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The mainstay of schizophrenia treatment is pharmacological therapy using various antipsychotics including first- and second-generation antipsychotics which have different pharmacokinetic and pharmacodynamic property leading to differential presentation of adverse events (AEs) and treatment effects such as negative symptoms, cognitive symptoms and cormorbid symptoms. Major treatment guidelines suggest the use of antipsychotic monotherapy (APM) as a gold standard in the treatment of schizophrenia. However, the effects of APM is inadequate and less potent to achieve symptom remission as well as functional recovery in real practice which has been consistently reported in numerous controlled clinical trials, large practical trials, independent small studies and systematic reviews till today. Therefore anti-psychotic polypharmacy (APP) regardless of the class of antipsychotics has been also commonly utilized for many reasons in real world practice. However, APP has also crucial pitfalls including increase of total psychotics including antipsychotics, high-doses of antipsychotics used, poor compliance, drug-drug interaction and risks for developing AEs, all of which are paradoxically related to poor clinical outcomes, whereas APP has also substantial advantages in reduction of re-hospitalization, severe psychopathology and targeted control of concurrent symptoms. Given currently limited therapeutic options, it is also important to properly utilize APP in order to maximize its clinical utility and minimize its risk for better treatment outcomes for patients with schizophrenia, based on risk/benefit with full understanding of pharmacological and clinical issues on APP. The present paper intends to address intriguing and important issues in the use of APP in real world practice.

Antipsychotic monotherapy (APM) is considered best-acceptable treatment option regardless of antipsychotic class and formulation types for treating schizophrenia. However, antipsychotic polypharmacy (APP) has been also widely utilized in routine clinical practice. Despite APP has some clinical benefits it has also numerous pitfalls in relation with increased total number and doses of APs leading to adverse events as well as decrease of treatment adherence and persistence resulting in poor clinical outcomes. Recent introduction of long-acting injectable antipsychotics (LAIs) to the market has offered a chance for better medication adherence/persistence and also provided a simplification of treatment regime leading to more stabilized treatment for schizophrenia patients. When we cannot stay away from APP in the treatment of schizophrenia, clinicians need to find more proper APP regimens and thereby utilization of APP in efficient way should be a practical strategy to benefit schizophrenia patient in a real world treatment setting. With this regard, LAIs can be one of available APP regimen for treatment of schizophrenia in routine practice since their clinical utility and pharmacokinetic stability over oral APs have been well-elaborated today. However, when we have to commence LAIs as a part of APP with oral APs or other LAIs, every effort should be made before doing so whether or not validated and available treatment options or other clinical factors were not done or evaluated yet. Any treatment guidelines do not support APP regardless of the formulation of APP regimen or address two or more LAIs for treatment of schizophrenia till today.

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.

Background: Coronavirus disease 2019 (COVID-19) has made ‘untact’ life a new standard (next normal) way of life, minimizing physical contacts among people. Emotional exchanges between people are rapidly being replaced by contact through the Internet, social networks, and over-the-top services.Current Concepts: People are expressing more stress and anxiety that are caused by fear of infection, and also embitterment due to perceived distrust and injustice is increasing. In the era of COVID-19, it is necessary and important to manage burnout, depression, and anxiety symptoms of medical staff and quarantine personnel. The pandemic and the resulting social changes intensifies loneliness, leading to deterioration in mental and physical health. The World Health Organization has warned that loneliness and social isolation are leading to the exacerbation of physical illness and increased mortality due to suicide and other mental health problems.Discussion and Conclusion: It is needed to establish a next standard of mental health service such as untact diagnosis and follow-up support system. Government and society should establish a sustainable system even after the COVID-19 crisis, rather than stopgap measures made with people’s sacrifice as collateral.

