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

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

The Potential Role of Aripiprazole Augmentation for Major Depressive Disorder with Anxious Distress in Naturalistic Treatment Setting.

Objective: : This study tried to observe clinical benefit of aripiprazole augmentation (ARPA) treatment for major depressive disorder with anxious distress (MDDA) in routine practice. Methods: : Retrospective chart review (n = 41) was conducted for clinical benefit of ARPA in patients with MDDA in routine practice. The primary endpoint was the mean change of Hamilton Anxiety Rating scale (HAMA) total scores from baseline to the endpoint. Additional secondary endpoints were also retrieved. Results: : The changes of primary endpoint HAMA (t = 5.731, -4.6, p = 0.001), and secondary endpoints including Hamilton Depression Rating scale (HAMD, t = 4.284, -3.4, p ＜ 0.001), Clinical Global Impression-Clinical Benefit (CGI-CB, -0.9, t = 1.821, p = 0.026), and Clinical Global Impression Score-Severity (CGI-S, t = 3.556, -0.4, p ＜ 0.001) scores were also significantly improved during the study. No significant adverse events were observed. Conclusion: : This study has shown additional benefit of ARPA treatment for MDDA patients in routine practice. However, adequately-powered and well-controlled studies are necessary for generalization of the present findings.

Embitterment in Vietnam War Veterans Predicted by Symptoms of Posttraumatic Stress Disorder.

OBJECTIVE: Research on the association between posttraumatic embitterment disorder (PTED) and other psychopathologies in veterans and adults aged ≥65 years is lacking. This study aimed to assess embitterment among elderly war veterans and its association with major psychopathological factors. METHODS: Participants included Vietnam War veterans who visited a psychiatric clinic. Based on the Posttraumatic Embitterment Disorder Self-Rating Scale (PTEDS) score, the participants were divided into the embitterment (PTED(+), mean score of PTEDS items [mPTEDS] ≥1.6) and non-embitterment (PTED(-), mPTEDS <1.6) groups. Demographic characteristics, combat exposure severity, depression, anxiety, sleep, and alcohol use disorder symptom scores of the participants were collected and compared between the PTED(+) and PTED(-) groups. A correlation analysis between symptom measure scores and the mPTEDS was conducted. The influence of psychopathology on embitterment was investigated using stepwise multiple linear regression analysis. RESULTS: In total, 60 participants (28 in PTED(+) and 32 in PTED(-)) were included. Among those in PTED(+), 21 (35.0%) showed mild embitterment symptoms (1.6≤ mPTEDS <2.5) and 7 (11.7%) reported moderate or severe embitterment symptoms (mPTEDS ≥2.5). The mean scores of posttraumatic stress disorder (PTSD), depression, and anxiety were significantly higher in the PTED(+) than in the PTED(-) group. The mPTEDS were significantly correlated with PTSD, depression, anxiety, and sleep disorder scores. The PTSD symptoms significantly explained the higher mPTEDS score in a regression model. CONCLUSION: Embitterment symptoms were associated with PTSD, depression, anxiety, and insomnia symptoms in elderly veterans, similar to the results of prior studies involving only the general population.

Circadian Rhythms and Depression in Adolescents: A Comparative Analysis of First Episode and Recurrent-Episode Groups.

