Cytokine levels reflect tic symptoms more prominently during mild phases.

Tic disorder is a neuropsychiatric condition that affects 3% of all children and can have a significant impact on their quality of life. Cytokines, interferons, interleukins, lymphokines, and tumor necrosis factors are involved in the neuroinflammatory circuitry of tic disorders. This study aimed to identify the cytokines involved in the pathogenesis of tic disorders. We enrolled 44 patients with tic disorder and 38 healthy controls. Patients were free of psychotropic medications for at least 3 weeks. Whole blood samples were analyzed using a Luminex® human cytokine multiplex assay kit. Patients were divided into groups with "mild tics" and "above moderate tics" based on Yale Global Tic Severity Scale (YGTSS) scores for comparison. The final analysis included 35 patients (28 male and 7 female) and 31 controls (20 male and 11 female). In the mild tic group, interleukin (IL)-12 p70 negatively correlated with motor tic scores. Granulocyte-macrophage colony-stimulating factor, IL-4, IL-8, and tumor necrosis factor (TNF)-α were positively correlated to phonic tic scores. IL-12 p40 and TNF-α were positively correlated to total tic scores. IL-12 p70 and IL-17a negatively correlated to impairment scores and total YGTSS scores. Tic disorder patients and healthy controls exhibit different cytokine profiles. Only patients with mild symptoms exhibit significant correlations, suggesting that the correlations between cytokine levels and tic symptoms are more relevant during the mild or remission phases. Our results present the importance of IL-1ß and TNF-α, among others, but the identification of key cytokines are still necessary.

Impact of the Coronavirus Disease Pandemic on Mental Health among Local Residents in Korea: a Cross Sectional Study.

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.

Pathways to care for people with dementia: An international multicentre study.

OBJECTIVE: The aim of the present study was to characterize the clinical pathways that people with dementia (PwD) in different countries follow to reach specialized dementia care. METHODS: We recruited 548 consecutive clinical attendees with a standardized diagnosis of dementia, in 19 specialized public centres for dementia care in 15 countries. The WHO "encounter form," a standardized schedule that enables data concerning basic socio-demographic, clinical, and pathways data to be gathered, was completed for each participant. RESULTS: The median time from the appearance of the first symptoms to the first contact with specialist dementia care was 56 weeks. The primary point of access to care was the general practitioners (55.8%). Psychiatrists, geriatricians, and neurologists represented the most important second point of access. In about a third of cases, PwD were prescribed psychotropic drugs (mostly antidepressants and tranquillizers). Psychosocial interventions (such as psychological counselling, psychotherapy, and practical advice) were delivered in less than 3% of situations. The analyses of the "pathways diagram" revealed that the path of PwD to receiving care is complex and diverse across countries and that there are important barriers to clinical care. CONCLUSIONS: The study of pathways followed by PwD to reach specialized care has implications for the subsequent course and the outcome of dementia. Insights into local differences in the clinical presentations and the implementation of currently available dementia care are essential to develop more tailored strategies for these patients, locally, nationally, and internationally.

Reduced plasma Fetuin-A is a promising biomarker of depression in the elderly.

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.

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.

Association between brain amyloid accumulation and neuropsychological characteristics in elders with depression and mild cognitive impairment.

OBJECTIVES: To investigate the presence of cerebral amyloidopathy and its associations with performances on neurocognitive tests and clinical features in depressed elders with mild cognitive impairment (MCI). METHODS/DESIGN: In total, 94 older adults with concomitant MCI and some depressive symptoms were included in this study. Cerebral amyloidopathy was evaluated using 18 F-florbetaben-positron emission tomography. A standardized neurocognitive test battery and brain magnetic resonance imaging (MRI) were administered to all subjects. We examined the Apolipoprotein E genotype using a polymerase chain reaction-based method. RESULTS: Among the 94 initial participants, seven participants were excluded because of failure to undergo MRI or complete the neuropsychological battery. Among 87 subjects, 45 elders (51.7%) had cerebral amyloidopathy and were classified as the concomitant depression and MCI with cerebral amyloid-accumulation-positive (CDAP) group; others were classified as the concomitant depression and MCI with cerebral amyloid-accumulation-negative (CDAN) group. Poorer performances on word list recall and constructional recall were observed in the CDAP group than in the CDAN group. CONCLUSIONS: The results indicate that around half of older adults with concomitant MCI and some depressive symptoms might be prone to have Alzheimer dementia. Results of neurocognitive tests possibly aid in discerning the presence of cerebral amyloidopathy.

Increased plasma complement factor H is associated with geriatric depression.

ABSTRACTBackground: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.

