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OBJECTIVES: Currently, there are no effective treatments for functional outcomes (i.e., role and social) and negative symptoms for youth at clinical high-risk (CHR) for psychosis. Investigations into possible mechanisms that may contribute to the improvement of functioning and negative symptoms are needed in CHR research to help inform psychosocial treatments. The present study examined whether functioning and negative symptoms were mediated by asocial beliefs, defeatist beliefs, self-efficacy, maladaptive schemas, anxiety, depression, social cognition, or attenuated psychotic symptoms (APS) in a large clinical trial. METHODS: CHR participants (n = 203; 104 females; 99 males) were recruited as part of a three-site randomized control trial comparing group cognitive-behavioural social skills training (CBSST) versus a supportive therapy group. Mediation analyses were conducted to test the relationships between treatment group, mediators (asocial beliefs, defeatist beliefs, self-efficacy, maladaptive schemas, anxiety, depression, social cognition, and APS), and outcome (social and role functioning, and negative symptoms). The mediation analyses employed conditional process path analysis via ordinary least squares regression. RESULTS: At the end of treatment, but not 12-month follow-up, more severe APS were found to mediate the impact of treatment on negative symptoms, and social and role functioning. The greater the severity of APS, the less likely that CBSST would result in improvement in negative symptoms and social and role functioning. Many of the other variables showed significant associations with social (less for role) functioning and negative symptoms but did not mediate the effect of treatment on these outcomes at the end of treatment or 12-month follow-up. CONCLUSIONS: There were no significant mediators except for APS at the end of treatment. Since more severe APS may result in participants being unable to fully participate in therapy and thus limit their gains, clinical implications may include offering some individual therapy to prepare these young people to benefit from the group treatment.

BACKGROUND: Patient participation in treatment decision making is a pillar of recovery-oriented care and is associated with improvements in empowerment and well-being. Although demand for increased involvement in treatment decision-making is high among veterans with serious mental illness, rates of involvement are low. Collaborative decision skills training (CDST) is a recovery-oriented, skills-based intervention designed to support meaningful patient participation in treatment decision making. An open trial among veterans with psychosis supported CDSTs feasibility and demonstrated preliminary indications of effectiveness. A randomized control trial (RCT) is needed to test CDSTs effectiveness in comparison with an active control and further evaluate implementation feasibility. METHODS: The planned RCT is a hybrid type 1 trial, which will use mixed methods to systematically evaluate the effectiveness and implementation feasibility of CDST among veterans participating in a VA Psychosocial Rehabilitation and Recovery Center (PRRC) in Southern California. The first aim is to assess the effectiveness of CDST in comparison with the active control via the primary outcome, collaborative decision-making behavior during usual care appointments between veterans and their VA mental health clinicians, and secondary outcomes (i.e., treatment engagement, satisfaction, and outcome). The second aim is to characterize the implementation feasibility of CDST within the VA PRRC using the Practical Robust Implementation and Sustainability Model framework, including barriers and facilitators within the PRRC context to support future implementation. DISCUSSION: If CDST is found to be effective and feasible, implementation determinants gathered throughout the study can be used to ensure sustained and successful implementation at this PRRC and other PRRCs and similar settings nationally. TRIAL REGISTRATION: ClinicalTrials.gov NCT04324944. Registered on March 27, 2020. Trial registration data can be found in Appendix 1.

The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aβ deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.

Individuals with Down syndrome (DS) have a partial or complete trisomy of chromosome 21, resulting in an increased risk for early-onset Alzheimer's disease (AD)-type dementia by early midlife. Despite ongoing clinical trials to treat late-onset AD, individuals with DS are often excluded. Furthermore, timely diagnosis or management is often not available. Of the genetic causes of AD, people with DS represent the largest cohort. Currently, there is a knowledge gap regarding the underlying neurobiological mechanisms of DS-related AD (DS-AD), partly due to limited access to well-characterized brain tissue and biomaterials for research. To address this challenge, we created an international consortium of brain banks focused on collecting and disseminating brain tissue from persons with DS throughout their lifespan, named the Down Syndrome Biobank Consortium (DSBC) consisting of 11 biobanking sites located in Europe, India, and the USA. This perspective describes the DSBC harmonized protocols and tissue dissemination goals.

