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Objective: Bipolar disorder is associated with high risk for suicidal acts. Observational studies suggest a protective effect of lithium against suicidal behavior. However, testing this effect in randomized clinical trials is logistically and ethically challenging. The authors tested the hypothesis that lithium offers bipolar patients with a history of suicide attempt greater protection against suicidal behavior compared to valproate.Method: Patients with bipolar disorder and past suicide attempts (N=98) were randomly assigned to treatment with lithium or valproate, plus adjunctive medications as indicated, in a double-blind 2.5-year trial. An intent-to-treat analysis was performed using the log-rank test for survival data. Two models were fitted: time to suicide attempt and time to suicide event (attempt or hospitalization or change in medication in response to suicide plans).Results: There were 45 suicide events in 35 participants, including 18 suicide attempts made by 14 participants, six from the lithium group and eight from the valproate group. There were no suicides. Intent-to-treat analysis using the log-rank test showed no differences between treatment groups in time to suicide attempt or to suicide event. Post hoc power calculations revealed that the modest sample size, reflective of challenges in recruitment, only permits detection of a relative risk of 5 or greater.Conclusions: Despite the high frequency of suicide events during the study, this randomized controlled trial detected no difference between lithium and valproate in time to suicide attempt or suicide event in a sample of suicide attempters with bipolar disorder. However, smaller clinically significant differences between the two drugs were not ruled out. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the link between antidepressants and suicidal behavior and ideation (suicidality) in youth, adverse events from pediatric clinical trials were classified in order to identify suicidal events. The authors describe the Columbia Classification Algorithm for Suicide Assessment (C-CASA), a standardized suicidal rating system that provided data for the pediatric suicidal risk analysis of antidepressants conducted by the Food and Drug Administration (FDA).Method: Adverse events (N=427) from 25 pediatric antidepressant clinical trials were systematically identified by pharmaceutical companies. Randomly assigned adverse events were evaluated by three of nine independent expert suicidologists using the Columbia classification algorithm. Reliability of the C-CASA ratings and agreement with pharmaceutical company classification were estimated.Results: Twenty-six new, possibly suicidal events (behavior and ideation) that were not originally identified by pharmaceutical companies were identified in the C-CASA, and 12 events originally labeled as suicidal by pharmaceutical companies were eliminated, which resulted in a total of 38 discrepant ratings. For the specific label of "suicide attempt," a relatively low level of agreement was observed between the C-CASA and pharmaceutical company ratings, with the C-CASA reporting a 50% reduction in ratings. Thus, although the C-CASA resulted in the identification of more suicidal events overall, fewer events were classified as suicide attempts. Additionally, the C-CASA ratings were highly reliable (intraclass correlation coefficient [ICC]=0.89).Conclusions: Utilizing a methodical, anchored approach to categorizing suicidality provides an accurate and comprehensive identification of suicidal events. The FDA's audit of the C-CASA demonstrated excellent transportability of this approach. The Columbia algorithm was used to classify suicidal adverse events in the recent FDA adult antidepressant safety analyses and has also been mandated to be applied to all anticonvulsant trials and other centrally acting agents and nonpsychotropic drugs. [ABSTRACT FROM AUTHOR]

Objective: Whether sex differences exist in clinical risk factors associated with suicidal behavior is unknown. The authors postulated that among men with a major depressive episode, aggression, hostility, and history of substance misuse increase risk for future suicidal behavior, while depressive symptoms, childhood history of abuse, fewer reasons for living, and borderline personality disorder do so in depressed women.Method: Patients with DSM-III-R major depression or bipolar disorder seeking treatment for a major depressive episode (N=314) were followed for 2 years. Putative predictors were tested with Cox proportional hazards regression analysis.Results: During follow-up, 16.6% of the patients attempted or committed suicide. Family history of suicidal acts, past drug use, cigarette smoking, borderline personality disorder, and early parental separation each more than tripled the risk of future suicidal acts in men. For women, the risk for future suicidal acts was sixfold greater for prior suicide attempters; each past attempt increased future risk threefold. Suicidal ideation, lethality of past attempts, hostility, subjective depressive symptoms, fewer reasons for living, comorbid borderline personality disorder, and cigarette smoking also increased the risk of future suicidal acts for women.Conclusions: These findings suggest that the importance of risk factors for suicidal acts differs in depressed men and women. This knowledge may improve suicide risk evaluation and guide future research on suicide assessment and prevention. [ABSTRACT FROM AUTHOR]

