Psychometric Evaluation of Screens for Common Mental Disorders, Severe Mental Disorders, Substance Use Disorders, and Suicide Risk in Mozambican Healthcare.

Globally, mental and substance use disorders are a leading cause of disease burden. In low- and middle-income countries, where there is an extreme shortage of trained mental health specialists, validated, brief screening tools for mental and substance use disorders are required for non-specialists to efficiently identify patients in need of mental health care. Mozambique, one of the poorest countries in the world, has fewer than two mental health specialists for every 100,000 people. In the present study, we evaluated a comprehensive set of seven measures for depression, anxiety, somatization, alcohol use disorder, substance use disorder, psychosis and mania, and suicide risk among N=911 Mozambican adults in general healthcare settings. All instruments demonstrated acceptable internal consistency (α > 0.75). Compared to diagnoses made by the Mini International Neuropsychiatric Interview, all measures showed good criterion validity (AUC > 0.75), except the Psychosis Screening Questionnaire, which showed low sensitivity (0.58) for psychotic disorder. No substantial differences were observed in internal consistency when stratifying by gender, age, education level, primary language, facility-type, and patient status; criterion validity showed some variability when stratified by sub-population, particularly for education, primary language, and whether the participant was seeking care that day. Exploratory factor analyses indicated that the measures best differentiate categories of diagnoses (common mental disorder, severe mental disorders, substance use disorders, and suicide risk) rather than individual diagnoses, suggesting the utility of a transdiagnostic approach. Our findings support the use of these measures in Mozambique to identify common mental disorders, substance use disorders, and suicide risk, but indicate further research is needed to develop an adequate screen for severe mental disorders. Given the limited mental health specialists in this and other LMIC settings, these brief measures can support non-specialist provision of mental health services and promote closure of the treatment gap.

Suicidal behaviour is pathological: implications for psychiatric euthanasia.

Some have challenged the validity of labelling suicidal thoughts and behaviours (STB) as pathological. In this paper, we argue that STB is indeed pathological, thereby, situating suicide prevention within the realm of medicine, complicating calls for the legalisation of medical assistance in dying for individuals whose sole condition is psychiatric (psychiatric medical assistance in dying (MAID)). Evidence shows STB predicts the risk of suicide; moreover, several mental illnesses are associated with STB, and 70%-90% of suicide deaths are linked to psychiatric illness. Treating psychiatric illnesses can prevent suicide. We contend that this clinical evidence not only warrants the classification of STB as pathological but also necessitates its treatment and prevention. This perspective poses a challenge to legislation that would legalise psychiatric MAID.

Relationships between serotonin 1A receptor DNA methylation, self-reported history of childhood abuse and gray matter volume in major depression.

BACKGROUND: Early life adversity is a risk factor for psychopathology and is associated with epigenetic alterations in the 5-HT1A receptor gene promoter. The 5-HT1A receptor mediates neurotrophic effects, which could affect brain structure and function. We examined relationships between self-reported early childhood abuse, 5-HT1A receptor promoter DNA methylation, and gray matter volume (GMV) in Major Depressive Disorder (MDD). METHODS: Peripheral DNA methylation of 5-HT1A receptor promoter CpG sites -681 and -1007 was assayed in 50 individuals with MDD, including 18 with a history of childhood abuse. T1-weighted structural magnetic resonance imaging (MRI) was performed. Voxel-based morphometry (VBM) was quantified in amygdala, hippocampus, insula, occipital lobe, orbitofrontal cortex, temporal lobe, parietal lobe, and at the voxel level. RESULTS: No relationship was observed between DNA methylation and history of childhood abuse. We observed regional heterogeneity comparing -681 CpG site methylation and GMV (p = 0.014), with a positive relationship to GMV in orbitofrontal cortex (p = 0.035). Childhood abuse history was associated with higher GMV considering all ROIs simultaneously (p < 0.01). In whole-brain analyses, childhood abuse history was positively correlated with GMV in multiple clusters, including insula and orbitofrontal cortex (pFWE = 0.005), and negatively in intracalcarine cortex (pFWE = 0.001). LIMITATIONS: Small sample size, childhood trauma assessment instrument used, and assay of peripheral, rather than CNS, methylation. CONCLUSIONS: These cross-sectional findings support hypotheses of 5-HT1A receptor-related neurotrophic effects, and of increased regional GMV as a potential regulatory mechanism in the setting of childhood abuse. Orbitofrontal cortex was uniquely associated with both childhood abuse history and 5-HT1A receptor methylation.

