Effect of Frailty on Depression among Patients with Late-life Depression: A Test of Anger, Anxiety, and Resilience as Mediators.

Objective: While the association between depression and frailty in the elderly population has been investigated, the psychological factors that mediate such a relationship remain unknown. The identification of psychological factors in interventions for depression treatment in the elderly may assist in the treatment and care. We aimed to explore the mediating effects of anger, anxiety, and resilience on the link between frailty and depression symptoms in patients with late-life depression. Methods: A sample of 203 older adults completed questionnaires that assessed depression, anger, resilience, and anxiety. To measure frailty, participants were evaluated using a self-rated health questionnaire, weight-adjusted waist index related to sarcopenia, and weight-adjusted handgrip strength to evaluate weakness. A mediation model was tested, hypothesizing that anger, anxiety, and resilience would partially mediate the strength of the frailty-depression link in the elderly. Results: Only self-rated health showed a significant association with depressive symptoms in late-life depression. Our study demonstrated that frailty has both direct and indirect associations with depression, mediated by anger, resilience, and anxiety. Conclusion: Given that anger, resilience, and anxiety influence the link between self-rated health and depression, interventions that lead to increased resilience and decreased anger and anxiety may be promising to reduce depressive symptoms in older adults with depression.

Investigating the effectiveness of a smart mental health intervention (inMind) for stress reduction during pharmacological treatment for mild to moderate major depressive disorders: Study protocol for a randomized control trial.

Background: Although psychological interventions for stress relief, such as cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR), have been developed, they have not been widely used in treating depression. The use of mobile devices can increase the possibility of actual use by integrating interventions and reducing the difficulty and cost burden of treatment application. This study aims to determine whether "inMind," an integrated mobile application for stress reduction, developed for the general population, decreases stress for patients with mild to moderate major depressive disorder during the pharmacological treatment period. Methods: This study is a single-blind, multicenter, randomized, controlled crossover trial. The App, developed in Republic of Korea, provides integrated interventions for stress reduction for the general population through three modules based on mindfulness-based stress reduction, cognitive behavior therapy, and relaxation sounds that are known to be effective in stress reduction ("meditation," "cognitive approach," and "relaxation sounds," respectively). Participants (n = 215) recruited via medical practitioner referral will be randomized to an App first group (fAPP) or a wait list crossover group (dAPP). The study will be conducted over 8 weeks; the fAPP group will use the App for the first 4 weeks and the dAPP group for the next 4 weeks. During all study periods, participants will receive their usual pharmacological treatment. The Depression Anxiety Stress Scale-21 is the primary outcome measure. The analysis will employ repeated measurements using a mixed-model approach. Discussion: The App can potentially be an important addition to depression treatment because of its applicability and the comprehensive nature of the interventions that covers diverse stress-relieving models. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT05312203, identifier 2021GR0585.

Microbiota-Gut-Brain Axis: Pathophysiological Mechanism in Neuropsychiatric Disorders.

Gut microbiota influence human behavior. The immunological, metabolic, and endocrine systems are involved in bidirectional communication between the gut and the brain, which is regulated by microbes through the microbiota-derived neurochemicals and metabolites. Gut microbiota have certain effects on neurodevelopment and maturation of immunity. However, gut dysbiosis can lead to neuropsychiatric disorders. Animal research and clinical case-control studies have demonstrated that gut dysbiosis has an adverse effect on human behavior through a variety of mechanisms. Recent meta-analysis on clinical studies confirmed gut dysbiosis in several major neuropsychiatric disorders. Microbiota-targeted intervention has recently been in the spotlight and meta-analyses have confirmed its effectiveness. In this chapter, we summarize the evidence for the interactions between microbiota and brain-gut network, as well as the potential pathophysiological mechanisms involved.

Sex differences in gastrointestinal dysfunction among patients with Parkinson's disease.