Background. Impulsiveness, hostility and aggressiveness are traits associated with suicidal behavior, but also with borderline personality disorder (BPD). The presence of large numbers of BPD subjects in past attempter samples may distort the relative importance of each of these traits to predicting suicidal behavior, and lead to prospective, biological and genetic models that systematically misclassify certain subpopulations of suicidal individuals.Method. Two hundred and seventy-five subjects with major depressive disorder (MDD), including 87 with co-morbid BPD (69 past suicide attempters, 18 non-attempters) and 188 without BPD (76 attempters, 112 non-attempters) completed standard impulsiveness, hostility and aggressiveness ratings. Differences between past suicide attempters and non-attempters were examined with the sample stratified by BPD status.Results. As expected, BPD subjects scored significantly higher than non-BPD subjects on all three trait measures. Stratifying by BPD status, however, eliminated attempter/non-attempter differences in impulsiveness and hostility in both patient subgroups. Past suicide attempters in each of the two subgroups of patients were only distinguished by higher levels of aggressiveness.Conclusions. Once BPD is accounted for, a history of aggressive behavior appears to be the distinguishing trait characteristic of suicide attempters with major depression, rather than global personality dimensions such as impulsiveness or hostility. Aggressiveness, and not these related traits, may be the ideal target for behavioral, genetic and biological research on suicidal behavior, as well as for the clinical assessment of suicide risk. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The lower expressing allele of the serotonin transporter gene 5' promoter region (5-HTTLPR) polymorphism is reported to be associated with susceptibility to depression and suicidality in response to stressful life events. The authors examined the relationship of a triallelic 5-HTTLPR polymorphism to stressful life events, severity of major depression, and suicidality. METHOD: Mood disorder subjects (N=191) and healthy volunteers (N=125), all Caucasian subjects of European origin, were genotyped for the triallelic 5-HTTLPR polymorphism (higher expressing allele: L(A); lower expressing alleles: L(G), S). All subjects underwent structured clinical interviews to determine DSM-IV diagnoses, ratings of psychopathology, stressful life events, developmental history, and suicidal behavior. CSF 5-HIAA was assayed in a subgroup of subjects. RESULTS: Lower expressing alleles independently predicted greater depression severity and predicted greater severity of major depression with moderate to severe life events compared with the higher expressing L(A) allele. No associations with suicidal behavior and CSF 5-HIAA were found. CONCLUSIONS: Lower expressing transporter alleles, directly and by increasing the impact of stressful life events on severity, explain 31% of the variance in major depression severity. The biological phenotype responsible for these effects remains to be elucidated. [ABSTRACT FROM AUTHOR]

OBJECTIVE: First-degree relatives of persons with mood disorder who attempt suicide are at greater risk for mood disorders and attempted or completed suicide. This study examined the shared and distinctive factors associated with familial mood disorders and familial suicidal behavior. METHOD: First-degree relatives' history of DSM-IV--defined mood disorder and suicidal behavior was recorded for 457 mood disorder probands, of whom 81% were inpatients and 62% were female. Probands' lifetime severity of aggression and impulsivity were rated, and probands' reports of childhood physical or sexual abuse, suicide attempts, and age at onset of mood disorder were recorded. Univariate and multivariate analyses were carried out to identify predictors of suicidal acts in first-degree relatives. RESULTS: A total of 23.2% of the probands with mood disorder who had attempted suicide had a first-degree relative with a history of suicidal behavior, compared with 13.2% of the probands with mood disorder who had not attempted suicide (odds ratio=1.99, 95% CI=1.21-3.26). Thirty percent (30.8%) of the first-degree relatives with a diagnosis of mood disorder also manifested suicidal behavior, compared with 6.6% of the first-degree relatives with no mood disorder diagnosis (odds ratio=6.25, 95% CI=3.44-11.35). Probands with and without a history of suicide attempts did not differ in the incidence of mood disorder in first-degree relatives (50.6% versus 48.1%). Rates of reported childhood abuse and severity of lifetime aggression were higher in probands with a family history of suicidal behavior. Earlier age at onset of mood disorder in probands was associated with greater lifetime severity of aggression and higher rates of reported childhood abuse, mood disorder in first-degree relatives, and suicidal behavior in first-degree relatives. CONCLUSIONS: Risk for suicidal behavior in families of probands with mood disorders appears related to early onset of mood disorders, aggressive/impulsive traits, and reported childhood abuse in probands. Studies of such clinical features in at-risk relatives are under way to determine the relative transmission of these clinical features. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Low levels of docosahexaenoic acid, a polyunsaturated fatty acid, and elevated ratios of omega-6/omega-3 fatty acids are associated with major depression and, possibly, suicidal behavior. Predicting risk of future suicidal behaviors by essential fatty acid status merits examination. METHOD: Plasma polyunsaturated fatty acid levels in phospholipids were measured in 33 medication-free depressed subjects monitored for suicide attempt over a 2-year period. Survival analysis examined the association of plasma polyunsaturated fatty acid status and pathological outcome. RESULTS: Seven subjects attempted suicide on follow-up. A lower docosahexaenoic acid percentage of total plasma polyunsaturated fatty acids and a higher omega-6/omega-3 ratio predicted suicide attempt. CONCLUSIONS: A low docosahexaenoic acid percentage and low omega-3 proportions of lipid profile predicted risk of suicidal behavior among depressed patients over the 2-year period. If confirmed, this finding would have implications for the neurobiology of suicide and reduction of suicide risk. [ABSTRACT FROM AUTHOR]