A Neural Signature for Reappraisal as an Emotion Regulation Strategy: Relationship to Stress-Related Suicidal Ideation and Negative Affect in Major Depression.

BACKGROUND: Impaired emotion regulation (ER) contributes to major depression, and suicidal ideation (SI) and behavior. ER is typically studied by explicitly directing participants to regulate, but this may not capture depressed individuals' spontaneous tendencies to engage ER in daily life. METHODS: In N=82 participants with major depressive disorder (MDD), we examined the relationship of spontaneous engagement of ER to real-world responses to stress. We used a machine learning-derived neural signature reflecting neural systems underlying cognitive reappraisal (an ER strategy) to identify reappraisal-related activity while participants recalled negative autobiographical memories under the following conditions: 1) unstructured recall; 2) distanced recall, a form of reappraisal; and 3) immersed recall (comparison condition). Participants also completed a week of ecological momentary assessment (EMA) measuring daily stressors, suicidal ideation (SI), and negative affect. RESULTS: Higher reappraisal signature output for the unstructured period, a proxy for the spontaneous tendency to engage ER, was associated with greater increases in SI following stressors (b=0.083, p=0.041). Higher signature output for distanced recall, a proxy for the capacity to engage ER when directed, was associated with lower negative affect following stressors (b=-0.085, p=0.029). Output for the immerse period was not associated with EMA outcomes. CONCLUSIONS: Findings suggest that, in MDD, the spontaneous tendency to react to negative memories with attempts to reappraise may indicate greater reactivity to negative cues; while intact capacity to use reappraisal when directed may be associated with more adaptive responses to stress. These data have implications for understanding stress-related increases in suicide risk in depression.

A cohort study of engagement in telehealth psychotherapy versus in-person services.

OBJECTIVE: Although telehealth psychotherapies have been studied for over 20 years, mental health services remained largely delivered in person until the COVID-19 pandemic forced clinics to reconsider the utility of telehealth psychotherapy. This study aims to compare patient engagement in in-person versus telehealth services in outpatient psychotherapy for mood and anxiety disorders. METHOD: A cohort investigation was conducted, using a propensity score matched sample, extracted from an electronic health record (EHR) to compare engagement in psychotherapy for 762 patients who used in-person services before the pandemic to a cohort of 762 patients who used telehealth psychotherapy after the onset of COVID-19. The authors compared cohorts on initial engagement in psychotherapy services following an initial intake, number of psychotherapy sessions attended, and the rate of missed sessions. RESULTS: There was a 26% increase in the total number of individual psychotherapy sessions attended when the clinics transitioned to telehealth services (p < .001). In addition, patients who received telehealth psychotherapy were five times more likely to not cancel or miss any scheduled sessions (p < .001). CONCLUSION: These results indicate that telehealth services may result in improved treatment engagement for outpatient centers focused on brief evidence-based psychotherapies for mood and anxiety disorders.

Leveraging Social Networks to Integrate Depression Treatment into Primary Health and Tuberculosis Care in Brazil.

Background: Tuberculosis (TB) and depression are highly comorbid and linked to higher rates of death and disability. Several evidence-based treatments for depression have been successfully implemented in low- and middle-income countries, but more knowledge is needed on how to bring these innovations to scale within complex 'real world' public health systems. Objective: To explore whether the principles of social network analysis could be used to enhance receptivity to integrating depression treatment into primary care for individuals with and without TB in Brazil. Methods: We used existing scales to identify settings and providers with high receptivity and connectivity within the primary care network. We trained and supervised existing staff in three primary care sites to deliver a brief evidence-based intervention over one year, coupled with active dissemination activities. Afterwards, we reassessed receptivity among individuals involved, and not involved, in the pilot. Results: Highly significant changes were observed in mental health literacy, attitudes towards evidence-based practices, work self-efficacy, and implementation leadership supporting our hypothesis. Limited social connections between primary care clinics precluded the examination of the hypothesis that targeting settings with high connectivity could capitalize on the information flow between and transcend the decentralized structure of the network, but leveraging the centralized nature of the TB program to integrate mental health services emerged as a promising alternative. Conclusions: The findings of this study strongly suggest that social networks may be leveraged to change individual providers' attitudes, thereby contributing to the enhanced dissemination of evidence-based interventions.

Occurrence and characteristics of suicidal ideation in psychiatrically healthy individuals based on ecological momentary assessment.