Circadian rhythm disruptions are a hallmark feature of mood disorders. Patients experiencing acute depressive episodes report noticeable changes in their sleep-wake cycles. This research explains the association between depression and various circadian rhythm metrics, explicitly focusing on adolescents diagnosed with depressive disorders. Adolescence is a critical period marked by significant physiological and psychological changes, making it imperative to understand how mood disorders manifest during this phase. However, there have been minimal specific studies in pediatric populations to determine whether circadian rhythm changes differ between adolescents with first and multiple-recurrent depressive episodes. Our study involved a group of 61 adolescents aged between 13 and 18. We performed a cross-sectional study of a clinical population of patients presenting to a child and adolescent psychiatry clinic diagnosed with depression. Participants were asked to complete self-report evaluations using several tools: the Korean version of the Biological Rhythms Interview of Assessment in Neuropsychiatry (K-BRIAN), the Korean Translation of Composite Scale to Measure Morningness-Eveningness (KtCS), and the Seasonal Pattern Assessment Questionnaire (SPAQ). Tools such as the Children's Depression Inventory (CDI), State-Trait Anxiety Inventory (STAI), and K-Mood Disorder Questionnaire (K-MDQ) were employed for the assessment of clinical characteristics of depression. Based on the frequency of their depressive episodes, participants were bifurcated into two distinct groups: those experiencing their first episode (n = 22, mean age: 15.09 ± 1.44 years) and those with recurrent episodes (n = 39, mean age: 15.95 ± 1.26 years). At first, the two groups' data revealed no significant differences regarding mood or circadian rhythm metrics (CDI: first episode 26.18 ± 10.54 and recurrent episode 25.90 ± 10.59, STAI-S: first episode 56.91 ± 12.12 and recurrent episode 57.49 ± 11.93, STAI-T: first episode 60.36 ± 11.63 and recurrent episode 59.09 ± 12.10, SPAQ-total: first episode 6.59 ± 4.86 and recurrent episode 6.77 ± 5.23, KtCS: first episode 30.32 ± 5.83 and recurrent episode 28.13 ± 7.36). However, we observed significant correlations between circadian rhythm disruptions and depression scales (CDI with SPAQ-weight (r = 0.26), KtCS (r = -0.48), K-BRIAN-sleep (r = 0.58), K-BRIAN-activity (r = 0.64), K-BRIAN-social (r = 0.71), and K-BRIAN-eating (r = 0.40)). These correlations were especially pronounced in the recurrent episode group, suggesting that with the progression and chronicity of depression, the relationship between circadian rhythms and depression becomes more intertwined and evident. In conclusion, especially in adolescents, as the severity and chronicity of depression increase, the interplay between circadian rhythms and mood disorders becomes more pronounced, warranting further research and clinical attention.

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.

Implication of findings from a two-wave survey on embitterment in South Korea for strategies to promote mental health of the general public.

OBJECTIVE: To examine the prevalence of embitterment by following individuals over time and to statistically evaluate how factors known as correlates of embitterment affect different groups with or without changes in embitterment over time. METHOD: Responses for the posttraumatic embitterment disorder (PTED) self-rating Scale were collected from the same 1,153 adults who participated in a follow-up survey delivered 14 months apart. Suggested cutoff points were applied to identify changes in embitterment and four groups were identified. For each group, the relative impacts of factors that affect changes in or maintenance of embitterment, such as negative life events (NLEs), belief in a just world (BJW), social support, relative deprivation, and resilience, were statistically analyzed. RESULTS: The average PTED scores were relatively high for both surveys (M = 1.73 and 1.58, respectively). "Persistent" or "increased" in embitterment was seen for 47.3% of the participants. In particular, 15.3% (Wave 1) and 12.1% (Wave 2) of participants experienced clinically relevant levels of embitterment. NLEs, BJW, relative deprivation, and resilience showed significant associations with the risk of persistence or deterioration of embitterment. CONCLUSIONS: Our study highlights embitterment as a dynamic emotion that can either be aggravated or moderated over time. Embitterment can be elicited by joint effects of multiple social and interactional factors including known embitterment correlates, and relative deprivation is confirmed as a possible core elicitor of embitterment in the context of comparative justice. These findings imply that additional longitudinal research and development of practices for mental health prevention in general populations are needed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Reliability and Validity of the Korean Version of the Brief Resilience Scale.

Objective: : To translate the Brief Resilience Scale into Korean and evaluate its reliability and validity. Methods: : To investigate the factor structure of the Brief Resilience Scale, we examined a two-factor model comprising positively and negatively worded items. Congruent and divergent validity of the Brief Resilience Scale were investigated using correlation analysis between the Brief Resilience Scale and resilience, depression, and perceived stress. By conducting an analysis of variance among groups classified by suicidality (no suicidality, only suicidal ideation, and suicidal ideation or suicidal plan groups), we evaluated how well the Brief Resilience Scale could detect people with a high risk of suicide. Results: : Confirmatory factor analysis results supported the construct validity of the Brief Resilience Scale using a two-factor model. Cronbach's alpha (0.91) and McDonald's omega (0.91) scores indicated high internal consistency. Correlation analysis showed that the Brief Resilience Scale scores were strongly associated with a questionnaire evaluating resilience, depression, and perceived stress. Analysis of variance and post-hoc tests showed that he Brief Resilience Scale scores were highest in the no suicidality group (p ＜ 0.001). Conclusion: : The Korean version of the Brief Resilience Scale is a valid and reliable instrument for evaluating resilience as the capacity to recover from adversity and endure obstacles or stress. This study also provides important evidence regarding the sensitivity of the Brief Resilience Scale to suicidal risk.