BACKGROUND AND OBJECTIVE: Sex differences in gastrointestinal dysfunction have not been systematically analyzed in patients with Parkinson's disease (PD). This study was aimed to investigate the sex differences in gastrointestinal dysfunctions among the patients with PD using a multicenter trial dataset. METHODS: We analyzed the baseline data of prospectively enrolled set of patients with gastrointestinal dysfunctions. Possible sex differences in gastrointestinal symptoms assessed on the Nepean Dyspepsia Index-Korean Version (NDI-K), gastrointestinal symptom diary, and Bristol stool scale were analyzed in association with clinical PD severity and antiparkinsonian drug dosages by multiple linear regression models. We also performed post hoc analysis of the dyspepsia symptom sub-items, adjusting for multiple comparisons. RESULTS: Sixty-six of the 144 participants were female (45.8%). There were no differences in age, PD duration, Hoehn and Yahr stage, and daily dopaminergic medication dosages between sexes. NDI-K symptom and dyspepsia scores were correlated with the activity of daily living in females but not in males. In the multiple regression analysis controlling for all possible variables, female patients were shown to have worse gastrointestinal symptoms than males. When we performed post hoc analysis of the dyspepsia symptoms, inability to finish a regular meal and nausea were significantly worse in female patients. Gastrointestinal symptom diary supported that female patients more frequently complained of early fullness and bloating in the upper abdomen after meals than males, and burning pain in upper abdomen was more severe in female patients. CONCLUSION: Gastrointestinal dysfunctions may differentially affect female and male PD patients.

Plasminogen Activator Inhibitor-1: Potential Inflammatory Marker in Late-life Depression.

Objective: Although several previous studies have examined the association between late-life depression and blood adipokine levels, a marker of chronic inflammation, no studies have comprehensively considered the effects of metabolic syndrome, which is known to affect blood adipokine levels. This study examined blood adipokine levels in geriatric depression after adjusting for the effects of metabolic syndrome. Methods: Participants were selected from the Ansan Geriatric Study (depression group [n = 76] and control group [n = 76]). Blood concentrations of four adipokines (adiponectin, resistin, neutrophil-gelatinase-associated lipocalin [NGAL], and plasminogen activator inhibitor-1 [PAI-1]) were measured using immunoassays. The effects of blood adipokine concentration on the diagnosis of depression were analyzed using multivariate logistic regression to adjust for the effects of metabolic syndrome and potential confounding factors. Results: When the effects of metabolic syndrome and potential confounding factors were adjusted, only PAI-1 could explain the diagnosis of depression among all the adipokines. The depression group showed a lower blood PAI-1 level than the control group. Adiponectin, resistin, and NGAL could not explain the diagnosis of depression when the effects of metabolic syndrome and potential confounding factors were adjusted. Conclusion: This study suggests the possibility that the blood PAI-1 levels in clinically pathological late-life depression may show contrasting results to those with subclinical depressive symptoms. Additionally, considering that most previous studies have been conducted with pre-geriatric populations, the study suggests the possibility that geriatric depression may show inflammatory changes with patterns that are different from those of depression in the pre-geriatric population.

Efficacy and Safety of Escitalopram, Desvenlafaxine, and Vortioxetine in the Acute Treatment of Anxious Depression: A Randomized Rater-blinded 6-week Clinical Trial.

Objective: Anxious depression is associated with greater chronicity, higher severity of symptoms, more severe functional impairment, and poor response to drug treatment. However, evidence for first-choice antidepressants in patients with anxious depression is limited. This study aimed to compare the efficacy and safety of escitalopram, desvenlafaxine, and vortioxetine in the acute treatment of anxious depression. Methods: Patients (n = 124) with major depressive disorder and high levels of anxiety were randomly assigned to an escitalopram treatment group (n = 42), desvenlafaxine treatment group (n = 40), or vortioxetine treatment group (n = 42) in a 6-week randomized rater-blinded head-to-head comparative trial. Changes in overall depressive and anxiety symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA), respectively. Results: Patients demonstrated similar baseline-to-endpoint improvement in scores and similar response and remission rates for HAMD and HAMA. Analysis of the individual HAMD items revealed that desvenlafaxine significantly reduced anxiety somatic scores (p = 0.013) and hypochondriasis scores (p = 0.014) compared to escitalopram. With respect to the individual HAMA items, desvenlafaxine treatment showed significantly lower scores for respiratory symptoms (p = 0.013) than escitalopram treatment and cardiovascular symptoms (p = 0.005) than vortioxetine treatment. The treatments were well tolerated, with no significant differences. Conclusion: Our results indicated no significant differences in the efficacy and tolerability of escitalopram, desvenlafaxine, and vortioxetine in this subtype of patients with anxious depression during the acute phase of treatment.

Suicide and Suicide Prevention Awareness in Korea During the COVID-19 Pandemic.

