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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.

A growing body of evidence has suggested that social capital is an upstream social determinant of mental health. We investigated the association of cognitive social capital, including interpersonal trust and reciprocity, with depressive symptoms in the elderly. We also explored the mediating role of cognitive social capital in the association between socioeconomic status (SES) and depressive symptoms and the moderating effect of SES on the relationship between social capital and depressive symptoms. Data from the 2012 Korea Welfare Panel Study (KOWEPS) was analyzed for 5969 participants aged 60 years or older. Cognitive components of social capital, including interpersonal trust and reciprocity, were evaluated using single-item questionnaires. Socioeconomic and health-related characteristics were investigated and depressive symptoms were evaluated by an 11-item version of the Center for Epidemiologic Studies Depression Scale. Low interpersonal trust and reciprocity levels were significantly associated with depressive symptoms in the elderly. Reciprocity level mediated the association between household income level and depressive symptoms. We did not observe any significant moderating effect of SES on the association between cognitive social capital and depressive symptoms. A significant association between cognitive social capital and depressive symptoms in Korean elderly was found. We elucidated how SES interacted with depressive symptoms through the mediation pathway of cognitive social capital using a representative sample of the Korean elderly population.

Schizophrenia (SCZ) is a common and severe mental disorder. Genetic factors likely play a role in its pathophysiology as well as in treatment response. In the present study, we investigated the effects of several single nucleotide polymorphisms (SNPs) within 9 genes involved with antipsychotic (AP) mechanisms of action. Two independent samples were recruited. The Korean sample included 176 subjects diagnosed with SCZ and 326 healthy controls, while the Italian sample included 83 subjects and 194 controls. AP response as measured by the positive and negative syndrome scale (PANSS) was the primary outcome, while the secondary outcome was the SCZ risk. Exploratory analyses were performed on (1) symptom clusters response (as measured by PANSS subscales); (2) age of onset; (3) family history; and (4) suicide history. Associations evidenced in the primary analyses did not survive to the FDR correction. Concerning SCZ risk, we partially confirmed the associations among COMT and MAPK1 genetic variants and SCZ. Finally, our exploratory analysis suggested that CHRNA7 and HTR2A genes may modulate both positive and negative symptoms responses, while PLA2G4A and SIGMAR1 may modulate respectively positive and negative symptoms responses. Moreover, GSK3B, HTR2A, PLA2G4A, and S100B variants may determine an anticipation of SCZ age of onset. Our results did not support a primary role for the genes investigated in AP response as a whole. However, our exploratory findings suggested that these genes may be involved in symptom clusters response.

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.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.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.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.

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.

Schizophrenia is a debilitating illness with a chronic impact on social function and daily living. Although various antipsychotics are available, there are still many challenges and unmet needs. Thus, many compounds with diverse mechanisms have been investigated, but all approved antipsychotics still require interactions with dopamine D2 receptors. Areas covered: We searched for investigational drugs using the key words 'dopamine' and 'schizophrenia' in American and European clinical trial registers (clinicaltrials.gov; clinicaltrialsregister.eu). Published articles were searched in PubMed, Embase, Medline, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Web of Science and the Cochrane Central Register of Controlled Trials Library. Expert opinion: The prospect of developing a dopamine antagonist is hopeful. Brexpiprazole and cariprazine, which were agents listed as 'investigational dopamine antagonists,' just received FDA approval. Novel agents such as BL 1020, ITI-007, and JNJ-37822681 have solid published data available, and agents such as L-THP, Lu AF35700, S33138, and SB-773812 are under vigorous investigation. However, the expected benefits of the newly developed antagonists may not be great because they offer little enhanced efficacy for negative symptoms, cognition and functional outcomes.

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.

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.

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.