Background: Desire for death is not generally considered a harbinger of more severe suicidal behavior and is not routinely included in suicide research and assessment interviews. We aimed to compare desire for death and suicidal ideation as clinical markers for suicide attempts.Methods: Using data from two nationally representative surveys (n=42,862 and n=43,093 respectively), we examined whether desire for death predicts suicide attempts. We compared the odds ratio (OR) and "Number Needed to be Exposed for one additional person to be Harmed" [NNEH] for lifetime suicide attempts among those with desire for death but no suicidal ideation; those with suicidal ideation but no desire for death, and those with both desire for death and suicidal ideation, compared to those with neither desire for death nor suicidal ideation.Results: The risk for lifetime suicide attempt was similar among those with lifetime desire for death with no suicidal ideation and those with lifetime suicidal ideation with no desire for death. Respondents with both lifetime desire for death and suicidal ideation had the highest risk for lifetime suicide attempts.Limitations: Cross-sectional design and self-reported suicidal ideation/attempts are viewed as limitations of this study.Conclusions: Querying individuals on desire for death has the same value as assessing suicidal ideation to examine risk for suicide attempt. A combination of desire for death and suicidal ideation is the best predictor for suicide attempts. This is of high clinical relevance since we suggest that desire for death should be included as a potential clinical marker of suicidality in clinical assessments. [ABSTRACT FROM AUTHOR]

Suicide is one of the leading causes of death, and suicidal ideation and attempts are a major public health concern. However, little is known about the relationship between ethnicity and suicidal behaviors. This article provides an update on the relationship between ethnicity and suicidal ideation and attempts. It reviews the rates of suicidal ideation/attempts across ethnic groups in the United States as well as the risk factors associated with suicide attempts in each ethnic group. The results of published studies have been inconsistent. Some studies have suggested that non-Hispanic Whites have significantly higher suicide attempt risk than other ethnic groups, while two studies using national data did not find any significant relationship between race/ethnicity and suicidal ideation or attempts. From the epidemiologic point of view, these findings underscore the need to conduct large studies in general population samples that include enough individuals from all ethnic groups and that are large enough to detect significant effects among those groups. From the clinical point of view, mental health professionals should focus on factors consistently found to be strongly associated with suicide attempts across different populations, including major depressive disorder and other psychiatric disorders, female gender, and young age. [ABSTRACT FROM AUTHOR]

Objective: Exposure to suicidal behavior in peers and relatives is thought to increase risk for suicidal behavior in vulnerable individuals, possibly as a result of imitation or modeling. This study examines exposure to suicidal behavior and likelihood of suicide attempt in a high-risk cohort of offspring of a depressed parent.Method: A total of 449 offspring of 255 probands with a mood disorder were enrolled in a family study. Probands and offspring were assessed for psychopathology and suicide attempt history, and offspring for suicide exposure. Generalized estimating equations (GEE) and generalized least squares models were used to compare suicide attempt history in exposed and nonexposed offspring as well as characteristics of exposure in exposed offspring suicide attempters and exposed nonattempters. GEE was used to compare exposure occurring before first attempt in attempter offspring and exposure occurring before the same age in matched nonattempter offspring.Results: Offspring reporting exposure to suicidal behavior were four times more likely to report a lifetime suicide attempt compared with unexposed offspring, controlling for age. Suicide attempt status was not associated with age at first exposure, total number or degree (attempt or threat) of exposures, or relationship. Analysis of exposure occurring before age at first suicide attempt found no association between exposure and suicide attempt.Conclusions: Offspring exposed to suicidal behavior are more likely to report a lifetime suicide attempt than nonexposed offspring. However, when examining the temporal sequence of exposure and attempt, the association is no longer significant, suggesting that imitation is not sufficient explanation. [ABSTRACT FROM AUTHOR]

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., (© 2024. The Author(s).)

