Changes in the prevalence of mental health problems during the first year of the pandemic: a systematic review and dose-response meta-analysis.

AIM: To describe the pattern of the prevalence of mental health problems during the first year of the COVID-19 pandemic and examine the impact of containment measures on these trends. METHODS: We identified articles published until 30 August 2021 that reported the prevalence of mental health problems in the general population at two or more time points. A crowd of 114 reviewers extracted data on prevalence, study and participant characteristics. We collected information on the number of days since the first SARS-CoV-2 infection in the study country, the stringency of containment measures and the number of cases and deaths. We synthesised changes in prevalence during the pandemic using a random-effects model. We used dose-response meta-analysis to evaluate the trajectory of the changes in mental health problems. RESULTS: We included 41 studies for 7 mental health conditions. The average odds of symptoms increased during the pandemic (mean OR ranging from 1.23 to 2.08). Heterogeneity was very large and could not be explained by differences in participants or study characteristics. Average odds of psychological distress, depression and anxiety increased during the first 2 months of the pandemic, with increased stringency of the measures, reported infections and deaths. The confidence in the evidence was low to very low. CONCLUSIONS: We observed an initial increase in the average risk of psychological distress, depression-related and anxiety-related problems during the first 2 months of the pandemic. However, large heterogeneity suggests that different populations had different responses to the challenges imposed by the pandemic.

Probing the neurocardiac circuit in trauma and posttraumatic stress.

The neurocardiac circuit is integral to physiological regulation of threat and trauma-related responses. However, few direct investigations of brain-behavior associations with replicable physiological markers of PTSD have been conducted. The current study probed the neurocardiac circuit by examining associations among its core regions in the brain (e.g., insula, hypothalamus) and the periphery (heart rate [HR], high frequency heart rate variability [HF-HRV], and blood pressure [BP]). We sought to characterize these associations and to determine whether there were differences by PTSD status. Participants were N = 315 (64.1 % female) trauma-exposed adults enrolled from emergency departments as part of the prospective AURORA study. Participants completed a deep phenotyping session (e.g., fear conditioning, magnetic resonance imaging) two weeks after emergency department admission. Voxelwise analyses revealed several significant interactions between PTSD severity 8-weeks posttrauma and psychophysiological recordings on hypothalamic connectivity to the prefrontal cortex (PFC), insula, superior temporal sulcus, and temporoparietaloccipital junction. Among those with PTSD, diastolic BP was directly correlated with right insula-hypothalamic connectivity, whereas the reverse was found for those without PTSD. PTSD status moderated the association between systolic BP, HR, and HF-HRV and hypothalamic connectivity in the same direction. While preliminary, our findings may suggest that individuals with higher PTSD severity exhibit compensatory neural mechanisms to down-regulate autonomic imbalance. Additional study is warranted to determine how underlying mechanisms (e.g., inflammation) may disrupt the neurocardiac circuit and increase cardiometabolic disease risk in PTSD.

Premature Death, Suicide, and Nonlethal Intentional Self-Harm After Psychiatric Discharge.