The aging population of the world is increasing at an unprecedented rate which is expected to lead to a corresponding unparalleled increase in age related diseases. Of particular concern are the large number of older adults expected to develop Alzheimers disease (AD), which will require extraordinary local, national and worldwide healthcare resources. In this context, innovative interventions are needed urgently to delay AD onset and thereby give our healthcare systems time to prepare and provide meaningful care to our aging populations. This focused review discusses the crucial role of frontal gamma oscillations as a therapeutic target to delay or ameliorate cognitive decline in AD. Frontal gamma oscillations, including from prefrontal cortical areas, serve as a biomarker for working memory and other cognitive functions, and their impairment is observed before clinical symptoms manifest. This review evaluates evidence from animal models and human subjects to highlight the correlation between gamma wave abnormalities and cognitive deterioration. Furthermore, the review summarizes 11 clinical studies using neuromodulation techniques designed to stimulate gamma oscillations in mild cognitive impairment (MCI) and AD patients, including transcranial electrical stimulation, transcranial magnetic stimulation, and rhythmic sensory stimulation. These interventions have shown promise in mitigating early-stage cognitive decline, as evidenced by improved performance on memory tests, increased gamma oscillatory responses, and some have even shown reduced brain atrophy. These early studies suggest that treatments that strengthen frontal gamma oscillatory responses through neuromodulation are a promising approach to delay cognitive decline, that may serve as an adjunct to other therapies or as a standalone treatment in some populations.

This scoping review explores what is currently understood about how masculinity norms interplay with loneliness and social connectedness among men in a Western context. Human beings inherently need social connections, and this review particularly addresses how traditional masculinity norms—emphasizing independence, emotional stoicism, and pain endurance—can increase vulnerability to loneliness and insufficient social connections. The review followed the Joanna Briggs Institute (JBI) methodology for scoping reviews and systematically assessed the literature published between September 2013 and September 2023. Initial literature searches were conducted using multiple databases, including EBSCO and PubMed. Of the 1,730 articles identified, 13 studies met the inclusion criteria and were quality assessed. Results show that men often formed social connections through productive activities. Still, these connections were restricted by conflicting masculine ideals such as self-reliance, which could be prioritized over social and emotional support. Masculine bonds were often formed and strengthened through collectively rejecting diversity. Nevertheless, there were some narratives where participants attempted to redefine masculinity to access permission to care and connect. This review highlights the urgent need for cultural and societal reevaluation of gender norms to support men’s social connectedness. This shift could reduce stigma around emotional vulnerability and in turn men’s opportunities for health and well-being.

Background The concept of an occupational pattern in occupational therapy and occupational science has evolved with varying definitions, ranging from activity patterns to patterns of daily occupation.Aims This study aimed to explore the concept of occupational pattern, develop an updated definition of the concept, and theoretically validate the concept’s definition.Method Walker and Avant’s concept analysis method was used, where both theoretical frameworks and peer-reviewed scientific literature were searched and synthesized to clarify and define the concept. Furthermore, seven occupational therapists theoretically validated the concept.Findings The analysis included forty-nine references from various research contexts and theoretical perspectives. The synthesis yielded a conceptualization of the concept of occupational pattern, outlining it into three overarching categories: ‘content in an individual’s occupational pattern’, ‘designing an occupational pattern’, and ‘balancing the occupational pattern’.Implications An updated operational definition of the multifaceted concept of an occupational pattern now exists, with practical implications for enhancing the education of occupational therapy students and guiding the utilization of the concept. Moreover, it holds significance for instrument development and outcome measurement in research; especially in lifestyle intervention studies within the field of occupational therapy.

