The effect of inflammation markers on cortical thinning in major depressive disorder: A possible mediator of depression and cortical changes.

BACKGROUND: Major depressive disorder (MDD) is a prevalent mental health condition with significant societal impact. Owing to the intricate biological diversity of MDD, treatment efficacy remains limited. Immune biomarkers have emerged as potential predictors of treatment response, underscoring the interaction between the immune system and the brain. This study investigated the relationship between cytokine levels and cortical thickness in patients with MDD, focusing on the corticolimbic circuit, to elucidate the influence of neuroinflammation on structural brain changes and contribute to a deeper understanding of the pathophysiology of MDD. METHOD: A total of 114 patients with MDD and 101 healthy controls (HC) matched for age, sex, and body mass index (BMI) were recruited. All participants were assessed for depression severity using the Hamilton Depression Rating Scale (HDRS), and 3.0 T T1 weighted brain MRI data were acquired. Additionally, cytokine levels were measured using a highly sensitive bead-based multiplex immunosorbent assay. RESULTS: Patients diagnosed with MDD exhibited notably elevated levels of interleukin-6 (p = 0.005) and interleukin-8 (p = 0.005), alongside significant cortical thinning in the left anterior cingulate gyrus and left superior frontal gyrus, with these findings maintaining significance even after applying Bonferroni correction. Furthermore, increased interleukin-6 and interleukin-8 levels in patients with MDD are associated with alterations in the left frontomarginal gyrus and right anterior cingulate cortex (ACC). CONCLUSIONS: This suggests a potential influence of neuroinflammation on right ACC function in MDD patients, warranting longitudinal research to explore interleukin-6 and interleukin-8 mediated neurotoxicity in MDD vulnerability and brain morphology changes.

Association of Depression With Atrial Fibrillation in South Korean Adults.

Importance: The risk of atrial fibrillation (AF) in people with depression is not fully known. Depression is associated with sympathetic activation and emotional stress, which might increase the risk of new-onset AF. Objective: To assess the incidence of new-onset AF in those with and without depression using data from a nationwide health care database. Design, Setting, and Participants: This cohort study obtained data from the Korean National Health Insurance Service database and enrolled people who underwent a nationwide health checkup in 2009. People younger than 20 years and those with a history of heart valve surgery, previous diagnosis of mitral stenosis, or who were diagnosed with AF between January 1, 2002 and December 31, 2008 were excluded. The risk of new-onset AF (occurring between 2009 and 2018) was compared in people who were and were not diagnosed with depression within a year before the 2009 nationwide health checkup. Data were analyzed between August 1, 2020 and October 31, 2020. Exposure: Previous diagnosis of depression. Main Outcomes and Measures: Cumulative incidence and risk of new-onset AF between 2009 and 2018 in participants with and without depression. Kaplan-Meier analysis was conducted to assess incidence of AF, and Cox proportional hazards regression was used to calculate adjusted and unadjusted hazard ratios (HRs) and 95% CIs. Results: A total of 5 031 222 individuals with a mean (SD) age of 46.99 (14.06) years (2 771 785 men [55.1%]) were included in the analysis; of these individuals, 148 882 (3.0%) had a diagnosis of depression in the year before the 2009 health checkup and 4 882 340 (97%) did not. People with depression vs those without depression were older (aged 56.7 vs 46.7 years) and more likely to be women (96 472 [64.8%] vs 2 162 965 [44.3%]). Prevalence of hypertension, diabetes, dyslipidemia, and heart failure was higher in the depression group. The cumulative incidence of new-onset AF was significantly higher in people with depression vs without depression in the Kaplan-Meier analysis and showed steady divergence throughout 10 years of follow-up (cumulative incidence, 4.44% vs 1.92%; log-rank P < .001). After adjusting for covariates, depression was associated with a 25.1% increased risk of new-onset AF (HR, 1.25; 95% CI, 1.22-1.29; P < .001). People with recurrent episodes of depression showed even higher risk of new-onset AF (HR, 1.32; 95% CI, 1.27-1.37; P < .001). Young age and female sex had significant interactions with depression, which suggests that young people and women with depression may have an increased risk of new-onset AF. Conclusions and Relevance: This study found that depression was associated with a significantly increased cumulative incidence and risk of new-onset AF. Recurrent episodes of depression were associated with even higher risk. These findings suggest the need for adequate screening for AF in people with depression, particularly in younger people and women.

How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies.

This narrative review discusses how peripheral and central inflammation processes affect brain function and structure in depression, and reports on recent peripheral inflammatory marker-based functional and structural magnetic resonance imaging (MRI) studies from the perspective of neural-circuit dysfunction in depression. Chronic stress stimulates the activity of microglial cells, which increases the production of pro-inflammatory cytokines in the brain. In addition, microglial activation promotes a shift from the synthesis of serotonin to the synthesis of neurotoxic metabolites of the kynurenine pathway, which induces glutamate-mediated excitotoxicity in neurons. Furthermore, the region specificity of microglial activation is hypothesized to contribute to the vulnerability of specific brain regions in the depression-related neural circuits to inflammation-mediated brain injury. MRI studies are increasingly investigating how the blood levels of inflammatory markers such as C-reactive protein, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α are associated with functional and structural neuroimaging markers in depression. Functional MRI studies have found that peripheral inflammatory markers are associated with aberrant activation patterns and altered functional connectivity in neural circuits involved in emotion regulation, reward processing, and cognitive control in depression. Structural MRI studies have suggested that peripheral inflammatory markers are related to reduced cortical gray matter and subcortical volumes, cortical thinning, and decreased integrity of white matter tracts within depression-related neural circuits. These neuroimaging findings may improve our understanding of the relationships between neuroinflammatory processes at the molecular level and macroscale in vivo neuralcircuit dysfunction in depression.

