Association between depressive symptoms and cardiovascular diseases in the Korean geriatric population: A nationwide retrospective cohort study.

INTRODUCTION: Depression has emerged as a modifiable risk factor for cardiovascular disease (CVD). However, evidence on whether depressive symptoms measured using a self-report questionnaire are associated with CVD incidence is scarce. Therefore, we aimed to investigate the association between depressive symptoms and CVD risk using data from national health examinations and insurance claim records. METHODS: This retrospective cohort study included participants who underwent the Korean National Screening Program for Transitional Ages at age 66 years between 2007 and 2017. The presence of depressive symptoms was defined as affirmative responses to any of three questions (loss of activities and interests, worthlessness, and hopelessness) selected from the Geriatric Depression Scale. Incident composite CVD event included myocardial infarction, stroke, heart failure, and CVD death. The association between depressive symptoms and CVD risk was evaluated using hazard ratios (HRs) and 95 % confidence intervals (CIs) estimated with Cox proportional hazards models. RESULTS: Among 88,765 participants (48.5 % women) aged 66 years, 4036 incident CVD events occurred during a mean follow-up of 6.8 years. Participants with depressive symptoms had a significantly higher risk of CVD than those without depressive symptoms (adjusted HR = 1.16 [95 % CI: 1.07-1.24]). The three individual depressive symptoms showed similar associations with CVD risk (loss of activities and interests, adjusted HR = 1.17 [95 % CI: 1.08-1.26]; worthlessness, 1.15 [1.03-1.29]; hopelessness, 1.13 [1.01-1.26]). LIMITATIONS: The study was limited to participants aged 66 years. Despite extensive adjustment for potential confounders and multiple sensitivity analyses, residual confounding and reverse causality could not be ruled out. CONCLUSION: The presence of depressive symptoms was associated with an increased risk of CVD. Screening for depressive symptoms in the general population may effectively mitigate the burden of CVD.

Serial mediating effects of childhood trauma and conduct behaviors on the impact of family history among patients with alcohol use disorder.

Family history (FH) of alcoholism increases the risk of alcohol use disorder (AUD); however, the contribution of childhood trauma (CT) in this respect remains unclear. This study investigated the relationship between FH and AUD-related clinical characteristics (social onset, antisocial tendency, and severity of problematic alcohol consumption) through the mediating effects of childhood trauma (CT) and conduct behaviors (CB) in a Korean male population with AUD. A total of 304 patients hospitalized for AUD at 16 psychiatric hospitals completed standardized questionnaires, including self-rated scales. Mediation analyses were performed using the SPSS macro PROCESS. Individuals with positive FH (133, 44%) had greater CT and CB and more severe AUD-related clinical characteristics than those without FH (171, 56%). In the present serial mediation model, FH had significant direct and indirect effects on AUD-related clinical characteristics through CT and CB. Indirect effects were 21.3% for social onset, 46.3%, antisocial tendency, and 37.9% for problematic drinking. FH directly contributed to AUD-related clinical characteristics, and CT and CB played mediating roles. This highlights the importance of careful intervention and surveillance of adverse childhood experiences and conduct disorder to prevent and mitigate alcohol-related problems in individuals with FH of AUD.

Rheumatoid Arthritis and Risk of Depression in South Korea.

