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.

The role of polyunsaturated fatty acids in the neurobiology of major depressive disorder and suicide risk.

Long-chain polyunsaturated fatty acids (LC-PUFAs) are obtained from diet or derived from essential shorter-chain fatty acids, and are crucial for brain development and functioning. Fundamentally, LC-PUFAs' neurobiological effects derive from their physicochemical characteristics, including length and double bond configuration, which differentiate LC-PUFA species and give rise to functional differences between n(omega)-3 and n-6 LC-PUFAs. LC-PUFA imbalances are implicated in psychiatric disorders, including major depression and suicide risk. Dietary intake and genetic variants in enzymes involved in biosynthesis of LC-PUFAs from shorter chain fatty acids influence LC-PUFA status. Domains impacted by LC-PUFAs include 1) cell signaling, 2) inflammation, and 3) bioenergetics. 1) As major constituents of lipid bilayers, LC-PUFAs are determinants of cell membrane properties of viscosity and order, affecting lipid rafts, which play a role in regulation of membrane-bound proteins involved in cell-cell signaling, including monoaminergic receptors and transporters. 2) The n-3:n-6 LC-PUFA balance profoundly influences inflammation. Generally, metabolic products of n-6 LC-PUFAs (eicosanoids) are pro-inflammatory, while those of n-3 LC-PUFAs (docosanoids) participate in the resolution of inflammation. Additionally, n-3 LC-PUFAs suppress microglial activation and the ensuing proinflammatory cascade. 3) N-3 LC-PUFAs in the inner mitochondrial membrane affect oxidative stress, suppressing production of and scavenging reactive oxygen species (ROS), with neuroprotective benefits. Until now, this wealth of knowledge about LC-PUFA biomechanisms has not been adequately tapped to develop translational studies of LC-PUFA clinical effects in humans. Future studies integrating neurobiological mechanisms with clinical outcomes may suggest ways to identify depressed individuals most likely to respond to n-3 LC-PUFA supplementation, and mechanistic research may generate new treatment strategies.

Accuracy of the PHQ-2 Alone and in Combination With the PHQ-9 for Screening to Detect Major Depression: Systematic Review and Meta-analysis.

Importance: The Patient Health Questionnaire depression module (PHQ-9) is a 9-item self-administered instrument used for detecting depression and assessing severity of depression. The Patient Health Questionnaire-2 (PHQ-2) consists of the first 2 items of the PHQ-9 (which assess the frequency of depressed mood and anhedonia) and can be used as a first step to identify patients for evaluation with the full PHQ-9. Objective: To estimate PHQ-2 accuracy alone and combined with the PHQ-9 for detecting major depression. Data Sources: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO, and Web of Science (January 2000-May 2018). Study Selection: Eligible data sets compared PHQ-2 scores with major depression diagnoses from a validated diagnostic interview. Data Extraction and Synthesis: Individual participant data were synthesized with bivariate random-effects meta-analysis to estimate pooled sensitivity and specificity of the PHQ-2 alone among studies using semistructured, fully structured, or Mini International Neuropsychiatric Interview (MINI) diagnostic interviews separately and in combination with the PHQ-9 vs the PHQ-9 alone for studies that used semistructured interviews. The PHQ-2 score ranges from 0 to 6, and the PHQ-9 score ranges from 0 to 27. Results: Individual participant data were obtained from 100 of 136 eligible studies (44 318 participants; 4572 with major depression [10%]; mean [SD] age, 49 [17] years; 59% female). Among studies that used semistructured interviews, PHQ-2 sensitivity and specificity (95% CI) were 0.91 (0.88-0.94) and 0.67 (0.64-0.71) for cutoff scores of 2 or greater and 0.72 (0.67-0.77) and 0.85 (0.83-0.87) for cutoff scores of 3 or greater. Sensitivity was significantly greater for semistructured vs fully structured interviews. Specificity was not significantly different across the types of interviews. The area under the receiver operating characteristic curve was 0.88 (0.86-0.89) for semistructured interviews, 0.82 (0.81-0.84) for fully structured interviews, and 0.87 (0.85-0.88) for the MINI. There were no significant subgroup differences. For semistructured interviews, sensitivity for PHQ-2 scores of 2 or greater followed by PHQ-9 scores of 10 or greater (0.82 [0.76-0.86]) was not significantly different than PHQ-9 scores of 10 or greater alone (0.86 [0.80-0.90]); specificity for the combination was significantly but minimally higher (0.87 [0.84-0.89] vs 0.85 [0.82-0.87]). The area under the curve was 0.90 (0.89-0.91). The combination was estimated to reduce the number of participants needing to complete the full PHQ-9 by 57% (56%-58%). Conclusions and Relevance: In an individual participant data meta-analysis of studies that compared PHQ scores with major depression diagnoses, the combination of PHQ-2 (with cutoff ≥2) followed by PHQ-9 (with cutoff ≥10) had similar sensitivity but higher specificity compared with PHQ-9 cutoff scores of 10 or greater alone. Further research is needed to understand the clinical and research value of this combined approach to screening.

