Functional Domains of Substance Use and their Implications to Trauma: A Systematic Review of Neuroimaging Studies.

Substance use disorder (SUD) is a significant health problem, and trauma exposure is a known risk factor for the escalation of substance use. However, the shared neural mechanisms through which trauma is associated with substance use are still unknown. Therefore, we systematically review neuroimaging studies focusing on three domains that may contribute to the overlapping mechanisms of SUD and trauma-reward salience, negative emotionality, and inhibition. Using PRISMA guidelines, we identified 45 studies utilizing tasks measuring these domains in alcohol, tobacco, and cannabis use groups. Greater reward, lesser regulation of inhibitory processes, and mixed findings of negative emotionality processes in individuals who use substances versus controls were found. Specifically, greater orbitofrontal cortex, ventral tegmental area, striatum, amygdala, and hippocampal activation was found in response to reward-related tasks, and reduced activation was found in the inferior frontal gyrus and hippocampus in response to inhibition-related tasks. Importantly, no studies in trauma-exposed individuals met our review criteria. Future studies examining the role of trauma-related factors are needed, and more studies should explore inhibition- and negative-emotionality domains in individuals who use substances to uncover clinically significant alterations in these domains that place an individual at greater risk for developing a SUD.

Predicting aggressive behaviors: Examining unique and interactive roles of PTSD and emotion dysregulation in a minority sample.

Aggression is a costly public health problem with severe and multi-faceted negative consequences and thus, identifying factors that contribute to aggression, particularly in understudied populations, is necessary to develop more effective interventions to reduce the public health cost of aggression. The goal this study was to test whether difficulties regulating emotions moderated the association between posttraumatic stress disorder (PTSD) symptoms and aggression in a community sample of predominantly Black females with high levels of trauma exposure. Furthermore, we explored unique relations between PTSD symptom clusters and distinct subscales of difficulties regulating emotions and aggression. The sample included 601 community participants recruited from an urban public hospital. Symptoms were assessed using self-report measures including the Difficulties in Emotion Regulation Scale (DERS) and Behavioral Questionnaire-Short. Regression analyses were conducted using PTSD symptoms and total DERS to test their interaction as predictors for aggression (using BQ-Short). We found that higher levels of PTSD arousal symptoms and difficulty controlling impulses when upset were positively related to aggression. We also conducted an exploratory analysis to examine the association between PTSD symptom clusters using the Alternative Symptom Clusters hybrid model. The results suggest that some PTSD symptoms (externalizing behavior) and some emotion dysregulation processes (difficulties controlling impulses when upset), relate to aggression in independent, rather than multiplicative ways. These results offer insights for new directions of research that focuses on the independent association between specific emotion dysregulation processes and PTSD symptoms on aggression.

The Neurophysiology of Interoceptive Disruptions in Trauma-Exposed Populations.

In the aftermath of psychological trauma, many individuals experience perturbations in interoception, a term that broadly references the ability to accurately detect body signals and integrate these signals with emotional states. These interoceptive disruptions can manifest in different ways, including blunting or amplification of sensitivity to internal physiological signals. In this chapter we review extant neurophysiological research on interoception in trauma-exposed populations, with a particular focus on the effects of chronic interpersonal trauma, such as childhood maltreatment and racial discrimination. We explore research that used different types of interoceptive assays, from self-report measures to electrophysiological and neuroimaging tools to characterize the disruptions in pain perception, interoceptive acuity, and physiological responses that may arise after a traumatic event. Finally, we discuss interventions that are designed to target interoceptive mechanisms, from exposure-based therapies to mindfulness-based practices, as well as future directions in trauma interoception research.

Moral injury, race-related stress and post-traumatic stress disorder in a trauma-exposed Black population.

