prevalence of comorbid psychiatric disorders in adults with ADHD compared with adults without ADHD. Thirty-two studies published before August 2022 were identified and classified according to diagnosis of other psychiatric disorder in those with ADHD. The most frequent comorbid psychiatric disorder in the ADHD group was substance use disorder (SUD), followed by mood disorders, anxiety disorders, and personality disorders. The prevalence of these four disorders was higher in the ADHD group, whether or not subjects were diagnosed with other psychiatric disorders. In addition, the diversity of ADHD diagnostic tools was observed. This also might have affected the variability in prevalence of comorbidities. Standardization of ADHD diagnostic tools is necessary in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The purpose of this study was to compare the efficacy and tolerability of continued olanzapine (OLA) versus amisulpride (AMI) augmentation in schizophrenic patients with poor response to OLA monotherapy., Methods: The present 4-week, randomized, rater-blinded study included 25 patients with schizophrenia who were partially or completely unresponsive to treatment with OLA monotherapy. Eligible subjects were randomly assigned at a 1:1 ratio to continuation of OLA monotherapy (OLA group) or OLA with AMI augmentation (AMI group). Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at 1, 2, and 4 weeks., Results: The changes in PANSS total score and PANSS-positive subscale score were significantly different ( p < 0.05) between the OLA and AMI groups. The differences between the two groups in PANSS-negative subscale, PANSS-general subscale, Brief Psychiatric Rating Scale, and Clinical Global Impression-Severity (CGI-S) scale scores were not statistically significant., Conclusion: AMI augmentation could be an effective strategy for patients with schizophrenia who show inadequate early response to OLA monotherapy.

Bipolar disorder is a mental illness that causes extreme mood swings and has a chronic course. However, the mechanism by which mood episodes with completely opposite characteristics appear repeatedly, or a mixture of symptoms appears, in patients with bipolar disorder remains unknown. Therefore, mood stabilizers are indicated only for single mood episodes, such as manic episodes and depressive episodes, and no true mood-stabilizing drugs effective for treating both manic and depressive episodes currently exist. Therefore, in this review, therapeutic targets that facilitate the development of mood stabilizers were examined by reviewing the current understanding of the neuromolecular etiology of bipolar disorder.

Objective: This study investigated the prevalence and comorbidities of attention deficit hyperactivity disorder (ADHD) among adults and children/adolescents in Korea., Methods: This study used data from the Korea Health Insurance Review and Assessment Service collected from 2008 to 2018. Study participants comprised patients with at least one diagnosis of ADHD (International Statistical Classification of Diseases and Related Health Provisions, 10th revision code F90.0). Prevalence rates and psychiatric comorbidities were also analyzed., Results: We identified 878,996 patients diagnosed with ADHD between 2008 and 2018. The overall prevalence rate of diagnosed ADHD increased steeply from 127.1/100,000 in 2008 to 192.9/100,000 in 2018; it increased 1.47 times in children/adolescents (≤ 18 years) and 10.1 times in adults (＞ 18 years) during this period. Among adult and children/ adolescent ADHD patients, 61.84% (95% confidence interval [95% CI] 61.74-61.93) and 78.72% (95% CI 78.53- 78.91) had at least one psychiatric comorbidity, respectively., Conclusion: Our results showed that the prevalence rate of diagnosed ADHD has increased in Korea; however, it is lower than the global average. Further studies are required to identify and treat vulnerable populations appropriately.