Big Data and Discovery Sciences in Psychiatry.

The modern society is a so-called era of big data. Whereas nearly everybody recognizes the "era of big data", no one can exactly define how big the data is a "big data". The reason for the ambiguity of the term big data mainly arises from the widespread of using that term. Along the widespread application of the digital technology in the everyday life, a large amount of data is generated every second in relation with every human behavior (i.e., measuring body movements through sensors, texts sent and received via social networking services). In addition, nonhuman data such as weather and Global Positioning System signals has been cumulated and analyzed in perspectives of big data (Kan et al. in Int J Environ Res Public Health 15(4), 2018 [1]). The big data has also influenced the medical science, which includes the field of psychiatry (Monteith et al. in Int J Bipolar Disord 3(1):21, 2015 [2]). In this chapter, we first introduce the definition of the term "big data". Then, we discuss researches which apply big data to solve problems in the clinical practice of psychiatry.

Adjunctive Brexpiprazole as a Novel Effective Strategy for Treating Major Depressive Disorder: A Systematic Review and Meta-Analysis.

PURPOSE/BACKGROUND: Brexpiprazole was approved for adjunctive treatment of major depressive disorder (MDD) in 2015. Because only a small number of randomized controlled trials have investigated the use of brexpiprazole in MDD, we performed a meta-analysis. METHODS/PROCEDURES: We systematically searched literatures in PubMed, Cochrane Library database, EMBASE, Google Scholar, and clinicaltrials.gov up to January 2016. The primary efficacy measure was the mean change in total Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline. Secondary efficacy measures were the mean change in total Hamilton Rating Scale for Depression (17 items) score from baseline and the response (≥50% reduction in MADRS total score) and remission (MADRS total score ≤ 10 with ≥50% reduction) rates. FINDINGS/RESULTS: Four studies fulfilled the inclusion criteria and were included in the analysis. Brexpiprazole showed superior efficacy over placebo with effect sizes (mean differences) of -1.76 (95% confidence interval [CI], -2.45 to -1.07) for MADRS and -1.21 (95% CI, -1.71 to -0.72) for the 17-item Hamilton Rating Scale for Depression. The risk ratios for response and remission were 1.57 (95% CI, 1.29-1.91) and 1.55 (95% CI, 1.22-1.96), respectively. The incidences of discontinuation due to adverse events, akathisia, and weight increase were higher in the brexpiprazole group than in the placebo group, with risk ratios of 3.44 (95% CI, 1.52-7.80), 3.39 (95% CI, 2.08-5.51), and 4.36 (95% CI, 2.45-7.77), respectively, and the incidence of akathisia was related to the brexpiprazole dose. IMPLICATIONS/CONCLUSIONS: Although our results suggest that brexpiprazole could be an effective adjunctive agent for MDD, they should be cautiously translated into clinical practice because the meta-analysis was based on only a handful of randomized controlled trials.

Adverse Events With Sustained-Release Donepezil in Alzheimer Disease: Relation to Body Mass Index.

PURPOSE/BACKGROUND: Sustained-release, high-dose (23 mg/d) donepezil has been approved for treatment of moderate to severe Alzheimer disease (AD). Based on a previous clinical trial, body weight of less than 55 kg is a risk factor for adverse events with donepezil 23 mg/d treatment in global population. METHODS/PROCEDURES: To clarify whether this finding is consistent across ethnic groups that vary in absolute body mass, we recruited Korean patients aged 45 to 90 years with moderate to severe AD who had been receiving standard donepezil immediate release 10 mg/d for at least 3 months. After screening, we analyzed a final cohort of 166 patients who received donepezil 23 mg/d for 24 weeks to compare the occurrence of treatment-emergent adverse events (TEAEs) between patients with high versus low body mass index (BMI) based on the World Health Organization overweight criteria for Asian populations (23 kg/m). FINDINGS/RESULTS: Treatment-emergent adverse events were reported by 79.45% of patients in the lower BMI group and 58.06% of patients in the higher BMI group (odds ratio, 2.79; 95% confidence interval, 1.39-5.63; χ = 7.58, P = 0.006). In a multivariable survival analysis, the group with lower BMI showed a higher occurrence of TEAEs (hazard ratio, 1.83; 95% confidence interval, 1.25-2.68; P = 0.002). IMPLICATIONS/CONCLUSIONS: In Korean patients with moderate to severe AD receiving high-dose donepezil over 24 weeks, TEAEs were significantly more common in those with lower BMI (not clinically overweight), especially nausea. This finding may inform clinical practice for Asian patients.