Importance: There is a need for representative research on serious adverse outcomes following discharge from psychiatric hospitalization. Objective: To compare rates of premature death, suicide, and nonlethal intentional self-harm after psychiatric discharge with rates in the general population and investigate associations of these outcomes with relevant variables associated with the index psychiatric hospitalization. Design, Setting, and Participants: This retrospective cohort study included all residents from Catalonia, Spain (7.6 million population), who had psychiatric hospitalizations between January 1, 2014, and December 31, 2018, and were older than 10 years at the index (first) hospitalization. Follow-up was until December 31, 2019. Statistical analysis was performed from December 1, 2022, through April 11, 2024. Exposures: Socioeconomic status, psychiatric diagnoses, duration of index hospitalization, and number of previous psychiatric hospitalizations. Main Outcomes and Measures: Postdischarge premature death (ie, all-cause death before age 70 years) and suicide (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code range X60-X84), identified using mortality data, and postdischarge nonlethal intentional self-harm, identified using electronic health record and self-harm case register data. Standardized mortality ratios (SMRs) compared rates of premature death and suicide between the cohort and the general population. Fully adjusted, multivariable, cause-specific Cox proportional hazards regression models for the 3 outcomes were fitted. Results: A total of 49 108 patients discharged from psychiatric hospitalization were included (25 833 males [52.6%]; mean [SD] age at discharge, 44.2 [18.2] years). During follow-up, 2260 patients (4.6%) died prematurely, 437 (0.9%) died by suicide, and 4752 (9.7%) had an episode of nonlethal intentional self-harm. The overall SMR for premature death was 7.5 (95% CI, 7.2-7.9). For suicide, SMR was 32.9 (95% CI, 29.9-36.0) overall and was especially high among females (47.6 [95% CI, 40.2-54.9]). In fully adjusted sex-stratified hazard models, postdischarge premature death was associated with cognitive disorders (adjusted hazard ratio [AHR], 2.89 [95% CI, 2.24-3.74] for females; 2.59 [95% CI, 2.17-3.08] for males) and alcohol-related disorders (AHR, 1.41 [95% CI, 1.18-1.70] for females; 1.22 [95% CI, 1.09-1.37] for males). Postdischarge suicide was associated with postdischarge intentional self-harm (AHR, 2.83 [95% CI, 1.97-4.05] for females; 3.29 [95% CI, 2.47-4.40] for males), with depressive disorders (AHR, 2.13 [95% CI, 1.52-2.97]) and adjustment disorders (AHR, 1.94 [95% CI, 1.32-2.83]) among males, and with bipolar disorder among females (AHR, 1.94 [95% CI, 1.21-3.09]). Postdischarge intentional self-harm was associated with index admissions for intentional self-harm (AHR, 1.95 [95% CI, 1.73-2.21] for females; 2.62 [95% CI, 2.20-3.13] for males) as well as for adjustment disorders (AHR, 1.48 [95% CI, 1.33-1.65] for females; 1.99 [95% CI, 1.74-2.27] for males), anxiety disorders (AHR, 1.24 [95% CI, 1.10-1.39] for females; 1.36 [95% CI, 1.18-1.58] for males), depressive disorders (AHR, 1.54 [95% CI, 1.40-1.69] for females; 1.80 [95% CI, 1.58-2.04] for males), and personality disorders (AHR, 1.59 [95% CI, 1.46-1.73] for females; 1.43 [95% CI, 1.28-1.60] for males). Conclusions and Relevance: In this cohort study of patients discharged from psychiatric hospitalization, risk for premature death and suicide was significantly higher compared with the general population, suggesting individuals discharged from psychiatric inpatient care are a vulnerable population for premature death and suicidal behavior.

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study.

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Predicting Suicide Among US Veterans Using Natural Language Processing-enriched Social and Behavioral Determinants of Health.

Despite recognizing the critical association between social and behavioral determinants of health (SBDH) and suicide risk, SBDHs from unstructured electronic health record (EHR) notes for suicide predictive modeling remain underutilized. This study investigates the impact of SBDH, identified from both structured and unstructured data utilizing a natural language processing (NLP) system, on suicide prediction within 7, 30, 90, and 180 days of discharge. Using EHR data of 2,987,006 Veterans between October 1, 2009, and September 30, 2015, from the US Veterans Health Administration (VHA), we designed a case-control study that demonstrates that incorporating structured and NLP-extracted SBDH significantly enhances the performance of three architecturally distinct suicide predictive models - elastic-net logistic regression, random forest (RF), and multilayer perceptron. For example, RF achieved notable improvements in suicide prediction within 180 days of discharge, with an increase in the area under the receiver operating characteristic curve from 83.57-84.25% (95% CI = 0.63%-0.98%, p-val < 0.001) and the area under the precision recall curve from 57.38-59.87% (95% CI = 3.86%-4.82%, p-val < 0.001) after integrating NLP-extracted SBDH. These findings underscore the potential of NLP-extracted SBDH in enhancing suicide prediction across various prediction timeframes, offering valuable insights for healthcare practitioners and policymakers.