Development of a Korean Version of the Child Mania Rating Scale: Korean Validity and Reliability Study.

OBJECTIVE: Clinical rating scales are essential in psychiatry. The Young Mania Rating Scale is the gold standard for assessing mania. However, increased attention to pediatric bipolar disorder has led to the development of the Child Mania Rating Scale (CMRS), which is a parent-reported rating scale designed to assess mania in children and adolescents. This study aimed to translate the CMRS into Korean and assess the validity and reliability of the Korean version of the CMRS (K-CMRS). METHODS: The original English version of the CMRS has been translated into Korean. We enrolled 33 patients with bipolar disorder and 26 patients with attention-deficit hyperactivity disorder (ADHD). All participants were evaluated using the translated K-CMRS, Mood Disorder Questionnaire (MDQ), and ADHD Rating Scale. RESULTS: The Cronbach's α was 0.907. Correlation analyses between K-CMRS and MDQ scores yielded significant positive correlations (r=0.529, p=0.009). However, the factor analysis was unsuccessful. The total K-CMRS scores of bipolar disorder and ADHD patients were compared. However, the differences were not statistically significant. CONCLUSION: The K-CMRS showed good internal consistency and reliability. The correlation between the K-CMRS and MDQ scores verifies its validity. The K-CMRS was designed to assess and score manic symptoms in children and adolescents but had difficulties in differentiating between bipolar disorder and ADHD. It is a valuable tool for evaluating the presence and severity of manic symptoms in pediatric patients with bipolar disorder.

Functional connectivity and network analysis in adolescents with major depressive disorder showing suicidal behavior.

BACKGROUND: This study aimed to gather a homogeneous sample of adolescent patients to analyze the differences in functional connectivity and brain network parameters between suicidal and non-suicidal major depressive disorder (MDD) patients using a data-driven whole-brain approach. METHODS: Patients recruited at the psychiatry department of Korea University Guro Hospital from November 2014 to March 2020 were diagnosed with MDD, were 13-18 years old, had IQ scores >80, had no family history of psychotic or personality disorders, had no smoking or alcohol consumption history, and were drug-naïve to psychotropic medication. Depressive symptoms were assessed using the Hamilton Depression Rating Scale and the Children's Depression Inventory. Structural and functional MRI scans were conducted and analyzed using the CONN toolbox. RESULTS: Of 74 enrolled patients, 62 were analyzed. Regions of interest (ROIs) showing higher betweenness centrality in non-suicidal patients were the left superior temporal gyrus and left supramarginal gyrus. ROIs showing higher betweenness centrality in suicidal patients were the right hippocampus, left intracalcarine cortex, right inferior temporal gyrus, and the lateral visual network. Suicidal patients also showed different resting state functional connectivity profiles from non-suicidal patients. LIMITATIONS: Small sample size. CONCLUSION: Suicidal patients may overthink and overvalue future risks while having a more negatively biased autobiographical memory. Social cognition and the ability to overcome egocentricity bias seem to weaken. Such features can disrupt cognitive recovery and resilience, leading to more suicidal behaviors. Therefore, increased suicidality is not acquired, but is an innate trait.

Additional Clinical Benefit of Agomelatine Treatment for Major Depressive Disorder in Naturalistic Treatment Setting.