BACKGROUND: Race-related stress (RRS) is an unrecognized source of moral injury (MI)-or the emotional and/or spiritual suffering that may emerge after exposure to events that violate deeply held beliefs. Additionally, MI has not been explored as a mechanism of risk for post-traumatic stress disorder (PTSD) in trauma-exposed civilians. We examined relations among exposure to potentially morally injurious events (moral injury exposure, MIE), related distress (moral injury distress, MID), and RRS in Black Americans. Potential indirect associations between RRS and PTSD symptoms via MID were also examined. METHODS: Black Americans (n = 228; 90.4% female; Mage = 31.6 years. SDage = 12.8 years) recruited from an ongoing study of trauma completed measures assessing civilian MIE and MID, RRS, and PTSD. Bivariate correlations were conducted with MIE and MID, and mediation analysis with MID, to examine the role of MI in the relationship between RRS and PTSD symptom severity. RESULTS: MIE was significantly correlated with cultural (r = 0.27), individual (r = 0.29), and institutional (r = 0.25) RRS; MID also correlated with cultural (r = 0.31), individual (r = 0.31), and institutional (r = 0.26) RRS (ps < 0.001). We found an indirect effect of RRS on PTSD symptoms via MID (ß = 0.10, p < 0.005). CONCLUSIONS: All types of RRS were associated with facets of MI, which mediated the relationship between RRS and current PTSD symptoms. MI may be a potential mechanism through which RRS increases the risk for PTSD in Black individuals.

The neurophysiological consequences of racism-related stressors in Black Americans.

Racism-related stressors, from experiences of both implicit and explicit racial discrimination to systemic socioeconomic disadvantage, have a cumulative impact on Black Americans' health. The present narrative review synthesizes peripheral (neuroendocrine and inflammation markers), psychophysiological (heart-rate variability, skin conductance), and neuroimaging (structural and functional) findings that demonstrate unique associations with racism-related stress. Emerging evidence reveals how racism-related stressors contribute to differential physiological and neural responses and may have distinct impacts on regions involved with threat and social processing. Ultimately, the neurophysiological effects of racism-related stress may confer biological susceptibility to stress and trauma-related disorders. We note critical gaps in the literature on the neurophysiological impact of racism-related stress and outline additional research that is needed on the multifactorial interactions between racism and mental health. A clearer understanding of the interactions between racism-related stress, neurophysiology, and stress- and trauma-related disorders is critical for preventative efforts, biomarker discovery, and selection of effective clinical treatments for Black Americans.

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup.

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals.

BACKGROUND: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. METHODS: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. RESULTS: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. CONCLUSIONS: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

C-reactive protein moderates associations between racial discrimination and ventromedial prefrontal cortex activation during attention to threat in Black American women.

Prior research has shown that racial discrimination (RD) impacts activation in threat network regions, including the ventromedial prefrontal cortex (vmPFC) and middle occipital cortex during attention to threat-relevant stimuli. However, little is known about the biological mechanisms that may modulate these effects; inflammation may be a pathway linking RD and threat network activation. As such, the current study aimed to explore whether systemic inflammation, measured by C-reactive protein (CRP) levels, may moderate the relationship between RD and activation in the vmPFC and middle occipital cortex during attention to threat. Blood samples for inflammatory marker (CRP) assays were obtained from forty Black American women (mean [SD] age, 39.93 [9.97] years; range, 22-58 years) recruited from an ongoing trauma study; participants also viewed threat-relevant stimuli as part of an attention task during fMRI. We found that CRP moderated the relationship between RD and vmPFC activation during attention to threat, such that participants with relatively higher concentrations of CRP ( ≥ 23.97 mg/L) demonstrated significant positive associations between RD and vmPFC activation [ß = 0.18, CI (0.04, 0.32), t = 2.65, p = 0.01]. No significant associations were observed for participants who showed moderate (10.89 mg/L) or low (0.20 mg/L) CRP concentrations. CRP did not moderate the relationship between RD and middle occipital cortex activation. Our data present a mechanism through which RD may influence immune system activation and, in turn, threat network activation. Inflammation may contribute to brain health vulnerabilities in Black Americans via its effects on threat circuits; this merits further investigation in large-scale studies.

Civilian Moral Injury and Amygdala Functional Connectivity During Attention to Threat.

