Immunological alterations in patients with current and lifetime suicide ideation and attempts: Examining the relationship with depressive symptoms.

Background: Suicidal ideation and attempt (SI/SA) have been associated with dysregulation of the immune response and inflammation. However, few studies have explored how innate and acquired cellular immunity impact on the peripheral immune response. Our study addresses this gap by examining the composition of peripheral immune cells and humoral markers among individuals with current SI/SA, individuals with a history of SI/SA, and healthy controls (HC). Additionally, we aim to explore whether depressive symptoms settle the relationship between inflammation and SI/SA. Methods: This is a multicenter case-control study that included 105 participants. Clinical and demographic characterists together with hemogram parameters, soluble pro and anti-inflamatory factors, and specific innate and adaptive immune cell populations were compared among patients with current SI/SA (n = 21), a history of lifetime SI/SA (n = 42), and HC (n = 42). Results: Patients with both current and lifetime SI/SA had a significant increase in the absolute count of monocytes and in the monocyte/lymphocyte ratio (MLR). Additionally, patients with current and lifetime SI/SA showed a significant increase in high-sensitivity C- reactive protein (hs-CRP), and patients with lifetime SI/SA also showed higher levels of Erythrocyte Sedimentation Rate (ESR). The cellular inflammatory status of patients with SI/SA was characterized by altered proportions of monocytes with higher levels of nonclassical and intermediate monocytes. No differences were observed in the number of lymphocytes and the proportion of CD4 and CD8 between patients and HC, but we found differences in markers of exhaustion of CD4 lymphocytes, with increased levels of Programmed cell death protein 1 (PD1) in Current SI/SA and Lymphocyte activation gene 3 (LAG3) in Current SI/SA and Lifetime SI/SA compared to HC. The plasmainflammatory status was marked by higher levels of soluble Triggering receptor expressed on myeloid cells 2 (sTREM2) in patients with lifetime SI/SA compared to HC. Finally, the multinomial analysis indicates that inflammation and depressive symptoms are independently associated with SI/SA. Conclusion: This study highlights the association of immunological alterations with SI/SA. Furthremore, SI/SA is independently influenced by depressive symptoms and inflammation. This may have important therapeutic implications, as in these patients, it may be necessary to treat the inflammatory process beyond treating the depressive symptoms.

Peripheral blood cellular immunophenotype in suicidal ideation, suicide attempt, and suicide: a systematic review and meta-analysis.

Previous meta-analyses have documented the association of immune-inflammatory pathways with the pathophysiology of Major Depressive Episode (MDE), as reflected by alterations in peripheral blood immune cell counts. However, it remains unclear whether these immunological changes are distinct in individuals experiencing suicidal ideation (SI) or suicidal behavior (SB), beyond the context of an MDE. This systematic review and meta-analysis aimed to examine peripheral immune cell profiles across samples with SI/SB and compare them to healthy controls or patients with MDE. A systematic literature search was conducted in MEDLINE, Embase, and PsycINFO for articles published from inception until June 12, 2023. Two independent reviewers screened the articles for inclusion, extracted data, and assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analyses were performed using a random-effects model to calculate standardized mean differences (SMDs) and 95% confidence intervals (CIs) for immune cell counts or ratios between groups with and without SI/SB. Heterogeneity across studies was assessed using the restricted maximum-likelihood estimator for tau statistic and I2-statistic and tested by the Q test. Publication bias was evaluated using the Egger´s test and funnel plots. Meta-regression analyses were conducted to explore the potential moderating effects of age, gender, current or lifetime SI/SB, and the type of self-harming behavior (SI or SB). The study was registered with PROSPERO (CRD42023433089). The systematic review included 30 studies, with data from 19 studies included in the meta-analyses comprising 139 unique comparisons. Eleven different cell populations or ratios were included, comprising 1973 individuals with SI/SB and 5537 comparison subjects. White blood cell (WBC) and neutrophil counts were higher in individuals with SI/SB than in controls (WBC: SMD = 0.458; 95% CI = 0.367-0.548; p value ≤ 0.001; I2 = 0.002% and; Neutrophils: SMD = 0.581; 95% CI = 0.408-0.753; p < 0.001), indicating an inflammatory process. The neutrophil-to-lymphocyte ratio (NLR) emerged as a potential marker, demonstrating a notable elevation in individuals with SI/SB (SMD = 0.695; 95% CI = 0.054-1.335; p value = 0.033; I2 = 94.281%; Q test p value ≤ 0.001). The elevated NLR appears to be primarily driven by the increase in neutrophil counts, as no significant differences were found in lymphocyte counts between groups. Comparisons among participants with and without SI/SB and depression revealed similar trends with increased NLR, monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) observed in depressed individuals with SI/SB compared to those without SI/SB. Broad alteration in the peripheral immune cell populations and their ratios were observed in individuals with SI/SB, indicating an immune activation or dysfunction. Notably, these immunological changes were also evident when comparing MDE individuals with and without SI/SB, suggesting that such immune dysfunction associated with suicidality cannot be solely attributed to or explained by depressive symptoms. The NLR, MLR, and PLR ratios, in combination with novel immune cellular and protein biomarkers, open new avenues in understanding the immunological underpinnings of SI/SB. These findings highlight the potential utility of immune markers as part of a multi-modal approach for risk stratification and therapeutic monitoring in SI/SB.