OBJECTIVE: Owing to prolonged social distancing and the resultant isolation, the prevalence of depression and suicidality has increased during the COVID-19 pandemic. This study aimed to investigate the severity of depression and suicidality in Korean community populations and examine their awareness of suicide and suicide prevention during the pandemic. METHODS: This study surveyed a community population in 2020 and 2021, involving 668 participants. We evaluated the severity of depression and suicidality using the Patient Health Questionnaire-9 and Beck Scale for Suicidal Ideation as well as questions about awareness of suicide. We performed a correlation analysis to confirm the association between variables, and compared participants' suicide awareness according to the severity of depression. RESULTS: The severity of depression and suicidality in the community population decreased in 2021 compared to 2020. Awareness of the importance of suicide prevention increased in 2021, but the percentage reporting that it is possible decreased slightly. The group with higher depressive symptoms reported a lower possibility of suicide prevention. CONCLUSION: Increasing social interest in suicide, as well as awareness of suicide prevention, is important for reducing suicide rates. Suicide prevention campaigns, education, and social policies are needed, particularly during the pandemic.

Acute Efficacy and Safety of Escitalopram Versus Desvenlafaxine and Vortioxetine in the Treatment of Depression With Cognitive Complaint: A Rater-Blinded Randomized Comparative Study.

OBJECTIVE: This study aimed to compare the efficacy and safety of escitalopram, vortioxetine, and desvenlafaxine for acute treatment of major depressive disorder (MDD) with cognitive complaint (CC). METHODS: A total of 129 patients with MDD who also complained of CC were randomized evenly to either escitalopram, vortioxetine, or desvenlafaxine group and underwent a multi-center, six-week, rater-blinded, and head-to-head comparative trial. Differences in depressive symptoms following treatment were measured using the Hamilton Depression Rating Scale (HAMD) and the Montgomery-Åsberg Depression Rating Scale (MADRS). Subjective cognitive function and the presence of adverse events were assessed. RESULTS: The three antidepressant treatment groups did not show significant differences in the improvement of depressive symptoms as measured by HAMD and MADRS. Desvenlafaxine treatment was associated with a superior treatment response rate in depressive symptoms compared to vortioxetine or escitalopram treatment. However, no significant differences were found in the remission rate of depressive symptoms. The three antidepressant treatment groups did not show significant differences in the improvement of CC. Adverse profiles of each treatment group were tolerable, with no significant differences. CONCLUSION: In acute antidepressant treatment for MDD with CC, escitalopram, vortioxetine, and desvenlafaxine presented similar efficacy in relief of depressive symptoms; however, desvenlafaxine was associated with a superior treatment. Further studies are needed to confirm these results by investigating the therapeutic efficacy and safety profile of long-term antidepressant treatment of MDD with CC (Clinical Trial Registry, http://cris.nih.go.kr/cris/en/: KCT0002173).

Synergy Through Integration of Wearable EEG and Virtual Reality for Mild Cognitive Impairment and Mild Dementia Screening.

Virtual reality (VR) technologies have shown promising potential in the early diagnosis of dementia by enabling accessible and regular assessment. However, previous VR studies were restricted to the analysis of behavioral responses, so information about degenerated brain dynamics could not be directly acquired. To address this issue, we provide a cognitive impairment (CI) screening tool based on a wearable EEG device integrated into a VR platform. Subjects were asked to use a hardware setup consisting of a frontal six-channel EEG device mounted on a VR device and to perform four cognitive tasks in VR. Behavioral response profiles and EEG features were extracted during the tasks, and classifiers were trained on extracted features to differentiate subjects with CI from healthy controls (HCs). Notably, the performance of the patient classification consistently improved when EEG characteristics measured during cognitive tasks were additionally included in feature attributes than when only the task scores or resting-state EEG features were used, suggesting that our protocol provides discriminative information for screening. These results propose that the integration of EEG devices into a VR framework could emerge as a powerful and synergistic strategy for constructing an easily accessible EEG-based CI screening tool.

Validation of the Korean version of the Generalized Anxiety Disorder 7 self-rating Scale.

This study examined the validity and reliability of the Korean version of the Generalized Anxiety Disorder-7 (GAD-7) scale. The GAD-7 was standardized with data from 112 patients at a psychiatric outpatient clinic. The GAD-7 revealed high internal consistency, good test-retest reliability, and convergent validity. The ROC analysis resulted in poor sensitivity and specificity for detecting anxiety disorders in a psychiatric setting. The GAD-7 may not be useful in diagnosing anxiety disorders in a psychiatric setting, even though it appears to be a reliable, efficient, and valid measurement tool for evaluating anxiety symptoms.