Objective In a number of controlled clinical trials and naturalistic studies, aripiprazole once monthly (AOM) has been found to be effective and safe as acute and maintenance treatment options for schizophrenia. However, such clinical data have been presented in selected patient population (i.e., antipsychotic monotherapy, etc.), in particular, clinical information on switching to AOM from antipsychotic polypharmacy and/or other long acting injectable antipsychotics (LAIs) has been scarce till today. Methods The study period was from the first switching day to AOM up to 12 months in patients with antipsychotic polypharmacy (APpoly)/LAIs (baseline, month 3, month 6, and month 12). Available demographics and clinical information were retrieved from electronic medical records (EMRs). Available scores of Global Assessment of Functioning (GAF), Clinical Global Impression-Clinical Benefit (CGI-CB), CGI-severity, Visual Analog Scale on Satisfaction-Patient/Health Professional (VAS-P/HP), and the Positive and Negative Syndrome Scale-Insigh (PANSS-I) scores were also taken from EMR. Proportional change of functional impairment before and after AOM was also captured. Results Data of 18 patients were available. Most commonly used combined APs before AOM were aripiprazole, blonanserin, quetiapine, and risperidone. At least 2 APs (n = 2.4) were combined before AOM. Scores of GAF (10.7% increase), CGI-CB (46.2% decrease), VAS-P (47.8% increase), VAS-HP (40.8% increase), and PANSS-I (27.9% increase) (all p = 0.001) were significantly improved from baseline to month 12, respectively. Approximately 59% of patients improved individual functioning with different level (i.e., employment, back to school, etc.) after AOM treatment at month 12. Conclusion The present study have clearly shown the clinical benefit and utility of switching to AOM for treatment of patients with APpoly/LAIs in routine practice. Subsequent, adequately-powered, well-controlled clinical trials may be necessary to confirm our findings in near future.

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.

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.

Background Elderly patients with late-life depression (LLD) often report mild cognitive impairment (MCI), so Alzheimer's disease (AD) is hard to identify in these patients. We aimed to identify the structural and functional differences between prodromal AD and LLD-related MCI. Methods We performed voxel-based morphometry and functional connectivity (FC) analyses in elderly patients with both LLD and MCI to compare alterations between those with cerebral amyloidopathy and those without. We subdivided patients into subthreshold depression (STD) and major depressive disorder (MDD) groups. Using florbetaben positron emission tomography (PET), we compared volume and connectivity between healthy controls and four STD and MDD groups with or without amyloid deposition(A): STD-MCI-A(+), MDD-MCI-A(+), STD-MCI-A(-), and MDD-MCI-A(-). Results Subjects with MDD or amyloid deposition showed greater volume reduction in the left middle temporal gyrus. MDD groups had lower FC than STD groups in the frontal, cortical, and limbic areas. The STD-MCI-A(+) group showed greater FC reduction than the MDD-MCI-A(-) and STD-MCI-A(-) groups, particularly in the hippocampus, parahippocampus, and frontal and temporal cortices. The functional differences associated with amyloid plaques were more evident in the STD group than in the MDD group. Limitations Limitations include disproportional sex ratios, inability to determine the longitudinal effects of amyloidopathy in large populations. Conclusions Regional gray matter loss and alterations in brain networks may reflect impairments caused by amyloid deposition and depression. Such changes may facilitate the detection of prodromal AD in elderly patients with both depression and cognitive dysfunction, allowing earlier intervention and more appropriate treatment.

Purpose Consensus is lacking on the management of treatment-resistant depression (TRD), resulting in significant variations on how TRD patients are being managed in real-world practice. A survey explored how clinicians managed TRD across Asia, followed by an expert panel that interpreted the survey results and provided recommendations on how TRD could be managed in real-world clinical settings. Methods Between March and July 2018, 246 clinicians from Hong Kong, Japan, Mainland China, South Korea, and Taiwan completed a survey related to their treatment approaches for TRD. Results The survey showed physicians using more polytherapy (71%) compared to maintaining patients on monotherapy (29%). The most commonly (23%) administered polytherapy involved antidepressant augmentation with antipsychotics that 19% of physicians also indicated as their most important approach for managing TRD. The highest number of physicians (34%) ranked switching to another class of antidepressants as their most important approach, while 16% and 9% chose antidepressant combinations and electroconvulsive therapy (ECT), respectively. Conclusion Taking into account the survey results, the expert panel made general recommendations on the management of TRD. TRD partial-responders to antidepressants should be considered for augmentation with second-generation antipsychotics. For non-responders, switching to another class of antidepressants ought to be considered. TRD patients achieving remission with acute treatment should consider continuing their antidepressants for at least another 6 months to prevent relapse. ECT is a treatment consideration for patients with severe depression or persistent symptoms despite multiple adequate trials of antidepressants. Physicians should also consider the response, tolerability and adherence to the current and previous antidepressants, the severity of symptoms, comorbidities, concomitant medications, preferences, and cost when choosing a TRD treatment approach for each individual patient.