Validation and calibration of the patient health questionnaire (PHQ-9) in Argentina.

BACKGROUND: The Patient Health Questionnaire-9 (PHQ-9) is a brief tool to assess the presence and severity of depressive symptoms. This study aimed to validate and calibrate the PHQ-9 to determine appropriate cut-off points for different degrees of severity of depression in Argentina. METHODS: We conducted a cross-sectional study on an intentional sample of adult ambulatory care patients with different degrees of severity of depression. All patients who completed the PHQ-9 were further interviewed by a trained clinician with the Mini International Neuropsychiatric Interview (MINI) and the Beck Depression Inventory-II (BDI-II). Reliability and validity tests, including receiver operating curve analysis, were performed. RESULTS: One hundred sixty-nine patients were recruited with a mean age of 47.4 years (SD = 14.8), of whom 102 were females (60.4%). The local PHQ-9 had high internal consistency (Cronbach's alpha = 0.87) and satisfactory convergent validity with the BDI-II scale [Pearson's correlation = 0.88 (p < 0.01)]. For the diagnosis of Major Depressive Episode (MDE) according to the MINI, a PHQ-9 ≥ 8 was the optimal cut-off point found (sensitivity 88.2%, specificity 86.6%, PPV 90.91%). The local version of PHQ-9 showed good ability to discriminate among depression severity categories according to the BDI-II scale. The best cut off points were 6-8 for mild cases, 9-14 for moderate and 15 or more for severe depressive symptoms respectively. CONCLUSIONS: The Argentine version of the PHQ-9 questionnaire has shown acceptable validity and reliability for both screening and severity assessment of depressive symptoms.

[Development of CALMA: A mobile APP for the prevention of suicide in adolescents and youth]. / Desarrollo de CALMA: una aplicación para dispositivos móviles inteligentes para la prevención del suicidio en adolescentes y jóvenes.

During the last 15 years, the suicide rate has doubled among individuals aged between 15 and 24 years in Argentina. This marks the need to develop new strategies for suicide prevention among this age group. Smartphones have become a good platform to provide evidence-based interventions universally, inexpensively and quickly. In particular, there is a high penetration of these devices locally and an acceptance of this technology among young people. In this article, the theoretical basis, as well as the technical design, and safety aspects used for the development of CALMA are described. CALMA is the frst Spanish tool-based mobile app for smartphones, which interacts with the user providing tools based on dialectical behavioral therapy (DBT) for the management of crisis situations and thus preventing suicide among adolescents and young people. CALMA also provides information, promoting activities aimed to reduce one's vulnerability in order to prevent new crises, and psychoeducational content about suicide and its prevention. The app was designed for teenagers and young people. It is available for free in Argentina since May 2017 and works with Android and iOS.

-759C>T Polymorphism of the HTR2C Gene is Associated with Second Generation Antipsychotic-Induced Weight Gain in Female Patients with Schizophrenia.