Insomnia in Emotional Labor: Its Role in Autonomic Nervous System Regulation.

OBJECTIVE: The relation between female emotional laborers' sleep quality and autonomic nervous system activity was investigated. METHODS: Thirty-three subjects' heart rate variability (HRV) data and results of self-reported scale on sleep, depression, anxiety and suicidality, were collected. Subjects were classified into good sleeper (GS) and poor sleeper (PS) groups relying on sleep quality. Changes of HRV between working time and resting time in each group were compared. RESULTS: The PS group showed significantly lower difference in root mean square of successive differences (RMSSD), percentage of successive normal-to-normal intervals that differ by more than 50 ms (pNN50), and natural logarithm high-frequency (LnHF) when they were working as compared to when they were resting, which means decreased function of the parasympathetic nervous system (PNS). Repeated measures analysis of covariance showed that the group effect was significant only for LnHF, with score of depression scale as a covariate. CONCLUSION: Female emotional laborers who complain of sleep difficulty may have decreased function of the PNS. Therefore, good sleep quality is essential for maintaining and promoting mental and physical health of women engage in emotional labor.

Changes in Brain Electrical Activity According to Post-traumatic Stress Symptoms in Survivors of the Sewol Ferry Disaster: A 1-year Longitudinal Study.

OBJECTIVE: The pathology of post-traumatic stress disorder (PTSD) is associated with changes in brain structure and function, especially in the amygdala, medial prefrontal cortex, hippocampus, and insula. Survivors of tragic accidents often experience psychological stress and develop post-traumatic stress symptoms (PTSS), regardless of the diagnosis of PTSD. This study aimed to evaluate electroencephalographic changes according to PTSS in victims of a single traumatic event. METHODS: This study enrolled 60 survivors of the Sewol ferry disaster that occurred in 2014 from Danwon High School and collected electroencephalographic data through 19 channels twice for each person in 2014 and 2015 (mean 451.88 [standard deviation 25.77] days of follow-up). PTSS was assessed using the PTSD Checklist-Civilian Version (PCL-C) and the participants were divided into two groups according to the differences in PCL-C scores between 2014 and 2015. Electroencephalographic data were converted to three-dimensional data to perform low-resolution electrical tomographic analysis. RESULTS: Significant electroencephalographic changes over time were observed. The group of participants with worsened PCL-C score showed an increased change of delta slow waves in Brodmann areas 13 and 44, with the largest difference in the insula region, compared to those with improved PCL-C scores. CONCLUSION: Our findings suggests that the electrophysiological changes in the insula are associated with PTSS changes.

Additional Reduction of Residual Symptoms with Aripiprazole Augmentation in the Patients with Partially Remitted Major Depressive Disorder.

OBJECTIVE: Many patients with major depressive disorder (MDD) suffer from residual symptoms without achieving remission. However, pharmacologic options for residual symptoms of MDD have been limited. This study aimed to investigate benefit of aripiprazole augmentation in the treatment of residual symptoms in the patients with partially remitted MDD. METHODS: We retrospectively analyzed the 8-week medical records of the patients. The enrolled patients did respond to treatment of antidepressant but were not remitted. The range of 17-item Hamilton Depression Rating Scale (HAMD) total score of the subjects were 8 to 15 points. All patients were currently taking antidepressants when they started aripiprazole. The primary endpoint was the mean change of Clinically Useful Depression Outcome Scale (CUDOS). Secondary endpoint measures were HAMD, Clinical Global Impression-severity (CGI-S) scores, Patient Health Questionnaire-15 (PHQ-15), Beck Anxiety Inventory (BAI), Perceived Deficit Questionnaire-depression (PDQ-D), Sheehan Disability Scale (SDS) and General Health Questionnaire/Quality of Life-12 (GHQ/QL-12). RESULTS: A total of 134 medical records were analyzed. The changes of CUDOS, HAMD, CGI-S, BAI, PHQ-15, PDQ-D, SDS and GHQ/QL-12 from baseline to the endpoint were -7.93, -3.29, -0.80, -4.02, -2.05, -4.35, -4.77 and -2.82, respectively (all p < 0.001). At the endpoint, the newly remitted subjects rate by HAMD score criteria were approximately 46%. CONCLUSION: Our preliminary findings have presented the effectiveness of aripiprazole augmentation for residual symptoms of partially remitted MDD patients in routine practice. This study assures subsequent well-controlled studies of the possibility of generalizing the above promising outcome in the future.