Objective: The confluence of conflict-, climate-, and public health-related emergencies in Mozambique increases the risk of posttraumatic stress disorder (PTSD). Few brief screening tools for PTSD have been validated in low- and middle-income countries. We aimed to validate the five-item Primary Care PTSD Screen for the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5 ), the PC-PTSD-5 in Mozambique., Method: This study recruited 957 participants who completed the Mini-International Neuropsychiatric Interview-Plus (MINI-Plus) and PC-PTSD-5, a convenience sample from primary and tertiary care settings in Maputo, Mozambique. Participants were administered a diagnostic interview for psychiatric disorders and the PC-PTSD-5 screening tool. We evaluated the criterion validity of the PC-PTSD-5 concerning the MINI-Plus diagnosis of PTSD, the internal construct validity and reliability using confirmatory factor analysis and Kuder-Richardson 20 (KR-20), discriminant validity of the PC-PTSD-5 in comparison to other common mental disorder and suicide risk screening tools, and measurement invariance of selected cutoffs by age, sex, and comorbidity., Results: Internal consistency of the PC-PTSD-5 was high (KR-20 = 0.837), and confirmatory factor analysis suggested that a single PTSD factor fits the data well. PC-PTSD-5 items were moderately correlated with other psychiatric symptoms. Criterion validity analyses revealed that a cutoff score of 3 provided high specificity (0.833) and moderate sensitivity (0.673). This cutoff score performed optimally across age and gender; however, a cutoff score of 2 was preferred if the participant had no psychiatric comorbidities., Conclusion: Screening with the PC-PTSD-5 may facilitate case detection and linkages to appropriate treatment for individuals affected by potentially traumatic events in Mozambique. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Competing Interests: Declaration of interests PM reports grants from National Institute for Health and Care Research (NIHR), the Medical Research Council (MRC), Bristol & Weston Hospitals Charity, and The Cassell Hospital Charitable Trust; and salary support from the NIHR Applied Research Collaboration Southwest, the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation, and Avon and Wiltshire Mental Health Partnership NHS Trust. NK reports grants from NIHR, Health Quality Improvement Partnership, and the Department of Health and Social Care; has received salary support from the Greater Manchester NIHR Patient Safety Research Collaboration, Mersey Care NHS Foundation Trust, and the University of Manchester; has chaired and contributed to committees for the National Institute for Health and Clinical Excellence (NICE) guidelines, including those on the management of self-harm; and is a member of the National Suicide Prevention Strategy Advisory Group (England). RCO is a trustee and science council member of MQ Mental Health Research, president of the International Association for Suicide Prevention, co-chair of the academic advisory group to the Scottish Government's National Suicide Prevention Leadership Group, and a board member of the International Academy of Suicide Research; was a member of the NICE guideline group for the management of self-harm; and reports grants from Medical Research Foundation, the Mindstep Foundation, Chief Scientist Office, MRC, Public Health Scotland, Scottish Government, NIHR, Shout 85258, Scottish Association for Mental Health, Zoetis Foundation, Jonathan's Voice, ADHD UK, and Barfil Charitable Trust. HC reports grants from the National Health and Medical Research Council (NHMRC), the Medical Research Future Fund, Paul Ramsay Foundation, and the Australian Government; is Scientia Professor at the University of New South Wales, supported by an NHMRC Elizabeth Blackburn Research Fellowship, and chief investigator on the NHMRC Centre for Research Excellence in Suicide Prevention; sits on the Million Minds Committee; and is a director of the Black Dog Institute Board and the Ramsay Health Care Research Foundation. MS declares salary support through academic scholar awards from Sunnybrook Health Sciences Centre and the University of Toronto. OJK is currently supported by a Research Foundation Flanders Senior Postdoctoral Fellowship; reports grants from Research Foundation Flanders and the King Baudouin Foundation; is co-chair of the International Association for Suicide Prevention Early Career Group, for which she receives complimentary student membership; is a former member of the Samaritans research ethics board; and has previously received travel grants and waived registration to present at conferences of the International Academy of Suicide Research. JP reports grants from NHMRC, the Medical Research Future Fund, Department of Health of the Australian Government, New South Wales Health, and the National Suicide Prevention Office. LFC is the vice president of the International Association for Suicide Prevention and is a permanent member of the Malaysian technical working group for suicide prevention; reports grants from the Centre of Pesticide Suicide Prevention at the University of Edinburgh; has received honorarium