Introduction: The HTR2C gene is an important candidate in pharmacogenetic studies of antipsychotic-induced weight gain (AIWG). However, inconsistent results have been obtained. The present study investigated the association between -759C>T, functional polymorphism of the HTR2C receptor, and AIWG. Methods: A prospective cohort of 48 female inpatients with schizophrenia and related illness treated according to normal clinical practice with second generation antipsychotics (SGAs) risperidone, clozapine, quetiapine, and olanzapine were evaluated. Patients were weighted at admission and again at 6 weeks of hospitalization. Weight gain was defined as an increase≥7% of baseline weight. The association between polymorphisms HTR2C and weight gain was evaluated. Multiple logistic regression was run to determine potential confounders. Results: Patients with the T allele at position -759 (TT or CT) gained less weight as compared to patients who did not have the allele. This association was not affected by possible confounding factors such as age, baseline BMI, and prior psychopharmacological treatment. Discussion: The T allele at position -759 protects against AIWG in female patients with schizophrenia.

Clozapine Rechallenge After Neutropenia or Leucopenia.

To rechallenge with clozapine for a patient who previously has experienced neutropenia or leucopenia or during clozapine treatment is a difficult clinical decision. Herein, we analyzed the results of such a rechallenge in 19 patients. We analyzed all the reports, from the database of the pharmacovigilance department of the Argentine National Administration of Drugs, Foods, and Medical Devices, of patients who were rechallenged with clozapine after a leucopenia or a neutropenia. Nineteen cases of rechallenge after leucopenia or neutropenia were reported between 1996 and 2014. One third of the patients re-exposed to clozapine developed a new hematologic adverse reaction. The second blood dyscrasia was less severe in 83% of the cases and had a shorter median latency as compared with the first (8 weeks vs 182 weeks, P = 0.0045). There were no significant differences for demographic and clinical characteristics of patients who developed a second dyscrasia as compared with those who did not. The present study shows that almost 70% of the patients rechallenged with clozapine after a leucopenia or a neutropenia did not develop a new hematological adverse effect, whereas the remaining 30% had a faster but less serious neutropenia.

Types of borderline personality disorder (BPD) in patients admitted for suicide-related behavior.

Borderline personality disorder (BPD) is determined by the presence of any five of nine diagnostic criteria, leading patients with heterogeneous clinical features to be diagnosed under the same label without an individualized clinical and therapeutic approach. In response to this problem, Oldham proposed five types of BPD: affective, impulsive, aggressive, dependent and empty. The present study categorized a sample of BPD patients hospitalized due to suicide-related behavior according to Oldham's BPD proposed subtypes, and evaluated their clinical and demographic characteristics. Data were obtained from a sample of 93 female patients admitted to the « Dr. Braulio A. Moyano ¼ Neuropsychiatric Hospital following suicide-related behavior. A total of 87 patients were classified as affective (26%), impulsive (37%), aggressive (4%), dependent (29%), and empty (5%). Patients classified as dependent were significantly older at the time of first suicide-related behavior (p = 0.0008) and reported significantly less events of previous suicide-related behaviors (p = 0.03), while patients classified as impulsive reported significantly higher rates of drug use (p = 0.02). Dependent, impulsive and affective BPD types were observed most frequently in our sample. Findings are discussed specific to demographic and clinical implications of BPD patients reporting concurrent suicidal behavior.

[The opportunity to transform the model of mental health care of Argentina to a model based on scientific evidence based on the National Mental Health Law]. / La oportunidad de transformar el modelo de atención en salud mental de la Argentina en un modelo basado en fundamentos científicos a partir de la Ley Nacional de Salud Mental.

Mental disorders significantly contribute to the burden of disease, reduce the quality of life, and pose vast economic and social costs. Furthermore, access to treatment and treatment quality is often poor, particularly in low- and middle-income countries. Indeed, WHO urged countries to develop policies and comprehensive mental health strategies. In response, Argentina promulgated a National Mental Health Law (NMHL, No. 26.657) that was regulated through the Regulatory Decree No. 603/2013 and implemented through the National Mental Health Plan (NMHP). The NMHL defines the vision, values, and principles for improving the mental health system for the country via urging that mental health care be based on scientific evidence adjusted to ethical principles. This is not new in other areas of health; however, it implies a paradigm shift for the mental health system in Argentina. Inconsistencies between the conceptual framework that raises the NMHL and operational instruments issued by the National Mental Health and Addiction Department were observed. These inconsistencies reflect the resistance to change in paradigm.

