Patients with major depression are at increased risk for suicide, and suicidal behavior can be manifested as a symptom of depression. Although the mechanism of suicidal behaviors in patients with depression is not fully understood, numerous attempts have been made to explain it over the past decades. This chapter aims to describe the genetic, psychological, and neurobiological aspects of suicidal behavior in major depression.

BACKGROUND The incidence and prognostic implications of mental disorders after implantable cardioverterdefibrillator (ICD) therapy remain underexplored. OBJECTIVES This study sought to investigate the incidence of newly diagnosed mental disorders after ICD implantation compared with the incidence in matched non-ICD control subjects and to evaluate the impact of these disorders on prognosis. METHODS Using the Korean National Health Insurance Service database, 6,356 patients with an ICD and 17,664 propensity score-matched control subjects were selected between 2010 and 2020. In the ICD group, long-term prognosis was compared between patients with and without mental disorders newly diagnosed postimplantation. RESULTS The 10-year cumulative incidence of newly diagnosed mental disorders was 37.3% in ICD patients, significantly higher than in the matched control subjects (34.5%; HR: 1.21; 95% CI: 1.14-1.29). The most frequent mental disorders were depressive disorder (18.4%), insomnia (16.8%), and anxiety disorder (5.8%). Among ICD patients, newly diagnosed mental disorders adversely affected long-term prognosis, with significantly higher all-cause mortality (HR: 2.00; 95% CI: 1.76-2.28), cardiac mortality (HR: 1.83; 95% CI: 1.53-2.18), severe heart failure events (HR: 2.12; 95% CI: 1.54-2.93), and any-cause readmissions (HR: 1.65; 95% CI: 1.50-1.82) compared with those without mental disorders. In particular, schizophrenia spectrum disorders and mental disorders diagnosed early (within 2.8 years' postimplantation) were strongly associated with worse clinical outcomes. The adverse effect of mental disorders on mortality was more pronounced in patients with atrial fibrillation than in those without atrial fibrillation (Pinteraction= 0.04). CONCLUSIONS Evidence-based ICD implantation, proactive screening, and timely management of mentaldisorders may mitigate adverse outcomesassociated with ICD therapy and mental disorders. (JACCClinElectrophysiol.2026;12:141-155) (c) 2026 by the American College of Cardiology Foundation.

Objective:Virtual reality (VR)-based biofeedback (BF) is being studied as a new type of treatment in the field of psychiatry. We explored the potential of VR-based BF on panic symptoms. Methods:Participants who scored ≥ 10 on Patient Health Questionnaire-9 or ≥ 9 on Panic Disorder Severity Scale (PDSS) were grouped as participants with depressive or anxiety symptoms (DAS), and were randomly distributed into two intervention groups: the VR-based BF (DAS/VR group) and the conventional BF with a therapist (DAS/BF group). Those who did not meet the criteria were classified as the healthy control group and received the VR-based BF intervention (VR group). The interventions were administered three times over the course of one month. A total of 116 participants were analyzed. Results:The DAS/VR group and DAS/BF group showed a significant decrease in PDSS, indicating that both VR-based BF and conventional BF significantly decreased panic symptoms in individuals with DAS. The mean reduction of PDSS total score for the DAS/VR group was 1.51 (standard deviation [SD] = 2.28), and for the DAS/BF group it was 1.11 (SD = 2.31). However, agoraphobic fear and avoidance (p = 0.003), panic and limited symptoms attacks (p = 0.002), and interference of panic on social activities (p = 0.008) showed a significant decrease only in the VR-based BF but not in conventional BF between baseline and 4 weeks of treatment. Both therapies showed improvement in severity of panic attacks and interference of panic on work. Conclusion:VR-based BF was effective in decreasing panic symptoms. Notably, it showed a significant reduction in agoraphobic fear and avoidance, whereas conventional BF did not.