from Johnson & Johnson as a consultant and speaker; and, through her institution, has received access to the industry-sponsored medication sampling programme (compassionate patient programme) for clinical use for medication samples of esketamine (Johnson & Johnson), brexpiprazole (Lundbeck), Abilify Maintena (Lundbeck), and Trinza (Johnson & Johnson). DK is funded through the Elizabeth Blackwell Institute for Health Research at the University of Bristol, which is supported by the Wellcome Trust; has received grants from the Centre for Pesticide Suicide Prevention and the American Foundation for Suicide Prevention; and is a steering group member of the UK's National Suicide Prevention Alliance, and the Migration Health and Development Research Initiative. VP has consulted with Google and Modern Health (unrelated to the scope of this project). AC reports grants from Wellcome Trust, Leverhulme Trust, Economic and Social Research Council; has received funded consultancy from the Scottish Government and Alcohol Change UK; and is a member of the academic advisory group to the Scottish Government's National Suicide Prevention Leadership Group. SPe reports a 2021–2024 Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research. NS is a lived experience advisor to the Wellcome Trust, consumer academic at the University of Melbourne, lived experience lead at the Royal Children's Hospital, member of the Lived Experience Air Academy for University of Wollongong's Project Air, lived experience director for the Australian BPD Foundation, and associate at yLab (a division of the Foundation for Young Australians); reports previous employment with Orygen, and previous roles with the Youth Affairs Council of Victoria, Victorian Department of Families, Fairness, and Housing, Victorian Department of Premier and Cabinet, and Moonee Valley City Council; funded travel through Black Dog Institute and International Association of Suicide Prevention; and a current research tie to Orygen. FSt reports a grant from the Burdett Trust for Nursing and support from Abertay University. PSFY is a member of the advisory committee on mental health for the government of the Hong Kong Special Administrative Region. All other authors declare no competing interests.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Early life adversity is a risk factor for psychopathology and is associated with epigenetic alterations in the 5-HT 1A receptor gene promoter. The 5-HT 1A receptor mediates neurotrophic effects, which could affect brain structure and function. We examined relationships between self-reported early childhood abuse, 5-HT 1A receptor promoter DNA methylation, and gray matter volume (GMV) in Major Depressive Disorder (MDD)., Methods: Peripheral DNA methylation of 5-HT 1A 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 (p FWE  = 0.005), and negatively in intracalcarine cortex (p FWE  = 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-HT 1A 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-HT 1A receptor methylation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Oquendo receives royalties from the Research Foundation for Mental Hygiene for the commercial use of the Columbia Suicide Severity Rating Scale. She serves as an advisor to Alkermes, Mind Medicine, Sage Therapeutics, St. George's University and Fundación Jimenez Diaz. Her family owns stock in Bristol Myers Squibb. Dr. Mann receives royalties from the Research Foundation for Mental Hygiene for commercial use of the C-SSRS. Dr. Sullivan is currently an employee of Tonix Pharmaceuticals Holding Corp and owns stock and stock options in the company. All other authors have no disclosures or competing interests to report. Dr. Miller has received research support from Evecxia and AbbVie Pharmaceuticals., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Conflict of Interests Statement: Dr. Oquendo receives royalties from the Research Foundation for Mental Hygiene for the commercial use of the Columbia Suicide Severity Rating Scale. She serves as an advisor to Alkermes, Mind Medicine, Sage Therapeutics, St. George’s University and Fundacion Jimenez Diaz. Her family owns stock in Bristol Myers Squibb. The other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Impaired emotion regulation (ER) contributes to major depression and suicidal ideation and behavior. ER is typically studied by explicitly directing participants to regulate, but this may not capture spontaneous tendencies of individuals with depression to engage ER in daily life., Methods: In 82 participants with major depressive disorder, 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 that underlie 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 measuring daily stressors, suicidal ideation, 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 suicidal ideation following stressors (b = 0.083, p = .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 = .029). Output for the immerse period was not associated with ecological momentary assessment outcomes., Conclusions: Findings suggest that in major depressive disorder, 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., (Copyright © 2024. Published by Elsevier Inc.)