Importance: Depression is among the most common comorbidities in rheumatoid arthritis (RA). There is a lack of data regarding the association of RA seropositivity and biologic agents with depression risk among individuals with RA. Objective: To investigate the risk of depression following RA diagnosis among patients in South Korea. Design, Setting, and Participants: This retrospective cohort study included 38 487 patients with RA and a comparison group of 192 435 individuals matched 1:5 for age, sex, and index date. Data were from the Korean National Health Insurance Service database. Participants were enrolled from 2010 to 2017 and were followed up until 2019. Participants who had previously been diagnosed with depression or were diagnosed with depression within 1 year after the index date were excluded. Statistical analysis was performed in May 2023. Exposures: Seropositive RA (SPRA) was defined with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes M05 and enrollment in the Korean Rare and Intractable Diseases program. Seronegative RA (SNRA) was defined with ICD-10 codes M06 (excluding M06.1 and M06.4) and a prescription of any disease-modifying antirheumatic drugs (DMARDs) for 270 days or more. Main Outcomes and Measures: Newly diagnosed depression (ICD-10 codes F32 or F33). Results: The mean (SD) age of the total study population was 54.6 (12.1) years, and 163 926 individuals (71.0%) were female. During a median (IQR) follow-up of 4.1 (2.4-6.2) years, 27 063 participants (20 641 controls and 6422 with RA) developed depression. Participants with RA had a 1.66-fold higher risk of depression compared with controls (adjusted hazard ratio [aHR], 1.66 [95% CI, 1.61-1.71]). The SPRA group (aHR, 1.64 [95% CI, 1.58-1.69]) and the SNRA group (aHR, 1.73 [95% CI, 1.65-1.81]) were associated with an increased risk of depression compared with controls. Patients with RA who used biologic or targeted synthetic DMARDs (aHR, 1.33 [95% CI, 1.20-1.47]) had a lower risk of depression compared with patients with RA who did not use these medications (aHR, 1.69 [95% CI, 1.64-1.74]). Conclusions and Relevance: This nationwide cohort study found that both SPRA and SNRA were associated with a significantly higher risk of depression. These results suggest the importance of early screening and intervention for mental health in patients with RA.

Altered cortical thickness of the superior frontal gyrus and fusiform gyrus in individuals with subthreshold social anxiety.

Subthreshold social anxiety (SSA) is a condition in which individuals experience social anxiety that does not reach the threshold required for a clinical diagnosis of a social anxiety disorder (SAD). Although SSA may not impair lives as severely as SAD, it can affect social functioning. However, only a few studies focused on structural neural correlates of SSA. We recruited 65 individuals with SSA and used the Leibowitz Social Anxiety Scale to assess their social and performance anxiety levels and other relevant measures of social anxiety. Voxel-wise whole-brain correlational analyses showed a positive association between the cortical thickness (CT) of the superior frontal gyrus (SFG) and social anxiety levels and a negative correlation between the CT of the fusiform gyrus (FG) and performance anxiety levels in individuals with SSA. Exploratory Pearson's correlation analyses showed significant positive correlations between the CT of the SFG and Generalized Anxiety Disorder-7 total scores and negative associations between the CT of the FG and Beck Anxiety Inventory total scores. Our study provides insight into the neural basis of SSA, particularly performance anxiety, by highlighting the association between CT in specific brain regions and SSA characteristics.

Microbiome analysis of circulating bacterial extracellular vesicles in obsessive-compulsive disorder.

AIM: The present study examined the microbiome abundance and composition of drug-naive or drug-free patients with obsessive-compulsive disorder (OCD) compared with healthy controls. In addition, in the OCD group, the microbiome composition was compared between early-onset and late-onset OCD. METHODS: Serum samples were collected from 89 patients with OCD and 107 age- and sex-matched healthy controls. Bacterial DNA was isolated from bacteria-derived extracellular vesicles in serum and then amplified and quantified using primers specific to the V3-V4 hypervariable region of the 16S ribosomal RNA gene. The 16S ribosomal DNA gene amplicon sequencing was performed. RESULTS: The pooled estimate showed that α-diversity was significantly reduced in patients with OCD compared with that in healthy controls (PShannon = 0.00015). In addition, a statistically significant difference was observed in ß-diversity between patients with OCD and healthy controls at the order (P = 0.012), family (P = 0.003), genus (P < 0.001), and species (P = 0.005) levels. In the microbiome composition, Pseudomonas, Caulobacteraceae (f), Streptococcus, Novosphingobium, and Enhydrobacter at the genus level were significantly less prevalent in patients with OCD than in controls. In addition, among patients with OCD, the microbial composition in the early-onset versus late-onset types was significantly different with respect to the genera Corynebacterium and Pelomonas. CONCLUSION: The present study showed an aberrant microbiome in patients with OCD, suggesting a role of the microbiota-brain interaction in the pathophysiology of OCD. Further longitudinal studies with larger sample sizes adjusting for various confounders are warranted.

Relationship between Mediterranean diet and depression in South Korea: the Korea National Health and Nutrition Examination Survey.

