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.

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.

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.

Formula for predicting OSA and the Apnea-Hypopnea Index in Koreans with suspected OSA using clinical, anthropometric, and cephalometric variables.

PURPOSE: This study developed formulas to predict obstructive sleep apnea (OSA) and the Apnea-Hypopnea Index (AHI) in Korean patients with suspected OSA using clinical, anthropometric, and cephalometric variables. METHODS: We evaluated relevant variables in 285 subjects with suspected OSA. These included demographic characteristics, sleep-related symptoms, medical history, clinical scales, anthropometric measurements including facial surface measurements, and cephalometric measurements. All participants underwent full-night laboratory polysomnography. The prediction formula for the probability of OSA was created by logistic regression analysis and confirmed by the bootstrap resampling technique. The formula for predicting the AHI was developed using multiple linear regression analysis. RESULTS: The probability of having OSA was as follows: p = 1 / (1 + exponential (exp)-f ), where f = -16.508 + 1.445 × loudness of snoring 4 + 0.485 × loudness of snoring 3 + 0.078 × waist circumference + 0.209 × subnasale-to-stomion distance + 0.183 × thickness of the uvula (UTH) supine + 0.041 × age. The AHI prediction formula was as follows: -112.606 + 3.516 × body mass index + 0.683 × mandibular plane-hyoid supine + 10.915 × loudness of snoring 4 + 6.933 × loudness of snoring 3 + 1.297 × UTH supine + 0.272 × age. CONCLUSION: This is the first study to establish formulas to predict OSA and the AHI in Koreans with suspected OSA using cephalometric and other variables. These results will contribute to prioritizing the order in which patients with suspected OSA are referred for polysomnography.

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.

A 13-week, randomized double-blind, placebo-controlled, cross-over trial of ziprasidone in bipolar spectrum disorder.

OBJECTIVE: Features of bipolarity in a major depressive disorder sample were used to define a "bipolar spectrum disorder" population for treatment with a neuroleptic agent, ziprasidone. METHODS: Forty-nine acutely depressed patients were randomized to ziprasidone-washout-placebo or placebo-washout-ziprasidone in this double-blind, prospective, 13-week crossover trial. All patients met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for a major depressive episode and were positive for at least 3 predictors of bipolarity: family history of bipolar disorder, antidepressant-induced mania, highly recurrent depressive episodes (>5), atypical depression, early onset of depression (

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.

The influence of AHI1 variants on the diagnosis and treatment outcome in schizophrenia.

The present study aimed to explore whether four single nucleotide polymorphisms (SNPs) within the AHI1 gene could be associated with schizophrenia (SCZ) and whether they could predict the clinical outcomes in SCZ patients treated with antipsychotics. Four hundred twenty-six (426) in-patients with SCZ and 345 controls were genotyped for four AHI1 SNPs (rs11154801, rs7750586, rs9647635 and rs9321501). Baseline and clinical measures for SCZ patients were assessed through the Positive and Negative Syndrome Scale (PANSS). Allelic and genotypic frequencies in SCZ subjects were compared with those of controls using the χ2 statistics. The repeated-measure ANOVA was used for the assessment of treatment outcomes measured by PANSS changes. The case-control analysis did not show any difference in the genotypic distribution of the SNPs, while in the allelic analysis, a weak association was found between the rs9647635 A allele and SCZ. Furthermore, in the haplotype analysis, three haplotypes resulted in being associated with SCZ. On the other hand, two SNPs (rs7750586 and rs9647635) were associated with clinical improvement of negative symptoms in the allelic analysis, although in the genotypic analysis, only trends of association were found for the same SNPs. Our findings suggest a possible influence of AHI1 variants on SCZ susceptibility and antipsychotic response, particularly concerning negative symptomatology. Subsequent well-designed studies would be mandatory to confirm our results due to the methodological shortcomings of the present study.

Efficacy and safety of selegiline transdermal system (STS) for the atypical subtype of major depressive disorder: pooled analysis of 5 short-term, placebo-controlled trials.