Objective: This study tried to observe additional benefit of agomelatine (AGO) treatment for major depressive disorder (MDD) in routine practice. Methods: Retrospective chart review (n = 63) was conducted for additional benefit of combination with or switching to AGO in MDD patients without full remission. The primary endpoint was the mean change of Clinical Global Impression-Clinical Benefit (CGI-CB) total scores from baseline to the endpoint. Additional secondary endpoints were also collected. Results: The changes of CGI-CB (Z = -3.073, p = 0.002) and Montgomery-Åsberg Depression Rating Scale (Z = -3.483, p < 0.001) total scores were significantly decreased from baseline to the endpoint, respectively. At the endpoint, the remission rate was 22.6% (n = 18) and 28.6% of patient had improvement in CGI-CB total scores at the endpoint. No significant adverse events were observed. Conclusion: This study has shown additional benefit of AGO treatment as combination or switching agent for MDD patients without full remission in routine practice. However, adequately-powered and well-controlled studies are necessary for generalization of the present findings.

Antidepressant-induced mania in panic disorder: a single-case study of clinical and functional connectivity characteristics.

Background: Mental health issues, including panic disorder (PD), are prevalent and often co-occur with anxiety and bipolar disorders. While panic disorder is characterized by unexpected panic attacks, and its treatment often involves antidepressants, there is a 20-40% risk of inducing mania (antidepressant-induced mania) during treatment, making it crucial to understand mania risk factors. However, research on clinical and neurological characteristics of patients with anxiety disorders who develop mania is limited. Methods: In this single case study, we conducted a larger prospective study on panic disorder, comparing baseline data between one patient who developed mania (PD-manic) and others who did not (PD-NM group). We enrolled 27 patients with panic disorder and 30 healthy controls (HCs) and examined alterations in amygdala-based brain connectivity using a seed-based whole-brain approach. We also performed exploratory comparisons with healthy controls using ROI-to-ROI analyses and conducted statistical inferences at a threshold of cluster-level family-wise error-corrected p < 0.05, with the cluster-forming threshold at the voxel level of uncorrected p < 0.001. Results: The patient with PD-mania showed lower connectivity in brain regions related to the default mode network (left precuneous cortex, maximum z-value within the cluster = -6.99) and frontoparietal network (right middle frontal gyrus, maximum z-value within the cluster = -7.38; two regions in left supramarginal gyrus, maximum z-value within the cluster = -5.02 and -5.86), and higher in brain regions associated with visual processing network (right lingual gyrus, maximum z-value within the cluster = 7.86; right lateral occipital cortex, maximum z-value within the cluster = 8.09; right medial temporal gyrus, maximum z-value within the cluster = 8.16) in the patient with PD-mania compared to the PD-NM group. One significantly identified cluster, the left medial temporal gyrus (maximum z-value within the cluster = 5.82), presented higher resting-state functional connectivity with the right amygdala. Additionally, ROI-to-ROI analysis revealed that significant clusters between PD-manic and PD-NM groups differed from HCs in the PD-manic group but not in the PD-NM group. Conclusion: Here, we demonstrate altered amygdala-DMN and amygdala-FPN connectivity in the PD-manic patient, as reported in bipolar disorder (hypo) manic episodes. Our study suggests that amygdala-based resting-state functional connectivity could serve as a potential biomarker for antidepressant-induced mania in panic disorder patients. Our findings provide an advance in understanding the neurological basis of antidepressant-induced mania, but further research with larger cohorts and more cases is necessary for a broader perspective on this issue.

Associations between Pharmacological Treatment Patterns during the Initial Treatment Period and the Relapse or Recurrence of Anxiety Disorders: A Nationwide Retrospective Cohort Study.

Although the importance of proper pharmacological treatment for preventing the relapse/recurrence of anxiety disorders is well known, a real-world data-based study has not been conducted. We aimed to investigate the effect of the initial pharmacological patterns related to continuous treatment and the choice of medication on the relapse/recurrence of anxiety disorders. We used claim data from the Health Insurance Review and Assessment Service, South Korea, of 34,378 adults who received psychiatric medications, including antidepressants, after being newly diagnosed with anxiety disorders. We compared the relapse/recurrence rate in the patients receiving continuous pharmacological treatment with those who discontinued treatment early using Cox's proportional-hazards model. Patients receiving continuous pharmacological treatment experienced a higher risk of relapse/recurrence than those who discontinued treatment. Using three or more antidepressants during the initial treatment period decreased the risk of relapse/recurrence (adjusted hazard ratio (aHR) = 0.229 (0.204-0.256)); however, the combined use of antidepressants from the beginning of treatment increased the risk (aHR = 1.215 (1.131-1.305)). Factors other than continuous pharmacological treatment should be considered to effectively prevent the relapse/recurrence of anxiety disorders. The active use of antidepressants, including switching or adding medications based on progress and frequent follow-up visits during the acute phase, were significantly associated with a reduction in the relapse/recurrence of anxiety disorders.