Background: Several studies have shown that adherence to the Mediterranean diet is associated with a lower risk of depression; however, little is known about the Asian population. This study investigated the relationship between adherence to the Mediterranean diet and depression in a sample of the South Korean population. Methods: In total, 5,849 adults from the 2014 and 2016 Korea National Health and Nutrition Examination Surveys were included in the study. The Mediterranean diet adherence was measured using a modified alternate Mediterranean diet score (mMED) developed to adjust for Korean dietary patterns. The mMED scores using the Food Frequency Questionnaire were divided into four categories (0-2, 3-4, 5-6, and 7-9 points). Subjects with depression were defined as having moderate-to-severe depressive symptoms using the Patient Health Questionnaire-9, with a cutoff value of 10. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A subgroup analysis was performed based on sex. Results: The results of logistic regression analysis indicated that individuals with higher mMED were 42-73% less likely to report depression compared to individuals with the lowest mMED [ORs (95% CIs) =0.58 (0.37-0.90), 0.50 (0.31-0.80), 0.27 (0.15-0.47)] after adjusting for socio-demographic and health-related variables. In women, individuals with mMED of 7-9 had 71% lower odds of depression [ORs (95% CIs): 0.29 (0.13-0.64)]. In men, individuals with mMED of 5-9 had 55% [ORs (95% CIs): 0.45 (0.23-0.91)] to 79% [ORs (95% CIs): 0.21 (0.08-0.57)] lower odds of depression. Conclusion: This study suggests that adherence to the Mediterranean diet is inversely associated with depression in both men and women among Korean adults. This study provides evidence that a Mediterranean diet is crucial in preventing depressive symptoms in Asian populations.

Self-compassion is associated with the superior longitudinal fasciculus in the mirroring network in healthy individuals.

Self-compassion (SC) involves taking an emotionally positive attitude towards oneself when suffering. Although SC has positive effects on mental well-being as well as a protective role in preventing symptoms in healthy individuals, few studies on white matter (WM) microstructures in neuroimaging studies of SC has been studied. Brain imaging data were acquired from 71 healthy participants. WM regions of mirroring network were analyzed using tract-based spatial statistics. After the WM regions associated with SC were extracted, exploratory correlation analysis with the self-forgiveness scale, the coping scale, and the world health organization quality of life scale abbreviated version was performed. We found that self-compassion scale total scores were negatively correlated with the fractional anisotropy (FA) values of the superior longitudinal fasciculus (SLF) in healthy individuals. The self-kindness and mindfulness subscale scores were also negatively correlated with FA values of the same regions. These FA values were negatively correlated with the total scores of self-forgiveness scale, and self-control coping strategy and confrontation coping strategy. Our findings suggest levels of SC may be associated with WM microstructural changes of SLF in healthy individuals. These lower WM microstructures may be associated with positive personal attitudes, such as self-forgiveness, self-control and active confrontational strategies.

Psychological factors associated with COVID-19 related anxiety and depression in young adults during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic and the corresponding lockdown have drastically changed our lives and led to high psychological distress and mental health problems. This study examined whether psychological factors such as loneliness, perfectionism, and health anxiety are associated with COVID-19 related anxiety and depression during the pandemic in young Korean adults, after controlling for various socio-demographic factors and early life stress. METHODS: A total of 189 participants (58.2% women) completed a cross-sectional online survey including the Fear of COVID-19 Scale, Center for Epidemiologic Studies Depression Scale, 3-item Revised UCLA Loneliness Scale, Frost Multidimensional Perfectionism Scale, and Whiteley Index-6. Hierarchical linear regression analyses with three blocks were employed to identify the factors that contributed to COVID-19 related anxiety and depressive symptoms. RESULTS: Hierarchical regression analyses showed that higher health anxiety was significantly associated with more severe COVID-19 related anxiety (standardized regression coefficient, ß = 0.599, p < 0.001). Additionally, higher levels of loneliness (ß = 0.482, p < 0.001), perfectionism (ß = 0.124, p = 0.035), and health anxiety (ß = 0.228, p < 0.001) were significantly associated with higher depression scores. The three psychological factors explained 32.8% of the total variance in depressive symptom scores, after taking all covariates into account. CONCLUSION: The results showed that health anxiety was a risk factor for both COVID-19 related anxiety and depression in young adults. Loneliness was the strongest predictor of depressive symptoms during the COVID-19 pandemic. These findings highlight the importance of identifying vulnerable individuals and encouraging psychological counselling and social connections to reduce the burden of psychiatric disorders during the pandemic.

