Major depressive disorder (MDD) contributes to suicide risk. Treating MDD effectively is considered a key suicide prevention intervention. Yet many patients with MDD do not respond to their initial medication and require a ‘next-step’. The relationship between next-step treatments and suicidal thoughts and behaviors is uncharted.

The VA Augmentation and Switching Treatments for Depression trial randomized 1522 participants to one of three next-step treatments: Switching to Bupropion, combining with Bupropion, and augmenting with Aripiprazole. In this secondary analysis, features associated with lifetime suicidal ideation (SI) and attempts (SA) at baseline and current SI during treatment were explored.

Compared to those with SI only, those with lifetime SI + SA were more likely to be female, divorced, or separated, unemployed; and to have experienced more childhood adversity. They had a more severe depressive episode and were more likely to respond to ‘next-step’ treatment. The prevalence of SI decreased from 46.5% (694/1492) at baseline to 21.1% (315/1492) at end-of-treatment. SI during treatment was associated with baseline SI; low positive mental health, more anxiety, greater severity and longer duration of current MDD episode; being male and White; and treatment with S-BUP or C-BUP as compared to A-ARI.

SI declines for most patients during next-step medication treatments. But about 1 in 5 experienced emergent or worsening SI during treatment, so vigilance for suicide risk through the entire 12-week acute treatment period is necessary. Treatment selection may affect the risk of SI.

Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms.

In total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006–2010, age = 55.0 ± 7.5 [40–70] years; second visit: 2014–2019; age = 62.7 ± 7.5 [44–80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and depressive symptoms on the second visit among 138 multimodal imaging phenotypes.

Longitudinal data were consistent with significant bidirectional causal relationship between SLEs and depressive symptoms. In cross-sectional analyses, SLEs were significantly associated with lower bilateral nucleus accumbal volume and lower fractional anisotropy of the forceps major. Depressive symptoms were significantly associated with extensive white matter hyperintensities, thinner cortex, lower subcortical volume, and white matter microstructural deficits, mainly in corticostriatal-limbic structures. Lower bilateral nucleus accumbal volume were the only imaging phenotypes with overlapping effects of depressive symptoms and SLEs (B = −0.032 to −0.023, p = 0.006–0.034). Depressive symptoms and SLEs significantly partially mediated the effects of each other on left and right nucleus accumbens volume (proportion of effects mediated = 12.7–14.3%, p < 0.001−p = 0.008). For the left nucleus accumbens, post-hoc seed-based analysis showed lower resting-state functional connectivity with the left orbitofrontal cortex (cluster size = 83 voxels, p = 5.4 × 10−5) in participants with high v. no SLEs.

The nucleus accumbens may play a key role in the reciprocity between stress and depressive symptoms.

Excessive and persistent fear of clusters of holes, also known as trypophobia, has been suggested to reflect cortical hyperexcitability and may be associated with mental health risks. No study, however, has yet examined these associations in representative epidemiological samples.

To examine the prevalence of trypophobia in a population-representative youth sample, its association with mental health and functioning, and its interaction with external stress.

A total of 2065 young people were consecutively recruited from a household-based epidemiological youth mental health study in Hong Kong. Trypophobia, symptoms of anxiety, depression and stress, and exposure to personal stressors were assessed. Logistic regression was used to assess the relationships between trypophobia and mental health. Potential additive and interaction effects of trypophobia and high stress exposure on mental health were also tested.

The prevalence of trypophobia was 17.6%. Trypophobia was significantly associated with severe symptoms of anxiety (odds ratio (OR) = 1.83, 95% CI = 1.32–2.53), depression (OR = 1.78, 95% CI = 1.24–2.56) and stress (OR = 1.68, 95% CI = 1.11–2.53), even when accounting for sociodemographic factors, personal and family psychiatric history, resilience and stress exposure. Dose–response relationships were observed, and trypophobia significantly potentiated the effects of stress exposure on symptom outcomes, particularly for depressive symptoms. Those with trypophobia also showed significantly poorer functioning across domains and poorer health-related quality of life.

Screening for trypophobia in young people may facilitate early risk detection and intervention, particularly among those with recent stress exposure. Nevertheless, the generally small effect sizes suggest that other factors have more prominent roles in determining recent mental health outcomes in population-based samples; these should be explored in future work.