[THE OPPORTUNITY TO TRANSFORM THE MODEL OF MENTAL HEALTH CARE OF ARGENTINA TO A MODEL BASED ON SCIENTIFIC EVIDENCE BASED ON THE NATIONAL MENTAL HEALTH LAW]. / La oportunidad de transformar el modelo de atención en salud mental de la Argentina en un modelo basado en fundamentos científicos a partir de la Ley Nacional de Salud Mental.

Mental disorders significantly contribute to the burden of disease, reduce the quality or life, and pose vast economic and social costs. Furthermore, access to treatment and treatment quality is often poor, particularly in low- and middle-income countries. Indeed, WHO urged countries to develop policies and comprehensive mental health strategies. In response, Argentina promulgated a National Mental Health Law (NMHL, No. 26.657) that was regulated through the Regulatory Decree No. 603/2013 and implemented through the National Mental Health Plan (NMHP). The NMHL defines the vision, values, and principles for improving the mental health system for the country via urging that mental health care be based on scientific evidence adjusted to ethical principles. This is not new in other areas of health; however, it implies a paradigm shift for the mental health system in Argentina. Inconsistencies between the conceptual framework that raises the NMHL and operational instruments issued by the National Mental Health and Addiction Department were observed. These inconsistencies reflect the resistance to change in paradigm.

[Intensive pharmacovigilance of clozapine in Argentina]. / Farmacovigilancia intensiva de clozapina en Argentina.

Approximately 12,000 individuals are treated with clozapine per year in Argentina. The use of this antipsychotic is associated with the occurrence of various side effects; the most serious of these is agranulocytosis, which can be fatal but reversible if detected early. For this reason, clozapine is under a pharmacovigilance intensive program centered by the National Administration of Drugs, Foods and Medical Devices. The present paper reviewed the current legislation for the use of clozapine in Argentina and compared the data obtained from the pharmacovigilance system with those reported in other countries. Further, difficulties that may arise during the reexposure of patients to clozapine are discussed.

Systematic review of risk factors for suicide and suicide attempt among psychiatric patients in Latin America and Caribbean.

OBJECTIVE: To analyze published evidence from the Latin America and Caribbean (LAC) region pertaining to risk factors for completed suicide and suicide attempts among psychiatric populations. METHODS: Potential studies were identified through systematic electronic searches in MEDLINE and LILACS. Included studies were cohort, case-control, and cross-sectional designed investigations of psychiatric samples in which suicide or a suicide attempt was reported as an outcome and evaluated with some measure of impact (odds ratio, risk ratio, or hazard ratio). Methodological quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations. RESULTS: Of the 2 987 identified studies, a total of 17 studies were reviewed to determine potential suicidal risk factors. Eleven studies used a case-control design, five used a cross-sectional design, and only one study used a prospective-cohort design. The main risk factors for suicide attempts in LAC included major depressive disorder (MDD), family dysfunction, and prior suicide attempt, while the main risk factors for completed suicide were male gender and MDD. The methodological quality of most of the studies was low. CONCLUSIONS: This review provides evidence that the majority of relevant risk factors for suicide and suicide attempts in the LAC region are similar to those observed in Western societies but different from those reported in Eastern societies. Studies of higher methodological quality from the region are needed to support these results.

[Patients hospitalized for suicidal ideation and suicide attempt in a Mental Health Hospital: Clinicodemographical features and 6-month follow-up]. / Pacientes hospitalizadas por ideación e intento de suicidio en un Hospital de Salud Mental: características clínico-demográficas y seguimiento a seis meses.