Background The 15-item geriatric depression scale (GDS-15) is a short form of GDS and is used to screen, diagnose, and evaluate depression in elderly individuals. Most previous studies evaluated the ability of GDS-15 to discriminate between depressive and non-depressive states. In this study, we investigated the multi-stage discriminating ability of GDS-15. Methods A total of 774 participants, over 65 years of age were included (normal, n = 650; minor depressive disorder [MnDD], n = 94; major depressive disorder [MDD], n = 30). Multi-category receiver operating characteristic (ROC) surfaces were evaluated to identify three stages of geriatric depression. The optimal cutoff points were selected based on the volume under the ROC surface (VUS) and the Youden index. Results In the results of multi-category classification analyses, VUS of the GDS-15 of 0.61 was obtained, and optimal cutoff points of the GDS-15 for multiple stages of depression of 4 (between normal and MnDD) and 11 (between MnDD and MDD) were derived. The Youden index for the GDS-15 was 0.49, and the derived optimal cutoff points were 5 and 10, for the multiple stages, respectively. The overall diagnostic accuracy based on the Youden index was superior to that based on the VUS in the GDS-15. Limitations The participants’ cognitive function has potential to affect the GDS-15 score; nevertheless, the study included those with mild cognitive impairment. Conclusions GDS-15 was a useful tool to classify stages of geriatric depression into either minor or major depressive disorder.

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

The Sewol ferry disaster is one of the most tragic events in Korea’s modern history. Among the 476 people on board, which included Danwon High School students (324) and teachers (14), 304 passengers died in the disaster (295 recovered corpses and 9 missing) and 172 survived. Of the rescued survivors, 72 were attending Danwon High School, located in Ansan City, and residing in a residence nearby. Because the students were young, emotionally susceptible adolescents, both the government and the parents requested the students be grouped together at a single hospital capable of appropriate psychiatric care. Korea University Ansan Hospital was the logical choice, as the only third-tier university-grade hospital with the necessary faculty and facilities within the residential area of the families of the students. We report the experiences and the lessons learned from the processes of preparing for and managing the surviving young students as a community-based hospital. (Disaster Med Public Health Preparedness. 2017;11:389–393)

The objective of this study was to investigate the risk factors of suicidal ideation and their population attributable fraction (PAF) in a representative sample of the elderly population in Korea.We examined the data set from the Survey of Living Conditions and Welfare Needs of Korean Older Persons, which was conducted by the Korea Institute for Health and Social Affairs (KIHASA) in 2011. In that survey, 10,674 participants were randomly selected from those older than age 65. Simultaneous multivariate logistic regression was used to investigate the risk factors of suicidal ideation in terms of their sociodemographic and health-related variables. Subsequently, the PAF was calculated with adjustment for other risk factors.The weighted prevalences of depression and suicidal ideation were 30.3% and 11.2%, respectively. In multivariate analysis, factors significantly associated with decreased risk of suicidal ideation included old-old age (odds ratio [OR] = 0.66 for 75 to 79 years, OR = 0.52 for 80 to 84 years, OR = 0.32 for older than 85 years), economic status (OR = 0.59 for 5th quintile; more than US$25,700 per year), whereas those associated with increased risk included poor social support (OR = 1.28), currently smoking (OR = 1.42), sleep problems (OR = 1.74), chronic illness (OR = 1.40), poor subjective health (OR = 1.56), functional impairment (OR = 1.45), and depression (OR = 4.36). Depression was associated with a fully adjusted PAF of 45.7%, followed by chronic illness (19.4%), poor subjective health status (18.9%), sleep problems (14.1%), functional impairment (4.9%), poor social support (4.2%), and currently smoking (3.6%).Preventive strategies focused particularly on depression might reduce the impact of suicidal ideation in the elderly population. Also, specific mental health centers focused on the specific needs of the elderly population should be established to manage suicidal risk.

Research on the associations between the ratio of second-to-fourth digit lengths (2D:4D ratio) and psychological variables could be a useful method of confirming sex hormone effects on human behavior tendencies. This study investigated the correlations between the 2D:4D ratio and characteristics of temperament and character in an urban community population. We hypothesized that the 2D:4D ratio correlates more strongly with temperament than with character. A total of 728 healthy adults (330 men and 398 women) ranging in age from 20 to 45 years were tested. Subjects completed the Temperament and Character Inventory (TCI) and were examined by measuring the 2D:4D ratio using a direct measurement method. Correlations between the 2D:4D ratio and psychological characteristics were explored. For women only, significant positive correlations with the 2D:4D ratio were found in the TCI-Temperament dimension (TCI-T), particularly in the two subscales of harm avoidance scale. Women with higher 2D:4D ratios had higher fear of uncertainly scores (rpartial = 0.206, p = 0.028) and shyness with strangers scores (rpartial = 0.252, p = 0.024). The 2D:4D ratio shows stronger correlations with temperament than with character. A higher 2D:4D ratio of woman is expected to indicate harm avoidance.