Depression and Cognitive Function in Mild Cognitive Impairment: A 1-Year Follow-Up Study.

BACKGROUND: The coexistence of depression with mild cognitive impairment (MCI) seems to increase the risk of dementia. However, the explanations of that relationship have been inconsistent. We investigated cognitive profiles in patients with MCI with and without depression and whether changes in depression symptoms affect cognition longitudinally. METHODS: For the study, 161 patients with MCI were divided into a depressed group (D+) and a nondepressed group (D-). After 1 year, we redivided the original D- group into D- and newly developed depression (Dd) groups and the D+ group into improved depression (Di) and nonimproved depression (Dn) groups. Neuropsychological tests assessing depression and cognitive domains were performed at baseline and follow-up. RESULTS: When age-adjusted, the D+ group showed significantly poorer performance in general cognition and some subtests regarding memory, executive function, and attention. At the 1-year follow-up, changes in the calculation test ( P = .005) and Controlled Oral Word Test (COWAT; P = .048) were significantly different between groups. Only the Di group showed significant improvement in calculation. The Dn group showed significant decrement in COWAT that was significantly different from that of the Di group, which showed no significant change. DISCUSSION: Patients with depression having MCI showed poorer cognitive function than nondepressed patients with MCI in some cognitive domains. Improvement in depression was related to improvement or prevention of decline in cognitive measures.

Cognitive performance norms from the Korean genome and epidemiology study (KoGES).

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.

Prevalence and Associated Factors of Depression in General Population of Korea: Results from the Korea National Health and Nutrition Examination Survey, 2014.

Depressive disorder is a common mental illness and remains a major cause of morbidity worldwide. The present study, a cross-sectional, nationwide, population-based survey assessed the prevalence of depression in the general population of Korea through a random sampling of the non-institutionalized population for the Korea National Health and Nutrition Examination Survey (KNHANES) VI. The Patient Health Questionnaire (PHQ)-9 was first introduced into the KNHANES to detect depression. The point prevalence of depression (PHQ score of 10 or higher) was 6.7% (95% confidence interval [CI], 5.7-7.6) in 4,949 subjects. Based on the analysis using the diagnostic algorithm of the PHQ-9, the prevalence of major depressive disorder was 2.7% (95% CI, 2.2-3.3). Multiple logistic regression analysis, after adjusting the sociodemographic variables, also showed that the factors associated with depression were perceived stress and health status. This study reported for the first time that the point prevalence of depression screened using the PHQ-9 in this nationwide survey of the Korean population was similar to that of the western countries. As the KNHANES to detect depression is conducted biennially, further studies on the accumulated data are expected in the future.

PDE7B, NMBR and EPM2A Variants and Schizophrenia: A Case-Control and Pharmacogenetics Study.

BACKGROUND: We investigated phosphodiesterase 7B (PDE7B), neuromedin B receptor (NMBR) and epilepsy progressive myoclonus type 2A (EPM2A) genes in schizophrenia (SCZ). To the best of our knowledge, these genes have been poorly investigated in studies of SCZ. METHODS: Five hundred and seventy-three SCZ inpatients of Korean ethnicity and 560 healthy controls were genotyped for 2 PDE7B, 3 NMBR and 3 EPM2A polymorphisms. Differences in the allelic and genetic frequencies among healthy subjects and patients were calculated using the x03C7;2 statistics. Repeated-measure ANOVA was used to test possible influences of single-nucleotide polymorphisms on treatment efficacy. In case of positive findings, clinical and demographic variables were added as covariates, in order to investigate possible stratixFB01;cation bias. RESULTS: The rs2717 and rs6926279 within the NMBR gene and rs702304 and rs2235481 within the EPM2A gene were associated with SCZ liability. rs1415744 was also associated with Positive and Negative Symptom Scale negative clinical improvement. The results remained the same after inclusion of the covariates and were partially confirmed in the allelic and haplotype analyses. CONCLUSION: Our preliminary findings suggest a possible role of NMBR and EPM2A genes in SCZ susceptibility and, for the second one, also in antipsychotic pharmacogenetics. Nonetheless, further research is needed to conxFB01;rm our findings.

Genes Involved in Neurodevelopment, Neuroplasticity, and Bipolar Disorder: CACNA1C, CHRNA1, and MAPK1.

