Aims/hypotheses. To improve our understanding of etiological factors for suicide-related outcomes (i.e., suicide, suicidal ideation, and self-harm behaviors), there is an emerging interest in the identification of transdiagnostic risk factors. Irritability, defined as an increased proneness to anger in response to frustration, has attracted increased attention in psychiatry. Yet, little is known about the role of irritability as a transdiagnostic factor for suicide-related outcomes. Given the putative role of irritability as a mediating factor in the developmental model of suicide, it is important to clarify its potential contribution to suicide risk. The goal of this project is to conduct a comprehensive investigation of associations between irritability and suicide-related outcomes. Our first aim is to quantify the strength of the association between irritability and suicide-related outcomes using an individual-participant data meta-analysis approach. We hypothesize that higher levels of irritability will be associated with increased risk of suicide-related outcomes both cross-sectionally and longitudinally. Our second aim is to investigate whether irritability contributes to suicide-related outcomes above and beyond concurrent psychopathology. We hypothesize that, although a proportion of the associations will be explained by concurrent internalizing and externalizing symptoms, irritability will be associated with suicide-related outcomes over and above co-occurring symptoms. Our third aim (exploratory) is to assess variations of these associations by participants’ and sample/design characteristics i.e., age, sex/gender, race/ethnicity, country, sample (clinical/nonclinical), design (cross-sectional/longitudinal).
Sample, measures, procedures. We will conduct an individual-participant data (IPD) meta-analysis leveraging the resource and structure of the Cross-Cultural Consortium on Irritability (C3I). Investigators of 48 datasets (from 4 continents) containing data on irritability and suicide-related outcomes will share their data with the C3I. A systematic review will be conducted to identify additional datasets. First, irritability measures, suicide-related outcomes, and covariates will be harmonized across datasets to enhance comparability. Second, associations between irritability and suicide-related outcomes will be estimated with the same unified protocol in each dataset separately. Third, estimates will be pooled across datasets using random-effect meta-analyses. We will fit an initial model adjusted for socioeconomic factors only (aim 1), and then a second model adjusted for co-occurring internalizing and externalizing symptoms (aim 2). Fourth, to address aim 3, we will generate separate estimates by sex (males vs females) and/or gender (men, women, and other available categories), race/ethnicity, and clinical characteristics, then follow the described steps to generate disaggregated estimates and pool them. Additionally, meta-regression and subgroup analyses will also be applied to study the effect of study-level characteristics (e.g., country, design). Power ≥80% will be achieved.
Potential impact, next steps. This project will generate robust findings that will advance our understanding of the role of irritability as a transdiagnostic risk factor in the pathway to suicide, contributing to refine our developmental model of suicide. Our findings will directly inform clinical practice by recognizing the role of irritability as transdiagnostic symptoms and help identifying individuals at risk. Our analyses revealing age-, sex/gender-, race/ethnicity- and culture-specific associations will inform personalized suicide prevention. Finally, our findings will inform future interventions aiming to target irritability to reduce suicide risk.