BACKGROUND: Moral injury references emotional and spiritual/existential suffering that may emerge following psychological trauma. Despite being linked to adverse mental health outcomes, little is known about the neurophysiological mechanisms of this phenomenon. In this study, we examined neural correlates of moral injury exposure and distress using the Moral Injury Exposure and Symptom Scale for Civilians. We also examined potential moderation of these effects by race (Black vs. White individuals) given the likely intersection of race-related stress with moral injury. METHODS: Forty-eight adults ages 18 to 65 years (mean age = 30.56, SD = 11.93) completed the Moral Injury Exposure and Symptom Scale for Civilians and an affective attentional control measure, the affective Stroop task (AS), during functional magnetic resonance imaging; the AS includes presentation of threat-relevant and neutral distractor stimuli. Voxelwise functional connectivity of the bilateral amygdala was examined in response to threat-relevant versus neutral AS distractor trials. RESULTS: Functional connectivity between the right amygdala and left postcentral gyrus/primary somatosensory cortex was positively correlated with the Moral Injury Exposure and Symptom Scale for Civilians exposure score (voxelwise p < .001, cluster false discovery rate-corrected p < .05) in response to threat versus neutral AS distractor trials. Follow-up analyses revealed significant effects of race; Black but not White participants demonstrated this significant pattern of amygdala-left somatosensory cortex connectivity. CONCLUSIONS: Increased exposure to potentially morally injurious events may lead to emotion-somatosensory pathway disruptions during attention to threat-relevant stimuli. These effects may be most potent for individuals who have experienced multilayered exposure to morally injurious events, including racial trauma. Moral injury appears to have a distinct neurobiological signature that involves abnormalities in connectivity of emotion-somatosensory paths, which may be amplified by race-related stress.

Neural correlates of PTSD in women with childhood sexual abuse with and without PTSD and response to paroxetine treatment: A placebo-controlled, double-blind trial.

Objective: Childhood sexual abuse is the leading cause of posttraumatic stress disorder (PTSD) in women, and is a prominent cause of morbidity and loss of function for which limited treatments are available. Understanding the neurobiology of treatment response is important for developing new treatments. The purpose of this study was to assess neural correlates of personalized traumatic memories in women with childhood sexual abuse with and without PTSD, and to assess response to treatment. Methods: Women with childhood sexual abuse with (N = 28) and without (N = 17) PTSD underwent brain imaging with High-Resolution Positron Emission Tomography scanning with radiolabeled water for brain blood flow measurements during exposure to personalized traumatic scripts and memory encoding tasks. Women with PTSD were randomized to paroxetine or placebo followed by three months of double-blind treatment and repeat imaging with the same protocol. Results: Women with PTSD showed decreases in areas involved in the Default Mode Network (DMN), a network of brain areas usually active when the brain is at rest, hippocampus and visual processing areas with exposure to traumatic scripts at baseline while women without PTSD showed increased activation in superior frontal gyrus and other areas (p < 0.005). Treatment of women with PTSD with paroxetine resulted in increased anterior cingulate activation and brain areas involved in the DMN and visual processing with scripts compared to placebo (p < 0.005). Conclusion: PTSD related to childhood sexual abuse in women is associated with alterations in brain areas involved in memory and the stress response and treatment with paroxetine results in modulation of these areas.

White matter predictors of PTSD: Testing different machine learning models in a sample of Black American women.

BACKGROUND: Machine learning neuroimaging studies of posttraumatic stress disorder (PTSD) show promise for identifying neurobiological signatures of PTSD. However, studies to date, have largely evaluated a single machine learning approach, and few studies have examined white matter microstructure as a predictor of PTSD. Further, individuals from minoritized racial groups, specifically, Black individuals, who experience disproportionate trauma frequency, and have relatively higher rates of PTSD, have been underrepresented in these studies. We used four different machine learning models to test white matter microstructure classifiers of PTSD in a sample of trauma-exposed Black American women with and without PTSD. METHOD: Participants included 45 Black women with PTSD and 89 trauma-exposed controls recruited from an ongoing trauma study. Current PTSD presence was estimated using the Clinician-Administered PTSD Scale. Average fractional anisotropy of 53 white matter tracts served as input features. Additional exploratory analysis incorporated estimates of interpersonal and structural racism exposure. Classification models included linear support vector machine, radial basis function support vector machine, multilayer perceptron, and random forest. RESULTS: Performance varied notably between models. With white matter features along, linear support vector machine demonstrated the best model fit and reached an average AUC = 0.643. Inclusion of estimates of exposure to racism increased linear support vector machine performance (AUC = 0.808). CONCLUSIONS: White matter microstructure had limited ability to predict PTSD presence in this sample. These results may indicate that the relationship between white matter microstructure and PTSD may be nuanced across race and gender spectrums.

Association between dimensions of trauma-related psychopathology and asthma in trauma-exposed women.