BACKGROUND: Bipolar disorder (BPD) is a common and severe mental disorder. The involvement of genetic factors in the pathophysiology of BPD is well known. In the present study, we tested the association of several single-nucleotide polymorphisms (SNPs) within 3 strong candidate genes (CACNA1C, CHRNA7, and MAPK1) with BPD. These genes are involved in monoamine-related pathways, as well as in dendrite development, neuronal survival, synaptic plasticity, and memory/learning. METHODS: One hundred and thirty-two subjects diagnosed with BPD and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within CACNA1C, CHRNA17, and MAPK1. Distribution of alleles and block of haplotypes within each gene were compared in cases and controls. Interactions between variants in different loci were also tested. RESULTS: Significant differences in the distribution of alleles between the cases and controls were detected for rs1016388 within CACNA1C, rs1514250, rs2337980, rs6494223, rs3826029 and rs4779565 within CHRNA7, and rs8136867 within MAPK1. Haplotype analyses also confirmed an involvement of variations within these genes in BPD. Finally, exploratory epistatic analyses demonstrated potential interactive effects, especially regarding variations in CACNA1C and CHRNA7. LIMITATIONS: Limited sample size and risk of false-positive findings. DISCUSSION: Our data suggest a possible role of these 3 genes in BPD. Alterations of 1 or more common brain pathways (e.g., neurodevelopment and neuroplasticity, calcium signaling) may explain the obtained results.

Genome-wide association study of antidepressant response: involvement of the inorganic cation transmembrane transporter activity pathway.

BACKGROUND: Genome-wide association studies (GWAS) represent the current frontier in pharmacogenomics. Thousands of subjects of Caucasian ancestry have been included in previous GWAS investigating antidepressant response. GWAS focused on this phenotype are lacking in Asian populations. METHODS: A sample of 109 major depressive disorder (MDD) patients of Korean origin in antidepressant treatment was collected. Phenotypes were response and remission according to the Hamilton Rating Scale for Depression (HRSD). Genome-wide genotyping was performed using the Illumina Human Omni2.5-8 platform. The same phenotypes were used in the STAR*D level 1 (n = 1677) for independent replication. In order to corroborate findings and increase the comparability between the two datasets, three levels of analysis (SNPs, genes and pathways) were carried out. Bonferroni correction, permutations, and replication across samples were used to reduce the risk of false positives. RESULTS: Among the genes replicated across the two samples (permutated p < 0.05 in both of them), CTNNA3 appeared promising. The inorganic cation transmembrane transporter activity pathway (GO:0022890) was associated with antidepressant response in both samples (p = 2.9e-5 and p = 0.001 in the Korean and STAR*D samples, respectively) and this pathway included CACNA1A, CACNA1C, and CACNB2 genes. CONCLUSIONS: The present study supported the involvement of genes coding for subunits of L-type voltage-gated calcium channel in antidepressant efficacy across different ethnicities but replication of findings is required before any definitive statement.

Characteristics of neurocognitive functions in mild cognitive impairment with depression.

BACKGROUND: Previous studies suggest that there is a strong association between depression and cognitive decline, and that concurrent depressive symptoms in MCI patients could contribute to a difference in neurocognitive characteristics compared to MCI patients without depression. The authors tried to compare neurocognitive functions between MCI patients with and without depression by analyzing the results of neuropsychological tests. METHODS: Participants included 153 MCI patients. Based on the diagnosis of major depressive disorder, the participants were divided into two groups: depressed MCI (MCI/D+) versus non-depressed MCI (MCI/D-). The general cognitive and functional statuses of participants were evaluated. And a subset of various neuropsychological tests was presented to participants. Demographic and clinical data were analyzed using Student t-test or χ 2 test. RESULTS: A total of 153 participants were divided into two groups: 94 MCI/D+ patients and 59 MCI/D- patients. Age, sex, and years of education were not significantly different between the two groups. There were no significant differences in general cognitive status between MCI/D+ and MCI/D- patients, but MCI/D+ participants showed significantly reduced performance in the six subtests (Contrasting Program, Go-no-go task, Fist-edge-palm task, Constructional Praxis, Memory Recall, TMT-A) compared with MCI/D- patients. CONCLUSIONS: There were significantly greater deficits in neurocognitive functions including verbal memory, executive function, attention/processing speed, and visual memory in MCI/D+ participants compared to MCI/D-. Once the biological mechanism is identified, distinct approaches in treatment or prevention will be determined.

Do Somatic Symptoms Predict the Severity of Depression? A Validation Study of the Korean Version of the Depression and Somatic Symptoms Scale.