Decedents with no known mental disorder comprise 5-40% of suicides, suggesting that suicide ideation (SI) and behavior may occur in the psychiatrically healthy with important implications for suicide risk screening. Healthy Volunteers (HV) and patients with Major Depressive Disorder (MDD) provided 7 days of Ecological Momentary Assessment (EMA) data about SI and stressors. Longitudinal mixed effects logistic regression models compared HV and patient SI and stressors. Mixed effects linear regression models compared HVs' and patients' SI score change from the previous epoch's SI score when each stressor occurred. HVs (n = 42) reported less frequent (p < 0.001) and less intense SI (p < 0.003) than patients (n = 80), yet did endorse SI and/or SI-related items in 44% of EMA epochs, endorsing SI items in 25% of epochs with non-zero SI scores. For 7 of 8 stressors, patients reported stressors more often than HVs (all p < 0.001) responding to them with increased SI (0.0001 < p < 0.0472). HVs were relatively resilient to stressors, reporting SI increases only in response to neglect (p < 0.0147). Although SI and SAs are documented among psychiatrically healthy individuals, scientific attention to these observations has been scant. Real-time SI measurement showed that HVs' SI was less pronounced than MDD patients', but was endorsed, nonetheless. Patients were more likely to report stressors than HVs, perhaps due to greater sensitivity to the environment, and reported SI in response to stressors, which was less common in HVs. Both MDD patients and HVs most often manifested passive SI (viz, "decreased wish to live"). However, passive SI (viz, "desire for death"), may predict suicide, even absent SI per se (thinking about killing yourself). This study validates the utility of real-time SI assessment, showing that HVs endorse SI items in 11% of epochs, which implies that suicide risk screening focused on those with mental disorders may be too narrow an approach.

Safety planning intervention and follow-up: A telehealth service model for suicidal individuals in emergency department settings: Study design and protocol.

BACKGROUND: The Safety Planning Intervention with follow-up services (SPI+) is a promising suicide prevention intervention, yet many Emergency Departments (EDs) lack the resources for adequate implementation. Comprehensive strategies addressing structural and organizational barriers are needed to optimize SPI+ implementation and scale-up. This protocol describes a test of one strategy in which ED staff connect at-risk patients to expert clinicians from a Suicide Prevention Consultation Center (SPCC) via telehealth. METHOD: This stepped wedge, cluster-randomized trial compares the effectiveness, implementation, cost, and cost offsets of SPI+ delivered by SPCC clinicians versus ED-based clinicians (enhanced usual care; EUC). Eight EDs will start with EUC and cross over to the SPCC phase. Blocks of two EDs will be randomly assigned to start dates 3 months apart. Approximately 13,320 adults discharged following a suicide-related ED visit will be included; EUC and SPCC samples will comprise patients from before and after SPCC crossover, respectively. Effectiveness data sources are electronic health records, administrative claims, and the National Death Index. Primary effectiveness outcomes are presence of suicidal behavior and number/type of mental healthcare visits and secondary outcomes include number/type of suicide-related acute services 6-months post-discharge. We will use the same data sources to assess cost offsets to gauge SPCC scalability and sustainability. We will examine preliminary implementation outcomes (reach, adoption, fidelity, acceptability, and feasibility) through patient, clinician, and health-system leader interviews and surveys. CONCLUSION: If the SPCC demonstrates clinical effectiveness and health system cost reduction, it may be a scalable model for evidence-based suicide prevention in the ED.

Lifetime Suicide Attempts in Otherwise Psychiatrically Healthy Individuals.