Despite replicated cross-sectional evidence of aberrant levels of peripheral inflammatory markers in individuals with major depressive disorder (MDD), there is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies.

To assess associations between plasma levels of pro-inflammatory markers and treatment response to escitalopram and adjunctive aripiprazole in adults with MDD.

In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10– 20 mg daily for 8 weeks. Responders continued on escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers – C-reactive protein, Interleukin (IL)-1β, IL-6, IL-17, Interferon gamma (IFN)-Γ, Tumour Necrosis Factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2) - measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyses to assess associations between inflammatory markers and treatment response.

Pre-treatment levels of IFN-Γ and CCL-2 were significantly higher in escitalopram non-responders compared to responders. Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.

Pre-treatment levels of IFN-Γ and CCL-2 were predictive of response to escitalopram. Increasing levels of these pro-inflammatory markers may predict non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.

None Declared

Undergraduate students encounter developmental challenges during their transition into adulthood. Previous studies have claimed that adults with later chronotypes usually manifest negative psychological effects: poor sleep quality, greater stress, depression, and cognitive dysfunction. However, knowledge about the relationship between chronotype, stress, and sleep quality among young adults is lacking.

The present study investigated the relationship between undergraduates’ chronotypes and perceived stress on sleep quality.

An online survey with a descriptive, cross-sectional design was conducted with a convenience sample of undergraduate students at a university in southern Taiwan. Those who were 20-25 years old and enrolled as a student were included; but who had been suspended or had deferred graduation were excluded. Students’ chronotype, stress, and sleep quality were assessed with three self-reported instruments: Munich Chronotype Questionnaire (MCTQ), Perceived Stress Scale (PSS), and Pittsburgh Sleep Quality Index (PSQI).

Of 161 undergraduates who completed the questionnaires, 51 reported using an alarm clock to wake and were removed from data analysis. One hundred and ten students’ mean age is 20.3 and perceived moderate stress. Sixty-one percent were poor-quality sleepers. The mean chronotype score was 5.7, and 85.5% had an intermediate chronotype, while 13.6% had an evening chronotype. Chronotype and perceived stress were positively correlated with sleep quality (p < .001). Social jetlag was positively correlated with chronotype (p =.036). Undergraduate’s later chronotype and higher stress perception predicted 30% of poorer sleep quality (p < .001).

Undergraduate students’ chronotype and perceived stress were positively correlated and acted as predictors of the sleep quality. The findings could help to develop health-promotion interventions for these emerging adults to adjust their daily routines; and reduce their social jetlag, stress levels, and sleep disturbance.

None Declared

Mental Health Literacy (MHL) includes four distinct but interrelated components: maintenance of positive mental health (MH), recognition of mental disorders (R), mental illness stigma attitudes (S), and help-seeking efficacy (E). A fifth component, help-seeking attitude (A) was included in a MHL model because it is a strong predictor of help-seeking behaviors. The five-factor model of MHL has been validated previously. In the study of multiple mediation model of MHL, it demonstrated the mediation role of help-seeking efficacy between recognition of mental disorders and help-seeking attitude (R-E-A path), but the roles of mental illness stigma attitudes or maintenance of positive mental health remain unknown.

The present study aimed to examine the theory-based multifaceted MHL model by utilizing a meta-analytic structural equation modeling analyses (MASEM) method.

Systematic search of articles from electronic databases, including APA PsycArticles, ERIC, MEDLINE, Psychology and Behavioral Sciences Collection, Pubmed, and Airiti Library (Chinese), from inception up to July 31, 2022, was conducted by raters independently assessed study eligibility, and extracted 127 empirical, quantitative, non-interventional studies with properly reported effect sizes (k=192). MASEM analyses were conducted via a two-stage approach. First, a pooled correlation matrix was obtained for each mediation model by applying a multivariate random-effects model using Comprehensive Meta-Analysis Version 3.3. Second, a structural equation model was fitted on the pooled correlation matrices to test for mediation effects (i.e., indirect effects) using IBM SPSS Amos.