OBJECTIVE: The objective of the present study is to investigate the efficacy and safety of the selegiline transdermal system (STS) in major depressive disorder (MDD) with atypical features. METHODS: This was a post-hoc analysis of 5 short-term trials. The atypical subtype was defined as the presence of at least 1 item with a score of 2 or greater from items 22-26 on the 28-item Hamilton Depression Rating Scale (HAMD-28), and a maximum score of 1 point for items 6 (insomnia late), 12 (somatic symptoms, gastrointestinal), and 16 (loss of weight) to exclude vegetative features of melancholic depression. The mean changes of HAMD-28 total score from baseline to the endpoint (response rate defined as ≥50% reduction in HAMD-28 scores and remission rate defined as ≤10 HAMD-28 total score at the treatment endpoint) were compared between atypical and nonatypical groups. RESULTS: In this analysis, 352 subjects (STS = 168 vs placebo = 184) met the definition of atypical subtype at baseline. STS (n = 641) significantly decreased HAMD-28 total score compared with placebo (n = 648) from beginning to end of treatment (-10.7 ± 9.3 vs -9.4 ± 9.3; p = 0.014). STS showed comparable efficacy in patients with the atypical subtype compared with the nonatypical subtype for placebo-subtracted mean change in HAMD-28 total score (-2.11 ± 1.01 vs. -1.0 ± 0.60; p = 0.34), odds ratio (OR) for response (1.41 vs 1.23, p = 0.62), and OR for remission (1.77 vs 1.18, p = 0.22). CONCLUSION: STS appears to be comparably efficacious and tolerable in atypical and nonatypical subtypes of MDD. Adequately powered, controlled, clinical trials are necessary to confirm our findings.

The influence of depression, anxiety and somatization on the clinical symptoms and treatment response in patients with symptoms of lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

This is the first study to investigate the influence of depression, anxiety and somatization on the treatment response for lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). The LUTS/BPH patients were evaluated with the Korean versions of the International Prostate Symptom Score (IPSS), the Patient Health Questionnaire-9 (PHQ-9), the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the PHQ-15. The primary endpoint was a responder rate defined by the total score of IPSS (≤ 7) at the end of treatment. The LUTS/BPH severity was significantly higher in patients with depression (whole symptoms P = 0.024; storage sub-symptom P = 0.021) or somatization (P = 0.024) than in those without, while the quality of life (QOL) was significantly higher in patients with anxiety (P = 0.038) than in those without. Anxious patients showed significantly higher proportion of non-response (odds ratio [OR], 3.294, P = 0.022) than those without, while somatic patients had a trend toward having more non-responders (OR, 2.552, P = 0.067). Our exploratory results suggest that depression, anxiety and somatization may have some influences on the clinical manifestation of LUTS/BPH. Further, anxious patients had a lower response to treatment in patients with LUTS/BPH. Despite of limitations, the present study demonstrates that clinicians may need careful evaluation of psychiatric symptoms for proper management of patients with LUTS/BPH.

The relationship between somatic symptoms and depression.

OBJECTIVE: We investigated the influence of somatic symptoms on the severity and clinical outcomes in female Korean patients with major depressive disorder (MDD) in routine practice. METHODS: Two hundred and seven female patients with MDD were prospectively recruited. Patients with somatic symptoms (PSS) was defined as a total score ≥ 10 on the Patient Health Questionnaire-15 (PHQ-15), others were classified as non PSS (NPSS). The PHQ-9 for de-pression, the Generalized Anxiety Disorder Scale (GAD-7) for anxiety, the Clinical Global Impression-Severity (CGI-S) for clinical status, and the Visual Analogue Scale (VAS) for health status were utilised. RESULTS: Of 207 participants, 126 (60.9%) were PSS and 81 (39.1%) were classified as NPSS. The proportion of patients showing severe symptoms (65.1% vs. 24.7%) and recurrence of depression (74.6% vs. 49.4%), the CGI-S (4.6 vs. 4.1), the PHQ-9 (16.8 vs. 11.1), and the GAD-7 (8.3 vs 6.7) scores were significantly higher in PSS than in NPSS, while the VAS (39.4 vs. 51.2) was significantly lower in PSS than in NPSS. The improvement of depressive symptoms (-1.3 vs. -2.0) measured by the changes in CGI-S was also significantly less in PSS than in NPSS after 6 months treatment. CONCLUSION: Our findings have shown the significant impact of somatic symptoms on the symptomatology as well as treatment outcomes in Korean female patients with MDD, indicating that clinicians should carefully evaluate somatic symptoms in patients with MDD in routine clinical practice. Due to the methodological shortcomings of the present study, further adequately powered and well-designed investigations are necessary.