Importance: Not all people who die by suicide have a psychiatric diagnosis; yet, little is known about the percentage and demographics of individuals with lifetime suicide attempts who are apparently psychiatrically healthy. If such suicide attempts are common, there are implications for suicide risk screening, research, policy, and nosology. Objective: To estimate the percentage of people with lifetime suicide attempts whose first attempt occurred prior to onset of any psychiatric disorder. Design, Setting, and Participants: This cross-sectional study used data from the US National Epidemiologic Study of Addictions and Related Conditions III (NESARC-III), a cross-sectional face-to-face survey conducted with a nationally representative sample of the US civilian noninstitutionalized population, and included persons with lifetime suicide attempts who were aged 20 to 65 years at survey administration (April 2012 to June 2013). Data from the NESARC, Wave 2 survey from August 2004 to September 2005 were used for replication. Analyses were performed from April to August 2023. Exposure: Lifetime suicide attempts. Main Outcomes and Measures: The main outcome was presence or absence of a psychiatric disorder before the first lifetime suicide attempt. Among persons with lifetime suicide attempts, the percentage and 95% CI of those whose first suicide attempt occurred before the onset of any apparent psychiatric disorders was calculated, weighted by NESARC sampling and nonresponse weights. Separate analyses were performed for males, females, and 3 age groups (20 to <35, 35-50, and >50 to 65 years). Results: In the total sample of 36 309 respondents, 1948 persons had lifetime suicide attempts; 66.8% (95% CI, 64.1%-69.4%) were female, and 6.2% (95% CI, 4.9%-7.4%) had no apparent lifetime psychiatric diagnoses when surveyed. In addition, 13.4% (95% CI, 11.6%-15.2%) made their first suicide attempt prior to psychiatric disorder onset. Thus, an estimated 19.6% of respondents first attempted suicide without an antecedent psychiatric disorder. No significant age or sex differences were detected in the percentage of those with lifetime suicide attempts absent psychiatric disorders, although females were more likely than males to attempt suicide in the year of psychiatric disorder onset (14.9% [95% CI, 12.5%-17.3%] vs 8.6% [95% CI, 6.0%-11.2%]; P < .001), and attempts were less frequent among those older than 50 to 65 years (3.9% [95% CI, 3.5%-4.4%] vs 6.1% [95% CI, 5.4%-6.8%] for 35-50 years and 6.2% [95% CI, 5.6%-6.9%] for 20 to <35 years; P < .001). Conclusions and Relevance: In this study, an estimated 19.6% of individuals who attempted suicide did so despite not meeting criteria for an antecedent psychiatric disorder. This finding challenges clinical notions of who is at risk for suicidal behavior and raises questions about the safety of limiting suicide risk screening to psychiatric populations.

An exposure-based implementation strategy to decrease clinician anxiety about implementing suicide prevention evidence-based practices: protocol for development and pilot testing (Project CALMER).

BACKGROUND: Clinicians often report that their own anxiety and low self-efficacy inhibit their use of evidence-based suicide prevention practices, including gold-standard screening and brief interventions. Exposure therapy to reduce clinician maladaptive anxiety and bolster self-efficacy use is a compelling but untested approach to improving the implementation of suicide prevention evidence-based practices (EBPs). This project brings together an interdisciplinary team to leverage decades of research on behavior change from exposure theory to design and pilot test an exposure-based implementation strategy (EBIS) to target clinician anxiety to improve suicide prevention EBP implementation. METHODS: We will develop, iteratively refine, and pilot test an EBIS paired with implementation as usual (IAU; didactic training and consultation) in preparation for a larger study of the effect of this strategy on reducing clinician anxiety, improving self-efficacy, and increasing use of the Columbia Suicide Severity Rating Scale and the Safety Planning Intervention in outpatient mental health settings. Aim 1 of this study is to use participatory design methods to develop and refine the EBIS in collaboration with a stakeholder advisory board. Aim 2 is to iteratively refine the EBIS with up to 15 clinicians in a pilot field test using rapid cycle prototyping. Aim 3 is to test the refined EBIS in a pilot implementation trial. Forty community mental health clinicians will be randomized 1:1 to receive either IAU or IAU + EBIS for 12 weeks. Our primary outcomes are EBIS acceptability and feasibility, measured through questionnaires, interviews, and recruitment and retention statistics. Secondary outcomes are the engagement of target implementation mechanisms (clinician anxiety and self-efficacy related to implementation) and preliminary effectiveness of EBIS on implementation outcomes (adoption and fidelity) assessed via mixed methods (questionnaires, chart-stimulated recall, observer-coded role plays, and interviews). DISCUSSION: Outcomes from this study will yield insight into the feasibility and utility of directly targeting clinician anxiety and self-efficacy as mechanistic processes informing the implementation of suicide prevention EBPs. Results will inform a fully powered hybrid effectiveness-implementation trial to test EBIS' effect on implementation and patient outcomes. TRIAL REGISTRATION: Clinical Trials Registration Number: NCT05172609 . Registered on 12/29/2021.

Antisuicidal effect of lithum in bipolar disorder: is there an age-specific effect?