Impact of the Coronavirus Disease Pandemic on Mental Health Among School Students in Korea During the COVID-19 Pandemic.

Objectives: The coronavirus disease (COVID-19) pandemic has had various effects on mankind, especially children and adolescents. Because children and adolescents spend a lot of time at school, COVID-19 has had a great impact on school mental health. In this study, we investigated the effect of prolonged COVID-19 on school mental health. Methods: We prepared self-report questionnaires for depression (Children's Depression Inventory, CDI), anxiety (Korean version of the Penn State Worry Questionnaire for Children; Generalized Anxiety Disorder-7, GAD-7), and post-traumatic stress (Primary Care Post-traumatic Stress Disorder, PC-PTSD) for administering to students aged between 7 and 18 years, recruited by a COVID-19 psychological prevention support group in the Gwangmyeong Mental Health Welfare Center for 2 years, in 2020 and 2021. Results: For children aged 7-12 years, there was no significant difference between the years 2020 and 2021 in the assessment of depression, anxiety, and post-traumatic stress. Conversely, for adolescents aged 13-18 years, there was a significant increase in the scale scores (CDI, PC-PTSD, and GAD-7). Conclusion: Prolonged COVID-19 might have had a significant impact on the mental health of adolescents who spent a lot of time at school. When comparing the years 2020 and 2021, middle and high school students were more affected by COVID-19 than elementary school students.

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

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

Feasibility of the virtual reality-based assessments in patients with panic disorder.

Introduction: Recurrences and diagnostic instability of panic disorder (PD) are common and have a negative effect on its long-term course. Developing a novel assessment tool for anxiety that can be used in a multimodal approach may improve these problems in panic disorder patients. This study assessed the feasibility of virtual reality-based assessment in panic disorder (VRA-PD). Methods: Twenty-five patients with PD (ANX group) and 28 healthy adults (CON group) participated in the study. VRA-PD consisted of four modules based on the key components of cognitive behavior therapy for an anxiety disorder: "Baseline evaluation module" (M0), "Daily environment exposure module" (M1), "Relaxation module" (M2), and "Interoceptive exposure module" (M3). Multiple evaluations, including self-rating anxiety scores (AS) and physiological responses [heart rate variability (HRV) index], were performed in three steps at M1, M2, and M3, and once at M0. Comparisons between patients with PD and healthy controls, factor analysis of variables in VRA-PD, changes in responses within modules, and correlation analysis between variables in VRA-PD and anxiety symptoms assessed by psychological scales were performed. Results: All participants completed the VRA-PD without discontinuation. The ANX group reported significantly higher AS for all steps and a smaller HRV index in M1 (steps 1 and 2) and M2 (step 1). Repeated-measures analysis of covariance (ANCOVA) revealed significant interaction effects for AS in M1 (F = 4.09, p = 0.02) and M2 (F = 4.20, p = 0.02), and HRV index in M2 (F = 16.22, p < 0.001) and M3 (F = 21.22, p = 0.02). The HRV index only indicated a good model fit for the three-factor model, reflecting the construct of the VRA-PD. Both AS and HRV indexes were significantly correlated with anxiety and depression symptoms. Discussion: The current study provides preliminary evidence that the VRA-PD could be a valid anxiety behavior assessment tool.

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

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

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

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

Altered TIMP-3 Levels in the Cerebrospinal Fluid and Plasma of Patients with Alzheimer's Disease.

Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment and is suggested to play an indirect role in regulating Aß production and the pathophysiology of Aß 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.

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

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