Objective: This study aimed to compare the efficacy and safety of atomoxetine (ATX) and OROS methylphenidate (MPH) as adjunctive to selective serotonin reuptake inhibitors (SSRIs) in adults with attention-deficit hyperactivity disorder (ADHD) with comorbid partially responsive major depressive disorder (MDD)., Methods: Sixty Korean adults with ADHD and comorbid partially responsive MDD were recruited in a 12-week, randomized, rater-blinded, active-controlled trial and were evenly randomized to ATX or OROS MPH treatment., Results: Depressive symptoms measured using the Hamilton Depression Rating Scale and Clinically Useful Depression Outcome Scale, and ADHD symptoms measured using the Adult ADHD Self-Report Scale, as well as the Clinical Global Impression-Severity, Clinical Global Impression-Improvement, and the Sheehan Disability Scale scores were significantly improved in both groups during the 12 weeks of treatment. The changes in all outcome measures during the 12-week treatment were not significantly different between the two groups (all p > 0.05). No serious adverse events were reported and there were no significant differences in systolic and diastolic blood pressure, pulse rate, weight, or body mass index between the ATX and MPH groups., Conclusion: Our findings suggest that ATX and MPH can be used as adjunctive treatments in adults with ADHD and comorbid partially responsive MDD. The efficacy and tolerability of ATX and MPH in adults with ADHD did not differ significantly. Further studies should be conducted to draw a definitive conclusion.

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.

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.

Objective: The aim of the present study is to identify the factors that affect retention in outpatients with psychiatric disorders as indicators of treatment adherence, including Minnesota Multiphasic Personality Inventory (MMPI) scores., Methods: The medical records of 146 patients diagnosed with major depressive disorder, bipolar disorder, or anxiety disorder for at least 10 years and discharged were retrospectively reviewed in the present study. The subjects were categorized based on the duration of outpatient treatment as < 6 months (L6) or ≥ 6 months (M6) groups and reclassified as < 36 months (L36) and ≥ 36 months (M36) groups. The demographic, clinical, and personality characteristics of the groups were compared., Results: Patients in M6 and M36 groups were more likely to have a higher educational level compared with those in the L6 and L36 groups, respectively. Patients in the M6 group showed significantly lower hypomania (Ma) scores on the MMPI test than did patients in the L6 group., Conclusion: The association between high Ma score on the MMPI test and early discontinuation of treatment suggests that impulsivity, hostility, and disinhibition confer higher risk of nonadherence.

Objective: Diverse resting-state functional magnetic resonance imaging (rs-fMRI) studies showed that rs-fMRI might be able to reflect the earliest detrimental effect of cerebral beta-amyloid (Aβ) pathology. However, no previous studies specifically compared the predictive value of different rs-fMRI parameters in preclinical AD. Methods: A total of 106 cognitively normal adults (Aβ+ group = 66 and Aβ- group = 40) were included. Three different rs-fMRI parameter maps including functional connectivity (FC), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo) were calculated. Receiver operating characteristic (ROC) curve analyses were utilized to compare classification performance of the three rs-fMRI parameters. Results: FC maps showed the best classifying performance in ROC curve analysis (AUC, 0.915, p < 0.001). Good but weaker performance was achieved by using ReHo maps (AUC, 0.836, p < 0.001) and fALFF maps (AUC, 0.804, p < 0.001). The brain regions showing the greatest discriminative power included the left angular gyrus for FC, left anterior cingulate for ReHo, and left middle frontal gyrus for fALFF. However, among the three measurements, ROI-based FC was the only measure showing group difference in voxel-wise analysis. Conclusion: Our results strengthen the idea that rs-fMRI might be sensitive to earlier changes in spontaneous brain activity and FC in response to cerebral Aβ retention. However, further longitudinal studies with larger sample sizes are needed to confirm their utility in predicting the risk of AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Kim, Kang, Um, Na, Woo, Lee, Bahk and Lim.)