Comparative effectiveness of remote digital gamified and group CBT skills training interventions for anxiety and depression among college students: Results of a three-arm randomised controlled trial.

Digital interventions can enhance access to healthcare in under-resourced settings. However, guided digital interventions may be costly for low- and middle-income countries, despite their effectiveness. In this randomised control trial, we evaluated the effectiveness of two digital interventions designed to address this issue: (1) a Cognitive Behavioral Therapy Skills Training (CST) intervention that increased scalability by using remote online group administration; and (2) the SuperBetter gamified self-guided CBT skills training app, which uses other participants rather than paid staff as guides. The study was implemented among anxious and/or depressed South African undergraduates (n = 371) randomised with equal allocation to Remote Group CST, SuperBetter, or a MoodFlow mood monitoring control. Symptoms were assessed with the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Intention-to-treat analysis found effect sizes at the high end of prior digital intervention trials, including significantly higher adjusted risk differences (ARD; primary outcome) in joint anxiety/depression remission at 3-months and 6-months for Remote Group CST (ARD = 23.3-18.9%, p = 0.001-0.035) and SuperBetter (ARD = 12.7-22.2%, p = 0.047-0.006) than MoodFlow and mean combined PHQ-9/GAD-7 scores (secondary outcome) significantly lower for Remote Group CST and SuperBetter than MoodFlow. These results illustrate how innovative delivery methods can increase the scalability of standard one-on-one guided digital interventions. PREREGISTRATION INTERNATIONAL STANDARD RANDOMISED CONTROLLED TRIAL NUMBER (ISRTCN) SUBMISSION #: 47,089,643.

Twelve-month prevalence, persistence, severity, and treatment of mood and anxiety disorders in Qatar's national mental health study.

OBJECTIVES: To estimate 12-month prevalence, persistence, severity, and treatment of mental disorders and socio-demographic correlates in Qatar. METHODS: We conducted the first national population-based telephone survey of Arab adults between 2019 and 2022 using the Composite International Diagnostic Interview and estimated 12-month DSM-5 mood and anxiety disorders and their persistence (the proportion of lifetime cases who continue to meet 12-month criteria). RESULTS: The 12-month prevalence of any disorder was 21.1% (10.4% mild, 38.7% moderate, and 50.9% severe) and was associated with: younger age, female, previously married, and with persistence of any disorder. Persistence was 74.7% (64.0% mood and 75.6% anxiety) and was significantly associated with secondary education or lower. Minimally adequate treatment received among those with any 12-month mental disorder was 10.6% (74.6% in healthcare and 64.6% non-healthcare sectors). Severity and the number of disorders significantly associated with each other and with treatment received (χ2 = 7.24, p = 0.027) including adequate treatment within the mental health specialty sector (χ2 = 21.42, p < 0.001). CONCLUSIONS: Multimorbidity and sociodemographics were associated with 12-month mental disorder. Treatment adequacy in Qatar are comparable to high-income countries. Low treatment contact indicate need for population-wide mental health literacy programes in addition to more accessible and effective mental health services.

Lifetime prevalence, risk, and treatment of mood and anxiety disorders in Qatar's national mental health study.

OBJECTIVES: To estimate lifetime prevalence, risk, and treatment for mental disorders and their correlates in Qatar's general population for the first time. METHODS: We conducted a national phone survey of 5,195 Qatari and Arab residents in Qatar (2019-2022) using the Composite International Diagnostic Interview Version 3.3 and estimated lifetime mood and anxiety defined diagnoses. Survival-based discrete time models, lifetime morbid risk, and treatment projections were estimated. RESULTS: Lifetime prevalence of any disorder was 28.0% and was associated with younger cohorts, females, and migrants, but lower formal education. Treatment contact in the year of disorder onset were 13.5%. The median delay in receiving treatment was 5 years (IQR = 2-13). Lifetime treatment among those with a lifetime disorder were 59.9% for non-healthcare and 63.5% for healthcare; it was 68.1% for any anxiety and 80.1% for any mood disorder after 50 years of onset. Younger cohorts and later age of onset were significantly predictors of treatment. CONCLUSIONS: Lifetime prevalence of mental disorders in Qatar is comparable to other countries. Treatment is significantly delayed and delivered largely in non-healthcare sectors thus the need for increased literacy of mental illness to reduce stigma and improve earlier help-seeking in healthcare settings.