Although alcohol consumption and depression are well-known risk factors for dementia, the effect of alcohol consumption in subjects with depression on the risk of dementia remains unclear. National claim data of South Korea were used in this study. A total of 1,856,078 patients diagnosed with depression who had received health examination within 2 years before diagnosis of depression were included. Based on drinking habit and the amount of alcohol consumption, subjects were categorized into three groups: non-drinkers, mild-to-moderate drinkers, and heavy drinkers. The occurrence of dementia (Alzheimer’s and vascular) was determined. Among eligible subjects, 1,246,750 non-drinkers, 504,112 mild-to-moderate drinkers, and 105,216 heavy drinkers were identified. Compared to non-drinkers, heavy drinkers showed an increased risk of dementia (aHR, 1.087; 95

Background:Use of virtual reality (VR)-based biofeedback (BF) represents an emerging nonpharmacological intervention for enhancing sleep quality in individuals exhibiting depressive symptoms, anxiety symptoms, or both. However, empirical evidence regarding its efficacy in addressing sleep disturbances remains limited and inconclusive. Objective:This 3-arm randomized controlled trial aimed (1) to compare the efficacy of VR-based BF with conventional BF in improving sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), among individuals with depressive symptoms, anxiety symptoms, or both (DAS); (2) to examine the effects of VR-based BF in a demographically similar healthy control (HC) group; and (3) to evaluate between-group differences in sleep quality improvements at the 4-week follow-up. Methods:Participants scoring ≥10 on the Patient Health Questionnaire-9 or ≥9 on the Panic Disorder Severity Scale were allocated to a group with DAS while others were assigned to a HC group. The DAS group was subsequently randomized into VR-based BF or conventional BF interventions with a therapist. All participants attended sessions at weeks 0, 2, and 4, completing assessments including the Montgomery-Asberg Depression Rating Scale, State-Trait Anxiety Inventory, and Visual Analog Scale in interviews. The PSQI was administered at baseline and postintervention to evaluate alterations in sleep quality over a 4-week period. Results:A total of 118 participants were randomized into a VR-based BF group (DAS/VR, n=40) or a conventional BF group (DAS/BF, n=38), and a control group (HC/VR, n=40) received VR-based BF. Sleep disturbance scores of both DAS/VR and DAS/BF groups had significant improvements (mean reductions of -0.58, SD 0.75 and -0.66, SD 0.75, respectively) compared to those preintervention, showing no significant difference after adjusting for age and sex (P=.49). The DAS/VR group had a greater improvement in sleep disturbance (mean -0.08, SD 0.53; P=0.0014) than the HC/VR group. Global PSQI scores in both DAS/VR and DAS/BF groups improved compared to those preintervention, showing decreases by -2.50 (SD 2.89) and -3.39 (SD 2.80), respectively. The difference between the 2 groups was not statistically significant (P=.14). The Global PSQI score in the DAS/VR group showed significant improvement (-0.95, SD 2.09; P=.01) compared to that in the HC/VR group. Conclusions:This study provides evidence that both VR-based BF and conventional BF with a therapist are efficacious psychological interventions for enhancing sleep quality in individuals with depressive symptoms, anxiety symptoms, or both, with no significant differences observed between these 2 approaches. Both interventions showed significant improvements compared to baseline measurements. These findings suggest potential applications of these interventions in clinical settings to improve sleep quality and mental well-being.

OBJECTIVE:This study investigates the impact of changes in physical activity (PA) on the risk of developing dementia in individuals diagnosed with depression, using a large-scale, retrospective national cohort dataset. METHODS:Using a cohort data from the National Health Insurance of South Korea, 1,291,706 clinically depressed subjects were analyzed to assess the relationship between PA and dementia onset. Subjects were classified into four groups-"never," "beginning," "discontinuation," or "maintenance"-based on their PA status before and after the diagnosis of depression. Hazard ratios with confidence intervals were calculated to determine the risk across different PA status groups. RESULTS:Among the total sample, 58,934 (4.56%) were newly diagnosed with dementia during the follow-up period. Our findings demonstrated that those who maintained PA post-diagnosis had the lowest risk of developing dementia. Also, beginning PA post-diagnosis is associated with a significantly lower risk of developing dementia compared to those who remained inactive or discontinued PA. Subgroup analyses indicated that the protective effect of PA against dementia is more pronounced in women than in men. CONCLUSION:Consistent engagement in PA, particularly after the onset of depression, is associated with a reduced risk of dementia. These findings underscore the importance of PA as a potential intervention for mitigating cognitive decline in depressed individuals.