In 2008, the first Dementia Management Plan was launched to focus on prevention and early diagnosis, the development of infrastructures and management, and raising awareness. In 2012, the Dementia Management Act was enacted. In addition, in 2008, Korea launched the Long-Term Care Insurance (LTCI) scheme, a social insurance scheme for elderly care and whose beneficiaries also include patients with mild dementia but who still need care. The third Plan launched in 2016 for the next 5 years (i.e. 2016–2020) focuses on investing in dementia research, setting up a robust dementia delivery system, and standardizing a dementia care pathway. The Korean healthcare system for dementia patients has universal health insurance coverage through the national health insurance. The national dementia policy in South Korea was announced as ‘Dementia Comprehensive Management Measures’ in September 2008, of which one of the primary measures is to provide early diagnosis of dementia through the establishment of dementia counselling centres in public health-improving centres.

Background Suicide is a critical complication of psychiatric disorders. Physical activity has a positive effect on mental health; however, its effects on suicidal ideation have received little attention compared to other psychiatric symptoms. Methods Data were obtained from the Korea National Health and Nutrition Examination Survey 2014. Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire-9. Physical activity was measured by the International Physical Activity Questionnaire (IPAQ) and categorized into three groups by activity level. Multiple logistic regression analysis was performed for the entire sample, men, and women. The following three models were used: Model 1 (adjusted for sociodemographic and health-related variables), Model 2 (additionally adjusted for subjective body image), and Model 3 (additionally adjusted for diagnosed depression). Results Compared to the low IPAQ group, the moderate IPAQ group was significantly associated with decreased suicidal ideation in Model 3 for the entire sample (OR, 0.733; 95% CI, 0.538–0.999) and in all models for women. However, the high IPAQ group showed no significant association. None of the IPAQ groups showed significant associations in men. Limitations This is a cross-sectional study. Therefore, the direction of causality cannot be determined. This study also investigated suicidal ideation over the past two weeks, which may be inconsistent with studies conducted over the past year. Conclusions The beneficial relationship between physical activity and suicidal ideation is weaker in men and individuals with high activity levels. Detailed guidelines on physical activity according to gender and activity level are recommended.

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.

Objective Genetics factors are likely to play a role in the risk, clinical presentation and treatment outcome in major depressive disorder (MDD). In this study, we investigated the role of three candidate genes for MDD; calcium voltage- gated channel subunit alpha1 C ( CACNA1C ), cholinergic receptor nicotinic alpha 7 subunit ( CHRNA7 ), and mitogen- activated protein kinase 1 ( MAPK1 ). Methods Two-hundred forty-two MDD patients and 326 healthy controls of Korean ancestry served as samples for the analyses. Thirty-nine single nucleotide polymorphisms (SNPs) within CACNA1C , CHRNA7 , and MAPK1 genes were genotyped and subsequently tested for association with MDD (primary analysis) and other clinical features (symptoms' severity, age of onset, history of suicide attempt, treatment outcome) (secondary analyses). Single SNPs, haplotypes and epistatic analyses were performed. Results Single SNPs were not associated with disease risk and clinical features. However, a combination of alleles (haplotype) within MAPK1 was found associated with MDD-status. Secondary analyses detected a possible involvement of CACNA1C haplotype in resistance to antidepressant treatment. Conclusion These data suggest a role for MAPK1 and CACNA1C in MDD risk and treatment resistance, respectively. However, since many limitations characterize the analysis, the results must be considered with great caution and verified.

Introduction Beta-amyloid is considered to be a pathophysiological marker in Alzheimer's disease (AD). Soluble amyloid precursor proteins (sAPPs) –α (sAPPα) and –β (sAPPβ), which are the byproducts of non-amyloidogenic and amyloidogenic process of APP, respectively, have been repeatedly observed in the cerebrospinal fluids (CSF) of AD patients. The present study focused on the determination of sAPP levels in peripheral blood. Methods The plasma protein levels of sAPPα and sAPPβ were measured with ELISA. Plasma from 52 AD patients, 98 amnestic mild cognitive impairment (MCI) patients, and 114 cognitively normal controls were compared. Results The plasma level of sAPPβ was significantly increased in AD patients than in cognitively healthy controls. However, no significant change in plasma sAPPα was observed among the three groups. Furthermore, the plasma sAPPβ levels significantly correlated with cognitive assessment scales, such as clinical dementia rating (CDR), and mini-mental status examination (MMSE). Interestingly, sAPPα and sAPPβ had a positive correlation with each other in blood plasma, similar to previous studies on CSF sAPP. This correlation was stronger in the MCI and AD groups than in the cognitively healthy controls. Conclusions These results suggest that individuals with elevated plasma sAPPβ levels are at an increased risk of AD; elevation in these levels may reflect the progression of disease.