Clinical reappraisal of the composite international diagnostic interview version 3.3 in Qatar's National Mental Health Study.

OBJECTIVES: Lifetime DSM-5 diagnoses generated by the lay-administered Composite International Diagnostic Interview for DSM-5 (CIDI) in the World Mental Health Qatar (WMHQ) study were compared to diagnoses based on blinded clinician-administered reappraisal interviews. METHODS: Telephone follow-up interviews used the non-patient edition of the Structured Clinician Interview for DSM-5 (SCID) oversampling respondents who screened positive for five diagnoses in the CIDI: major depressive episode, mania/hypomania, panic disorder, generalized anxiety disorder, and obsessive-compulsive disorder. Concordance was also examined for a diagnoses of post-traumatic stress disorder based on a short-form versus full version of the PTSD Checklist for DSM-5 (PCL-5). RESULTS: Initial CIDI prevalence estimates differed significantly from the SCID for most diagnoses ( χ 1 2 ${\chi }_{1}^{2}$  = 6.6-31.4, p = 0.010 < 0.001), but recalibration reduced most of these differences and led to consistent increases in individual-level concordance (AU-ROC) from 0.53-0.76 to 0.67-0.81. Recalibration of the short-form PCL-5 removed an initially significant difference in PTSD prevalence with the full PCL-5 (from χ 1 2 ${\chi }_{1}^{2}$  = 610.5, p < 0.001 to χ 1 2 ${\chi }_{1}^{2}$  = 2.5, p = 0.110) while also increasing AU-ROC from 0.76 to 0.81. CONCLUSIONS: Recalibration resulted in valid diagnoses of common mental disorders in the Qatar National Mental Health Survey, but with inflated prevalence estimates for some disorders that need to be considered when interpreting results.

Can the potential benefit of individualizing treatment be assessed using trial summary statistics alone?

Individualizing treatment assignment can improve outcomes for diseases with patient-to-patient variability in comparative treatment effects. When a clinical trial demonstrates that some patients improve on treatment while others do not, it is tempting to assume that treatment effect heterogeneity exists. However, if outcome variability is mainly driven by factors other than variability in the treatment effect, investigating the extent to which covariate data can predict differential treatment response is a potential waste of resources. Motivated by recent meta-analyses assessing the potential of individualizing treatment for major depressive disorder using only summary statistics, we provide a method that uses summary statistics widely available in published clinical trial results to bound the benefit of optimally assigning treatment to each patient. We also offer alternate bounds for settings in which trial results are stratified by another covariate. Our upper bounds can be especially informative when they are small, as there is then little benefit to collecting additional covariate data. We demonstrate our approach using summary statistics from a depression treatment trial. Our methods are implemented in the rct2otrbounds R package, which is available at https://github.com/ngalanter/rct2otrbounds.

Factors associated with satisfaction and perceived helpfulness of mental healthcare: a World Mental Health Surveys report.