Purpose An Asia-Pacific expert consensus defined treatment-resistant depression (TRD) as failure of ≥2 antidepressants given at adequate doses for 6–8 weeks during a major depressive episode. A survey examined how TRD was being diagnosed in real-world practices across Asia. An expert panel then interpreted the results and provided practical recommendations. Methods Between March and July 2018, 246 clinicians from Hong Kong, Japan, Mainland China, South Korea, and Taiwan were surveyed on how they identified TRD patients according to their own definitions. Results Most physicians described antidepressant failure as “no response” (79%) or “inadequate response” (82%); fewer chose “failure to achieve remission” (45%). About 40% did not routinely use clinical tools to assess response. Around 52% defined adequate dose target as achieving the label’s upper dose limit. About 58% would treat for 4–8 weeks before determining antidepressant failure. Most (76%) required the ≥2 qualifying antidepressant failures to be from different classes. Approximately 60% considered antidepressant failure(s) from previous depressive episode(s) when diagnosing TRD. Conclusion Considering the survey results, antidepressant failure can be defined as a failure to achieve remission, or more practically as

Objective Genetic variations in the gene encoding zinc finger protein 804A gene (ZNF804A) have been associated with major depression and bipolar disorder. In this work we focused on the potential influence of ZNF804A variations on the risk of developing specific sub-phenotypes as well as the individual response to available treatments. Methods We used two samples of different ethnic origin: a Korean sample, composed by 242 patients diagnosed with major depression and 132 patients diagnosed with bipolar disorder and 326 healthy controls; an Italian sample composed 151 major depression subjects, 189 bipolar disorder subjects and 38 outpatients diagnosed for a primary anxiety disorder. Results Our analyses reported an association of rs1344706 with psychotic phenotype in the cross-diagnostic pooled sample (geno p = 4.15 × 10-4, allelic p = 1.06 × 10-4). In the cross-diagnosis Italian sample but not in the Korean one, rs7597593 was involved with depressive symptoms improvement after treatment (geno p = 0.025, allelic p = 0.007). Conclusion The present study evidenced the role of ZNF804A alterations in symptoms improvement after treatment. Both manic and depressive symptoms seem to be modulated by ZNF804A, though the latter was observed in the bipolar pooled sample only. The role of this factor is likely related to synaptic development and maintenance; however, further analyses will be needed to better understand the molecular mechanics involved with ZNF804A.

Objective This study was done for collection of real world data of Aripiprazole Once Monthly (AOM) in patients with schizophrenia. Methods The observation was up to 12 months from the first use of AOM in patients with antipsychotic polypharmacy (APpoly)/other long acting injectable antipsychotics (LAIs) for treatment of schizophrenia in daily practice. Demographics and available clinical information such as The Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-severity (CGI-S) scores were retrieved from the electronic medical record (EMR). Adverse events were also noted as described in EMR. Results Eighteen patients were found to be switched from APpoly/LAIs. Mean numbers of previous APs treatment failure and immediate prior APs were 2.2 and 2.4, respectively; most commonly used APs before AOM were aripiprazole, blonanserin, quetiapine, and risperidone. Mean number of combined APs before AOM significantly decreased from 2.4 use to 0.7 at month 12 (p < 0.0001). The PANSS total (71.7 to 62.1, p = 0.000) and CGI-S (3.4 to 3.1, p = 0.008) scores were also significantly decreased from baseline (first use of AOM) to month 12, respectively. Other various psychotropics including anxiolytics were also significantly and substantially decreased at some point from baseline throughout the observation period as well. Mild hand tremor and akathisia were developed in 3 patients. Conclusion The present observation study clearly confirmed the use of AOM should be also effective and tolerable treatment option for patients with APpoly/LAIs in the real world practice. Subsequent, adequately-powered, and well-controlled clinical trials are warranted in near future.

Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment and is suggested to play an indirect role in regulating Aβ production and the pathophysiology of Aβ deposition in brains. However, studies on the amount of TIMP-3 in bodily fluids of Alzheimer’s disease (AD) patients have not been conducted. Here, we investigated the relationship between fluid TIMP-3 levels and AD pathology. We first showed that the fluid levels of TIMP-3 were lower in AD dementia patients compared with in non-AD patients. ELISA results revealed that plasma levels of TIMP-3 in 65 patients with AD were significantly lower than those in 115 healthy control subjects and 71 mild cognitive impairment (MCI) subjects. Furthermore, we found that cerebrospinal fluid (CSF) level of TIMP-3 was decreased in AD compared with that in healthy control. These data suggest that fluid TIMP-3 levels negatively correlated with progress of cognitive decline. Collectively, our study suggests that alterations of fluid TIMP-3 levels might be associated with AD pathology.

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).

Objective The present study aimed to observe potential benefit of aripiprazole augmentation in the treatment of major depressive disorder with mixed specifier (MDDM) in naturalistic treatment setting. Methods Data were collected from MDDM patients using a retrospective chart review for 8 weeks (week –8 and week 0) in routine practice. All patients were on current antidepressants upon starting of aripiprazole. Patients were treated without restriction of doses of aripiprazole. The primary endpoint was the mean change of Montgomery–Åsberg Depression Rating Scale (MADRS) total scores along with various secondary endpoint measures. Results In total 38 patients were analyzed. The changes of MADRS, Clinical Global Impression (CGI)-severity, Young Mania Rating Scale, Sheehan Disability Scale, and CGI-clinical benefit total scores from baseline to the endpoint were −7.1, −0.8, −4.9, −4.1, and −3.6, respectively (all p < 0.0001). At the endpoint, the responder and remitter rates by MADRS score criteria were approximately 32% and 21%, respectively. Conclusion The present findings have clearly shown the effectiveness and tolerability of aripiprazole augmentation for MDDM patients in routine practice. The present study warrants subsequent, adequately-powered, well-controlled studies for generalizability near future.

Depressive symptoms have been found to be associated with decreased hand-grip strength (HGS) and low socioeconomic status (SES) in older adults. We aimed to investigate the potential moderating effect of SES on the association between HGS and depressive symptoms and the potential mediating effect of HGS on the association between SES and depressive symptoms using a nationally representative sample of older adults.Data from 3169 community-dwelling adults aged 60 years or older were acquired from the Korea National Health and Nutrition Examination Survey conducted in 2014 and 2016. HGS was measured using a digital hand-grip dynamometer. Depressive symptoms were evaluated using the 9-item version of the Patient Health Questionnaire-9 (PHQ-9). SES was assessed using equivalent monthly household income and education level.Older adults in the lowest tertile of HGS measures were more likely to have experienced depressive symptoms compared to those in the highest tertile (odds ratio = 1.95, 95% confidence interval = 1.25-2.74). A significant moderating effect of household income level was observed on the association between HGS and PHQ-9 score (P = 0.014). Older adults with a low income had a stronger inverse correlation between HGS and PHQ-9 score compared to those with a high income (low income: beta = -0.162, P 0.001; high income: beta = -0.119, P = 0.036). HGS partially mediated the association between low income and depressive symptoms.Our findings indicate that there may be a stronger relationship between low HGS and depressive symptoms in socioeconomically deprived older people. Further research on muscle strength and income level in older adults is required regarding depression risk assessment.