Alzheimer’s disease (AD) is characterized by amyloid plaques and pathologic cerebrovascular remodeling. Cerebrovascular abnormalities may contribute to the pathology of AD, but the molecular mechanisms are not fully understood. In this study, we evaluated blood–brain barrier (BBB) disruption and the role of VE-cadherin in the progression of amyloid pathology. Here, we determined that levels of VE-cadherin are decreased in brain vessels of AD patients and mouse model of AD.In vitroexperiments showed that the disappearance of VE-cadherin by beta-amyloid at the endothelial cell surface was due to cleavage of VE-cadherin. VE-cadherin cleavage was inhibited by a γ-secretase and ADAM10 inhibitor. The disappearance of VE-cadherin in brain vessels was also seen in amyloid precursor protein transgenic mice. In the postmortem brain of individuals with AD, furthermore, levels of VE-cadherin were significantly reduced in vessels. Dementia patients showed a distinct blood biochemical profile characterized by high soluble VE-cadherin (sVEC). There was a strong association between plasma sVEC (adjusted odds ratio = 3.41,P< 0.001) and dementia. These results suggest that measurements of plasma VE-cadherin could have the potential for predicting the risk of progressive AD.

Objective Pharmacogenomic-based antidepressant treatment (PGATx) may result in more precise pharmacotherapy of major depressive disorder (MDD) with better drug therapy guidance. Methods An 8-week, randomized, single-blind clinical trial was conducted to evaluate the effectiveness and tolerability of PGATx in 100 patients with MDD. All recruited patients were randomly allocated either to PGATx (n=52) or treatment as usual (TAU, n=48) groups. The primary endpoint was a change of total score of the Hamilton Depression Rating Scale-17 (HAMD-17) from baseline to end of treatment. Response rate (at least 50% reduction in HAMD-17 score from baseline), remission rate (HAMD-17 score ≤7 at the end of treatment) as well as the change of total score of Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER) from baseline to end of treatment were also investigated. Results The mean change of HAMD-17 score was significantly different between two groups favoring PGATx by -4.1 point of difference (p=0.010) at the end of treatment. The mean change in the FIBSER score from baseline was significantly different between two treatment groups favoring PGATx by -2.5 point of difference (p=0.028). The response rate (71.7 % vs. 43.6%, p=0.014) were also significantly higher in PGATx than in TAU at the end of treatment, while the remission rate was numerically higher in PGATx than in TAU groups without statistical difference (45.5% vs. 25.6%, p=0.071). The reason for early drop-out associated with adverse events was also numerically higher in TAU (n=9, 50.0%) than in PGATx (n=4, 30.8%). Conclusion The present study clearly demonstrate that PGATx may be a better treatment option in the treatment of MDD in terms of effectiveness and tolerability; however, study shortcomings may limit a generalization. Adequately-powered, well-designed, subsequent studies should be mandatory to prove its practicability and clinical utility for routine practice.

Background The lack of uniformity in the definition of treatment resistant depression (TRD) within the Asia-Pacific (APAC) region may have implications for patient management. We aimed to characterize the most commonly used TRD definition in selected APAC countries. Methods A systematic literature review of TRD definitions in APAC countries was conducted in Medline and Embase (2010–2016) and conference proceedings (2014 and 2016). TRD guidelines (APAC, Europe regional, US, or international) were also searched. An expert-panel explored APAC nuances in TRD definitions to achieve consensus for a regional-level definition. Results Ten guidelines and 89 studies qualified for study inclusion. Among the studies, variations were observed in definitions regarding: number of antidepressants failed (range: ≥1 to ≥3), classes of antidepressants (same or different; 59% did not specify class), duration of previous treatments (range: 4–12 weeks), dosage adequacy, and consideration of adherence (yes/no; 88% of studies did not consider adherence). No TRD-specific guidelines were identified. The emerging consensus from the literature review and panel discussion was that TRD is most commonly defined as failure to ≥2 antidepressant therapies given at adequate doses, for 6–8 weeks during a major depressive episode. Limitations Few studies provided definitions of TRD used in daily clinical practice, and a limited number of countries were represented in the included studies and expert panel. Conclusion Attaining consensus on TRD definition may promote accurate, and possibly early detection of patients with TRD to enable appropriate intervention that may impact patient outcomes and quality of life.