Research focused on Down syndrome continued to gain momentum in the last several years and is advancing our understanding of how trisomy 21 (T21) modifies molecular and cellular processes. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome. During the COVID pandemic, T21RS held its first virtual conference program, sponsored by the University of California at Irvine, on June 8-10, 2021 and brought together 342 scientists, families, and industry representatives from over 25 countries to share the latest discoveries on underlying cellular and molecular mechanisms of T21, cognitive and behavioral changes, and comorbidities associated with Down syndrome, including Alzheimers disease and Regression Disorder. Presentations of 91 cutting-edge abstracts reflecting neuroscience, neurology, model systems, psychology, biomarkers, and molecular and pharmacological therapeutic approaches demonstrate the compelling interest and continuing advancement toward innovating biomarkers and therapies aimed at ameliorating health conditions associated with T21.

AIM: Difficulties in social functioning have been observed in youth at clinical high-risk (CHR) of psychosis even in those who do not go on to develop a psychotic illness. Few treatment studies have attempted to improve social functioning in this population. The aim of this study was to conduct a randomized trial comparing the effects of Cognitive-Behavioral Social Skills Training (CBSST) with a supportive therapy (ST). METHODS: Both CBSST and ST were weekly group therapies, delivered over 18 weeks. This was a 2-arm trial with single-blinded ratings and intention-to-treat analyses. Assessments occurred at baseline, end-of-treatment, and 12 months after the baseline assessment. The primary outcome was social and role functioning and defeatist performance attitudes were the secondary outcome. Attenuated positive and negative symptoms, anxiety, depression, self-efficacy, and beliefs about self and others were examined as exploratory outcomes. RESULTS: There were no significant differences between the 2 groups at baseline or either of the 2 follow-ups. However, at follow-ups, in each group there were significant improvements in clinical symptoms. These could not be attributed to group treatment since there was no control or wait-list group. CONCLUSIONS: Since poor social functioning is one of the most observed difficulties in CHR individuals, and a decline in social functioning may be a significant predictor of later transition to psychosis, future work will be needed to find effective treatments for this decline in functioning for CHR youth.

Author(s): Camilla Bekker Mortensen [sup.1] [sup.2] [sup.3], Nina Christine Andersen-Ranberg [sup.1] [sup.3], Lone Musaeus Poulsen [sup.1] [sup.3], Anders Granholm [sup.3] [sup.4], Bodil Steen Rasmussen [sup.3] [sup.5] [sup.6], Maj-Brit Nørregaard Kjær [...], Purpose We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo. Methods We conducted pre-planned analyses of 1-year outcomes in the Agents Intervening against Delirium in the ICU (AID-ICU) trial, including mortality and health-related quality of life (HRQoL) assessed by Euroqol (EQ) 5-dimension 5-level questionnaire (EQ-5D-5L) index values and EQ visual analogue scale (EQ VAS) (deceased patients were assigned the numeric value zero). Outcomes were analysed using logistic and linear regressions with bootstrapping and G-computation, all with adjustment for the stratification variables (site and delirium motor subtype) and multiple imputations for missing HRQoL values. Results At 1-year follow-up, we obtained vital status for 96.2% and HRQoL data for 83.3% of the 1000 randomised patients. One-year mortality was 224/501 (44.7%) in the haloperidol group versus 251/486 (51.6%) in the placebo group, with an adjusted absolute risk difference of - 6.4%-points (95% confidence interval [CI] - 12.8%-points to - 0.2%-points; P = 0.045). These results were largely consistent across the secondary analyses. For HRQoL, the adjusted mean differences were 0.04 (95% CI - 0.03 to 0.11; P = 0.091) for EQ-5D-5L-5L index values, and 3.3 (95% CI - 9.3 to 17.5; P = 0.142) for EQ VAS. Conclusions In acutely admitted adult ICU patients with delirium, haloperidol treatment reduced mortality at 1-year follow-up, but did not statistically significantly improve HRQoL.