Objective This study aimed to demonstrate that the Patient Health Questionnaire (PHQ)-8 is not less useful than the PHQ-9 as a screening test for major depressive disorder (MDD). Methods We performed a retrospective analysis of 567 patients in psychiatric outpatient units. The Mini International Neuropsychiatric Interview was used to diagnose MDD. We derived the validity and reliability of the PHQ-8 and PHQ-9. To evaluate the ability of the PHQ-8 and PHQ-9 to discriminate MDD, we drew receiver operating characteristic (ROC) curves and compared the areas under the curves (AUCs). Results Of the 567 participants, 207 (36.5%) were diagnosed with MDD. Cronbach's αs for the PHQ-8 and PHQ-9 were 0.892 and 0.876, respectively. Similar to the PHQ-9, the PHQ-8 was also associated with scores on the Hamilton Depression Rating Scale in a correlation analysis. When we drew ROC curves for the PHQ-8 and PHQ-9, there was no statistically significant difference in the AUCs. With a cutoff score of 10, the PHQ-8 showed a sensitivity of 58.3%, specificity of 83.1%, positive predictive value of 53.4%, and negative predictive value of 85.7%. Conclusion In a psychiatric outpatient sample, the PHQ-8 was as useful as the PHQ-9 for MDD screening.

Background Adolescence is a period that witnesses many changes in lifestyle, such as in social activity and school life, and it is vulnerable to the depressive disorder. Therefore, we intended to evaluate the factors affecting the onset of depressive episodes. Methods We conducted a secondary analysis using the 2019 Korean Youth Risk Behavior Web-based survey data, including a total of 57,303 subjects from the first year of middle school to the third year of high school and selected among 400 schools. Factors including dietary habits, physical activity, study time, internet use time and other health risk behaviors were included in the analysis. Logistic regression analysis was performed to evaluate the risk of occurrence of depressive episodes. Results Physical activity, internet use for more than three hours on weekdays, and a study time of more than two hours on weekends were assessed as risk factors of depressive episodes. On the other hand, internet use on weekends and having breakfast regularly were suggested as a protective way to reduce risk in Korean students. Conclusion We identified the factors influencing the depressive episode of adolescents. We suggest that activities appropriate to the culture and lifestyle of adolescents should be recommended in order to reduce the occurrence of depressive episodes.

Background This study aimed to evaluate traumatic stress and mental health problems associated with the prolonged coronavirus disease pandemic and to determine the differences across different age groups. Methods A total of 1,151 individuals who visited Gwangmyeong City Mental Health Welfare Center, South Korea, or accessed the website from September 1 to December 31, 2020, were included in the study. Mental health problems such as traumatic stress (Primary Care Posttraumatic Stress Disorder Screen for the Diagnostic and Statistical Manual of Mental Disorder-5); depression (Patient Health Questionnaire-9 and Children's Depression Inventory); anxiety (Generalized Anxiety Disorder-7 and Penn State Worry Questionnaire for Children); suicide risk (P4 Screener); and demographic information were evaluated. The participants were divided into three groups based on age group: children and adolescents, adults, and the elderly. Results The results showed that 24.7%, 20.9%, 16.8%, and 20.5% of the participants were at high-risk for traumatic stress, depression, anxiety, and suicide, respectively. The difference in the proportion of high-risk groups by age of all participants was significant for traumatic stress, depression, anxiety, and suicide risk. In particular, the percentage of high-risk groups in all areas was the highest in the adult group. Also, in most areas, the ratio of the high-risk groups for children and adolescent group was the lowest, but the suicide risk-related ratio was not (adolescent group: 20.9%, adult group: 25%, elderly group 9.3%). Conclusion These results suggest that there is a need for continued interest in the mental health of the general population even after the initial period of coronavirus disease. Additionally, this study may be helpful when considering the resilience or risk factors of mental health in a prolonged disaster situation., Graphical Abstract