Alzheimer’s disease (AD) is a major cause of dementia. Growing evidence suggests that dysregulation of autophagy, a cellular mechanism essential for self-digestion of damaged proteins and organelles, is involved in neurological degenerative diseases including AD. Previously, we reported that autophagosomes are increased in the brains of AD mouse model. However, the plasma levels of autophagic markers have not yet been investigated in patients with AD. In this study, we investigated the expression of autophagy-related genes 5 and 12 (ATG5 and ATG12, respectively) in cells in vitro upon amyloid-beta (Aβ) treatment and in the plasma of AD patients. ATG5-ATG12 complex levels were increased in primary rat cortical neurons and human umbilical vein endothelial cells after Aβ treatment. Furthermore, we compared plasma from 69 patients with dementia, 82 patients with mild cognitive impairment (MCI), and 127 cognitively normal control participants. Plasma levels of ATG5 were significantly elevated in patients with dementia (149.3 ± 7.5 ng/mL) or MCI (152.9 ± 6.9 ng/mL) compared with the control subjects (129.0 ± 4.1 ng/mL) (p = 0.034, p = 0.016, respectively). Our results indicate that alterations in the plasma ATG5 levels might be a potential biomarker in patients at risk for AD.

Background Intimate partner violence (IPV) has a serious detrimental effect on mental health outcomes. We aimed to investigate the association of verbal or physical IPV with incidence of depressive symptoms in both married women and men according to the victim-perpetrator role. The potential mediating role of verbal or physical IPV in the association between satisfaction level with family relationships or childhood adversity and the incidence of depressive symptoms in married adults was also explored. Methods The Korea Welfare Panel Study (KOWEPS) in 2006 and 2007 dataset was analyzed for 9217 married respondents aged 19 years or older. Physical and verbal IPV was assessed according to victim-perpetrator role in 2006. Depressive symptoms were evaluated by the Center for Epidemiologic Studies Depression Scale, 11-item version in 2006 and 2007. Association of IPV with incidental depressive symptoms was investigated with logistic regression analysis fully-adjusted for all potential confounding factors. Results The bidirectional role of verbal IPV and victimization by physical IPV led to incidence of depressive symptoms in married women. Verbal IPV significantly mediated the association between satisfaction level with the family relationship and incidental depressive symptoms in women. Limitations We did not investigate the influence of premorbid depressive symptoms on new-onset IPV. Conclusions This study is the first to demonstrate that gender and the victim-perpetrator role are critical moderating factors in the association between IPV and depressive symptom incidence using a nationally representative sample

Introduction Mood disorders are common and disabling disorders. Despite the availability of over 100 psychotropic compounds, only one-third of patients benefit from first-line treatments. Over the past 20 years, many studies have focused on the biological factors modulating disease risk and response to treatments, but with still inconclusive data. In order to improve our current knowledge, in this study, we investigated the role of a set of genes involved in different pathways (neurotransmission, neuroplasticity, circadian rhythms, transcription factors, signal transduction and cellular metabolism) in the treatment outcome of major depressive disorder (MDD) and bipolar disorder (BD) after naturalistic pharmacological treatment. Methods Totals of 242 MDD, 132 BD patients and 326 healthy controls of Asian ethnicity (Koreans) were genotyped for polymorphisms within 19 genes. Response and remission after 6–8 weeks of treatment with antidepressants and mood stabilizers were evaluated. In secondary analyses, genetic associations with disease risk and some disease-associated features (age of onset, suicide attempt and psychotic BD) were also tested. Results None of the variants within the investigated genes was significantly associated with treatment outcomes. Some marginal association (uncorrected p

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.

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 under standing 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– Asberg 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 shortterm (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.