Introduction: Exposure to traumatic events and stressful life experiences are associated with a wide range of adverse mental and physical health outcomes. Studies have found post-traumatic stress disorder (PTSD), depression, and anxiety sensitivity occurrence to be common in addition to inflammatory diseases like asthma, especially in women. Moreover, overlapping neurobiological mechanisms have been linked to both PTSD and asthma. Methods: In the current study, n = 508 women reported on presence of lifetime asthma diagnosis and symptoms of trauma-related psychopathology including PTSD and depression. A separate group of female participants (n = 64) reported on asthma, PTSD, depression and anxiety sensitivity, and underwent functional MRI scans during a fearful faces task, and their anterior insula responses were analyzed. Results: Overall, PTSD and depression severity were significantly higher in those with asthma versus those without asthma. There was a positive association between anterior insula response to social threat cues and depression symptoms only among individuals without a lifetime presence of asthma. Discussion: These findings provide continued evidence on the interactions between stress, neural mechanisms involved in interoception and salience detection, and trauma-related psychopathology.

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium.

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Civilian moral injury: associations with trauma type and high-frequency heart rate variability in two trauma-exposed community-based samples.

BACKGROUND: Moral injury exposure (MIE) and distress (MID) may indirectly affect the relationship between trauma exposure and alterations in autonomic regulation [assessed via high-frequency heart rate variability (hfHRV)] in civilians, but this has not been tested in prior research. We conducted two exploratory studies to examine trauma types' associations with MIE and MID among civilian medical patients (Study 1) and explore how these facets may indirectly affect the relationship between trauma type and hfHRV among civilians seeking mental health services (Study 2). METHODS: Participants recruited from a public hospital and/or community advertisements (Study 1, n = 72, 87.5% Black, 83.3% women; Study 2, n = 46, 71.7% Black, 97.8% women) completed measures assessing trauma type, MIE, and MID. In Study 1, trauma types that emerged as significant correlates of MIE and MID were entered into separate linear regression analyses. Trauma types identified were included as predictors in indirect effects models with MIE or MID as the mediator and resting hfHRV (assayed via electrocardiography) as the outcome. RESULTS: Childhood sexual abuse emerged as the only significant predictor of MIE, b = 0.38, p < 0.001; childhood sexual abuse, b = 0.26, p < 0.05, and adulthood sexual assault, b = 0.23, p < 0.05 were significant predictors of MID. Participants with greater MIE and MID demonstrated lower hfHRV. Adulthood sexual assault showed an indirect effect on hfHRV through MID, B = -0.10, s.e. = 0.06, 95%CI (-0.232 to -0.005). CONCLUSIONS: Moral injury was uniquely associated with sexual violence and lower hfHRV in civilians. Data highlight moral injury as a pathway through which autonomic dysregulation may emerge and its salience for trauma treatment selection.

Moral injury appraisals and dissociation: Associations in a sample of trauma-exposed community members.

Appraisal of trauma is a critical factor in the development of impairing post-traumatic stress symptoms, such as dissociation. Individuals may appraise trauma as morally injurious (i.e., moral injury exposure [MIE]) and experience subsequent moral distress related to this exposure (i.e., moral injury distress [MID]). To date, however, investigation into the relations between moral injury appraisals and dissociation has been limited, particularly within community populations. This study investigated MIE and MID in relation to six facets of dissociation (disengagement, depersonalization, derealization, memory disturbances, emotional constriction, identity dissociation) in a sample of trauma-exposed community members (n = 177, 58.2% Black, 89.3% female) recruited from a public hospital and/or community advertisements. Participants completed measures assessing trauma exposure, MIE, MID, dissociation, and posttraumatic stress disorder (PTSD) symptoms. Partial correlation analyses revealed that after controlling for PTSD symptoms, MIE was correlated with disengagement, r = .23, p ≤ .025, and depersonalization, r = .25, p ≤ .001, and MID was correlated with depersonalization, r = .19, p ≤ .025. Sex moderated each association, with stronger associations observed for female participants. Findings suggest that moral injury appraisals are linked to more severe dissociative symptoms among female civilians, and as such, may need to be specifically targeted in empirically supported treatments.

Differing associations of depersonalization with physiological response during rest and breath-focused mindfulness in a trauma-exposed female population.