Objective The genetic background of mood disorders is gradually emerging through the use of large multicenter samples but a detailed phenotyping is complementary in elucidating the role of modulating variants. Methods In the present paper we focused on the possible modulatory effects of ARC gene variants on two independent mood disorder samples of European (n = 246 bipolar disorder) and Korean (n = 132 bipolar disorder; n = 242 major depressive disorder [MDD]) ancestry. Results No result survived Bonferroni correction, however we evidenced promising trend toward possible association between ARC gene variants and mood disorder phenotypes. In particular, we evidenced weak correlations of ARC single nucleotide polymorphisms with depressive symptoms severity (evaluated through Hamilton depression rating scale scores) in the MDD Korean (rs7465272) and European (rs11167152) samples. Additionally rs10110456 was found to be related to Family History, while rs7465272 was related to suicide risk in the Korean sample. Finally, rs7465272 was associated with body mass index in the European sample. Conclusion Overall, ARC gene variants may have a partial role in modulatory effect on treatment efficacy or phenotypes of mood disorders. Further studies, on larger samples may provide a better understanding on the role of ARC gene variants in the symptom severity and treatment outcomes in patients with mood disorders.

Purpose An Asia-Pacific expert consensus defined treatment-resistant depression (TRD) as failure of ≥2 antidepressants given at adequate doses for 6–8 weeks during a major depressive episode. A survey examined how TRD was being diagnosed in real-world practices across Asia. An expert panel then interpreted the results and provided practical recommendations. Methods Between March and July 2018, 246 clinicians from Hong Kong, Japan, Mainland China, South Korea, and Taiwan were surveyed on how they identified TRD patients according to their own definitions. Results Most physicians described antidepressant failure as “no response” (79%) or “inadequate response” (82%); fewer chose “failure to achieve remission” (45%). About 40% did not routinely use clinical tools to assess response. Around 52% defined adequate dose target as achieving the label’s upper dose limit. About 58% would treat for 4–8 weeks before determining antidepressant failure. Most (76%) required the ≥2 qualifying antidepressant failures to be from different classes. Approximately 60% considered antidepressant failure(s) from previous depressive episode(s) when diagnosing TRD. Conclusion Considering the survey results, antidepressant failure can be defined as a failure to achieve remission, or more practically as

Purpose Consensus is lacking on the management of treatment-resistant depression (TRD), resulting in significant variations on how TRD patients are being managed in real-world practice. A survey explored how clinicians managed TRD across Asia, followed by an expert panel that interpreted the survey results and provided recommendations on how TRD could be managed in real-world clinical settings. Methods Between March and July 2018, 246 clinicians from Hong Kong, Japan, Mainland China, South Korea, and Taiwan completed a survey related to their treatment approaches for TRD. Results The survey showed physicians using more polytherapy (71%) compared to maintaining patients on monotherapy (29%). The most commonly (23%) administered polytherapy involved antidepressant augmentation with antipsychotics that 19% of physicians also indicated as their most important approach for managing TRD. The highest number of physicians (34%) ranked switching to another class of antidepressants as their most important approach, while 16% and 9% chose antidepressant combinations and electroconvulsive therapy (ECT), respectively. Conclusion Taking into account the survey results, the expert panel made general recommendations on the management of TRD. TRD partial-responders to antidepressants should be considered for augmentation with second-generation antipsychotics. For non-responders, switching to another class of antidepressants ought to be considered. TRD patients achieving remission with acute treatment should consider continuing their antidepressants for at least another 6 months to prevent relapse. ECT is a treatment consideration for patients with severe depression or persistent symptoms despite multiple adequate trials of antidepressants. Physicians should also consider the response, tolerability and adherence to the current and previous antidepressants, the severity of symptoms, comorbidities, concomitant medications, preferences, and cost when choosing a TRD treatment approach for each individual patient.