Objective: We performed a meta-analysis of randomized double-blinded placebo controlled trials (DB-RCTs) to investigate efficacy and safety of intranasal esketamine in treating major depressive disorder (MDD) including treatment resistant depression (TRD) and major depression with suicide ideation (MDSI)., Methods: Mean change in total scores on Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to different time-points were our primary outcome measure. Secondary efficacy measures included rate of remission of depression and resolution of suicidality., Results: Eight DB-RCTs (seven published and one un-published) covering 1,488 patients with MDD were included. Esketamine more significantly improved MADRS total scores than placebo starting from 2-4 hours after the first administration (standardized mean difference, -0.41 [95% CI, -0.58 to -0.25], p < 0.00001), and this superiority maintained until end of double-blinded period (28 days). Sub-group analysis showed that superior antidepressant effects of esketamine over placebo in TRD and MDSI was observed from 2-4 hours, which was maintained until 28 days. Resolution of suicide in MDSI was also greater for esketamine than for placebo at 2-4 hours (OR of 2.04, 95% CIs, 1.37 to 3.05, p = 0.0005), but two groups did not statistically differ at 24 hours and day 28. Total adverse events (AEs), and other common AEs including dissociation, blood pressure increment, nausea, vertigo, dysgeusia, dizziness, and somnolence were more frequent in esketamine than in placebo group., Conclusion: Esketamine showed rapid antidepressant effects in patients with MDD, including TRD and MDSI. The study also suggested that esketamine might be associated with rapid anti-suicidal effects for patients with MDSI.

Objective: There are animal models associating dopamine dysfunction with behavioral impairments that model attention deficit hyperactivity disorder (ADHD). Erythropoietin (EPO) has trophic effects on dopaminergic neurons. The aim of this study was to examine the EPO plasma levels and determine whether there was any correlation between plasma EPO levels and clinical characteristics of ADHD., Methods: Plasma EPO levels were measured in 78 drug-naïve children with ADHD and in 81 healthy children. The severity of ADHD symptoms was determined by scores on the Korean ADHD Rating Scale (K-ARS) in ADHD children and healthy controls., Results: The difference between median plasma EPO levels in ADHD children and in healthy controls was not statistically significant. Adjusting for age and sex, a linear regression analysis showed that inattention score was significantly higher in the second highest tertile of plasma EPO compared to those in the lowest tertile. Hyperactivity-impulsivity score was significantly higher in the highest tertile of plasma EPO compared to those in the lowest tertile. Moreover, total K-ARS scores were significantly higher in the second highest tertile of plasma EPO compared to those in the lowest tertile., Conclusion: These findings suggest that plasma EPO levels were related to some ADHD symptoms, which could be used in the monitoring of the disorder.

No reliable quantitative and objective measurement method for virtual reality (VR) sickness has been firmly established to date. Electroencephalography (EEG) may be a strong candidate to evaluate VR sickness objectively. However, no test-retest evaluation has been made for VR sickness using EEG. To recruit VR sickness-sensitive participants, we tested 858 participants (age = 20's-50's) using the Motion Sickness Susceptibility Questionnaire (MSSQ). Among them, we recruited 21 males (average age = 25.0) who obtained the 75th percentile of scores on the MSSQ (32.9 ± 5.7). VR sickness was evaluated twice (one week apart) using EEG with VR video content designed to cause VR sickness. A Simulation Sickness Questionnaire (SSQ) was also used to evaluate VR sickness. In terms of the reliability of EEG, ICC and Cronbach's alpha analyses showed that three waves (delta, theta, and alpha) were consistent in two areas (frontal and central). A significant difference in EEG was also found repeatedly between the baseline and VR sickness (delta, theta, and alpha) in two areas (frontal and central). We evaluated EEG for its reliability and found specific waves and areas that showed good consistency and significant changes associated with VR sickness. These findings may support further research of VR sickness evaluation., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Alzheimer's disease (AD) is the most common type of dementia and the prevalence rapidly increased as the elderly population increased worldwide. In the contemporary model of AD, it is regarded as a disease continuum involving preclinical stage to severe dementia. For accurate diagnosis and disease monitoring, objective index reflecting structural change of brain is needed to correctly assess a patient's severity of neurodegeneration independent from the patient's clinical symptoms. The main aim of this paper is to develop a random forest (RF) algorithm-based prediction model of AD using structural magnetic resonance imaging (MRI)., Methods: We evaluated diagnostic accuracy and performance of our RF based prediction model using newly developed brain segmentation method compared with the Freesurfer's which is a commonly used segmentation software., Results: Our RF model showed high diagnostic accuracy for differentiating healthy controls from AD and mild cognitive impairment (MCI) using structural MRI, patient characteristics, and cognitive function (HC vs. AD 93.5%, AUC 0.99; HC vs. MCI 80.8%, AUC 0.88). Moreover, segmentation processing time of our algorithm (<5 minutes) was much shorter than of Freesurfer's (6-8 hours)., Conclusion: Our RF model might be an effective automatic brain segmentation tool which can be easily applied in real clinical practice.