OBJECTIVE: Our group reported previously a comparable overall antisuicidal effect of lithium and valproate in bipolar patients. We investigated factors associated with higher antisuicidal efficacy of lithium in older individuals. METHODS: The age-related antisuicidal effect of lithium and valproate was compared in ninety-four (n = 94) high-risk bipolar suicide attempters who participated in a 2.5-year randomized, double-blind trial. RESULTS: Age significantly moderated the effect of lithium vs. valproate on the risk of suicide event during the study (z = -1.98, p = 0.049). We found that those who were 42 years or older (above the 75th percentile), and on lithium had significantly lower risk of suicidal behavior than older patients on valproate (>42y) or younger (<42 y) patients on either medication (interaction HR = 0.09, 95%CI: 0.01-0.89, z = -2.07, p = 0.039). This difference in risk differences was not explained away by age-related differences in the proportion of participants with bipolar II disorder (Fisher's test p = 0.020) or higher lethality of past suicide attempts in younger participants (Wilcoxon test p = 0.024); neither was there any correlation with age in the longitudinally measured blood lithium levels (t = 1.04, df = 36, p = 0.307) or valproate levels (t = -0.50, df = 41, p = 0.621). LIMITATIONS: Besides the fact that this is a secondary analysis, a limitation is that the study is not powered to detect suicide deaths or suicide attempts. CONCLUSION: Bipolar patients randomized to lithium and older than 42 years had less suicidal behavior compared to same aged patients on valproate or younger patients (<42 y) on either medication. This effect was independent of clinical and sociodemographic characteristics.

Relationship of stress-reactive cortisol to suicidal intent of prior attempts in major depression.

Higher intent suicide attempts carry elevated risk of future suicidal behavior. Abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis is both linked to nonfatal suicidal behavior and suicide deaths in major depressive disorder. Few studies, however, have identified biological markers of a high-intent suicidal subgroup. We examined HPA axis output and reactivity to the Trier Social Stress Test (TSST) via salivary cortisol in depressed individuals (N=68) with a suicide attempt (SA) history. A median split of higher and lower suicidal intent scores was used to define groups. Individuals with high intent SA had attenuated total cortisol output (AUCg), F(1,60)=10.04, SE=5.095, p=.003, and lower HPA-axis stress responsivity to the TSST (AUCi), F(1,60)=4.50, SE=4.604, p=.039, compared with the low intent SA group. The high intent group also reported more pronounced negative affect than the low intent group (F[1,61]=6.413, SE=10.55, p=.014) both at baseline (meandiff=22.32, p=.038) and in response to the stressor task (meandiff=37.62, p=.003). Vulnerability to suicidal behavior in high-intent individuals may be related to the combined profile of impaired physiological responses to stress and greater negative affectivity. This clinical and biologic subgroup may benefit from targeted suicide prevention interventions.

Brain serotonin 1A receptor binding: relationship to peripheral blood DNA methylation, recent life stress and childhood adversity in unmedicated major depression.

BACKGROUND: Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms. AIMS: We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT1A) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and in vivo 5-HT1A receptor binding potential (BPF) determined by positron emission tomography (PET) in 13 a priori brain regions, in participants with major depressive disorder (MDD) and healthy volunteers (controls). METHOD: Medication-free participants with MDD (n = 192: 110 female, 81 male, 1 other) and controls (n = 88: 48 female, 40 male) were interviewed about childhood adversity and recent stressors and genotyped for rs6295. DNA methylation was assayed at three upstream promoter sites (-1019, -1007, -681) of the 5-HT1A receptor gene. A subgroup (n = 119) had regional brain 5-HT1A receptor BPF quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BPF. RESULTS: Recent stress correlated positively with blood monocyte methylation at the -681 CpG site, adjusted for diagnosis, and had positive and region-specific correlations with 5-HT1A BPF in participants with MDD, but not in controls. In participants with MDD, but not in controls, methylation at the -1007 CpG site had positive and region-specific correlations with binding potential. Childhood adversity was not associated with methylation or BPF in participants with MDD. CONCLUSIONS: These findings support a model in which recent stress increases 5-HT1A receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.

Examination of the Factor Structure of Psychopathology in a Mozambican Sample.

Factor-analytic studies are needed in global samples to advance understanding of psychopathology. We aimed to examine the structure of psychopathology and a general psychopathology ('p') factor using data from a cross-sectional study of 971 adults (63% women) from Maputo City, Mozambique. We used confirmatory factor analyses of symptoms from 15 psychiatric disorders to test common models of the structure of psychopathology. Models including internalizing, substance use, and thought disorder factors as well as a general p-factor fit the data well. Measurement invariance testing revealed that factor loadings on p differed by gender. Higher levels of p, internalizing, and thought disorder factors were associated with greater suicide risk, psychiatric comorbidity, chronic medical illnesses, and poorer functioning. A general psychopathology ('p') factor and internalizing, substance use, and thought disorder factors are identifiable in this Mozambican sample. Understanding psychopathology dimensions is a step toward building more scalable mental health service approaches globally.