Food Insecurity and Mental Health among Venezuelan Migrants and Refugees Living in Peru: Secondary Data Analysis of a Cross-Sectional Survey.

The objective of this study was to analyze the association between food insecurity and mental health in Venezuelan migrants and refugees residing in Peru using data from the Survey Directed at the Venezuelan Population Residing in the Country (ENPOVE) conducted in 2022. The analysis included 7739 Venezuelan adults. The presence of mental health problems was self-reported, and household food insecurity was measured using the Food Insecurity Experience Scale. The study found that 4 out of 10 participants lived in households with moderate to severe food insecurity, and around 10% reported experiencing some mental health problem in the last month. The study identified a positive association between living in households with moderate to severe food insecurity and having some mental health problem compared to living in households without food insecurity. The findings suggest that food insecurity is a common problem among the Venezuelan migrant population residing in Peru, and measures are required to address this problem and mitigate its consequences on mental health and other health problems. The study highlights the need for international organizations to provide assistance and support to these populations and ensure adequate and sustainable follow-up of food insecurity at the national level. It is also necessary to implement early detection tests for mental health problems in the migrant population, especially in individuals exposed to food insecurity. This study provides relevant evidence for addressing public health in the Venezuelan migrant population residing in Peru.

Gender Differences in the Factors Associated with Alcohol Binge Drinking: A Population-Based Analysis in a Latin American Country.

Alcohol consumption is a public health problem in Peru, fostered by traditional practices, where promoting social interaction in celebrations, facilitating field work as a source of energy and warmth, and achieving objectives in certain labor negotiations, play an important role. However, research on the risk factors of binge drinking according to gender is limited. The study aim was to determine the factors associated with binge drinking in the Peruvian adult population by gender. An analytical study of secondary data from the 2018 Peruvian Demographic and Family Health Survey was conducted. The dependent variable was binge drinking in the last 30 days. Adjusted prevalence ratios (aPR) were estimated for the association between sociodemographic and health-related variables with binge drinking. A total of 32,020 adults were included. Binge drinking was found in 22.4%. Men (32.6%; 95% confidence interval [CI]: 31.4-33.8) presented a higher consumption pattern compared to women (12.8%; 95% CI: 12.0-13.6). For both genders, differences were found in binge drinking according to sociodemographic characteristics (age and wealth quintile was associated in both genders while the educational level was associated only for men, and ethnic self-identification and marital status for women) and health- characteristics related (health insurance, smoking in the last 30 days, overweight and obesity were associated in both genders). Several factors are associated with binge drinking according to gender in the Peruvian population, including age and education level among men, as well as marital status and ethnic self-identification among women.

Comparison of traditional model-based statistical methods with machine learning for the prediction of suicide behaviour.