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.

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.

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Brown and Oquendo receive royalties from the Research Foundation for Mental Hygiene, Inc. for the commercial use of the Columbia-Suicide Severity Rating Scale. Dr. Brown has equity in Oui Therapeutics. Dr. Oquendo consults for Alkermes, MindMed, and Sage Therapeutics. Her family owns stock in Bristol Myers Squibb. The other authors declare that they have no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Dinesh Bhugra is a past president of the World Psychiatric Association, the Royal College of Psychiatrists, and the British Medical Association. Maria A. Oquendo is a past president of the American Psychiatric Association and is a member of the International Advisory Board for The Lancet Regional Health—Americas. All other authors declare no competing interests.

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., Competing Interests: CONFLICT OF INTEREST Dr. Milton Wainberg is on the Editorial Advisory Board of the Journal of Current Psychiatry Research and Reviews.

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., (© 2023. The Author(s).)

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., Competing Interests: Declaration of competing interest Drs. Oquendo and Mann receive royalties from the Research Foundation for Mental Hygiene for the commercial use of the Columbia Suicide Severity Rating Scale. Dr. Oquendo owns shares in Mantra, Inc. and serves as an advisor to Alkermes, Mind Med, Sage Therapeutics, St. George's University and Fundacion Jimenez Diaz. Her family owns stock in Bristol Myers Squibb. Dr. Sullivan is a member of the scientific advisory board for TONIX Pharmaceuticals. Dr. Mann has received grant support from GlaxoSmithKline and Novartis. Dr. Dervic and Dr. Sher report no conflict of interest., (Published by Elsevier B.V.)

Valid mental and substance use disorders and suicide risk screening tools are needed for community case finding of individuals who may not otherwise seek care. We evaluated the Proxy Mental Wellness Tool-3 (mwTool-3-proxy) a three-item screener that asks about the mental health of another adult, against a diagnostic gold standard in Mozambique and South Africa. The mwTool-3-proxy adapts the three items of the Mental Wellness Tool-3, developed in Mozambique using Mini International Neuropsychiatric Interview diagnoses as the criterion standard, regression modeling and expert consultation to determine the best three items for identifying any mental disorder. The Mental Wellness Tool-3 has been validated in South Africa, Spain and the United States, and is being validated in three countries in the Asia-Pacific and Israel. Pairs of adults in South Africa and Mozambique at primary and tertiary healthcare facilities were separately screened with the mwTool-3-proxy and diagnosed using the Mini International Neuropsychiatric Interview. We calculated the sensitivities and specificities for predicting any mental and/or substance use disorder and suicide risk among the proxy individual. We performed additional analyses restricted to respondents who were relatives of one another and who lived in the same household. The prevalence of any Mini International Neuropsychiatric Interview-diagnosed disorder among the 229 pairs in both countries was 35.6% (38.5% in Mozambique; 32.9% in South Africa). The pooled sensitivity of the mwTool-3-proxy for identifying any disorder among the proxy individual was 73.01 (95%CI: 65.5-79.65) - 70.24 (95%CI: 59.27-79.73) in Mozambique and 80.00 (95%CI 69.17-88.35) in South Africa. The mwTool-3-proxy is a culturally-relevant, ultra-brief valid measure that can improve mental and substance use disorders and suicide risk case detection with strong sensitivity at the community and household level and offer a means to efficiently and feasibly collect clinical and population-level service needs data., Competing Interests: Conflicts of Interest Statement The authors have no conflicts of interest to declare.

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-HT 1A ) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and in vivo 5-HT 1A receptor binding potential (BP F ) 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-HT 1A receptor gene. A subgroup ( n = 119) had regional brain 5-HT 1A receptor BP F quantified by PET. Multi-predictor models were used to test associations between diagnosis, recent stress, childhood adversity, genotype, methylation and BP F ., 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-HT 1A BP F 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 BP F in participants with MDD., Conclusions: These findings support a model in which recent stress increases 5-HT 1A receptor binding, via methylation of promoter sites, thus affecting MDD psychopathology.