Virtual Reality-Biofeedback (VR-BF) has emerged as a novel digital intervention for reducing anxiety and depressive symptoms. This study aimed to assess the relationship between cybersickness, presence, treatment satisfaction, and symptom change following VR-BF. In this prospective clinical study, 80 drug-naive adults were enrolled and classified into two groups: those with subclinical depressive and anxiety symptoms (n = 40) and healthy controls (n = 40). All participants completed three sessions of a self-developed VR-BF intervention over four weeks. Clinical outcomes related to depression and anxiety symptoms were assessed using established psychological scales, along with post-intervention evaluations of presence, cybersickness, and treatment satisfaction. Higher presence was associated with greater reductions in anxiety (ΔSTAI: β = -0.24, SE = 0.06, P < 0.001), stress (ΔVAS: β = -0.37, SE = 0.13, P = 0.008), and depressive symptoms (ΔPHQ-9: β = -0.07, SE = 0.02, P = 0.008), and with greater treatment satisfaction (β = 0.07, SE = 0.01, P < 0.001). Cybersickness was inversely correlated with presence (ρ = -0.38, P < 0.001) and satisfaction (β = -0.11, SE = 0.04, P = 0.013) and was associated with smaller improvements in anxiety (ΔSTAI: β = 0.62, SE = 0.30, P = 0.044) and depressive symptoms (ΔPHQ-9: β = 0.28, SE = 0.12, P = 0.019). Female sex and older age were associated with greater clinical improvement and higher satisfaction. These findings underscore the relevance of experiential process factors in VR-BF and support further development of user-centered, tolerable, and clinically effective VR-based interventions.

Importance:Living alone and mental health disorders, including depression and anxiety, are associated with high suicide risk, but their combined impact remains underexplored. Objective:To examine the association of living arrangements and depression or anxiety with suicide risk. Design, Setting, and Participants:This population-based cohort study used data from the Korean National Health Insurance Service database from January 1, 2009, to December 31, 2021, that included adults aged 20 years or older who participated in the General Health Screening Program in Korea in 2009. Individuals with incomplete data and those who died by suicide within the first year were excluded to minimize the possibility of reverse causation. Data were analyzed from December 28, 2023, to December 27, 2024. Exposures:Living arrangements, categorized as living alone (≥5 years) or living with others, and depression and anxiety, determined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Main Outcomes and Measures:The primary outcome was death by suicide, identified through national death records. Multivariable Cox proportional hazards regression models were used to estimate adjusted hazard ratios (AHRs) and 95% CIs for suicide risk. Results:The study included 3 764 279 adults (mean [SD] age, 47.2 [14.0] years; 55.8% male). Of these individuals, 112 460 (3.0%) had depression, 232 305 (6.2%) had anxiety, and 319 993 (8.5%) lived alone. Compared with individuals who had neither depression nor anxiety nor lived alone, individuals living alone with both depression and anxiety exhibited a 558% increased risk of suicide (AHR, 6.58 [95% CI, 4.86-8.92]). Living alone with depression was associated with a 290% increased risk (AHR, 3.91 [95% CI, 2.96-5.16]), and living alone with anxiety was associated with a 90% increased risk (AHR, 1.90 [95% CI, 1.48-2.43]). The AHRs were higher for the association between living alone and suicide among middle-aged individuals (aged 40 to 64 years) and men compared with other demographic groups. Conclusions and Relevance:In this cohort study of 3 764 279 individuals, living alone with depression or anxiety was associated with an increased risk of suicide, particularly among middle-aged individuals and men. These findings underscore the importance of preventing mental illness, such as depression and anxiety, while addressing living arrangements as a critical factor in suicide risk assessments for individuals with these conditions.