BACKGROUND: Mental health service providers are increasingly interested in patient perspectives. We examined rates and predictors of patient-reported satisfaction and perceived helpfulness in a cross-national general population survey of adults with 12-month DSM-IV disorders who saw a provider for help with their mental health. METHODS: Data were obtained from epidemiological surveys in the World Mental Health Survey Initiative. Respondents were asked about satisfaction with treatments received from up to 11 different types of providers (very satisfied, satisfied, neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied) and helpfulness of the provider (a lot, some, a little, not at all). We modelled predictors of satisfaction and helpfulness using a dataset of patient-provider observations (n = 5,248). RESULTS: Most treatment was provided by general medical providers (37.4%), psychiatrists (18.4%) and psychologists (12.7%). Most patients were satisfied or very satisfied (65.9-87.5%, across provider) and helped a lot or some (64.4-90.3%). Spiritual advisors and healers were most often rated satisfactory and helpful. Social workers in human services settings were rated lowest on both dimensions. Patients also reported comparatively low satisfaction with general medical doctors and psychiatrists/psychologists and found general medical doctors less helpful than other providers. Men and students reported lower levels of satisfaction than women and nonstudents. Respondents with high education reported higher satisfaction and helpfulness than those with lower education. Type of mental disorder was unrelated to satisfaction but in some cases (depression, bipolar spectrum disorder, social phobia) was associated with low perceived helpfulness. Insurance was unrelated to either satisfaction or perceived helpfulness but in some cases was associated with elevated perceived helpfulness for a given level of satisfaction. CONCLUSIONS: Satisfaction with and perceived helpfulness of treatment varied as a function of type of provider, service setting, mental status, and socio-demographic variables. Invariably, caution is needed in combining data from multiple countries where there are cultural and service delivery variations. Even so, our findings underscore the utility of patient perspectives in treatment evaluation and may also be relevant in efforts to match patients to treatments.

Sex Differences in Response Inhibition-Related Neural Predictors of Posttraumatic Stress Disorder in Civilians With Recent Trauma.

BACKGROUND: Females are more likely to develop posttraumatic stress disorder (PTSD) than males. Impaired inhibition has been identified as a mechanism for PTSD development, but studies on potential sex differences in this neurobiological mechanism and how it relates to PTSD severity and progression are relatively rare. Here, we examined sex differences in neural activation during response inhibition and PTSD following recent trauma. METHODS: Participants (n = 205, 138 female sex assigned at birth) were recruited from emergency departments within 72 hours of a traumatic event. PTSD symptoms were assessed 2 weeks and 6 months posttrauma. A Go/NoGo task was performed 2 weeks posttrauma in a 3T magnetic resonance imaging scanner to measure neural activity during response inhibition in the ventromedial prefrontal cortex, right inferior frontal gyrus, and bilateral hippocampus. General linear models were used to examine the interaction effect of sex on the relationship between our regions of interest and the whole brain, PTSD symptoms at 6 months, and symptom progression between 2 weeks and 6 months. RESULTS: Lower response inhibition-related ventromedial prefrontal cortex activation 2 weeks posttrauma predicted more PTSD symptoms at 6 months in females but not in males, while greater response inhibition-related right inferior frontal gyrus activation predicted lower PTSD symptom progression in males but not females. Whole-brain interaction effects were observed in the medial temporal gyrus and left precentral gyrus. CONCLUSIONS: There are sex differences in the relationship between inhibition-related brain activation and PTSD symptom severity and progression. These findings suggest that sex differences should be assessed in future PTSD studies and reveal potential targets for sex-specific interventions.

The epidemiology of obsessive-compulsive disorder in the Kingdom of Saudi Arabia: Data from the Saudi National Mental Health Survey.

AIMS: There is ongoing debate about the extent to which the epidemiology of OCD is similar across the world, given the lack of nationally representative data from key regions like the Middle East and North Africa. Using the nationally representative dataset from the Saudi National Mental Health Survey (SNMHS), we aimed to delineate the epidemiological profile of OCD in the Saudi population. METHODS: A subsample of 1981 participants from the SNMHS was assessed. Prevalence estimates and correlates of OCD were determined using logistic regressions and cross tabulations. RESULTS: The lifetime, 12-month, and 30-day prevalence estimates for OCD were 4.2%, 1.8%, and 1.6%, respectively, with hoarding being the most common symptom dimension. The mean age-of-onset of OCD was 16.8 years. In over two-thirds of respondents with lifetime (72.2%) or 12-month (71.2%), OCD was accompanied by comorbid mental disorder, particularly impulse control, anxiety, and mood disorders. Among individuals with 12-month OCD, 77.5% reported severe impairment, and only 9.2% received treatment. CONCLUSIONS: In Saudi Arabia, OCD is a prevalent and persistent condition, characterized by early onset, high odds of mental comorbidity, and significant associated impairment. These findings emphasize the universality of OCD epidemiology and the need for improved diagnosis and treatment globally.