Altered DNA Methylation of the Serotonin Transporter Gene Associated with Early Life Stress and White Matter Microalterations in Korean Patients with Panic Disorder.

INTRODUCTION: Changes in the DNA methylation of 5-HTTLPR are associated with the pathophysiology of panic disorder (PD). This study was conducted to investigate the association between stressful life events and the level of 5-HTTLPR methylation in patients with PD. We also examined whether these factors were associated with white matter alterations in psychological trauma-related regions. METHODS: The participants comprised 232 patients with PD and 93 healthy adults of Korean descent. DNA methylation levels of five cytosine-phosphate-guanine (CpG) sites in the 5-HTTLPR region were analyzed. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the trauma-related regions. RESULTS: PD patients showed significantly lower levels of the DNA methylation at 5-HTTLPR 5 CpG sites than healthy controls. In patients with PD, the DNA methylation levels at 5-HTTLPR 5 CpG sites showed significant negative association with the parental separation-related psychological distress, and positive correlations with the fractional anisotropy values of the superior longitudinal fasciculus (SLF) which might be related to trait anxiety. CONCLUSION: Early life stress was significantly associated with DNA methylation levels at 5-HTTLPR related to the decreased white matter integrity in the SLF region in PD. Decreased white matter connectivity in the SLF might be related to trait anxiety and is vital to the pathophysiology of PD.

COVID-19 pandemic's impact on networks of depression and anxiety in naturalistic transdiagnostic sample of outpatients with non-psychotic mental illness.

Background: The 2019 coronavirus disease (COVID-19) pandemic has caused an unprecedented disruption of daily lives and a mental health crisis. The present study examined how the depression and anxiety symptom network changed during the COVID-19 pandemic in a naturalistic transdiagnostic sample with non-psychotic mental illness. Materials and methods: A total of 224 psychiatric outpatients before the pandemic and 167 outpatients during the pandemic were included in the study and were assessed for the Patient Health Questionnaire and the Beck Anxiety Inventory. The network of depression and anxiety symptoms before and during the pandemic were estimated separately and were assessed differences. Results: The network comparison analysis showed a significant structural difference between the networks before and during the pandemic. Before the pandemic, the most central symptom in the network was feelings of worthlessness, while in the during pandemic network, somatic anxiety emerged as the most central node. Somatic anxiety, which showed the highest strength centrality during the pandemic, showed significantly increased correlation with suicidal ideation during the pandemic. Limitations: The two cross-sectional network analyses of individuals at one point in time cannot demonstrate causal relationships among measured variables and cannot be assumed to generalize to the intraindividual level. Conclusion: The findings indicate that the pandemic has brought a significant change in the depression and anxiety network and somatic anxiety may serve as a target for psychiatric intervention in the era of the pandemic.

Differences in Functional Level and Central Symptom of Network Structures in the Patients Seeking Treatment for Panic Disorder Before and During the COVID-19 Pandemic.

OBJECTIVE: Mental health problems such as anxiety, panic, and depression have been exacerbated by the coronavirus disease-2019 (COVID-19). This study aimed to compare the symptom severities and overall function before and during the COVID-19 pandemic among patients with panic disorder (PD) seeking treatment compared to healthy controls (HCs). METHODS: Baseline data were collected from the two groups (patients with PD and HCs) in two separate periods: before COVID-19 (Jan 2016-Dec 2019) and during COVID-19 (Mar 2020-Jul 2022). A total 453 participants (before COVID-19: 246 [139 patients with PD and 107 HCs], during COVID-19: 207 [86 patients with PD and 121 HCs]) was included. Scales for panic and depressive symptoms and overall function were administered. Additionally, network analyses were performed to compare the two groups within the patients with PD. RESULTS: The results of two-way analysis of variance analyses showed that patients with PD enrolled during COVID-19 showed higher levels of interoceptive fear and lower overall functioning. In addition, a network comparison test revealed that a significantly high strength and expected influence for agoraphobia and avoidance in patients with PD during COVID-19. CONCLUSION: This study suggested that the overall function could have worsened, and the importance of agoraphobia and avoidance as a central symptom may have increased in patients with PD seeking treatment during COVID-19.