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 (AUC g ), F(1,60)=10.04, SE=5.095, p=.003, and lower HPA-axis stress responsivity to the TSST (AUC i ), 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 (mean diff =22.32, p=.038) and in response to the stressor task (mean diff =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., Competing Interests: Declaration of Competing Interest Drs. Mann, Oquendo and Stanley receive royalties for commercial use of the Columbia Suicide Severity Rating Scale from the Research Foundation for Mental Hygiene. Dr. Oquendo serves as an advisor to Alkermes, Mind Medicine, Sage Therapeutics, St. George's University and Fundacion Jimenez Diaz. Her family owns stock in Bristol Myers Squibb., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Suicide is a leading cause of death worldwide. In 2020, some 12.2 million Americans seriously contemplated suicide, 3.2 million planned suicide attempts, and 1.2 million attempted suicide. Traditionally, the approach to treating suicidal behavior (SB) has been to treat the "underlying" psychiatric disorder. However, the number of diagnoses associated with SB is considerable. We could find no studies describing the range of disorders reported to be comorbid with SB. This narrative review summarizes literature documenting the occurrence of SB across the lifespan and the full range of psychiatric diagnoses, not only BPD and those that comprise MDE, It also describes the relevance of these observations to clinical practice, research, and nosology. The literature searches contained the terms "suicid*" and each individual psychiatric diagnosis and identified 587 studies. We did not include case reports, case series, studies only addressing suicidal ideation or non-suicidal self-injury (NSSI), studies on self-harm, not distinguishing between SB and NSSI and studies that did not include any individuals that met criteria for a specific DSM-5 diagnosis (n = 366). We found that SB (suicide and/or suicide attempt) was reported to be associated with 72 out of 145 diagnoses, although data quality varied. Thus, SB is not exclusively germane to Major Depressive Episode (MDE) and Borderline Personality Disorder (BPD), the only conditions for which it is a diagnostic criterion. That SB co-occurs with so many diagnoses reinforces the need to assess current and past SB regardless of diagnosis, and supports the addition of charting codes to the DSM-5 to indicate current or past SB. It also comports with new data that specific genes are associated with SB independent of psychiatric diagnoses, and suggests that SB should be managed with specific suicide prevention interventions in addition to treatments indicated for co-occurring diagnoses. SB diagnostic codes would help researchers and clinicians document and measure SB's trajectory and response to treatment over time, and, ultimately, help develop secondary and tertiary prevention strategies. As a separate diagnosis, SB would preclude situations in which a potentially life-threatening behavior is not accounted for by a diagnosis, a problem that is particularly salient when no mental disorder is present, as is sometimes the case., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: COI: Dr. Oquendo reports receipt of royalties from the Research Foundation for Mental Hygiene; ownership of shares in Mantra, Inc.; and service as an advisor to Alkermes and Otsuka. She reports her family owns stock in Bristol Myers Squibb. The other authors report no financial relationships with commercial interests.

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 [ 11 C]DASB and [ 11 C]CUMI-101 positron emission tomography (PET) imaging. Binding potential (BP ND ) to the serotonin transporter (5-HTT) and serotonin 1A (5-HT 1A ) 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-HT 1A BP ND were unrelated to EMA stress. There were region-specific effects of 5-HTT (p=0.002) and 5-HT 1A BP ND (p=0.03) in attempters vs. nonattempters. In attempters, region-specific associations between 5-HTT (p=0.03) and 5-HT 1A (p=0.005) BP ND and EMA stress emerged. While no post-hoc 5-HTT BP ND correlations were significant, 5-HT 1A BP ND 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-HT 1A 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-HT 1A binding with stress among attempters specifically may suggest that a serotonergic phenotype might be a key determinant of risk or resiliency for suicidal behavior., Competing Interests: Declaration of Competing Interest Drs. Bartlett, Zanderigo, Stanley, Choo, Galfalvy, Pantazatos, Sublette, and Miller declares that they have no conflict of interest. Drs. Oquendo and Mann receive royalties from the Research Foundation for Mental Hygiene for the commercial use of the Columbia Suicide Severity Rating Scale. Dr. Oquendo serves as an advisor to Alkermes, Otsuka, Mind Medicine, St. George's University and Fundacion Jimenez Diaz. Her family owns stock in Bristol Myers Squibb., (Copyright © 2023 Elsevier B.V. and ECNP. All rights reserved.)

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., (© 2023. The Author(s).)