Brain dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma.

This study examines the association between brain dynamic functional network connectivity (dFNC) and current/future posttraumatic stress (PTS) symptom severity, and the impact of sex on this relationship. By analyzing 275 participants' dFNC data obtained ~2 weeks after trauma exposure, we noted that brain dynamics of an inter-network brain state link negatively with current (r=-0.179, pcorrected= 0.021) and future (r=-0.166, pcorrected= 0.029) PTS symptom severity. Also, dynamics of an intra-network brain state correlated with future symptom intensity (r = 0.192, pcorrected = 0.021). We additionally observed that the association between the network dynamics of the inter-network brain state with symptom severity is more pronounced in females (r=-0.244, pcorrected = 0.014). Our findings highlight a potential link between brain network dynamics in the aftermath of trauma with current and future PTSD outcomes, with a stronger protective effect of inter-network brain states against symptom severity in females, underscoring the importance of sex differences.

Effectiveness of the Minder Mobile Mental Health and Substance Use Intervention for University Students: Randomized Controlled Trial.

BACKGROUND: University attendance represents a transition period for students that often coincides with the emergence of mental health and substance use challenges. Digital interventions have been identified as a promising means of supporting students due to their scalability, adaptability, and acceptability. Minder is a mental health and substance use mobile app that was codeveloped with university students. OBJECTIVE: This study aims to examine the effectiveness of the Minder mobile app in improving mental health and substance use outcomes in a general population of university students. METHODS: A 2-arm, parallel-assignment, single-blinded, 30-day randomized controlled trial was used to evaluate Minder using intention-to-treat analysis. In total, 1489 participants were recruited and randomly assigned to the intervention (n=743, 49.9%) or waitlist control (n=746, 50.1%) condition. The Minder app delivers evidence-based content through an automated chatbot and connects participants with services and university social groups. Participants are also assigned a trained peer coach to support them. The primary outcomes were measured through in-app self-assessments and included changes in general anxiety symptomology, depressive symptomology, and alcohol consumption risk measured using the 7-item General Anxiety Disorder scale, 9-item Patient Health Questionnaire, and US Alcohol Use Disorders Identification Test-Consumption Scale, respectively, from baseline to 30-day follow-up. Secondary outcomes included measures related to changes in the frequency of substance use (cannabis, alcohol, opioids, and nonmedical stimulants) and mental well-being. Generalized linear mixed-effects models were used to examine each outcome. RESULTS: In total, 79.3% (589/743) of participants in the intervention group and 83% (619/746) of participants in the control group completed the follow-up survey. The intervention group had significantly greater average reductions in anxiety symptoms measured using the 7-item General Anxiety Disorder scale (adjusted group mean difference=-0.85, 95% CI -1.27 to -0.42; P<.001; Cohen d=-0.17) and depressive symptoms measured using the 9-item Patient Health Questionnaire (adjusted group mean difference=-0.63, 95% CI -1.08 to -0.17; P=.007; Cohen d=-0.11). A reduction in the US Alcohol Use Disorders Identification Test-Consumption Scale score among intervention participants was also observed, but it was not significant (P=.23). Statistically significant differences in favor of the intervention group were found for mental well-being and reductions in the frequency of cannabis use and typical number of drinks consumed. A total of 77.1% (573/743) of participants in the intervention group accessed at least 1 app component during the study period. CONCLUSIONS: In a general population sample of university students, the Minder app was effective in reducing symptoms of anxiety and depression, with provisional support for increasing mental well-being and reducing the frequency of cannabis and alcohol use. These findings highlight the potential ability of e-tools focused on prevention and early intervention to be integrated into existing university systems to support students' needs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05606601; https://clinicaltrials.gov/ct2/show/NCT05606601. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/49364.

Developing an individualized treatment rule for Veterans with major depressive disorder using electronic health records.