Objective: Network analysis can be used in terms of a novel psychopathological approach for depressive syndrome. We aimed to estimate the successive network structures of depressive symptoms in patients with depressive disorder using data from the Clinical Research Center for Depression study., Methods: We enrolled 1,152 South Korean adult patients with depressive disorders who were beginning treatment for first-onset or recurrent depressive episodes. We examined the network structure of the severities of the items on the Hamilton Depression Rating Scale (HAMD) at baseline and at weeks 2, 12, 25, and 52. The node strength centrality of all the HAMD items at baseline and at week 2, 12, 25, and 52 in terms of network analysis., Results: In the severity networks, the anxiety (psychic) item was the most centrally situated in the initial period (baseline and week 2), while loss of weight was the most centrally situated item in the later period (weeks 25 and 52). In addition, the number of strong edges (i.e., edges representing strong correlations) increased in the late period compared to the initial period., Conclusion: Our findings support a period-specific and symptom-focused therapeutic approach that can provide complementary information to the unidimensional total HAMD score.

Beginning with the concept of the brain-gut axis, the importance of the interaction between the brain and the gastrointestinal tract has been extended to the microbiome with increasing clinical applications. With the recent development of various techniques for microbiome analysis, the number of relevant preclinical and clinical studies on animals and human subjects has rapidly increased. Various psychotic symptoms affect the intestinal microbiome through the hypothalamus-pituitary-adrenal gland axis. Conversely, the intestinal microbiome regulates the gastrointestinal tract environment and affects psychological factors by means of the microorganisms or their metabolites, either acting directly on the brain or through the synthesis of various neurotransmitters. This review discusses the clinical applicability of the brain-gut-microbiome axis and directions for improving psychological symptoms based on the studies published to date.

Close connections between depression and type 2 diabetes (T2DM) have been suggested by many epidemiological and experimental studies. Disturbances in insulin sensitivity due to the disruption of various molecular pathways cause insulin resistance, which underpins many metabolic disorders, including diabetes, as well as depression. Several anti-hyperglycemic agents have demonstrated antidepressant properties in clinical trials, probably due to their action on brain targets based on the shared pathophysiology of depression and T2DM. In this article, we review reports of clinical trials examining the antidepressant effect of these medications, including insulin, metformin, glucagon like peptide-1 receptor agonists (GLP-1RA), and peroxisome proliferator-activated receptor (PPAR)-γ agonists, and briefly consider possible molecular mechanisms underlying the associations between amelioration of insulin resistance and improvement of depressive symptoms. In doing so, we intend to suggest an integrative perspective for understanding the pathophysiology of depression.

Post-growth graphene transfer to a variety of host substrates for circuitry fabrication has been among the most popular subjects since its successful development via chemical vapor deposition in the past decade. Fast and reliable evaluation tools for its morphological characteristics are essential for the development of defect-free transfer protocols. The implementation of conventional techniques, such as Raman spectroscopy, atomic force microscopy (AFM), and transmission electron microscopy in production quality control at an industrial scale is difficult because they are limited to local areas, are time consuming, and their operation is complex. However, through a one-shot measurement within a few seconds, phase-shifting interferometry (PSI) successfully scans ≈1 mm 2 of transferred graphene with a vertical resolution of ≈0.1 nm. This provides crucial morphological information, such as the surface roughness derived from polymer residues, the thickness of the graphene, and its adhesive strength with respect to the target substrates. Graphene samples transferred via four different methods are evaluated using PSI, Raman spectroscopy, and AFM. Although the thickness of the nanomaterials measured by PSI can be highly sensitive to their refractive indices, PSI is successfully demonstrated to be a powerful tool for investigating the morphological characteristics of the transferred graphene for industrial and research purposes., (© 2020 Wiley-VCH GmbH.)