The predictor analysis of response to routine treatment in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVE: This study tried to test predictors of response to routine treatment in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). METHODS: Subjects were evaluated at baseline and at week 12 following routine treatment for LUTS/BPH using the Korean version of the International Prostate Symptom Score (IPSS) to measure the severity of LUTS/BPH. Demographics and various clinical variables were analyzed by regression analysis. RESULTS: Ninety three patients received routine treatment for LUTS/BPH for 12 weeks in a naturalistic treatment setting. None of demographics and clinical variables was different between responders and non-responders. According to multivariate regression analysis, the presence of anxiety (OR=0.203), lower improvement in the GAD-7 total score (OR=0.755) and lower improvement in the PHQ-15 total score (OR=0.811) were independent predictors of treatment response after 12 weeks routine treatment. CONCLUSIONS: We found the positive association of improvement in anxiety and somatization with treatment response, while presence of anxiety was negatively associated with treatment response, in patients with LUTS/BPH. However, additional studies with adequate power and improved designs are necessary to support the present findings.

Usefulness of the Patient Health Questionnaire-9 for Korean medical students.

OBJECTIVE: Depression may be highly prevalent among medical students, lowering their functioning and quality of life. Using appropriate extant depression scales to screen for depression and determining factors associated with depression can be helpful in managing it. This study examines the validity and reliability of the Patient Health Questionnaire-9 (PHQ-9) for medical students and the relationship between their scores and sociodemographic variables. METHODS: This study surveyed 174 medical students using demographic questionnaires, the PHQ-9, the Beck Depression Inventory (BDI), the Patient Heath Questionnaire-15 (PHQ-15), the Beck Anxiety Inventory (BAI), and the Perceived Stress Scale (PSS). It calculated the Cronbach's α for internal consistency and Pearson's correlation coefficients for test-retest reliability and convergent validity of the PHQ-9. In order to examine the relationship between depression and demographic variables, this study performed independent t tests, one-way analysis of variance, chi-square, and binary logistic regressions. RESULTS: The PHQ-9 was reliable (Cronbach's α = 0.837, test-retest reliability, r = 0.650) and valid (r = 0.509-0.807) when employed with medical students. Total scores on the PHQ-9 were significantly higher among low-perceived academic achievers than among high-perceived academic achievers (p < 0.01). Depression was more prevalent in poor-perceived academic achievers than in high-perceived academic achievers. Similarly, poor-perceived academic achievers were at greater risk of depression than were high-perceived academic achievers (odds ratio [95 % confidence interval] 3.686 [1.092-12.439], p < 0.05). CONCLUSIONS: The PHQ-9 has satisfactory reliability and validity in medical students in South Korea. Depression is related to poor-perceived academic achievement when measured with the PHQ-9. Early screening for depression with the PHQ-9 in medical students and providing prompt management to high scorers may not only be beneficial to students' mental health but also improve their academic performance.

Lack of influence of rs4680 (COMT) and rs6276 (DRD2) on diagnosis and clinical outcomes in patients with major depression.

OBJECTIVE: The gene coding for the catechol-O-methyltransferase (COMT) and the one coding for the dopamine receptor 2 (DRD2) have been linked with major depression (MD) and with the response to antidepressants in several studies. However, contrasting findings have been reported as well. The aim of the present study is, therefore, to investigate possible influences of rs4680 within COMT and rs6276 within DRD2, analyzed both individually and in combination, on the diagnosis and clinical outcomes in a sample of Korean MD patients treated with antidepressants. METHODS: Totally, 184 Korean in-patients suffering from MD treated with either paroxetine or venlafaxine and 220 healthy control subjects were included in the present study. Depression severity was assessed by means of the Hamilton Rating Scale for Depression. RESULTS: We were not able to find any association between the two variants under investigation and diagnosis of MD, as well as with antidepressant response. CONCLUSIONS: Although limited by several factors, including the small sample size and the impossibility to extend our findings to patients treated with different antidepressants, the results of our study provide support to the notion that these variants might not play a major role in the etiology and clinical outcomes of MD.

Current Understanding on Psilocybin for Major Depressive Disorder: A Review Focusing on Clinical Trials.

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a "breakthrough therapy" for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin's potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials [DB-RCTs]) trials exploring psilocybin's impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over six months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.

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.