In the single-mediator model analysis, there was a significant partial mediation effect of help-seeking efficacy and Mental illness stigma attitudes on the relationship between recognition of mental disorders and help-seeking attitude (R-E-A path & R-S-A path, p <.05). The multiple-mediator model has showed adequate fit (RMSEA = 0.09, SRMR = 0.04, CFI = 0.93, GFI = .99). It confirmed the help-seeking efficacy served as a mediator. A sequential mediation of maintenance of positive mental health and mental illness stigma attitudes was found (p <.05) between recognition of mental disorders and help-seeking attitude (R-MH-S-A path).

There is a robust mediation effect of Help-seeking efficacy on the relationship between recognition of mental disorders and help-seeking attitude either in the single mediation model or the multiple mediation model. Furthermore, increased recognition of mental disorder was related to increased maintenance of positive mental health, therefore decreased mental illness stigma attitude, and eventually increased help-seeking attitude. Future research directions regarding pathways in the MHL models were discussed.

None Declared

With persistent incidence, incomplete vaccination rates, confounding respiratory illnesses, and few therapeutic interventions available, COVID-19 continues to be a burden on the pediatric population. During a surge, it is difficult for hospitals to direct limited healthcare resources effectively. While the overwhelming majority of pediatric infections are mild, there have been life-threatening exceptions that illuminated the need to proactively identify pediatric patients at risk of severe COVID-19 and other respiratory infectious diseases. However, a nationwide capability for developing validated computational tools to identify pediatric patients at risk using real-world data does not exist.

HHS ASPR BARDA sought, through the power of competition in a challenge, to create computational models to address two clinically important questions using the National COVID Cohort Collaborative: (1) Of pediatric patients who test positive for COVID-19 in an outpatient setting, who are at risk for hospitalization? (2) Of pediatric patients who test positive for COVID-19 and are hospitalized, who are at risk for needing mechanical ventilation or cardiovascular interventions?

This challenge was the first, multi-agency, coordinated computational challenge carried out by the federal government as a response to a public health emergency. Fifty-five computational models were evaluated across both tasks and two winners and three honorable mentions were selected.

This challenge serves as a framework for how the government, research communities, and large data repositories can be brought together to source solutions when resources are strapped during a pandemic.

There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD).

In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10–20 mg daily for 8 weeks. Responders continued escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers—C-reactive protein, interleukin (IL)-1β, IL-6, IL-17, interferon-gamma (IFN)-Γ, tumor necrosis factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2)—measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyzes to assess associations between inflammatory markers and treatment response.

Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.

Higher pre-treatment levels of IFN-Γ and CCL-2 were associated with non-response to escitalopram. Increasing levels of these pro-inflammatory markers may be associated with non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.

This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive.

A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors.

Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001).

Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer’s disease while considering the burden on the healthcare system.

Patients with major depressive disorder (MDD) often do not respond to antidepressant (ADT) monotherapy alone and may require adjunctive treatment to provide adequate symptom relief. Cariprazine (CAR) is a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist approved to treat adults with schizophrenia and manic, mixed, or depressive episodes of bipolar I disorder. Post hoc analysis of data from a randomized controlled trial evaluated clinically relevant improvements in depressive symptom severity with adjunctive cariprazine in patients with MDD and inadequate response to ADT monotherapy.

Post hoc analysis evaluated data from a randomized, double-blind, placebo-controlled MDD trial (NCT03738215) in patients treated with CAR (1.5 mg/d or 3 mg/d) + ADT or placebo + ADT; the primary outcome was change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Post hoc analysis evaluated category shifts from baseline to week 6 in MADRS severity (normal <6, mild 7–19, moderate 20–34, severe ≥35). MADRS severity shifts were reported as the percentage of patients with no change or worsened severity, 1 category improvement, ≥1 category improvement, and ≥2 category improvement. Examples of categorical shifts in depressive symptoms at week 6 include change from severe at baseline to moderate (1 category improvement) and change from severe at baseline to mild (2 category improvement).