Objective: Despite multiple drugs available, a large proportion of patients with generalized anxiety disorder (GAD) do not show adequate response and remission. Thus, additional novel pharmacological agents are needed to increase treatment option for GAD. We aimed to investigate efficacy and safety of agomelatine in the treatment of GAD by conducting a meta-analysis., Methods: An extensive search of multiple databases and clinical trial registries were conducted. Mean change in total scores on Hamilton Anxiety Rating Scale (HAM-A) from baseline to endpoint was our primary outcome measure. Secondary efficacy measures included response and remission rates, as defined by a 50% or greater reduction in HAM-A total scores and a score of 7 or less in HAM-A total scores at study endpoint respectively., Results: Four published double blinded, randomized, placebo-controlled trials were included in this meta-analysis. Agomelatine more significantly (standardized mean difference = -0.56, p = 0.004) improved HAM-A total scores than placebo. The odds ratios (ORs) of agomelatine over placebo for response and remission rates were 3.75 ( p < 0.00001) and 2.74 ( p < 0.00001), respectively. Agomelatine was generally well tolerated with insignificance in dropout rate, somnolence, headache, nasopharyngitis, and dizziness compared with placebo. However, agomelatine showed significantly higher incidence of liver function increment (OR = 3.13, p = 0.01) and nausea (OR = 3.27, p = 0.02)., Conclusion: We showed that agomelatine may be another treatment option in patients with GAD. However, the results should be interpreted and translated into clinical practice with caution because the meta-analysis was based on limited numbers of clinical trials.

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., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

Background: Although mood stabilizers such as lithium (LIT), valproate (VAL), and lamotrigine (LMT) appear to be efficacious treatments for bipolar disorder (BD) in research settings, the long-term response to these mood stabilizers in clinical practice is highly variable among individuals. Thus, the present study examined the characteristics associated with good or insufficient responses to long-term treatment with LIT, VAL, or LMT for BD., Methods: This study retrospectively analyzed the medical records of patients who visited an outpatient clinic with a diagnosis of BD I or II. Data from patients who were treated with one of three mood stabilizing medications (LIT, VAL, or LMT) for more than 6 months were selected, and the long-term treatment responses were evaluated using the Alda scale. For the purposes of this study, two response categories were formed: insufficient response (ISR), including non-response or poor response (Alda total score ≤ 6), and good response (GR; Alda total score ≥ 7)., Results: Of the 645 patients included in the present study, 172 were prescribed LIT, 320 were prescribed VAL, and 153 were prescribed LMT for at least 6 months. A binary logistic regression analysis revealed that a diagnosis of BD II (odds ratio [OR], 8.868; 95% confidence interval [CI], 1.123-70.046; p = 0.038), comorbid alcohol/substance use disorder (OR, 4.238; 95% CI, 1.154-15.566; p = 0.030), and a history of mixed episodes (OR, 4.363; 95% CI, 1.191-15.985; p = 0.026) were significant predictors of LIT-ISR. Additionally, a depressive-predominant polarity significantly predicted LMT-GR (OR, 8.586; 95% CI, 2.767-26.644; p < 0.001)., Conclusion: The present findings demonstrated that patients with a diagnosis of BD II, a comorbid alcohol/substance problem, or a history of mixed episodes were not likely to respond to LIT treatment. Additionally, LMT might be a better treatment choice for patients with a depressive-predominant polarity., Competing Interests: The authors have declared that no competing interests exist.