Background:Complement factor H (CFH) plays a key role in regulating the cascade of the alternative pathway of the complement system. Dysregulation of CFH may be involved in the pathophysiology of various inflammation-mediated diseases including neuropsychiatric illnesses. This study aimed to investigate this relationship by examining determining CFH levels in elderly individuals with and without depression.Methods:A total of 152 elderly individuals (major depressive disorder (MDD) group, n = 76; comparison sample, n = 76) were selected from the Ansan Geriatric study. The plasma level of CFH was measured. MDD was diagnosed with the Mini-International Neuropsychiatric Interview as per DSM-IV criteria. The severity of depression was evaluated with the geriatric depression scale (GDS). Mean CFH levels were compared using the Mann–Whitney U test. After adjusting for possible confounding factors including age, sex, marital status, education, alcohol use, hemoglobin levels, and the Korean version of the Mini-Mental State Examination (MMSE-KC), a multiple regression analysis was conducted. The GDS score and plasma level of CFH were analyzed using Spearman's correlation.Results:Plasma CFH level was significantly higher in individuals with MDD than in the comparison sample (289.51 ± 21.16 vs. 339.67 ± 66.23, p < 0.001). In a regression model adjusted for possible confounders, CFH was significantly associated with geriatric depression (p < 0.001). CFH levels were not significantly related to GDS scores in the depressed group.Conclusion:This study revealed an association between high plasma levels of CFH and geriatric depression, thereby suggesting the alternative pathway of the complement system contributing to the development of geriatric depression.

Objective The Korean Dementia Screening Questionnaire (KDSQ) is an informant-based instrument used to screen for cognitive dysfunction. However, its ability to only dichotomously discriminate between dementia and normal cognition has been previously investigated. This study investigated the ability of the KDSQ to classify not only dichotomous but also multiple stages of cognitive dysfunction. Methods We examined 582 participants. Receiver operating characteristic (ROC) curves were used to determine dichotomous classification parameters. Multi-category ROC surfaces were evaluated to classify the three stages of cognitive dysfunction. Results Dichotomous classification using the ROC curve analyses showed that the area under the curve was 0.92 for dementia for subjects without dementia and 0.96 for dementia in controls. Simultaneous multi-category classification analyses showed that the volume under the ROC surface (VUS) was 0.57 and that the derived optimal cut-off points were 2 and 8 for controls, MCI, and dementia. The estimated Youden index for the KDSQ was 0.48, and the derived optimal cut-off points were 5 and 10. The overall classification accuracy of the VUS and Youden index was 61.2% and 58.6%, respectively. Conclusion The KDSQ is useful for classifying dichotomous and multi-category stages of cognitive dysfunction.

Background:While normative data on neuropsychological performance provide baseline metrics for the assessment and diagnosis of mild cognitive impairment and dementia, a lack of comparative normative data in non-Caucasian populations makes it difficult to conduct similar evaluations and studies in individuals from diverse backgrounds. The current paper aims to provide normative data on a range of cognitive measures in a Korean general population sample and investigate various demographic and health variables associated with cognitive performance in this representative population.Method(s):The study population was 1,528 stroke and dementia-free individuals who participated in the Korean Genome and Epidemiology study (KoGES) (mean age 60.43 ± 7.30, 52.42% female). All participants underwent a comprehensive neuropsychological test battery that included verbal and visual memory, language, attention, and executive function measures. A health examination and a questionnaire-based interview were also administered.Results:The majority of cognitive test results were associated with age, education, and gender. In general, higher education and younger age was associated with better cognitive performance. Explained variance increased modestly in models that included measures of general health and depressive symptoms.Conclusion:Normative data of cognitive performance in a community based Korean population are presented. These norms provide reference values in a non-Caucasian middle to older aged sample.

Objective This study was aimed at evaluating the diagnostic validity of the Korean version of the Clinically Useful Depression Outcome Scale (CUDOS) with varying follow-up in a typical clinical setting in multiple centers. Methods In total, 891 psychiatric outpatients were enrolled at the time of their intake appointment. Current diagnostic characteristics were examined using the Structured Clinical Interview for DSM-IV (41% major depressive disorder). The CUDOS was measured and compared with three clinician rating scales and four self-report scales. Results The CUDOS showed excellent results for internal consistency (Cronbach’s α, 0.91), test-retest reliability (patients at intake, r=0.81; depressed patients in ongoing treatment, r=0.89), and convergent and discriminant validity (measures of depression, r=0.80; measures of anxiety and somatization, r=0.42). The CUDOS had a high ability to discriminate between different levels of depression severity based on the rating of Clinical Global Impression for depression severity and the diagnostic classification of major depression, minor depression, and non-depression. The ability of the CUDOS to identify patients with major depression was high (area under the receiver operating characteristic curve=0.867). A score of 20 as the optimal cutoff point was suggested when screening for major depression using the CUDOS (sensitivity=89.9%, specificity=69.5%). The CUDOS was sensitive to change after antidepressant treatment: patients with greater improvement showed a greater decrease in CUDOS scores (p