This study aimed at exploring the psychometric characteristics of the Korean Version of the Depression and Somatic Symptoms Scale (DSSS) in a clinical sample, and investigating the impact of somatic symptoms on the severity of depression. Participants were 203 consecutive outpatients with current major depressive disorders (MDD) or lifetime diagnosis of MDD. The DSSS was compared with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the 17-items Hamilton Depression Rating Scale (HAMD). The DSSS showed a two-factor structure that accounted for 56.8% of the variance, as well as excellent internal consistency (Cronbach's alpha = 0.95), concurrent validity (r = 0.44-0.82), and temporal stability (intraclass correlation coefficient = 0.79). The DSSS had a high ability to identify patients in non-remission (area under receiver operating characteristic [ROC] curve = 0.887). Maximal discrimination between remission and non-full remission was obtained at a cut-off score of 22 (sensitivity = 82.1%, specificity = 81.4%). The number of somatic symptoms (the range of somatic symptoms) and the scores on the somatic subscale (SS, the severity of somatic symptoms) in non-remission patients were greater than those in remission patients. The number of somatic symptoms (slope = 0.148) and the SS score (slope = 0.472) were confirmed as excellent predictors of the depression severity as indicated by the MADRS scores. The findings indicate that the DSSS is a useful tool for simultaneously, rapidly, and accurately measuring depression and somatic symptoms in clinical practice settings and in consultation fields.

Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder.

BACKGROUND: Vortioxetine was approved by the U.S. Food and Drug Administration (FDA) in September 2013 for treating major depressive disorder (MDD). Thus far, a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) of vortioxetine have been conducted in patients with MDD. We performed a meta-analysis to increase the statistical power of these studies and enhance our current understanding of the role of vortioxetine in the treatment of MDD. METHODS: We performed an extensive search of databases and the clinical trial registry. The mean change in total scores on the 24-item Hamilton Rating Scale for Depression (HAM-D) and the Montgomery- Åsberg Depression Rating Scale (MADRS) from the baseline were the primary outcome measures. The secondary efficacy measures were the response and remission rates, as defined by a 50% or greater reduction in HAM-D/MADRS total scores and as a score of 10 or less in the MADRS and 7 or less in the HAM-D total scores at the end of treatment. RESULTS: We included 7 published and 5 unpublished short-term (6-12 wk) RCTs in our meta-analysis. Vortioxetine was significantly more effective than placebo, with an effect size (standardized mean difference [SMD]) of -0.217 (95% confidence interval [CI] -0.313 to -0.122) and with odds ratios (ORs) for response and remission of 1.652 (95% CI 1.321 to 2.067) and 1.399 (95% CI 1.104 to 1.773), respectively. Those treated with vortioxetine did not differ significantly from those treated with selective norepinephrine reuptake inhibitors/agomelatine with regard to the SMD of the primary outcome measure (0.081, -0.062 to 0.223) or for response (OR 0.815, 95% CI 0.585 to 1.135) and remission (OR 0.843, 95% CI 0.575 to 1.238) rates. Discontinuation owing to lack of efficacy (OR 0.541, 95% CI 0.308 to 0.950) was significantly less common among those treated with vortioxetine than among those who received placebo, whereas discontinuation owing to adverse events (AEs; OR 1.530, 95% CI 1.144 to 2.047) was significantly more common among those treated with vortioxetine than among those receiving placebo. There was no significant difference in discontinuation rates between vortioxetine and comparators owing to inefficacy (OR 0.983, 95% CI 0.585 to 1.650), whereas discontinuation owing to AEs was significantly less common in the vortioxetine than in the comparator group (OR 0.728, 95% CI 0.554 to 0.957). LIMITATIONS: Studies examining the role of vortioxetine in the treatment of MDD are limited. CONCLUSION: Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of heterogeneous RCTs.

Is there an MCI reversion to cognitively normal? Analysis of Alzheimer's disease biomarkers profiles.

BACKGROUND: We investigated the characteristics of Alzheimer's disease (AD) biomarkers for mild cognitive impairment (MCI) reversion to cognitively normal (CN). METHODS: Of a total of 1,233 participants from the ADNI database, 42 participants with MCI reversion to CN (MCIr), 778 with MCI, and 413 CN were obtained. We evaluated demographics, clinical outcomes, medication use, MCI type, and AD biomarkers, including genetic, cerebrospinal fluid, imaging, and neuropsychological data. RESULTS: This study showed that the differences between MCIr and CN were only age, Mini-Mental State Examination, and Clinical Dementia Rating - Sum of Boxes, but the differences between MCIr and MCI were not only clinical outcomes but also AD biomarkers, including genetic, cerebrospinal fluid, imaging, and neuropsychological data. Overall, MCIr may be similar to CN and not MCI in clinical characteristics. CONCLUSIONS: With assessment of MCI reversion to CN, the possibility of false-positive errors should be considered. With the assistance of AD biomarkers, MCI can be evaluated more accurately than the conventional criteria.