Association between high-sensitivity C-reactive protein levels and depression: Moderation by age, sex, obesity, and aerobic physical activity.

BACKGROUND: Low-grade systemic inflammation evidenced by elevated serum high-sensitivity C-reactive protein (hsCRP) levels can be a biomarker for depression. This study aimed to investigate the association between serum hsCRP levels and depressive symptoms and to explore the potential moderating effects of age, sex, body mass index (BMI), and aerobic physical activity on the association. METHODS: Data of 10,702 adults (≥ 19 years) were obtained from the nationwide cross-sectional Korea National Health and Nutrition Examination Surveys of 2016 and 2018. Significant depressive symptoms were defined as ≥ 10 on the Patient Health Questionnaire-9, and high hsCRP level was defined as > 3.0 mg/L. RESULTS: Adults with high hsCRP levels were more likely to have depressive symptoms (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.07-1.84) and suicidal ideation (OR: 1.39, 95% CI: 1.07-1.80) than those with low hsCRP levels. In the age- and sex-stratified analysis, high hsCRP levels were associated with depressive symptoms in the non-geriatric population (age ≤ 64 years) alone, with a higher OR in males than females. In subgroup analyses, the association between them was observed only among obese adults and adults without aerobic physical activity. LIMITATIONS: Causal interpretation is limited due to the cross-sectional design. CONCLUSIONS: Our results replicate previous findings of an association between high hsCRP levels and depressive symptoms in adults using a large nationally representative sample. The association between them was more prominent in the non-geriatric population, males, obese adults, and those without aerobic physical activity.

Effect of physical activity on suicidal ideation differs by gender and activity level.

BACKGROUND: Suicide is a critical complication of psychiatric disorders. Physical activity has a positive effect on mental health; however, its effects on suicidal ideation have received little attention compared to other psychiatric symptoms. METHODS: Data were obtained from the Korea National Health and Nutrition Examination Survey 2014. Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire-9. Physical activity was measured by the International Physical Activity Questionnaire (IPAQ) and categorized into three groups by activity level. Multiple logistic regression analysis was performed for the entire sample, men, and women. The following three models were used: Model 1 (adjusted for sociodemographic and health-related variables), Model 2 (additionally adjusted for subjective body image), and Model 3 (additionally adjusted for diagnosed depression). RESULTS: Compared to the low IPAQ group, the moderate IPAQ group was significantly associated with decreased suicidal ideation in Model 3 for the entire sample (OR, 0.733; 95% CI, 0.538-0.999) and in all models for women. However, the high IPAQ group showed no significant association. None of the IPAQ groups showed significant associations in men. LIMITATIONS: This is a cross-sectional study. Therefore, the direction of causality cannot be determined. This study also investigated suicidal ideation over the past two weeks, which may be inconsistent with studies conducted over the past year. CONCLUSIONS: The beneficial relationship between physical activity and suicidal ideation is weaker in men and individuals with high activity levels. Detailed guidelines on physical activity according to gender and activity level are recommended.

Chronic medical conditions and metabolic syndrome as risk factors for incidence of major depressive disorder: A longitudinal study based on 4.7 million adults in South Korea.

BACKGROUND: The assessment of comorbid physical illness and metabolic or cardiovascular risk factors as potential risk factors for onset of major depressive disorder (MDD) is crucial. We aimed to investigate potential risk factors for the development of MDD among individuals with chronic medical conditions and metabolic and behavioral risk factors using a large population-based retrospective cohort from the data of the National Health Insurance Service (NHIS) in South Korea. METHODS: The population-based retrospective cohort included data from 2,370,815 adults (age ≥20 years) diagnosed with MDD between January 1, 2010, and December 31, 2016 and age- and gender-matched 2,370,815 healthy controls obtained from the claims data of the NHIS. The data of the regular health checkup provided by the NHIS were also included (age ≥40 years). Logistic regression analyses were performed to investigate the potential risk factors for the incidence of MDD. RESULTS: Chronic medical conditions such as Parkinson's disease (odds ratio [OR] = 7.808, 95% confidence interval [CI] = 7.517-8.11), epilepsy (OR = 6.119, 95% CI = 6.019-6.22), multiple sclerosis (OR = 5.532, 95% CI = 4.976-6.151), Huntington's disease (OR = 5.387, 95% CI = 3.258-8.909), migraine (OR = 4.374, 95% CI = 4.341-4.408), stroke (OR = 4.074, 95% CI = 4.032-4.117), and cancer; metabolic syndrome (OR = 1.049, 95% CI = 1.041-1.057) and several of its components including central obesity, elevated fasting blood glucose and triglyceride levels, and reduced high-density lipoprotein level; and cigarette smoking, frequent alcohol consumption, and low physical activity are potential risk factors for the development of MDD. CONCLUSION: Our results may support previous evidence on the association between physical conditions and the incidence of MDD as reported by individual population-based studies with modest sample sizes.