BACKGROUND: Suicide is an issue of high public health impact. In Argentina there are few published studies on suicide and suicide attempt. OBJECTIVE: To determine the percentage of hospitalizations caused by suicidal attempt or suicidal ideation in a Mental Health Hospital of the City of Buenos Aires, describe the clinical and demographic characteristics of these patients and to analyze the frequency of adverse events at a 6-month follow-up. METHODS: In the present study, baseline and follow-up data of an analytical, observational, prospective cohort study are used. RESULTS: Baseline data show that of all patients who entered the Emergency Department, 27% did so for ideation or suicide attempt. The most frequent diagnoses were: borderline personality disorder (41%), major depressive disorder (38%), bipolar disorder (20%) and schizophrenia (16%). The method most commonly used during the suicide attempt was drug poisoning. In half of the patients, the suicidal process was developed in less than 10 minutes. Monitoring data show that 22% of patients had a new attempted suicide and 34% had a readmission in a 6-month period. CONCLUSIONS: Together, these results describe the characteristics of suicide patients admitted to a Mental Health Hospital and show the low efficacy of interventions and the need to devise new strategies for the management of suicidal patients.

Decoding the inflammatory signature of the major depressive episode: insights from peripheral immunophenotyping in active and remitted condition, a case-control study.

Depression is a prevalent and incapacitating condition with a significant impact on global morbidity and mortality. Although the immune system's role in its pathogenesis is increasingly recognized, there is a lack of comprehensive understanding regarding the involvement of innate and adaptive immune cells. To address this gap, we conducted a multicenter case-control study involving 121 participants matched for sex and age. These participants had either an active (or current) major depressive episode (MDE) (39 cases) or a remitted MDE (40 cases), including individuals with major depressive disorder or bipolar disorder. We compared these 79 patients to 42 healthy controls (HC), analyzing their immunological profiles. In blood samples, we determined the complete cell count and the monocyte subtypes and lymphocyte T-cell populations using flow cytometry. Additionally, we measured a panel of cytokines, chemokines, and neurotrophic factors in the plasma. Compared with HC, people endorsing a current MDE showed monocytosis (p = 0.001), increased high-sensitivity C-reactive protein (p = 0.002), and erythrocyte sedimentation rate (p = 0.003), and an altered proportion of specific monocyte subsets. CD4 lymphocytes presented increased median percentages of activation markers CD69+ (p = 0.007) and exhaustion markers PD1+ (p = 0.013) and LAG3+ (p = 0.014), as well as a higher frequency of CD4+CD25+FOXP3+ regulatory T cells (p = 0.003). Additionally, patients showed increased plasma levels of sTREM2 (p = 0.0089). These changes are more likely state markers, indicating the presence of an ongoing inflammatory response during an active MDE. The Random Forest model achieved remarkable classification accuracies of 83.8% for MDE vs. HC and 70% for differentiating active and remitted MDE. Interestingly, the cluster analysis identified three distinct immunological profiles among MDE patients. Cluster 1 has the highest number of leukocytes, mainly given by the increment in lymphocyte count and the lowest proinflammatory cytokine levels. Cluster 3 displayed the most robust inflammatory pattern, with high levels of TNFα, CX3CL1, IL-12p70, IL-17A, IL-23, and IL-33, associated with the highest level of IL-10, as well as ß-NGF and the lowest level for BDNF. This profile is also associated with the highest absolute number and percentage of circulating monocytes and the lowest absolute number and percentage of circulating lymphocytes, denoting an active inflammatory process. Cluster 2 has some cardinal signs of more acute inflammation, such as elevated levels of CCL2 and increased levels of proinflammatory cytokines such as IL-1ß, IFNγ, and CXCL8. Similarly, the absolute number of monocytes is closer to a HC value, as well as the percentage of lymphocytes, suggesting a possible initiation of the inflammatory process. The study provides new insights into the immune system's role in MDE, paving the ground for replication prospective studies targeting the development of diagnostic and prognostic tools and new therapeutic targets.

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.

A randomized 3-month, parallel-group, controlled trial of CALMA m-health app as an adjunct to therapy to reduce suicidal and non-suicidal self-injurious behaviors in adolescents: study protocol.