BACKGROUND: Despite considerable research efforts during the last five decades, the prediction of suicidal behaviour (SB) using traditional model-based statistical has been weak. This marks the need to explore new statistical methods. OBJECTIVE: To compare the performance of Cox regression models versus Random Survival Forest (RSF) to predict SB. METHODS: Using a data set of more than 300 high-risk suicidal patients from a multicenter prospective cohort study, we compare Cox regression models with RSF to address predictors of time to suicide reattempt. Cross-validation was used to assess model prediction performance, including the area under the receiver operator curve (AUC), precision, Integrated Brier Score (IBS), sensitivity, and specificity. RESULTS: A variant of the RSF denominated the RSFElimin, in which irrelevant predictor variables were eliminated from the model, presented the best accuracy, sensitivity, AUC and IBS. At the same time, the sensitivity of this method was slightly lower than that obtained with the Cox regression model with all predictor variables (CoxComp). CONCLUSION: The RSF, a machine learning model, seems more sensitive and precise than the traditional Cox regression model in predicting suicidal behaviour.

Depression in the Peruvian population and its associated factors: analysis of a national health survey.

BACKGROUND: To date, the factors associated with the presence of depression or depressive symptoms in the Peruvian population have not been described. This study aimed to determine the prevalence of clinically relevant depressive symptoms in the Peruvian population and its associated factors. METHODS: A cross-sectional analytical study of secondary data from 2018 Demographic and Family Health Survey was conducted. The survey database includes 31,996 participants over 18 years of age. The dependent variable of the analysis was the presence of depression during the 14 days before the survey measured by the Patient Health Questionnaire (PHQ-9). Factors associated with the presence of depression were estimated with a proportional odds logistic regression model. RESULTS: The overall prevalence of clinically relevant depressive symptoms was 6.4% (moderate and severe symptomatology in 3.9% [95% CI: 3.6-4.3] and 2.5% [95% CI: 2.2-2.7], respectively). Being a woman, belonging to the age groups of 45 to 64 years or 65 or older, living in the Andean region, and having high blood pressure or diabetes mellitus or some disability increased the probability of having clinically relevant depressive symptoms. LIMITATIONS: The use of the PHQ-9 tool to assess depressive symptomatology limits the evaluation to a period of two weeks before the survey, requiring further study for diagnosis confirmation. CONCLUSION: Six out of 100 Peruvians presented moderate to severe clinically relevant depressive symptoms in 2018. Strategies for depression should contemplate population subgroups , such as women and patients with chronic diseases and disabilities.

Pro-inflammatory monocyte profile in patients with major depressive disorder and suicide behaviour and how ketamine induces anti-inflammatory M2 macrophages by NMDAR and mTOR.

BACKGROUND: Depression is a highly prevalent disorder that is one of the leading causes of disability worldwide. Despite an unknown aetiology, evidence suggests that the innate and adaptive immune systems play a significant role in the development and maintenance of major depressive disorder (MDD). The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), has demonstrated rapid and robust efficacy as an antidepressant when administered at sub-anaesthetic doses. METHODS: Our goal was to characterize the pro-inflammatory profile of patients with MDD by measuring pro-inflammatory cytokines in plasma and circulating monocyte subsets and to understand how ketamine induces an anti-inflammatory program in monocyte and macrophages in vitro and vivo. FINDING: Our results show that patients with MDD without other comorbidities (N = 33) exhibited significantly higher levels of pro-inflammatory IL-12 and IL-6 in plasma and that these cytokines were associated with increased numbers of non-classical (CD11b+CD16brightCD14neg) monocytes and increased activation state (CD40+CD86+) of classical monocytes in circulation. Remarkably, we have demonstrated that sub-anaesthetic doses of ketamine programs human monocytes into M2c-like macrophages by inducing high levels of CD163 and MERTK with intermediate levels of CD64 and stimulating mTOR-associated gene expression in vitro. The NMDAR antagonist MK-801, but not the α-amino-3­hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antagonist, NBQX, also polarizes macrophages to an M2c-like phenotype, but this phenotype disappears upon mTOR pathway inhibition. Sub-anaesthetic doses (10 mg/kg) of ketamine administration in mice both promote reduction of circulating classical pro-inflammatory monocytes and increase of alternative M2 macrophage subtypes in the spleen and CNS. INTERPRETATION: Our results suggest an anti-inflammatory property of ketamine that can skew macrophages to an M2-like phenotype, highlighting potential therapeutic implications not only for patients with MDD but also other inflammatory-based diseases. FUNDING: This study was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT-FONCYT).