N-cadherin is a synaptic adhesion molecule stabilizing synaptic cell structure and function. Cleavage of N-cadherin by γ-secretase produces a C-terminal fragment, which is increased in the brains of Alzheimer disease (AD) patients. Here, we investigated the relationship between fluid N-cadherin levels and AD pathology. We first showed that the cleaved levels of N-cadherin were increased in homogenates of postmortem brain from AD patients compared with that in non-AD patients. We found that cleaved N-cadherin levels in the cerebrospinal fluid were increased in AD dementia compared with that in healthy control. ELISA results revealed that plasma levels of N-cadherin in 76 patients with AD were higher than those in 133 healthy control subjects. The N-cadherin levels in the brains of an AD mouse model, APP Swedish/PS1delE9 Tg (APP Tg) were reduced compared with that in control. The N-terminal fragment of N-cadherin produced by cleavage at a plasma membrane was detected extravascularly, accumulated in senile plaques in the cortex of an APP Tg mouse. In addition, N-cadherin plasma levels were increased in APP Tg mice. Collectively, our study suggests that alteration of N-cadherin levels might be associated with AD pathology.

Notch signaling is an evolutionarily conserved pathway that regulates cell-cell interactions through binding of Notch family receptors to their cognate ligands. Notch signaling has an essential role in vascular development and angiogenesis. Recent studies have reported that Notch may be implicated in Alzheimer's disease (AD) pathophysiology. We measured the levels of soluble Notch1 (sNotch1) in the plasma samples from 72 dementia patients (average age 75.1 y), 89 subjects with amnestic mild cognitive impairment (MCI) (average age 73.72 y), and 150 cognitively normal controls (average age 72.34 y). Plasma levels of sNotch1 were 25.27% lower in dementia patients as compared to healthy control subjects. However, the level of Notch1 protein was significantly increased in human brain microvascular endothelial cells (HBMECs) after amyloid-beta treatment. Also, Notch1 mRNA level was significantly increased in HBMECs and iPSC-derived neuronal cells from AD patient compared to normal control. These results indicate that altered expression of Notch1 might be associated with the risk of Alzheimer's disease.

Depression affects 7% of the elderly population, and it often remains misdiagnosed or untreated. Peripheral biomarkers might aid clinicians by allowing more accurate and well-timed recognition of the disease. We sought to determine if plasma protein levels predict the severity of depressive symptomatology or distinguish patients from healthy individuals. The severity of depressive symptoms and global cognitive functioning were assessed by the Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE) in 152 elderly subjects, 76 of which with major depressive disorder (MDD). Plasma levels of 24 proteins were measured by multiplexing and analyzed as continuous predictors or dichotomized using the median value. The association between individual plasma proteins and MDD risk or depressive symptoms severity was investigated using multiple logistic and linear regressions including relevant covariates. Sensitivity analyses were performed excluding cognitively impaired individuals or non-acute patients with MDD. After adjusting for possible confounders and false discovery rate (FDR) correction, we found lower Fetuin-A levels in MDD patients vs. controls (pFDR = 1.95 × 10–6). This result was confirmed by the sensitivity and dichotomized analyses. Lower prolactin (PRL) levels predicted more severe depressive symptoms in acute MDD patients (pFDR = 0.024). Fetuin-A is a promising biomarker of MDD in the elderly as this protein was negatively associated with the disorder in our sample, regardless of the global cognitive functioning. Lower PRL levels may be a peripheral signature of impaired neuroprotective processes and serotoninergic neurotransmission in more severely depressed patients.