Objective Non-adherence to medication is a recognized problem in psychiatric patients and may be one of the most challenging aspects of treatment for patients with schizophrenia. Failure of follow-up care after discharge greatly increases non-adherence to prescribed medications, relapse and rehospitalization. However, it is still unknown whether and how much outpatient follow-up visits can mitigate the risk of rehospitalization. Therefore we sought to investigate the continuity and effectiveness of outpatient care after inpatient discharge and its effect on rehospitalization of patients with schizophrenia. Methods Data were extracted from National Health Insurance Claim Database covering the period from 2007 through 2010. We identified 10,246 patients aged 18 years or older who were admitted in psychiatric facilities with the diagnosis of schizophrenia between January 1 and December 31 in 2007. The number of outpatient visits within 60 days after discharge from index admission was defined as the indicator for the continuous care and rehospitalization was inspected during the following 36-month period. Cox's proportional hazard model was used to examine the factors affecting the risk of rehospitalization including the number of outpatient visits, age, sex, comorbidities, antipsychotics, and characteristics of medical institution. Results We found that 12.7% (n=1,327) of the patients visited psychiatric outpatient department once within 60 days after hospital discharge, 34.8% (n=3,626) twice, and 27.8% (n=2,900) more than three times. Patients taking atypical antipsychotics showed higher proportion in 2 or more outpatient visits, whereas patients taking typical antipsychotics showed higher proportion in one or no outpatient visits. Cox hazard ratios of rehospitalization for the factor of 3 or more outpatient visits referenced to that of no follow-up visit were 0.567 (0.428-0.750, 95% confidence interval) within 90 days, 0.673 (0.574-0.789) within 180 days, 0.800 (0.713-0.898) within a year, 0.906 (0.824-0.997) within 2 years, and 0.993 (0.910-1.084) within 3 years. Conclusion Although continuous outpatient treatment is important for relapse prevention, patients with schizophrenia showed a low rate of outpatient visit as 62.6% of total patients in 2 or more visits within 60 days after discharge. Lack of follow-up treatment might lead to increase psychotic symptoms and raised risk of relapse and rehospitalization. Our data suggest that the number of outpatient visits within 60 days after discharge in patients with schizophrenia is an important indicator of rehospitalization within a year. Therefore, further efforts to examine factors affecting failure of outpatient follow-up after discharge are warranted.

Schizophrenia is a devastating illness with high direct costs and even higher indirect costs related to unemployment and disability. Even though antipsychotics are the mainstay of treatment in pati...

We investigated the effect of a set of SNPs within 5 genes identified by GWASs as possible risk genes for schizophrenia (SCZ) in two independent samples, comprising 176 SCZ patients and 326 controls of Korean origin and 83 SCZ patients and 194 controls of Italian origin. The PANSS was used to assess psychopathology severity and antipsychotic response (AR). Several clinical features were assessed at recruitment. In the Korean sample, the SP4 gene haplotype rs2282888-rs2237304-rs10272006-rs12673091 (p = 0.02) was associated with SCZ. In the Italian sample, PPP3CC rs11780915 (genotypic: p = 0.006; allelic: p = 0.001) and rs2249098 (genotypic: p = 0.0004; allelic: p = 0.00006) were associated with SCZ, as well as the PPP3CC rs11780915-rs10108011-rs2249098 and the ZNF804A rs7603001-rs1344706 haplotypes (p = 0.03 and p = 0.02). Several RORA variants were associated with AR in both the samples, although only the haplotype rs1020729-rs1871858 in the Korean sample survived to the statistical correction (p = 0.01). Exploratory analyses suggested that: (1) PPP3CC, ST8SIA2, and SP4 genes may modulate psychotic symptoms, and (2) RORA and ZNF804A genes may influence AR. Our results partially support a role for these genes in SCZ and AR. Analyses in well phenotyped samples may help to refine the role of the genes identified by GWASs.