The Behavioral Effects of Combination Therapy of Memantine and Acetylcholinesterase Inhibitors Compared with Acetylcholinesterase Inhibitors Alone in Patients with Moderate Alzheimer's Dementia: A Double-Blind Randomized Placebo-Controlled Trial.

OBJECTIVE: This study aimed to investigate treatment effects of combination therapy of memantine and acetylcholinesterase inhibitors (AchEIs) compared with AchEIs alone on behavioral and psychological symptoms of dementia (BPSD) in patients with moderate Alzheimer's dementia (AD). METHODS: This was a 12-week, double-blind, randomized, placebo-controlled trial. A total of 148 patients with moderate AD participated in this study. Mini-Mental State Examination, Neuropsychiatric Inventory (NPI), Clinician's Interview-Based Impression of Change plus caregiver input, Gottfries-Bråne-Steen Scale, and Zarit Burden Interview were used as assessment scales. RESULTS: There were no significant differences in age, sex, or education between AChEIs alone and combination groups. The combination group showed significantly more improvement of NPI-disinhibition score (0.76±2.15) than the AChEIs alone group (-0.14±1.71) after 12 weeks. CONCLUSION: Our findings suggest that the combination therapy of memantine and AchEIs might be a beneficial option for reducing disinhibition symptoms of patients with moderate AD compared with AchEIs alone. We believe that clinicians need to consider additional memantine treatment when patients with moderate AD complain disinhibition symptom. A larger clinical trial is needed to further determine the efficacy and advantages of such combination therapy of memantine and AchEIs for treating BPSD of patients with moderate AD.

Standardization of the Korean Version of the Patient Health Questionnaire-4 (PHQ-4).

OBJECTIVE: The Patient Health Questionnaire-4 (PHQ-4) has been used for screening owing to ease of use and brevity. In this study, we developed the Korean version of the PHQ-4 and tested its validity. METHODS: One hundred sixteen new adult outpatients at the Department of Psychiatry of the Korea University Ansan Hospital participated in the study. We simultaneously administered other depression/anxiety scales: the Hamilton Rating Scale for Depression, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Beck Anxiety Inventory. RESULTS: The mean PHQ-4 score was 6.52 (standard deviation = 3.45). Cronbach's α was 0.792, and the intraclass correlation coefficient of test and 2-week interval retest was 0.827 (p < 0.01). The Pearson correlation coefficients between the PHQ-4 total score and other depression/anxiety scales were all over 0.6. Confirmatory factorial analysis showed acceptable convergent validity and reliability but questionable discriminant validity for some model fit values. CONCLUSION: The Korean version of the PHQ-4 has sufficient internal consistency, test-retest reliability, and construct validity, but its two-factor structure showed incompleteness. However, we suggest that it should be used as a brief screening measure for common psychiatric distress that warrants further detailed assessment, but not to separately assess the severity of depression and anxiety symptoms.

Double-Blind, Randomized, Placebo-Controlled Trial of DA-9701 in Parkinson's Disease: PASS-GI Study.

OBJECTIVES: This study aimed to assess the efficacy of DA-9701 on gastrointestinal symptom-related quality of life in patients with Parkinson's disease on stable dopaminergic medications. METHODS: This multicenter, double-blind, placebo-controlled, phase 4 trial included a total of 144 patients with Parkinson's disease with gastrointestinal dysfunctions based on predefined criteria. Participants were randomized to take either DA-9701 or placebo for 4 weeks, and then both groups were administered DA-9701 for an additional 8 weeks while antiparkinsonian medications were unchanged. The primary outcome measure was gastrointestinal symptoms and related quality-of-life changes assessed on the Korean Nepean dyspepsia index after 4 and 12 weeks of therapy. We also evaluated the impact of DA-9701 therapy on parkinsonian motor symptoms at each time point. RESULTS: The gastrointestinal symptom-related quality-of-life score significantly improved in the DA-9701-treated group compared with the placebo-treated group after 4weeks (adjusted P = 0.012 by linear mixed effect model analysis). The overall gastrointestinal symptom and dyspepsia sum scores improved at 12 weeks after intervention in the DA-9701-first treated group (adjusted P = 0.002 and 0.014, respectively) and also in the placebo-first treated group (adjusted P = 0.019 and 0.039) compared with the baseline. Parkinsonian motor severity was not significantly affected by DA-9701 treatment in both groups at 4 and 12 weeks after intervention. There were no drug-related serious adverse events throughout the trial. CONCLUSIONS: DA-9701 therapy improved gastrointestinal symptom-related quality of life, and 12 weeks of daily administration can relieve the overall severity of gastrointestinal symptoms in patients with Parkinson's disease without affecting motor symptoms. (Clinical trial identifier: NCT02775591.) © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Efficacy of Buspirone Augmentation of Escitalopram in Patients with Major Depressive Disorder with and without Atypical Features: A Randomized, 8 Week, Multicenter, Open-Label Clinical Trial.