Melatonin is a hormone that is secreted by the pineal gland. To date, melatonin is known to regulate the sleep cycle by controlling the circadian rhythm. However, recent advances in neuroscience and molecular biology have led to the discovery of new actions and effects of melatonin. In recent studies, melatonin was shown to have antioxidant activity and, possibly, to affect the development of Alzheimer's disease (AD). In addition, melatonin has neuroprotective effects and affects neuroplasticity, thus indicating potential antidepressant properties. In the present review, the new functions of melatonin are summarized and a therapeutic target for the development of new drugs based on the mechanism of action of melatonin is proposed.

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., (© 2019 John Wiley & Sons, Ltd.)

Objective: This study was performed to investigate the efficacy and tolerability of blonanserin in schizophrenic patients who were previously treated with other antipsychotics but, due to insufficient response, were switched to blonanserin., Methods: A total of 52 patients with schizophrenia who were unresponsive to treatment with antipsychotic monotherapy or combination therapy were recruited into this 12-week, open-label, prospective, multicenter study. Patients were switched to blonanserin from their existing antipsychotics over a maximum 2-week tapering-off period. Efficacy was primarily evaluated using the 18-item Brief Psychiatric Rating Scale (BPRS). Assessments were performed at baseline, and at weeks 1, 2, 4, 8, and 12., Results: Switching to blonanserin resulted in a significant decrease in the mean total score on the BPRS from baseline (56.8 ± 9.4) to week 12 (42.1 ± 13.8, p > 0.001). The most common adverse events were extrapyramidal symptoms (n = 12, 23.1%), insomnia (n = 10, 19.2%), and emotional arousal (n = 6, 11.5%). Overweight or obese patients (body mass index ≥ 23 kg/m 2 , n = 33) who switched to blonanserin exhibited significant weight loss from 75.2 ± 9.3 kg at baseline to 73.5 ± 9.2 kg at week 12 ( p = 0.006). The total cholesterol (baseline, 236.1 ± 47.6 mg/dl; endpoint [week 12], 209.9 ± 28.0 mg/dl; p = 0.005) and prolactin levels (baseline, 80.0 ± 85.2 ng/ml; endpoint [week 12], 63.2 ± 88.9 ng/ml; p = 0.003) were also significantly improved in patients with hypercholesterolemia or hyperprolactinemia., Conclusion: The results of the present study suggest that switching to blonanserin may be an effective strategy for schizophrenic patients unresponsive to other antipsychotic treatments.

Objective: The Depression in Old Age Scale (DIA-S) is a new screening tool for assessing depression in the elderly. The primary aims of this study were to describe the validation of the Korean version of the DIA-S (K-DIA-S) and to compare its validity with that of other depression screening questionnaires used in elderly outpatients in medical settings., Methods: A total of 385 elderly outpatients completed the K-DIA-S and underwent the Mini International Neuropsychiatric Interview to diagnose depressive disorders. Other measures included the 15-item short form of the Geriatric Depression Scale (SGDS), the 9-item depression module of the Patient Health Questionnaire (PHQ-9), and the Montgomery-Asberg Depression Rating Scale (MADRS). Reliability and validity tests, an optimal cutoff point estimate, and receiver operating characteristic curve analysis were performed to investigate the diagnostic validity of the K-DIA-S. Areas under the curves (AUCs) for the K-DIA-S, SGDS, and PHQ-9 were compared statistically., Results: The K-DIA-S showed good internal consistency and strong correlations with the SGDS ( r = 0.853), PHQ-9 ( r = 0.739), and MADRS ( r = 0.772). The cut-off point of the K-DIA-S that can be recommended for screening depressive symptoms was a score of 4. For "any depressive disorder", the AUC (standard error) for the K-DIA-S was 0.896 (0.015), which was significantly larger than that for the PHQ-9 ( p = 0.033)., Conclusion: The present findings suggest that the K-DIA-S has good psychometric properties and is a valid and reliable tool for assessing depressive symptoms in elderly populations and medically ill patients.