Item does not contain fulltext BACKGROUND: A reliable and valid global staging scale has been lacking within dementia care. OBJECTIVE: To develop an easy-to-use multi-dimensional clinical staging schedule for dementia. METHODS: The schedule was developed through: i) Two series of focus groups (40 and 48 participants, respectively) in Denmark, France, Germany, Netherlands, Spain, Switzerland, and UK with a multi-disciplinary group of professionals working within dementia care, to assess the need for a dementia-staging tool and to obtain suggestions on its design and characteristics; ii) A pilot-study over three rounds to test inter-rater reliability of the newly developed schedule using written case histories, with five members of the project's steering committee and 27 of their colleagues from Netherlands, France, and Spain as participants; and iii) A field-study to test the schedule's inter-rater reliability in clinical practice in France, Germany, Netherlands, Spain, Italy, Turkey, South Korea, Romania, and Serbia, which included 209 dementia patients and 217 of their caregivers as participants. RESULTS: Focus group participants indicated a clear need for a culture-fair international dementia staging scale and reached consensus on face validity and content validity. Accordingly, the schedule has been composed of seven dimensions including behavioral, cognitive, physical, functional, social, and care aspects. Overall, the schedule showed adequate face validity, content validity, and inter-rater reliability; in the nine field-sites, intraclass correlation coefficients (ICCs; absolute agreement) for individual dimensions ranged between 0.38 and 1.0, with 84.4% of ICCs over 0.7. ICCs for total sum scores ranged between 0.89 and 0.99 in the nine field-sites. CONCLUSION: The IDEAL schedule looks promising as tool for the clinical and social management of people with dementia globally, though further reliability and validity testing is needed.

Objective This study is a prospective observational study on 75 late-adolescent survivors of a large passenger ship accident from immediately after the accident to one year later. Methods Assessments of student survivors were conducted on day 2 and at months 1, 6, and 12. The PTSD Checklist (PCL), Patient Health Questionnaire-9 (PHQ-9), State subscale of the State and Trait Anxiety Inventory (STAI-S), Athens Insomnia Scale (AIS), and Brief Resilience Scale (BRS) were administered. Results When the assessments for day 2 and month 12 were compared, all the scales, except the PCL-avoidance subscale, showed a significant improvement in symptoms among males. However, among females, all the scales, except the PCL-re-experience subscale and the STAI-S, failed to show a significant improvement. All the symptoms for both males and females showed a pattern that decreased to the lowest level at month 1 (camp-based controlled intervention period), then increased at months 6 and 12 (voluntary individual treatment after returning to school). Conclusion The rapid deterioration of psychological symptoms was found during the chronic phase, when students returned to their daily routines and received voluntary individual therapy. There is a need to screen high-risk adolescents and be more attentive to them during this period.

Countless antidepressant randomized trials were conducted and showed statistically significant benefits of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) over placebo. Meanwhile, critics are increasing regarding the efficacy of antidepressants in the treatment of MDD because at least a proportion of clinical trials could be hampered by various biases. In contrast, number of failed trials is increasing in the recent years which have made developing psychiatric medications progressively more time-consuming and expensive. Areas covered: Biases and related issues in clinical trials for antidepressants can be identified as an important common contributing factor to the two paradoxical phenomenon. This review identifies possible biases that can occur before, during, and after clinical trials of antidepressant. Expert commentary: Recent studies not only may over-estimate efficacy of antidepressants, but also may exaggerate placebo response because of various biases. Sponsorship and publication biases have been one of the targets of the criticism and ethical debate. Thus, initiating new trend of research by re-organizing academic-industry partnership will be the most important task in the next five years.

Tinnitus is strongly associated with psychiatric symptoms, including depression and suicidality. We aimed to further investigate the association of tinnitus with depressive mood and/or suicidal ideation, and explore the shared risk factors for these within a representative sample of the adult general population. We also investigated potential mediation pathways among tinnitus, suicidal ideation, depression, shared risk factors, and perceived stress levels. We analysed data from 28,930 adults (aged ≥19 years) from the fourth and fifth Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2008 to 2012 in South Korea. We investigated the presence and severity of tinnitus, depressive mood, suicidal ideation, perceived usual stress level, and socioeconomic and health-related variables. We conducted logistic regression and mediation analyses. Tinnitus and its severity were significantly associated with depressive mood and suicidal ideation. Tinnitus, depressive mood, and suicidal ideation shared common socioeconomic and health-related risk factors. Tinnitus significantly mediated the association of shared risk factors for depressive mood and suicidal ideation. Perceived usual stress level mediates the association of tinnitus with depressive mood and suicidal ideation. The correlation of perceived usual stress levels with depression and suicidal ideation was also mediated by tinnitus. Our findings implicate that tinnitus may contribute substantially to the development of depressive symptom and suicidal ideation in adults via apparent interactions with shared risk factors and stress levels.