Core clinical symptoms and suicidal ideation in patients with obsessive-compulsive disorder: A network analysis.

INTRODUCTION: Suicidality in obsessive-compulsive disorder (OCD) is underestimated and it is important for clinicians to understand the factors that contribute to suicidal ideation. The present study aimed to estimate a network of the core clinical symptoms of OCD including obsessions, compulsions, and obsessive-compulsive (OC) symptom dimensions, depressive symptoms, and psychological traits, and to examine which symptoms contribute to suicidal ideation in patients with a primary diagnosis of obsessive-compulsive disorder. METHODS: A total of 444 patients with OCD were assessed with the Yale-Brown Obsessive-Compulsive Scale, the Montgomery-Asberg Depression Rating Scale, and various other measures. Network analysis was conducted to estimate the network of obsessive-compulsive and depressive symptoms, psychological traits including alexithymia and impulsivity, and demographic covariates. Symptoms directly related to suicidal ideation in the network were examined for their relative contribution to suicidal ideation. RESULTS: Suicidal ideation was directly related to degree of control over compulsive behaviors, distress associated with compulsive behaviors, time spent performing compulsive behaviors, and unacceptable thoughts, along with depressive symptoms and alexithymia. In the network of OC and depressive symptoms the most central symptoms among the former were interference due to compulsive behaviors and interference due to obsessive thoughts, and among the latter were pessimistic thoughts and reported sadness. CONCLUSION: The findings suggest that along with depressive symptoms and alexithymia, compulsions and unacceptable thoughts dimension may contribute to suicidality, and thus, should be carefully monitored in patients with OCD.

White matter microstructure of superior longitudinal fasciculus II is associated with intelligence and treatment response of negative symptoms in patients with schizophrenia.

Although the potential role of superior longitudinal fasciculus (SLF) in intellectual deficits and treatment response (TR) in patients with schizophrenia (SZ) has been previously described, little is known about the white-matter (WM) integrity of SLF subcomponents (SLF I, II, III, and arcuate fasciculus) and their particular relationships with the clinical presentations of the illness. This study examined the associations between fractional anisotropy (FA) of SLF subcomponents and intelligence level and 6-month treatment response (TR) of negative symptoms (NS) in patients with SZ. At baseline, 101 patients with SZ and 101 healthy controls (HCs) underwent structural magnetic resonance imaging. Voxel-wise group comparison analysis showed significant SLF FA reductions in patients with SZ compared with HCs. Voxel-wise correlation analyses revealed significant positive correlations of FAs of right SLF II with Korean-Wechsler Adult Intelligence Scale at baseline and the percentage reduction of negative syndrome subscale of the Positive and Negative Syndrome Scales at 6 months. These findings suggest that aberrance in WM microstructure in SLF II may be associated with intellectual deficits in patients with SZ and TR of NS, which may support the potential role of SLF II as a novel neuroimaging biomarker for clinical outcomes of the illness.

Dysfunctional coronavirus anxiety in nonpsychotic psychiatric outpatients during the COVID-19 pandemic: A network analysis.