Suicide in Global Mental Health.

PURPOSE OF REVIEW: We review recent research on the epidemiology and etiology of suicide in the global context. We focus on data from low- and middle-income countries (LMIC), with the goal of highlighting findings from these under-researched, over-burdened settings. RECENT FINDINGS: Prevalence of suicide in LMIC adults varies across region and country income-level, but is, on average, lower than in high-income countries. Recent gains in suicide reduction, however, have been smaller in LMIC compared to global rates. LMIC youth have much higher rates of suicide attempts than youth from high-income countries. Females as well as people with psychiatric disorders, those living with HIV, those who are LGBTQ + , and those with poor socioeconomic status are highly vulnerable populations in LMIC. Limited and low-quality data from LMIC hinder clear interpretation and comparison of results. A greater body of more rigorous research is needed to understand and prevent suicide in these settings.

Association between mental disorders and adherence to antiretroviral treatment in health facilities in two Mozambican provinces in 2018: a cross-sectional study.

INTRODUCTION: Lower adherence to antiretroviral treatment (ART) has been found among people with HIV (PWH) who have comorbid mental disorders like depression and alcohol use in Sub-Saharan African. However, there has been less exploration with regards to other mental disorders. METHODS: This study assessed the association of multiple mental disorders and adherence to ART based on the data from primary/tertiary health care facilities in Maputo and Nampula, Mozambique. We administered a sociodemographic questionnaire, Mini International Neuropsychiatric Interview (MINI) Plus 4.0.0 adapted for use in Mozambique to assess mental conditions, and a 3-item self-report to measure ART adherence. RESULTS: 395 HIV-positive (self-report) participants on ART, with an average age of 36.7 years (SD = 9.8), and 30.4% were male. The most common mental disorders were major depressive disorder (27.34%) followed by psychosis (22.03%), suicidal ideation/behavior (15.44%), and alcohol-use disorder (8.35%). Higher odds of missing at least one dose in the last 30 days (OR = 1.45, 95% CI: 1.01, 2.10) were found in participants with any mental disorder compared to those without a mental disorder. The highest levels of non-adherence were observed among those with drug use disorders and panic disorder. CONCLUSIONS: In Mozambique, PWH with any co-occurring mental conditions had a lower probability of ART adherence. Integrating comprehensive mental health assessment and treatment and ART adherence interventions tailored to PWH with co-occurring mental disorders is necessary to attain optimal ART adherence and reach the UNAIDS ART target.

In vivo serotonin transporter and 1A receptor binding potential and ecological momentary assessment (EMA) of stress in major depression and suicidal behavior.

We examined relationships between the serotonin system and stress in major depression and suicidal behavior. Twenty-five medication-free depressed participants (13 suicide attempters) underwent same-day [11C]DASB and [11C]CUMI-101 positron emission tomography (PET) imaging. Binding potential (BPND) to the serotonin transporter (5-HTT) and serotonin 1A (5-HT1A) receptor, respectively, was quantified using the NRU 5-HT atlas, reflecting distinct spatial distributions of multiple serotonin targets. Ecological momentary assessment (EMA) measured current stress over one week proximal to imaging. EMA stress did not differ between attempters and non-attempters. In all depressed participants, 5-HTT and 5-HT1A BPND were unrelated to EMA stress. There were region-specific effects of 5-HTT (p=0.002) and 5-HT1A BPND (p=0.03) in attempters vs. nonattempters. In attempters, region-specific associations between 5-HTT (p=0.03) and 5-HT1A (p=0.005) BPND and EMA stress emerged. While no post-hoc 5-HTT BPND correlations were significant, 5-HT1A BPND correlated positively with EMA stress in attempters in 9/10 regions (p-values<0.007), including the entire cortex except the largely occipital region 5. Brodmann-based regional analyses found diminished effects for 5-HTT and subcortically localized positive corrrelations between 5-HT1A and EMA stress, in attempters only. Given comparable depression severity and childhood and current stress between attempters and nonattempters, lower 5-HTT binding in attempters vs. nonattempters may suggest a biological risk marker. Localized lower 5-HTT and widespread higher 5-HT1A binding with stress among attempters specifically may suggest that a serotonergic phenotype might be a key determinant of risk or resiliency for suicidal behavior.