Background: Suicidal and non-suicidal self-injurious behaviors are among the leading causes of death and injury in adolescents and youth worldwide. Mobile app development could help people at risk and provide resources to deliver evidence-based interventions. There is no specific application for adolescents and young people available in Spanish. Our group developed CALMA, the first interactive mobile application with the user in Spanish, which provides tools based on Dialectical Behavioral Therapy to manage a crisis of suicidal or non-suicidal self-directed violence with the aim of preventing suicide in adolescents and youth. Methods: To test the effectiveness, safety and level of engagement of the CALMA app in people aged 10 to 19 who are treated in mental health services of two public hospitals, we will conduct a parallel-group, two-arm randomized controlled trial. Participants will be assessed face-to-face and via video call at four timepoints: day-0 (baseline), day-30, day-60, and day-90. A total of 29 participants per group will be included. Change in the frequency of suicidal and non-suicidal self-injurious behaviors will be compared between groups, as well as the level of emotional dysregulation, level of app engagement and time of psychiatric admission during the follow-up period. Discussion: This study is particularly relevant to young people given their widespread use of mobile technology, while there are currently no available smartphone app-based self-guided psychological strategies in Spanish that attempt to reduce suicidal behavior in adolescents who are assisted in the public health sector from low and middle-income countries in Latin America. Clinical trial registration: https://clinicaltrials.gov/, NCT05453370.

Body mass index, waist circumference, insulin, and leptin plasma levels differentiate between clozapine-responsive and clozapine-resistant schizophrenia.

BACKGROUND: Between 25% and 50% of patients suffering from treatment-resistant schizophrenia fail to achieve a clinical response with clozapine. The rapid identification and treatment of this subgroup of patients represents a challenge for healthcare practice. AIMS: To evaluate the relationship between metabolic alterations and the clinical response to clozapine. METHODS: A multicenter, observational, case-control study was performed. Patients diagnosed with schizophrenia treated with clozapine were eligible (minimum dose 400 mg/d for at least 8 weeks and/or clozapine plasma levels ⩾ 350 µg/mL). According to the Positive and Negative Syndrome Scale (PANSS) total score, patients were classified as clozapine-responsive (CR) (<80 points) or clozapine non-responsive (CNR) (⩾80 points). Groups were compared based on demographic and treatment-related characteristics, together with body mass index (BMI), waist circumference, insulin, leptin, and C-reactive protein plasma levels. Plasma levels of clozapine and its main metabolite, nor-clozapine, were measured in all the participants. In addition, the potential relationship between PANSS scores and leptin or insulin plasma levels was assessed. RESULTS: A total of 46 patients were included: 25 CR and 21 CNR. BMI and waist circumference, fasting insulin and leptin plasma levels were lower in the CNR group, while C-reactive protein was not different. Moreover, significant negative correlations were observed between PANSS positive and general psychopathology subscores, on one hand, and insulin and leptin plasma levels, on the other hand, as well as between PANSS negative subscores and leptin plasma levels. CONCLUSIONS: Our results suggest that the lack of metabolic effect induced by clozapine is associated with the lack of clinical response.

Immune-related biomarkers and suicidal behaviors: A meta-analysis.

Biomarkers that can differentiate between psychiatric disorders with and without suicidal behavior history from each other and from healthy volunteers may explain part of the pathogenesis of suicidal behavior. We conducted the hitherto largest meta-analysis comparing immune biomarkers between subjects with and without suicide attempt history or death by suicide. The study protocol was registered with PROSPERO, CRD42020212841. Standardized mean differences (SMD) were pooled with random-effects models. Heterogeneity between studies was assessed with the I2-statistic and publication bias was evaluated by the Egger test and funnel plots. Data were based on 36 studies including 2679 persons with suicidal behaviors and 6839 comparison subjects, and four immune-related biomarkers (CRP, IL-6, TNF-α and IL-1ß). Suicidal behavior was associated with higher CRP blood levels compared with: healthy controls (SMD [95%CI] = 1.42[0.85-1.98]); patients with depression alone (SMD [95%CI] = 1.23[0.20-2.26]); and patients with any psychiatric disorders (SMD [95%CI] = 0.39[0.22-0.55]). IL-6 blood level was higher in patients with suicidal behaviors compared with healthy controls (SMD [95%CI] = 1.13[0.45-1.82]) and when compared with psychiatric patients without suicidal behaviors (SMD [95%CI] = 0.22 [0.11-0.33]). Meta-regression and subgroup analyses revealed that increased CRP in suicidal behavior is primarily driven by recent suicidal behavior. These results implicate the immune system and inflammatory response in suicidal behavior independent of a relationship to major psychiatric disorders, and that these biological measures are predominantly state-dependent markers. Future studies are needed to determine the cause-and-effect relationship of these immune system biomarkers with suicidal behavior, and their potential predictive properties.