Efforts to develop an individualized treatment rule (ITR) to optimize major depressive disorder (MDD) treatment with antidepressant medication (ADM), psychotherapy, or combined ADM-psychotherapy have been hampered by small samples, small predictor sets, and suboptimal analysis methods. Analyses of large administrative databases designed to approximate experiments followed iteratively by pragmatic trials hold promise for resolving these problems. The current report presents a proof-of-concept study using electronic health records (EHR) of n = 43,470 outpatients beginning MDD treatment in Veterans Health Administration Primary Care Mental Health Integration (PC-MHI) clinics, which offer access not only to ADMs but also psychotherapy and combined ADM-psychotherapy. EHR and geospatial databases were used to generate an extensive baseline predictor set (5,865 variables). The outcome was a composite measure of at least one serious negative event (suicide attempt, psychiatric emergency department visit, psychiatric hospitalization, suicide death) over the next 12 months. Best-practices methods were used to adjust for nonrandom treatment assignment and to estimate a preliminary ITR in a 70% training sample and to evaluate the ITR in the 30% test sample. Statistically significant aggregate variation was found in overall probability of the outcome related to baseline predictors (AU-ROC = 0.68, S.E. = 0.01), with test sample outcome prevalence of 32.6% among the 5% of patients having highest predicted risk compared to 7.1% in the remainder of the test sample. The ITR found that psychotherapy-only was the optimal treatment for 56.0% of patients (roughly 20% lower risk of the outcome than if receiving one of the other treatments) and that treatment type was unrelated to outcome risk among other patients. Change in aggregate treatment costs of implementing this ITR would be negligible, as 16.1% fewer patients would be prescribed ADMs and 2.9% more would receive psychotherapy. A pragmatic trial would be needed to confirm the accuracy of the ITR.

Blood-based DNA methylation and exposure risk scores predict PTSD with high accuracy in military and civilian cohorts.

Background: Incorporating genomic data into risk prediction has become an increasingly useful approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not. Methods: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts. Results: The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p-0.003), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p < 0.001) predictive power for post-deployment PTSD. Conclusion: Results, especially those from the eMRS, reinforce earlier findings that methylation and trauma are interconnected and can be leveraged to increase the correct classification of those with vs. without PTSD. Moreover, our models can potentially be a valuable tool in predicting the future risk of developing PTSD. As more data become available, including additional molecular, environmental, and psychosocial factors in these scores may enhance their accuracy in predicting the condition and, relatedly, improve their performance in independent cohorts.

Polygenic risk for suicide attempt is associated with lifetime suicide attempt in US soldiers independent of parental risk.

BACKGROUND: Suicide is a leading cause of death worldwide. Whereas some studies have suggested that a direct measure of common genetic liability for suicide attempts (SA), captured by a polygenic risk score for SA (SA-PRS), explains risk independent of parental history, further confirmation would be useful. Even more unsettled is the extent to which SA-PRS is associated with lifetime non-suicidal self-injury (NSSI). METHODS: We used summary statistics from the largest available GWAS study of SA to generate SA-PRS for two non-overlapping cohorts of soldiers of European ancestry. These were tested in multivariable models that included parental major depressive disorder (MDD) and parental SA. RESULTS: In the first cohort, 417 (6.3 %) of 6573 soldiers reported lifetime SA and 1195 (18.2 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.26, 95%CI:1.13-1.39, p < 0.001] per standardized unit SA-PRS]. In the second cohort, 204 (4.2 %) of 4900 soldiers reported lifetime SA, and 299 (6.1 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.20, 95%CI:1.04-1.38, p = 0.014]. A combined analysis of both cohorts yielded similar results. In neither cohort or in the combined analysis was SA-PRS significantly associated with NSSI. CONCLUSIONS: PRS for SA conveys information about likelihood of lifetime SA (but not NSSI, demonstrating specificity), independent of self-reported parental history of MDD and parental history of SA. LIMITATIONS: At present, the magnitude of effects is small and would not be immediately useful for clinical decision-making or risk-stratified prevention initiatives, but this may be expected to improve with further iterations. Also critical will be the extension of these findings to more diverse populations.