The prevalence and clinical characteristics of depressive disorders differ between women and men; however, the genetic contribution to sex differences in depressive disorders has not been elucidated. ...To evaluate sex-specific differences in the genetic architecture of depression, whole exome sequencing of samples from 1000 patients (70.7% female) with depressive disorder was conducted. Control data from healthy individuals with no psychiatric disorder (n = 72, 26.4% female) and East-Asian subpopulation 1000 Genome Project data (n = 207, 50.7% female) were included. The genetic variation between men and women was directly compared using both qualitative and quantitative research designs. Qualitative analysis identified five genetic markers potentially associated with increased risk of depressive disorder in females, including three variants (rs201432982 within PDE4A, and rs62640397 and rs79442975 within FDX1L) mapping to chromosome 19p13.2 and two novel variants (rs820182 and rs820148) within MYO15B at the chromosome 17p25.1 locus. Depressed patients homozygous for these variants showed more severe depressive symptoms and higher suicidality than those who were not homozygotes (i.e., heterozygotes and homozygotes for the non-associated allele). Quantitative analysis demonstrated that the genetic burden of protein-truncating and deleterious variants was higher in males than females, even after permutation testing. Our study provides novel genetic evidence that the higher prevalence of depressive disorders in women may be attributable to inherited variants.
Cortisol, a steroid hormone, is a main biomarker of psychological stress. Early diagnosis and proper treatment of such stress is crucial to prevent the excessive secretion of cortisol. However, ...cortisol has a low molecular weight and cannot provide sufficient recognition sites for sandwich immunoreaction; it has previously been measured using a competitive immunoassay instead of a general sandwich immunoassay. The disadvantage of this approach is that quantitative measurements are limited because of the narrow measurable range that is key for biosensors. To overcome this limitation, we propose a new detection platform that enables small molecules such as cortisol to be quantified with high detection sensitivity. A trap lateral flow immunoassay (trapLFI) sensor has deletion and detection zones instead of the test and control zones in general lateral flow immunoassay (LFI) sensors. The conjugates used to minimize possible detection targets at low concentration are gold nanoparticles that include an antibody against cortisol and an enzyme for signal generation. Target-bound conjugates are captured in the detection zone, whereas conjugates not binding with targets are trapped in the deletion zone. Using this platform, enzyme-catalyzed color signals increase in the detection zone and decrease in the deletion zone with the concentration of cortisol. The ratio of signal from deletion zone and detection zone supplied a wide analytical range (0.01-100 ng mL-1) with high detection sensitivity (9.9 pg mL-1). Analysis of 15 human saliva samples showed a good correlation with conventional ELISA results (R2 = 0.9432).
The risk of depression has risen in the general population during the COVID-19 epidemic. This study was conducted to explore risk and protective factors associated with depression among the general ...population uninfected by COVID-19.
A cross-sectional study was conducted with 1,500 representative South Korean citizens aged 19-65 years through an anonymous online survey. Depression was defined as a Patient Health Questionnaire-9 score of 10 or higher. Other questionnaires included one measuring psycho-behavioural and social changes, and stress, due to COVID-19, a six-item version of the Gratitude Questionnaire (GQ-6), and a three-item version of the UCLA loneliness scale.
Of the 1492 participants not infected by COVID-19, 312 (20.9%) exhibited depression. Multiple logistic regression analysis revealed that depression was positively associated with COVID-19-related stress and psycho-behavioural variables such as disturbances in eating and sleeping, younger age, smoking, underlying mental illness, and loneliness scale scores. In contrast, exercise three or more times per week and GQ-6 scale scores were inversely associated with depression.
During the COVID-19 pandemic, maintaining daily routines including eating, sleeping, and regular exercise and focusing on gratitude may be important for the prevention of depression. In addition, more attention should be paid to vulnerable populations, including young people, those with mental illnesses, and smokers, who might be more susceptible to depression.
