Genomics-driven screening for causal determinants of suicide attempt.

OBJECTIVE: Each year, around one million people die by suicide. Despite its recognition as a public health concern, large-scale research on causal determinants of suicide attempt risk is scarce. Here, we leverage results from a recent genome-wide association study (GWAS) of suicide attempt to perform a data-driven screening of traits causally associated with suicide attempt. METHODS: We performed a hypothesis-generating phenome-wide screening of causal relationships between suicide attempt risk and 1520 traits, which have been systematically aggregated on the Complex-Traits Genomics Virtual Lab platform. We employed the latent causal variable (LCV) method, which uses results from GWAS to assess whether a causal relationship can explain a genetic correlation between two traits. If a trait causally influences another one, the genetic variants that increase risk for the causal trait will also increase the risk for the outcome inducing a genetic correlation. Nonetheless, a genetic correlation can also be observed when traits share common pathways. The LCV method can assess whether the pattern of genetic effects for two genetically correlated traits support a causal association rather than a shared aetiology. RESULTS: Our approach identified 62 traits that increased risk for suicide attempt. Risk factors identified can be broadly classified into (1) physical health disorders, including oesophagitis, fibromyalgia, hernia and cancer; (2) mental health-related traits, such as depression, substance use disorders and anxiety; and (3) lifestyle traits including being involved in combat or exposure to a war zone, and specific job categories such as being a truck driver or machine operator. CONCLUSIONS: Suicide attempt risk is likely explained by a combination of behavioural phenotypes and risk for both physical and psychiatric disorders. Our results also suggest that substance use behaviours and pain-related conditions are associated with an increased suicide attempt risk, elucidating important causal mechanisms that underpin this significant public health problem.

The Future Proofing Study: Design, methods and baseline characteristics of a prospective cohort study of the mental health of Australian adolescents.

OBJECTIVES: The Future Proofing Study (FPS) was established to examine factors associated with the onset and course of mental health conditions during adolescence. This paper describes the design, methods, and baseline characteristics of the FPS cohort. METHODS: The FPS is an Australian school-based prospective cohort study with an embedded cluster-randomized controlled trial examining the effects of digital prevention programs on mental health. Data sources include self-report questionnaires, cognitive functioning, linkage to health and education records, and smartphone sensor data. Participants are assessed annually for 5 years. RESULTS: The baseline cohort (N = 6388, M = 13.9 years) is broadly representative of the Australian adolescent population. The clinical profile of participants is comparable to other population estimates. Overall, 15.1% of the cohort met the clinical threshold for depression, 18.6% for anxiety, 31.6% for psychological distress, and 4.9% for suicidal ideation. These rates were significantly higher in adolescents who identified as female, gender diverse, sexuality diverse, or Aboriginal and/or Torres Strait Islander (all ps < 0.05). CONCLUSIONS: This paper provides current and comprehensive data about the status of adolescent mental health in Australia. The FPS cohort is expected to provide significant insights into the risk, protective, and mediating factors associated with development of mental health conditions during adolescence.

Associations of loneliness, belongingness and health behaviors with psychological distress and wellbeing during COVID-19.

BACKGROUND: The aim of this study was to assess the effects of loneliness, belongingness and other modifiable factors on psychological distress and wellbeing and whether the effects of COVID-19 modulated these relationships. METHODS: The current study reported on 1217 participants aged 18 years or older who completed an online survey from 28 to 31 March 2020. Survey measures included demographic characteristics; exposure to COVID-19; impact of COVID-19 on employment, finance, and work and social adjustment; loneliness, thwarted belongingness, and health behavior changes as modifiable factors. Outcome measures were psychological distress and wellbeing. RESULTS: Linear regression models revealed that COVID-19 related work and social adjustment difficulties, financial distress, loneliness, thwarted belongingness, eating a less healthy diet poorer sleep and being female were all associated with increased psychological distress and reduced wellbeing (p < 0.05). Psychological distress was more elevated for those with high difficulties adjusting to COVID-19 and high levels of thwarted belongingness (p < 0.005). Similarly, as COVID-19 related work and social adjustment difficulties increased, wellbeing reduced. This was more pronounced in those who felt lower levels of loneliness (p < 0.0001). Other interactions between COVID-19 impacts were observed with gender and poorer diet for psychological distress and cigarette use, age and gender for wellbeing (p < 0.05). LIMITATIONS: The study was cross-sectional, preventing causal interpretation of the relationships. CONCLUSION: Modifiable factors, age and gender had significant impacts on psychological distress and wellbeing. Public health and policy approaches to improving social, economic and lifestyle factors may mitigate the negative mental health effects of the pandemic and its restrictions.

Development and Validation of Static and Adaptive Screeners to Assess Suicidal Thoughts and Behavior.