BACKGROUND: The 2019 coronavirus disease (COVID-19) pandemic has had a profound impact on the mental health of people worldwide. This study examined dysfunctional coronavirus anxiety in nonpsychotic psychiatric outpatients during the pandemic using the coronavirus anxiety scale (CAS) and examined the relationship between coronavirus anxiety and clinical symptoms using network analysis. METHODS: In this cross-sectional study, 192 patients who first visited the psychiatric outpatient clinic of Severance Hospital during the COVID-19 pandemic with chief complaints of depressed mood, anxiety, somatic symptoms, or insomnia were included. We compared the clinical characteristics of patients with and without dysfunctional coronavirus anxiety. Network analysis was conducted to estimate the network of coronavirus anxiety and depressive, anxious, and hypochondriacal psychopathology. RESULTS: The results showed that 7.8% of patients exhibited dysfunctional coronavirus anxiety (CAS ≥ 5). Patients with dysfunctional coronavirus anxiety showed higher levels of health worry, somatic preoccupation, and subjective anxiety compared to patients without dysfunctional coronavirus anxiety. In the network analysis, the health worry node (Item 6 of the WI) showed the greatest number of connections with coronavirus anxiety nodes. CONCLUSIONS: These findings suggest that health worry may be an important bridge symptom that connects coronavirus anxiety and other clinical psychopathology. Patients with elevated health worries should be carefully monitored during the COVID-19 pandemic for exacerbation of previous symptoms and COVID-19-related psychopathology. Understanding the psychological factors in the face of the pandemic and their relationships with clinical psychiatric symptoms would help people prevent and overcome mental health problems during the pandemic.

White matter correlates of impulsivity in frontal lobe and their associations with treatment response in first-episode schizophrenia.

BACKGROUND: It is known that increased impulsivity in schizophrenia patients causes poor treatment outcomes by increasing cost, stigma, hospitalization, treatment challenge, and physical harm. Dysfunction in the prefrontal cortex appears to be involved in the impulsivity associated with schizophrenia; nonetheless, there is a dearth of research on specific white matter alterations in the prefrontal cortex related to impulsivity. METHODS: We enrolled in the present study 119 first-episode schizophrenia patients. We measured their symptom severity at baseline and after eight weeks of treatment, using the positive and negative syndrome scale. We performed neuroimaging analysis using the Tract-Based Spatial Statistics program and by specifying the prefrontal white matter as a region of interest. RESULTS: In voxel-wise correlational analysis, we observed white matter regions showing significant positive correlations with poor impulse control scores, in both the right dorsolateral prefrontal cortex and the right frontal pole region. The fractional anisotropy values of these areas correlated positively with symptom severity at baseline. Moreover, after eight weeks, treatment non responders showed significantly higher fractional anisotropy values in the same areas. CONCLUSIONS: The results of the present study suggest that white matter tracts in the right dorsolateral prefrontal cortex and the right frontal pole may underlie dysfunctional impulse control and could be potential predictive markers for short-term treatment in patients with first-episode schizophrenia.

A nationwide nested case-control study of new-onset obsessive-compulsive disorder following antipsychotics use in schizophrenia.

OBJECTIVE: A substantial proportion of patients with schizophrenia suffer from comorbid obsessive-compulsive disorder (OCD) possibly associated with antipsychotics. However, little is known about the comparative risks of the antipsychotics. The present study aimed to investigate the risk of new-onset OCD following the initiation of different antipsychotic medications for schizophrenia relative to haloperidol. METHODS: Using the Korean national claims data, patients aged 15-60 years newly diagnosed with schizophrenia between 2010 and 2018 were identified. Of the 47,808 patients with schizophrenia treated with nine commonly prescribed antipsychotics, 775 new-onset OCD patients were matched to 3,100 patients without OCD using nested case-control design with 1:4 case-control matching based on the sex, age of index date, date of schizophrenia diagnosis, observation period, locations of medical institutions, and level of medical facilities. Using multivariable conditional logistic regression analysis, odd ratios (ORs) for new-onset OCD comparing each antipsychotic agent relative to haloperidol were computed. RESULTS: The risk for new-onset OCD during treatment with clozapine was significantly higher than that with haloperidol (adjusted OR 2.86; 95% confidence interval [1.63-5.03]). The risks for new-onset OCD with other antipsychotics were not significantly different from that with haloperidol. In subgroup analysis, the early and intermediate, but not late-onset schizophrenia group showed significant risk for OCD associated with clozapine use. CONCLUSION: The present findings, based on real-world national representative data, provide reliable evidence for the risk of new-onset OCD in patients with schizophrenia receiving clozapine at a population level.

Genetic association of FKBP5 with trait resilience in Korean male patients with alcohol use disorder.