Statins, which are widely used to treat hypercholesterolemia, have anti-inflammatory and anti-oxidant effects. These are thought to be responsible for the potential effects of statins on various ...psychiatric disorders. In this study, we comprehensively review the literature to investigate the effects of statins on various psychiatric disorders including depression, schizophrenia, and dementia. In addition, we review adverse effects and drug interactions of statins to give clinically useful information guiding statin use in the psychiatric field. Statins seem useful in reducing depression, particularly in patients with physical disorders such as cardiovascular disease. In patients with schizophrenia, negative symptoms may be reduced by adjuvant statin therapy. Studies on cohorts at risk for dementia have generally shown protective effects of statins, while those on treatment for dementia show inconsistent results. In conclusion, statins used in combination with conventional psychotropic medications may be effective for various psychiatric disorders including depression, schizophrenia, and dementia. Further study is required to determine optimal doses and duration of statin use for the treatment of psychiatric disorders.
The dramatic changes in people's daily lives caused by the 2019 coronavirus (COVID-19) pandemic have had a huge impact on their emotions and behaviors. This study aimed to examine psychosocial ...responses to COVID-19 using network analysis. A total of 1,500 urban residents of South Korea, selected from an online public panel, were surveyed using self-rating questionnaires addressing daily life changes, fear of infection, and distress related to COVID-19. Participants also completed a 10-item Perceived Stress Scale survey. We constructed regularized partial correlation networks, estimated global and local network metrics, tested network accuracy and stability, and compared the estimated networks between men and women. The network of the psychosocial responses consisted of 24 nodes that were classified into five groups: 'fear of infection', 'difficulty with outside activities', 'economic loss', 'altered eating and sleeping', and 'adaptive stress'. The node centralities indicated that 'distress in obtaining daily necessities' and 'concern about harming others' were the most important issues in people's responses to COVID-19. These nodes were connected by a negative edge, reflecting individual- and community-level issues, respectively. The overall level of perceived stress was linked to the network by the connection node 'anger toward others or society', which was associated with economic problems in men, but with distress from changes in daily activities in women. The results suggest that two contrasting feelings-personal insecurity regarding basic needs and a collectivistic orientation-play roles in the response to unusual experiences and distress due to COVID-19. This study also showed that public anger could arise from the psychological stress under the conditions imposed by COVID-19.
Objectives
This study aimed to investigate whether acute and chronic poststroke depression (PSD) were associated with cardio–cerebrovascular events (CVEs).
Methods
A total of 423 patients with recent ...stroke were recruited from 2006 to 2009. They were diagnosed with major or minor depressive disorder during the acute phase (within 2 weeks) after stroke. Of these, 284 completed the same diagnostic evaluation during the chronic phase (1 year) after stroke. An average 12‐year (range 8.7–14.1 years) follow‐up was conducted to assess composite CVEs including recurrent stroke, myocardial infarction, and vascular death after the index stroke. During the follow‐up, Kaplan–Meier event rates for outcomes were calculated, and hazard ratios were estimated using Cox regression models after adjusting for a range of covariates.
Results
The composite CVE incidence was higher in patients with acute or chronic PSD than in those without. Composite event incidence was highest in patients with PSD during both the acute and chronic phases.
Conclusions
The presence of depression at acute and chronic phase of stroke predicted worse long‐term cardio–cerebrovascular outcomes. Evaluation of PSD during both the acute and chronic phases is recommended.
Key points
Acute or chronic phase poststroke depression (PSD) is associated with higher risk of composite cardio–cerebrovascular events.
Persistent PSD leads to worse long‐term outcomes.
PSD should continuously be evaluated in the late as well as acute phase.