OBJECTIVE: The aim of the current study was to use a 23-item bank of self-reported symptoms of suicidal thoughts and behaviors to develop new brief measures of suicide risk using data-driven methods. Collectively referred to as the Rapid Measurement Toolkit for Suicidality (RMTS), the new brief static and adaptive measures would allow more efficient screening for suicide risk in clinical and research settings. METHOD: Data for the current study consist of 3,175 Australian adults who form the development sample and 3,755 Australian adults who form the validation sample. Both samples were independently recruited online using Facebook advertisements. Item response theory (IRT) was applied to the 23-item suicide item bank to develop a brief static dimensional measure and to simulate various computerized adaptive algorithms. RESULTS: A 5-item brief static dimensional screener was developed, which performed as well as the commonly used Suicidal Behaviors Questionnaire-Revised (SBQ-R), with marginally greater sensitivity and more information across the continuum of suicidality. An adaptive screener required a mean of 6.2 items and correlated 0.98 with the full item bank. CONCLUSIONS: The RMTS provides reliable and valid brief static and adaptive screeners for the measurement of suicide risk in community, research, and clinical settings.

Personality Predicts Mortality Risk: An Integrative Data Analysis of 15 International Longitudinal Studies.

This study examined the Big Five personality traits as predictors of mortality risk, and smoking as a mediator of that association. Replication was built into the fabric of our design: we used a Coordinated Analysis with 15 international datasets, representing 44,094 participants. We found that high neuroticism and low conscientiousness, extraversion, and agreeableness were consistent predictors of mortality across studies. Smoking had a small mediating effect for neuroticism. Country and baseline age explained variation in effects: studies with older baseline age showed a pattern of protective effects (HR<1.00) for openness, and U.S. studies showed a pattern of protective effects for extraversion. This study demonstrated coordinated analysis as a powerful approach to enhance replicability and reproducibility, especially for aging-related longitudinal research.

Development and community-based validation of eight item banks to assess mental health.

There is a need for precise but brief screening of mental health problems in a range of settings. The development of item banks to assess depression and anxiety has resulted in new adaptive and static screeners that accurately assess severity of symptoms. However, expansion to a wider array of mental health problems is required. The current study developed item banks for eight mental health problems: social anxiety disorder, panic disorder, post-traumatic stress disorder, obsessive-compulsive disorder, adult attention-deficit hyperactivity disorder, drug use, psychosis and suicidality. The item banks were calibrated in a population-based Australian adult sample (N=3175) by administering large item pools (45-75 items) and excluding items on the basis of local dependence or measurement non-invariance. Item Response Theory parameters were estimated for each item bank using a two-parameter graded response model. Each bank consisted of 19-47 items, demonstrating excellent fit and precision across a range of -1 to 3 standard deviations from the mean. No previous study has developed such a broad range of mental health item banks. The calibrated item banks will form the basis of a new system of static and adaptive measures to screen for a broad array of mental health problems in the community.

The panic disorder screener (PADIS): Development of an accurate and brief population screening tool.

The Panic Disorder Screener (PADIS) was developed as a new screener to identify panic disorder in the community and to assess severity of symptoms. The PADIS was developed to fill a gap in existing screening measures, as there are no brief panic screeners available that assess severity. The current study aimed to test the performance of the screener relative to the Patient Health Questionnaire-panic scale (PHQ-panic). The 4-item PADIS was administered to 12,336 young Australian adults, together with the PHQ-panic. A subsample of 1674 participants also completed a phone-based clinical interview to determine whether they met DSM-IV criteria for panic disorder. The PADIS (77% sensitivity, 84% specificity) had higher sensitivity for identifying panic disorder based on clinical criteria than the PHQ-panic (57% sensitivity, 91% specificity), although with reduced specificity. Administration of the PADIS required a mean of 1.9 items, compared to 4.7 items for the PHQ-panic. Each one-point increase in PADIS score was associated with 69% increased odds of meeting clinical criteria for panic disorder. The PADIS was found to be a valid, reliable and brief panic screener that is freely available for use in research and clinical settings.

Systematic item selection process applied to developing item pools for assessing multiple mental health problems.

OBJECTIVES: Given high rates of comorbidity among mental disorders, better methods to rapidly screen across multiple mental disorders are needed. Building on existing Patient Reported Outcomes Measurement Information System (PROMIS) item banks, the present study aimed to select items to assess panic disorder, social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder, adult attention-deficit hyperactivity disorder, substance use disorder, suicidal thoughts and behaviors, and psychosis. STUDY DESIGN AND SETTING: A four-stage process to select items involved systematic literature searches, item refinement and standardization, obtaining feedback from consumers and experts, and reduction of item pools in preparation for calibration in a population-based sample. RESULTS: From 6,900 items collected across the eight mental health conditions, 2,002 were standardized and rated by small groups of consumers and experts. Expert ratings of item relevance tended to correlate moderately with consumer ratings, with variation across conditions. An algorithm was used to generate final item pools ranging from 45 to 75 items. CONCLUSION: The study successfully applied a systematic process to select items for assessing a range of mental disorders. This process for item selection may be applied to additional mental and physical health conditions. The calibration of the present item pools into final item banks will enable the development of flexible measures to assess risk of mental health problems, although more effectively accounting for comorbidity.