INTRODUCTION:Smoking is a known risk factor for dementia, but the effects of changes in smoking behavior after a depression diagnosis remain unclear. METHODS:We conducted a nationwide cohort study of 1,290,530 individuals newly diagnosed with depression in South Korea between 2009 and 2012. Participants were categorized by smoking status before and after diagnosis. Incident dementia, including Alzheimer disease (AD) and vascular dementia (VD), was tracked through 2018. Adjusted hazard ratios (HRs) were estimated using Cox models. RESULTS:Continued smoking showed the highest dementia risk (HR 1.338 for all-cause; 1.323 for AD; and 1.524 for VD). Quitting reduced risk but remained higher than in persistent non-smokers. Middle age was a key risk period for AD. For VD, men had consistently higher risk, while women had increased risk only in the cessation group. CONCLUSIONS:Changes in smoking behavior after depression diagnosis influence dementia risk, underscoring the need for cessation strategies.

IntroductionAlthough the gender differences in suicide and smoking are well-known, studies exploring the impact of gender on the relationship between smoking and suicide are limited. This population-based nationwide cohort study examines the association between smoking and suicide risk among1.8 million depressed patients, analyzed separately by gender.MethodsThis longitudinal cohort study included 1,827,249 adults diagnosed with depression between 2010 and 2015 from the Korean National Health Insurance Service database. Smoking status (never, former, current) was self-reported during health screenings, and suicides were identified via national mortality records. Cox proportional hazards models adjusted for demographic, clinical, and psychiatric covariates assessed hazard ratios (HRs) for suicide risk. Subgroup analyses explored effect modifications by covariates, including age, income, and alcohol use.ResultsOver a median follow-up of 6.8 years, 6,318 individuals (0.35%) died by suicide. Smoking was associated with increased suicide risk in both men and women, with a stronger association in women. Current smoking showed a higher risk in women (HR = 2.646, 95% CI: 2.287-3.062) compared to men (HR = 1.376, 95% CI: 1.277-1.483). In men, factors such as younger age and alcohol consumption intensified this association, whereas in women, low income was a significant modifier; the highest suicide risk was observed in low-income former smokers.ConclusionSmoking is associated with increased suicide risk among individuals with depression, with notable gender differences in risk magnitude and modifying factors. These findings highlight the need for gender-specific suicide prevention strategies. Limitations include reliance on self-reported smoking data and lack of time-varying measures of exposure.

OBJECTIVE:To examine the long-term risk of childbirth and breastfeeding on suicide in women. METHODS:The data from the National Health Insurance Sharing Service database and linked data from Statistics Korea were used. In total, 2,357,914 women aged ≥30 years were eligible for this study. The number of childbirths and the duration of breastfeeding were categorized, and the subsequent incidence of suicide death was followed up. RESULTS:The mean age of participants was 53.8 years (SD, 11.5 years). During an average follow-up period of 12.1 years (SD, 1.5 years), 4493 died by suicide. The risk of suicide was reduced in those who had given childbirth compared to those who had never given childbirth (aHR, 0.67; 95 % CI, 0.57 to 0.79). The risk was lower among those with ≥2 childbirths than among those with only one childbirth. The risk of suicide was lower in those who had breastfed compared to those who had never breastfed (aHR, 0.86; 95 % CI, 0.77 to 0.95). CONCLUSIONS:Childbirth and breastfeeding were associated with a decreased risk of suicide. In addition, the risk showed a pattern of decreasing with increasing number of childbirths and the duration of breastfeeding.