This study investigated the potential modifying effects of the level of the serum interleukin-18 (IL-18) on the association between
methylation status and long-term cardiovascular outcomes in ...patients with acute coronary syndrome (ACS). Hospitalized ACS patients were recruited sequentially from 2006 to 2012. At baseline, the IL-18 level and
methylation status were evaluated in 969 patients who were followed for major adverse cardiac events (MACEs) for 5-12 years, until 2017 or death. The time to first composite or individual MACE was compared between individuals with lower and higher average
methylation levels (in the low- and high-IL-18 groups, respectively) using a Cox proportional hazards model. After adjusting for potential covariates, the modifying effects of IL-18 and average
methylation levels on the initial composite and individual MACEs were examined. In the high-IL-18 group, but not in the low-IL-18 group, a higher average
methylation level was associated with increases in composite MACEs (HR (95% CI) = 2.15 (1.42-3.26)), all-cause mortality (HR (95% CI) = 1.89 (1.11-3.22)), myocardial infarction (HR (95% CI) = 1.98 (1.07-3.67)), and percutaneous coronary intervention (HR (95% CI) = 1.81 (1.01-3.23)), independent of confounding variables. The interaction effect between the IL-18 and average
methylation levels on composite MACEs (
= 0.019) and myocardial infarction (
= 0.027) was significant after adjusting for covariates. Analysis of
methylation status and IL-18 levels may help identify ACS patients who are most likely to have adverse clinical outcomes.
Acute coronary syndrome (ACS) is related to an increased risk of suicide. Although both diabetes and the brain-derived neurotrophic factor (BDNF) pathway are closely associated with ACS and suicide, ...the effects of these factors on suicidal behavior in ACS patients have not been assessed. We investigated the individual and interaction effects of diabetes and BDNF-related markers, namely the serum BDNF (sBDNF) level and the BDNF Val66Met polymorphism, on suicidal ideation (SI) in ACS patients. The presence of diabetes was ascertained, and sBDNF levels and the presence of the BDNF Val66Met polymorphism were measured in 969 patients within 2 weeks after an ACS episode. 711 patients were followed up at 1 year after the ACS episode. SI was assessed using the relevant items of the Montgomery-Åsberg Depression Rating Scale at baseline (acute SI) and the 1-year follow-up (chronic SI). Significant individual effects of low sBDNF levels were found on acute SI. The presence of both diabetes and a low sBDNF level or the BDNF Met/Met genotype was associated with acute SI, with multivariate logistic regression analyses revealing significant interaction effects. The highest frequency of chronic SI was seen in diabetic patients with an sBDNF level in the lowest tertile or with the BDNF Met/Met genotype, although the interaction terms were not statistically significant. Our study suggests that the combination of diabetes and BDNF-related markers, such as the sBDNF level and the BDNF Val66Met polymorphism, might provide a useful predictor of acute SI in ACS patients.
Despite the recognized antidepressant role of serotonin (5-hydroxytryptamine 5-HT) signaling pathways in the central nervous system, the association between baseline peripheral 5-HT level and the ...antidepressant treatment response in clinical studies remains debatable. We investigated the interaction effects of baseline serum 5-HT level and age on the 12-week remission in outpatients with depressive disorders who received stepwise antidepressant treatment. Baseline serum serotonin levels were measured and the age of 1094 patients recorded. The patients received initial antidepressant monotherapy; then, patients with an insufficient response or who experienced uncomfortable side effects received alternative treatments every 3 weeks (3, 6, and 9 weeks). Subsequently, 12-week remission, defined as a Hamilton Depression Rating Scale (HAMD) score of ≤ 7, was evaluated. Individual and interaction effects of serum 5-HT level (as a binary low vs. high, based on the median value of 72.6 ng/mL or continuous variable) and age (as a binary < 60 vs. ≥ 60 years or continuous variable) on the 12-week remission rate were analyzed using logistic regression models after adjusting for relevant covariates. High 5-HT (≥ 72.6 ng/mL) and age ≥ 60 years were associated with the highest 12-week remission rates and a significant multiplicative interaction effect. The interaction effect of the two variables on the 12-week remission rate was significant even when analyzed as a continuous variable. Our study suggests that the association between baseline serum 5-HT level and 12-week antidepressant treatment outcomes differs according to patient age.
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