The association between change in cognitive ability and cause-specific mortality in a community sample of older adults.

While there is consistent evidence that initial levels of cognitive ability predict mortality, there is mixed evidence for a relationship between changes in cognition and mortality. There have been few studies that have examined whether the level and slope of cognitive performance is predictive of subsequent mortality from all causes or from cardiovascular disease, stroke, heart disease, respiratory disease, or cancer. This study aimed to assess whether the level and slope of cognitive ability were associated with all-cause or cause-specific mortality. A cohort of 896 community-based elderly people in Australia was interviewed four times over 12 years, with vital status followed for up to 17 years. Of these, 592 participants completed two or more interviews and were included in survival models of six mortality outcomes. Cognitive change in five domains of ability was estimated using latent growth models. Poorer initial processing speed or verbal fluency was significantly associated with greater all-cause and/or cardiovascular mortality. In addition, declines in global ability were associated with greater all-cause, cardiovascular, and heart disease mortality. Vocabulary and episodic memory were not associated with mortality, and none of the cognitive tests significantly predicted respiratory or cancer mortality. Initial levels of cognitive ability tended to be better predictors of subsequent mortality than were changes in ability. The results suggest that vascular events may be largely responsible for the overall relationship between cognition and mortality.

Funding for mental health research: the gap remains.

OBJECTIVES: To examine the levels and growth rates of absolute funding to mental health research from 2001 to 2010, compared with other National Health Priority Areas (NHPAs), and the relative rate of mental health funding compared with other NHPAs, by taking disease burden into account. The quality of Australian research in mental health was also examined using objective indicators of research strength. DESIGN AND SETTING: Retrospective analysis of levels of funding overall and as a function of mental health domains using data from the National Health and Medical Research Council, with and without adjustment for burden of disease. A keyword analysis was used to assess the success rate of mental health project grant applications. Objective indicators of the quality of Australian mental health research were sought from citation indicators. MAIN OUTCOME MEASURES: Funding for mental health research relative to disease burden; funding according to disease category; project grant success rates. RESULTS: Using actual and adjusted figures, mental health research received a lower proportion of health funding than other NHPAs, including cancer, diabetes and cardiovascular disease. Research projects into substance misuse and autism were proportionately better funded than those in anxiety, depression or schizophrenia. A significant proportion of mental health research funding was awarded to research into ageing. Citation data indicated that mental health research in Australia performed better than research in neuroscience, clinical medicine, microbiology, and pharmacology and toxicology, and at a comparable level to immunology research, despite poor levels of funding. CONCLUSIONS: Low levels of funding for mental health research appear to be largely attributable to low capacity. Mental health research in Australia is of high quality, and efforts are needed to build capacity.

A population study comparing screening performance of prototypes for depression and anxiety with standard scales.

BACKGROUND: Screening instruments for mental disorders need to be short, engaging, and valid. Current screening instruments are usually questionnaire-based and may be opaque to the user. A prototype approach where individuals identify with a description of an individual with typical symptoms of depression, anxiety, social phobia or panic may be a shorter, faster and more acceptable method for screening. The aim of the study was to evaluate the accuracy of four new prototype screeners for predicting depression and anxiety disorders and to compare their performance with existing scales. METHODS: Short and ultra-short prototypes were developed for Major Depressive Disorder (MDD), Generalised Anxiety Disorder (GAD), Panic Disorder (PD) and Social Phobia (SP). Prototypes were compared to typical short and ultra-short self-report screening scales, such as the Centre for Epidemiology Scale, CES-D and the GAD-7, and their short forms. The Mini International Neuropsychiatric Interview (MINI) version 6 1 was used as the gold standard for obtaining clinical criteria through a telephone interview. From a population sample, 225 individuals who endorsed a prototype and 101 who did not were administered the MINI. Receiver operating characteristic (ROC) curves were plotted for the short and ultra short prototypes and for the short and ultra short screening scales. RESULTS: The study found that the rates of endorsement of the prototypes were commensurate with prevalence estimates. The short-form and ultra short scales outperformed the short and ultra short prototypes for every disorder except GAD, where the GAD prototype outperformed the GAD 7. CONCLUSIONS: The findings suggest that people may be able to self-identify generalised anxiety more accurately than depression based on a description of a prototypical case. However, levels of identification were lower than expected. Considerable benefits from this method of screening may ensue if our prototypes can be improved for Major Depressive Disorder, Social Phobia and Panic Disorder.