Viruses have evolved diverse immune evasion strategies, including the targeting of host pattern recognition receptors. The role of viral non-coding RNAs in modulating pattern recognition receptor activity is unclear. Here we show that human cytomegalovirus (HCMV) produces long non-coding RNA4.9 that counteracts the nuclear cyclic GMP-AMP synthase (cGAS)-mediated immune response to facilitate viral infection in human foreskin fibroblasts. RNA4.9 interacts with host cGAS via its 75-nucleotide RNA region with predicted hairpin loops. Binding of RNA4.9 to cGAS inhibits cGAS enzymatic activity as well as downstream interferon response and facilitates productive viral replication. Sterically blocking the folding of the 75-nucleotide region with antisense oligonucleotides during HCMV infection restores cGAS activity and impairs viral replication. In addition, we found that the specific localization of RNA4.9, which concentrates near HCMV DNA, is correlated with its efficient binding to cGAS and subsequent immune suppression. Our findings identify viral non-coding RNAs as key regulators of cGAS and highlight their potential as therapeutic targets.

Suicide, which involves a decision-making process biased toward a lethal option that may result in the loss of one's own life, remains a major public health concern, particularly among young adults with major depressive disorder (MDD). This study investigates whether impaired decision-making in the context of loss distinguishes young adults with MDD and suicidal ideation (MDSI) from those without suicidal ideation (MDNSI) and healthy controls (HC), and explores the underlying neurocomputational mechanisms. A total of 110 young adults (23 MDSI, 31 MDNSI, and 56 HC) underwent resting-state functional magnetic resonance imaging (fMRI) and completed a two-armed bandit decision-making task designed to separate loss and reward contexts. Accuracy and computational parameters reflecting decision impulsivity were compared among groups using analysis of covariance. Logistic regression was performed to identify features predicting MDSI among MDD patients. Response time modeling was conducted to differentiate loss-related impulsivity from indecisiveness. Functional connectivity analyses focused on the ventral tegmental area (VTA) and habenula networks to identify alterations mediating loss-decision impulsivity in MDSI. MDSI patients uniquely exhibited premature, value-insensitive impulsive decisions in the loss context, distinguishing them from MDNSI patients independent of depression severity. These decision abnormalities were not attributable to indecisiveness. In contrast, reward-based decision impairments were shared across both MDD subgroups. Disruptions in resting-state functional connectivity within the VTA-orbitofrontal and habenula-default mode networks in MDSI fully mediated their loss-specific impulsivity. These findings highlight loss-specific decision impulsivity and associated neural dysconnectivity as potential early markers of suicide risk, offering novel insights into targeted intervention strategies.

BackgroundDespite a high tuberculosis incidence in Korea, the association between tuberculosis and depression remains underexplored. This study aims to assess depression risk in tuberculosis survivors.MethodsUtilizing South Korea’s National Health Insurance Sharing Service (NHISS) database, we conducted a gender-age-matched analysis comparing depression risk between tuberculosis survivors and the general population.ResultsThis study included 137,996 participants, of whom 34,499 had tuberculosis history, and 103,497 age- and sex-matched individuals were selected as the control group. The risk of developing depression was higher in tuberculosis survivors than in the control group (aHR 1.20, 95% CI 1.15-1.25). In men, the risk of developing depression was 1.32 times (95% CI 1.25-1.39) compared with 1.05 times (95% CI 0.98-1.12) in women. Those taking para-aminosalicylate, cycloserine, and prothionamide had a higher risk of developing depression compared to those using other anti-tuberculosis drugs, with the risk ratio ranging from 1.27 to 1.61.ConclusionTuberculosis survivors had a higher risk of developing depression compared to the control group. Although the prevalence of depression was higher in women compared to men, the risk of developing depression was higher in male tuberculosis survivors than in the control group, in contrast to the findings in women. The risk of developing depression in tuberculosis survivors differed depending on the anti-tuberculosis drug used and was mainly high in most of the second-line anti-tuberculosis drugs.