Validation of the Spanish ASQ translation: Screening pediatric patients for suicide-risk in Argentina.

BACKGROUND: The high frequency of suicide risk in adolescents necessitates the development and validation of specific tools for systematic screening. To date, there are translated, but not validated suicide risk screening tools in Spanish. OBJECTIVE: To validate the Spanish version of the Ask Suicide-Screening Questions (ASQ) for suicide risk screening in pediatric patients in Argentina. METHOD: Using a cross-sectional multicenter design, a convenience sample of pediatric patients aged 10 to 18 years old were recruited from outpatient/inpatient medical settings and private psychiatric clinics. The Spanish version of the Suicidal Ideation Questionnaire (SIQ) assessment tool was used as a standard criterion to validate the ASQ. RESULTS: A total of 301/380 pediatric patients were screened for suicide risk. Twentyeight percent of the entire sample (83/301) of youth screened positive on the ASQ, and 21% (62/301) screened positive on the SIQ/SIQ-JR and were considered "at risk" for suicide. Compared with the SIQ, the Spanish ASQ yielded a sensitivity of 96.8% (95% Confidence Interval [CI]: 88.8-99.6%), specificity of 90.4% (95% CI: 85.9-93.8%), positive predictive value of 72.3% (95 CI: 61.4-81.6%), and negative predictive value of 99.1% (95% CI: 96.7-99.9%). The positive Likelihood Ratio (LR) was 10.1 (95% CI: 6.1-14.0), and the negative LR was 0.03 (95% CI: -0.01-0.09). Kappa was 0.77 (95% CI: 0.69-0.86), and the Area Under the Curve was 0.94 (95% CI: 0.91-0.97). CONCLUSION: The Spanish language ASQ demonstrated strong psychometric properties, providing initial evidence that it is a valid tool for identifying Spanish-speaking youth at risk for suicide.

Comparison of the accuracy of the 7-item HADS Depression subscale and 14-item total HADS for screening for major depression: A systematic review and individual participant data meta-analysis.

The seven-item Hospital Anxiety and Depression Scale Depression subscale (HADS-D) and the total score of the 14-item HADS (HADS-T) are both used for major depression screening. Compared to the HADS-D, the HADS-T includes anxiety items and requires more time to complete. We compared the screening accuracy of the HADS-D and HADS-T for major depression detection. We conducted an individual participant data meta-analysis and fit bivariate random effects models to assess diagnostic accuracy among participants with both HADS-D and HADS-T scores. We identified optimal cutoffs, estimated sensitivity and specificity with 95% confidence intervals, and compared screening accuracy across paired cutoffs via two-stage and individual-level models. We used a 0.05 equivalence margin to assess equivalency in sensitivity and specificity. 20,700 participants (2,285 major depression cases) from 98 studies were included. Cutoffs of ≥7 for the HADS-D (sensitivity 0.79 [0.75, 0.83], specificity 0.78 [0.75, 0.80]) and ≥15 for the HADS-T (sensitivity 0.79 [0.76, 0.82], specificity 0.81 [0.78, 0.83]) minimized the distance to the top-left corner of the receiver operating characteristic curve. Across all sets of paired cutoffs evaluated, differences of sensitivity between HADS-T and HADS-D ranged from -0.05 to 0.01 (0.00 at paired optimal cutoffs), and differences of specificity were within 0.03 for all cutoffs (0.02-0.03). The pattern was similar among outpatients, although the HADS-T was slightly (not nonequivalently) more specific among inpatients. The accuracy of HADS-T was equivalent to the HADS-D for detecting major depression. In most settings, the shorter HADS-D would be preferred. (PsycInfo Database Record (c) 2023 APA, all rights reserved).