Of the 751 patients in the intent-to-treat (ITT) population (CAR: 1.5 mg/d=250, 3.0 mg/d=252; placebo=249), baseline MADRS severity was mild in 1.5%, moderate in 64%, and severe in 35%. Fewer CAR + ADT patients compared to placebo + ADT had no change or worsened MADRS severity at week 6 (CAR: 1.5 mg/d=32%, 3.0 mg/d=33%; placebo=42%). Approximately 68% of patients treated with CAR + ADT demonstrated a MADRS severity improvement of 1 category or greater by week 6 (CAR: 1.5 mg/d=68%, 3.0 mg/d=67%; placebo=58%). A greater percentage of patients in the CAR 1.5 mg/d group also had a 2 or greater category improvement versus CAR 3.0 mg/d or placebo 6 (CAR: 1.5 mg/d=28%, 3.0 mg/d=17%; placebo=19%).

In this post hoc analysis, CAR + ADT was associated with a greater proportion of patients with improvements in depressive symptom severity categories compared with placebo + ADT. These results may suggest that CAR + ADT is associated with clinically meaningful depressive symptom improvement in MDD patients.

AbbVie

Face masks reduce disease transmission by protecting the wearer from inhaled pathogens and reducing the emission of infectious aerosols. Although methods quantifying efficiency for wearer protection are established, current methods for assessing face mask containment efficiency rely on measurement of a low concentration of aerosols emitted from an infected or noninfected individual.

A small port enabled the introduction of 0.05 µm sodium chloride particles at a constant rate behind the mask worn by a study participant. A condensation particle counter monitored ambient particle numbers 60 cm in front of the participant over 3-minute periods of rest, speaking, and coughing. The containment efficiency (%) for each mask and procedure was calculated as follows: 100 × (1 − average ambient concentration with face covering worn/average ambient concentration with a sham face covering in place). The protection efficiency (%) was also measured using previously published methods. The probability of transmission (%) from infected to uninfected (a function of both the containment efficiency and the protection efficiency) was calculated as follows: {1 − (containment efficiency/100)}×{1 − (protection efficiency/100)}×100.

The average containment efficiencies for each mask over all procedures and repeated measures were 94.6%, 60.9%, 38.8%, and 43.2%, respectively, for the N95 mask, the KN95 mask, the procedure face mask, and the gaiter. The corresponding protection efficiencies for each mask were 99.0%, 63.7%, 45.3%, and 24.2%, respectively. For example, the transmission probability for 1 infected and 1 uninfected individual in close proximity was ∼14.2% for KN95 masks, compared to 36%–39% when only 1 individual wore a KN95 mask.

Overall, we detected a good correlation between the protection and containment that a face covering afforded to a wearer.

Policymakers and researchers have little evidence on prevalence rates of intellectual disability (ID) or their changes over time to tailor healthcare interventions. Prevalence rates and trends of ID are especially lacking in regions with lower socio-demographic development. Additionally, the assessment of inequalities in the prevalence of ID across regions with varying socio-demographic development is understudied. This study assessed variations in prevalence rates of ID from 1990 to 2019 and the related inequalities between low and high socio-demographic index (SDI) regions.

This study used global data from 1990 to 2019 for individuals with ID from the 2019 Global Burden of Diseases study. Data analyses were performed from September 2021 to January 2022. Prevalence for individuals with ID was extracted by sex, age groups and SDI regions. Annual percentage change (APC) was estimated for each demographic group within SDI regions to assess their prevalence trends over 30 years. Relative and absolute inequalities were calculated between low and high SDI regions for the various age groups.

In 2019, there were 107.62 million (1.74%) individuals with ID, with an APC of −0.80 (−0.88 to −0.72). There was a slightly higher prevalence among males (1.42%) than females (1.37%). The highest prevalence rates were found in the low-middle SDI regions (2.42%) and the lowest prevalence rates were in the high SDI regions (0.33%). There was a large reduction in the prevalence rate between the youngest age group v. the oldest age group in all the SDI regions and at all time points. The relative inequalities between low and high SDI regions increased over three decades.

While an overall decrease in global prevalence rate for ID was found, relative inequalities continue to increase with lower SDI regions needing more comprehensive support services. The demographic trends indicate a significantly higher mortality rate among those with ID v. the rest of the population. Our study highlights the necessity for policies and interventions targeting lower SDI regions to mobilise resources that better support individuals with ID and achieve sustainable development goals proposed by the United Nations.