Mental disorders are associated with an increased risk of premature death, including suicide. This study aimed to examine the risk of suicide and all-cause death in patients with mental disorders after considering demographic, clinical, and lifestyle factors. Data from the National Health Insurance Sharing Service database and linked data from Statistics Korea were used. In total, 3,951,398 people aged ≥20 years were eligible for this study. Among the participants, 14 types of mental disorders were identified, and the subsequent incidences of suicide and all-cause death were monitored. The mean age of those with mental disorders and those without mental disorders was 56.5 (SD, 13.6) years and 46.6 (SD, 13.6) years, respectively. During an average follow-up period of 11.1 years (SD, 1.5), 249,830 participants died, of whom 12,290 died by suicide. Overall, the risk of suicide and all-cause death was higher in people with mental disorders than in controls. The risk of suicide was the highest among those with personality disorders, followed by those with bipolar disorder and schizophrenia spectrum disorder. The risk of all-cause death was the highest among those with intellectual disability, followed by those with schizophrenia spectrum disorder and alcohol use disorder. In conclusion, the risk of suicide and all-cause death increased among those with mental disorders, but there was substantial variation between the types of mental disorders for both suicide and all-cause death.

This study, based on South Korea's National Health Insurance Service data, aimed to determine which cardiovascular diseases risk factors increased the risk of developing depressive disorder in women compared to men, synergistically with the gender effect. After adjustments, women had a 1.58 times higher risk of depressive disorder than men, with particularly elevated risks in smoking (1.98 times) and heavy alcohol consumption (1.93 times) groups. Women with diabetes, hypertension, and dyslipidemia also exhibited higher risks. Notably, women aged 45–49 faced the highest risk. Smoking and heavy alcohol use synergistically heightened risks in women, while certain cardiovascular diseases-related conditions reduced gender differences. Menopause posed the highest risk for depressive disorder in women, and depressive disorder prevalence increased with age in both genders.

IntroductionThe aim of this study was to determine associations between changes of metabolic parameters and the development of BD using nationally representative data.MethodsWe used health examination data provided by the South Korean National Health Insurance System (NHIS) (n = 8,326,953). The variability of each metabolic parameter including weight circumference, blood pressure, fasting blood glucose, high-density lipoprotein cholesterol, and triglyceride levels was caculated using variability independent of mean (VIM) indices. The presence of metabolic syndrome was associated with new onset BD. Each metabolic parameter with high variability was associated with a higher risk of new onset BD compared to those with low variability after adjusting for age, sex, smoking, alcohol drinking, regular exercise, income status, baseline diabetes, hypertension, and dyslipidemia.ResultsAs the number of highly variable metabolic parameters increased, the risk for new onset depression also increased even after covariates adjustment. The associations between new onset BD and metabolic variability were greater in populations with age > 50 years. In addition, these associations remained significant after adjusting for the presence of depression prior to diagnoses of BD.DiscussionOur results suggest possibility of metabolic variability as an independent environmental risk factor for BD even after adjusting for the presence of metabolic syndrome.

OBJECTIVE:Previous studies have investigated obesity and appetite changes in patients with depression, which consisted of a small age range of adults and used body mass index rather than abdominal obesity. The objective of this study is to examine the relationship between abdominal obesity and the risk of depression by sex and age groups. METHODS:This study utilized the National Health Insurance Sharing Service (NHISS) database of South Korea, which includes those over 20 years old and who had undergone a health examination in 2009 and their claims data between 2009 and 2018. The diagnosis of depressive episodes was based on the International Statistical Classification of Disease and Related Health Problems 10th revision. Abdominal obesity was measured by waist circumference (WC) and was divided into six levels (cm). Cox proportional-hazard regression analyses were conducted to examine the relationship between abdominal obesity and the risk of depression by sex and age groups. RESULTS:Among 9,041,751 participants, 1,376,279 were diagnosed with depression. Those with higher WC (90 cm or higher for males, 85 cm or higher for females) showed an increased risk for depression in both sexes (hazard ratio [HR]=1.09, 95% confidence interval [CI]: 1.07-1.11 for males, HR=1.03, 95% CI: 1.02-1.05 for females). Underweight males (WC<80 cm) also showed an increased risk for depression (HR=1.05, 95% CI: 1.04-1.05). CONCLUSION:It has been found that higher WC was associated with increased risks of depression in both sexes. Although underweight males showed an elevated risk of depression, a healthy weight is associated with fewer depression symptoms.