The FKBP5 gene is known to have an important role in alcohol use disorder (AUD) in response to stress and has been reported to affect stress responses by interacting with childhood trauma. This study investigated the effects of the FKBP5 polymorphism rs1360780 and childhood trauma on trait resilience in male patients with AUD. In addition, allele-specific associations between FKBP5 DNA methylation and resilience were examined. In total, 297 men with AUD were assessed for alcohol use severity, childhood trauma, resilience, and impulsivity. Genotyping for FKBP5 rs1360780 and DNA methylation were analyzed. The effects of the rs1360780 single nucleotide polymorphism (SNP) and clinical variables on resilience were tested using linear regression analysis. Possible associations between FKBP5 DNA methylation and resilience were tested with partial correlation analysis. The rs1360780 risk allele, a low education level, and high impulsivity were associated with diminished resilience, whereas no significant main or interaction effect of childhood trauma with the SNP rs1360780 genotype on resilience was shown. No significant association between FKBP5 DNA methylation and resilience was found. The present study demonstrated the involvement of the rs1360780 risk allele in trait resilience in men with AUD, suggesting that the genetic vulnerability of FKBP5 may influence resilience related to AUD.

Alterations of cellular aging markers in obsessive- compulsive disorder: mitochondrial DNA copy number and telomere length.

BACKGROUND: The present study examined whether mitochondrial DNA copy number (mtDNAcn) and telomere length - key markers of cellular aging - were altered in male and female participants with obsessive-compulsive disorder (OCD) compared to healthy controls. We also tested for associations between these alterations and OCD-related clinical features and inflammatory index. METHODS: A total of 235 patients with OCD (38.7% female) and 234 healthy controls (41.5% female) were included. We quantified whole-blood mtDNAcn and leukocyte telomere length using quantitative polymerase chain reaction. We also calculated the neutrophil-to-lymphocyte ratio from complete blood cell counts. RESULTS: Multivariate analysis of covariance showed that OCD status had a significant overall effect on cellular aging markers in men (Wilks λ = 0.889, F2,275 = 17.13, p < 0.001) and women (Wilks λ = 0.742, F2,182 = 31.61, p < 0.001) after controlling for age, body mass index and childhood trauma. In post-hoc comparisons, men with OCD had lower mtDNAcn than controls (p < 0.001), but we found no between-group difference for telomere length (p = 0.55). Women with OCD had a significantly lower mtDNAcn (p < 0.001) and shortened telomere length (p = 0.023) compared to controls. Moreover, the lower mtDNAcn shown in the OCD group was significantly correlated with an increase in systemic inflammation for both sexes, as measured by neutrophil-to-lymphocyte ratio. LIMITATIONS: The present cross-sectional design did not allow us to infer a causal relationship between OCD disease status and cellular aging markers. CONCLUSION: The present study is, to our knowledge, the first to demonstrate alterations in mtDNAcn and telomere shortening in OCD. These results suggest that aging-associated molecular mechanisms may be important in the pathophysiology of OCD.

Use of serotonin reuptake inhibitors and risk of subsequent bone loss in a nationwide population-based cohort study.

This study examined whether the use of SRIs is associated with an increased risk of bone loss using a nested case-control design with a nationwide population-based cohort in Korea. Using the Korean National Health Screening Cohort, subjects newly diagnosed with osteoporosis or osteopenia (n = 55,799) were matched with controls (n = 278,995) at a ratio of 1:5. We stratified the participants by their time-dependent use of SRIs and sex and controlled for various confounders, including lifestyle habits, laboratory data, and comorbidities. Conditional logistic regression showed that both recent and former users of SRIs had an increased risk of subsequent bone loss compared with non-users: men [recent users: odds ratio (OR) 1.35, 95% confidential interval (CI) 1.20, 1.53; former-users: OR 1.10, 95% CI 1.01, 1.20]; women (recent users: OR 1.38, 95% CI 1.28-1.48; former-users: OR 1.07, 95% CI 1.02, 1.21). The use of SRIs was associated with an increased risk of bone loss in both men and women. In particular, the association was stronger in recent users. These findings provide population-level evidence for the risk of bone loss associated with SRI exposure and highlight the importance of monitoring the bone health of SRI users.