OBJECTIVE: This study investigated the treatment response and cognitive enhancement effects of buspirone augmentation of escitalopram in patients with major depressive disorder (MDD), according to atypical feature subtypes of MDD. METHODS: An 8 week, randomized, parallel-controlled, open-label study was conducted. The Columbia Atypical Depression Diagnostic Scale was administered to evaluate atypical features. Patients were assigned randomly to the buspirone augmentation or non-buspirone groups. Symptom severity and cognitive function were evaluated using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Depression Inventory, Beck Anxiety Inventory, digit span test, word fluency test, and Trail Making Tests A and B. RESULTS: A total of 89 patients were recruited. There were no significant differences in the measures between the groups; however, among the MDD patients without atypical features, the digit span and word fluency tests were improved by treatment. In the MDD patients without atypical features, the buspirone augmentation group showed a significant improvement on the digit span test compared to the non-buspirone group. CONCLUSION: Buspirone augmentation did not demonstrate significant benefits in MDD patients; however, buspirone augmentation showed greater efficacy for the improvement of cognitive function in MDD patients without atypical features. Our study suggests that atypical features are an important factor for cognitive enhancement in buspirone augmentation treatment in patients with MDD.

Normative data and psychometric properties of the Patient Health Questionnaire-9 in a nationally representative Korean population.

BACKGROUND: The Patient Health Questionnaire-9 (PHQ-9) has been standardized in several populations and is widely used in clinical practice and health care. However, it has not been appropriately standardized in the Korean general population, and no normative data have been presented. The aim of this study was to provide the normative data and psychometric properties of the PHQ-9 in the nationally representative population of Korea. METHODS: We used the nationwide cross-sectional survey data of Korea from 2014 to 2016. The data of 10,759 individuals aged over 19 years were analyzed in this study. As the distribution of the PHQ-9 scores was not normative, the percentile ranks for raw scores were provided. The survey questionnaires included the PHQ-9, The EuroQol-5 Dimension (EQ-5D), and demographic characteristics. We analyzed the construct validity and internal consistency of the PHQ-9. RESULTS: The normative data of the PHQ-9 were generated according to the sex and different age categories. The correlation coefficient between the sum of the PHQ-9 scores and the EQ-5D index was 0.44, which was moderate. The most appropriate model was the two-factor model with five 'affective-somatic' labeled items and four 'cognitive' labeled items. Cronbach's α for the PHQ-9 was 0.79. CONCLUSIONS: Our result supports reliability and validity with two-factor structure of PHQ-9 for measuring depression in the Korean nationally representative population. The Korean normative data on the PHQ-9 according to percentile rank can assist in interpreting and comparing scores with other populations.

Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives.

Major depressive disorder (MDD) is a serious psychiatric illness that causes functional impairment in many people. While monoaminergic antidepressants have been used to effectively treat MDD, these antidepressants have limitations in that they have delayed onset of action and many patients remain treatment-resistant. Therefore, there is a need to develop antidepressants with a novel target, and researchers have directed their attention to the glutamatergic system. Ketamine, although developed as an anesthetic, has been found to produce an antidepressant effect at sub-anesthetic doses via N-Methyl-D-aspartic acid (NMDA) receptor blockade as well as NMDA receptor- independent pathways. A single infusion of ketamine produced rapid improvement in clinical symptoms to a considerable level and led to the resolution of serious depressive symptoms, including imminent suicidal ideation, in patients with MDD. A series of recent randomized controlled trials have provided a high level of evidence for the therapeutic efficacy of ketamine treatment in MDD and presented new insights on the dose, usage, and route of administration of ketamine as an antidepressant. With this knowledge, it is expected that ketamine treatment protocols for MDD will be established as a treatment option available in clinical practice. However, long-term safety must be taken into consideration as ketamine has abuse potential and it is associated with psychological side effects such as dissociative or psychotomimetic effects.