BACKGROUND: Dissociative and posttraumatic stress disorder (PTSD) symptoms are commonly co-occurring responses to psychological trauma. Yet, these two groups of symptoms appear to be related to diverging patterns of physiological response. To date, few studies have examined how specific dissociative symptoms, namely, depersonalization and derealization, relate to skin conductance response (SCR), a marker of autonomic function, within the context of PTSD symptoms. We examined associations among depersonalization, derealization, and SCR during two conditions - resting control and breath-focused mindfulness - in the context of current PTSD symptoms. METHODS: Sixty-eight trauma-exposed women (82.4% Black; Mage = 42.5, SDage = 12.1) were recruited from the community for a breath-focused mindfulness study. SCR data were collected during alternating resting control and breath-focused mindfulness conditions. Moderation analyses were conducted to examine relations among dissociative symptoms, SCR, and PTSD for these different conditions. RESULTS: Moderation analyses revealed that depersonalization was linked to lower SCR during resting control, B = 0.0005, SE = 0.0002, p = .006, in participants low-to-moderate PTSD symptoms; however, depersonalization was associated with higher SCR during breath-focused mindfulness, B = -0.0006, SE = 0.0003, p = .029, in individuals with similar levels of PTSD symptoms. No significant interaction between derealization and PTSD symptoms on SCR was observed. CONCLUSIONS: Depersonalization symptoms may associate with physiological withdrawal during rest, but greater physiological arousal during effortful emotion regulation in individuals with low-to moderate levels of PTSD, which has significant implications for barriers to treatment engagement as well as treatment selection in this population.

Neurophysiological changes associated with vibroacoustically-augmented breath-focused mindfulness for dissociation: targeting interoception and attention.

BACKGROUND: Dissociative symptoms can emerge after trauma and interfere with attentional control and interoception; disruptions to these processes are barriers to mind-body interventions such as breath-focused mindfulness (BFM). To overcome these barriers, we tested the use of an exteroceptive augmentation to BFM, using vibrations equivalent to the amplitude of the auditory waveform of the actual breath, delivered via a wearable subwoofer in real time (VBFM). We tested whether this device enhanced interoceptive processes, attentional control and autonomic regulation in trauma-exposed women with dissociative symptoms. METHODS: 65 women, majority (82%) Black American, aged 18-65 completed self-report measures of interoception and 6 BFM sessions, during which electrocardiographic recordings were taken to derive high-frequency heart rate variability (HRV) estimates. A subset (n = 31) of participants completed functional MRI at pre- and post-intervention, during which they were administered an affective attentional control task. RESULTS: Compared to those who received BFM only, women who received VBFM demonstrated greater increases in interoception, particularly their ability to trust body signals, increased sustained attention, as well as increased connectivity between nodes of emotion processing and interoceptive networks. Intervention condition moderated the relationship between interoception change and dissociation change, as well as the relationship between dissociation and HRV change. CONCLUSIONS: Vibration feedback during breath focus yielded greater improvements in interoception, sustained attention and increased connectivity of emotion processing and interoceptive networks. Augmenting BFM with vibration appears to have considerable effects on interoception, attention and autonomic regulation; it could be used as a monotherapy or to address trauma treatment barriers.

Concurrent validity and reliability of suicide risk assessment instruments: A meta-analysis of 20 instruments across 27 international cohorts.

OBJECTIVE: A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behavior. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. METHOD: Here, we examine this issue through two approaches: (a) an extensive literature search on the reliability and concurrent validity of the most commonly used instruments and (b) by pooling data (N ∼ 6,000 participants) from cohorts from the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Major Depressive Disorder and ENIGMA-Suicidal Thoughts and Behaviour working groups, to assess the concurrent validity of instruments currently used for assessing suicidal thoughts or behavior. RESULTS: We observed moderate-to-high correlations between measures, consistent with the wide range (κ range: 0.15-0.97; r range: 0.21-0.94) reported in the literature. Two common multi-item instruments, the Columbia Suicide Severity Rating Scale and the Beck Scale for Suicidal Ideation were highly correlated with each other (r = 0.83). Sensitivity analyses identified sources of heterogeneity such as the time frame of the instrument and whether it relies on self-report or a clinical interview. Finally, construct-specific analyses suggest that suicide ideation items from common psychiatric questionnaires are most concordant with the suicide ideation construct of multi-item instruments. CONCLUSIONS: Our findings suggest that multi-item instruments provide valuable information on different aspects of suicidal thoughts or behavior but share a modest core factor with single suicidal ideation items. Retrospective, multisite collaborations including distinct instruments should be feasible provided they harmonize across instruments or focus on specific constructs of suicidality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).