BACKGROUND: Cognitive tasks delivered during ecological momentary assessment (EMA) may elucidate the short-term dynamics and contextual influences on cognition and judgements of performance. This paper provides initial validation of a smartphone task of facial emotion recognition in serious mental illness. METHODS: A total of 86 participants with psychotic disorders (non-affective and affective psychosis), aged 19-65, were administered in-lab gold standard affect recognition, neurocognition, and symptom assessments. They subsequently completed 10 days of the mobile facial emotion recognition task, assessing both accuracy and self-assessed performance, along with concurrent EMA of psychotic symptoms and mood. Validation focused on task adherence and predictors of adherence, gold standard convergent validity, and symptom and diagnostic group variation. RESULTS: The mean rate of adherence to the task was 79%; no demographic or clinical variables predicted adherence. Convergent validity was observed with in-lab measures of facial emotion recognition, and no practice effects were observed on the mobile facial emotion recognition task. EMA reports of more severe voices, sadness, and paranoia were associated with worse performance, whereas mood more strongly associated with self-assessed performance. CONCLUSION: The mobile facial emotion recognition task was tolerated and demonstrated convergent validity with in-lab measures of the same construct. Social cognitive performance, and biased judgements previously shown to predict function, can be evaluated in real-time in naturalistic environments.

Childhood trauma (CT) is associated with suicidal ideation and behaviors (SI/SB) in people with psychosis. The interpersonal psychological theory of suicide (IPTS) suggests that there are four factors that increase suicide risk: thwarted belongingness, perceived burdensomeness, acquired capacity for suicide, and hopelessness. The IPTS constructs and social cognitive biases are associated with SI/SB in psychotic disorders. However, the role of CT in IPTS constructs and social cognitive biases has not been examined in psychosis. In an outpatient community sample of persons with psychotic disorders (N = 96) assessed with the Childhood Trauma Questionnaire, the aims of this study were to a) evaluate rates of CT in this sample, b) determine the relationship between CT types and lifetime SI/SB, and c) explore the relationship between CT types, IPTS constructs, and social cognitive biases. All participants reported experiencing CT. Emotional abuse was associated with greater SI severity and higher rates of lifetime suicide attempts, as well as with greater perceived burdensomeness and more severe negative social cognitive biases. Other CT types were minimally associated with SI/SB or IPST constructs; hopelessness was not associated. Overall, negative interpersonal beliefs and social cognitive biases may explain how CT increases suicide risk in psychosis.

With recent developments in medical and psychiatric research surrounding pupillary response, cheap and accessible pupillometers could enable medical benefits from early neurological disease detection to measurements of cognitive load. In this paper, we introduce a novel smartphone-based pupillometer to allow for future development in clinical research surrounding at-home pupil measurements. Our solution utilizes a NIR front-facing camera for facial recognition paired with the RGB selfie camera to perform tracking of absolute pupil dilation with sub-millimeter accuracy. In comparison to a gold standard pupillometer during a pupillary light reflex test, the smartphone-based system achieves a median MAE of 0.27mm for absolute pupil dilation tracking and a median error of 3.52% for pupil dilation change tracking. Additionally, we remotely deployed the system to older adults as part of a usability study that demonstrates promise for future smartphone deployments to remotely collect data in older, inexperienced adult users operating the system themselves.

ObjectiveNegative symptoms and cognitive impairment in schizophrenia (SZ) remain unmet treatment needs as they are highly prevalent, associated with poor functional outcomes, and resistant to pharmacologic treatment. The current pilot randomized controlled trial examined the efficacy of an integrated Cognitive-Behavioral Social Skills Training and Compensatory Cognitive Training (CBSST-CCT) intervention compared to Goal-focused Supportive Contact (SC) on negative symptoms and cognitive performance.MethodsFifty-five adults with SZ or schizoaffective disorder with moderate-to-severe negative symptoms were randomized to receive 25 twice-weekly, 1-h manualized group sessions (12.5 weeks total duration) of either CBSST-CCT or SC delivered by master's level clinicians in five community settings. Assessments of negative symptom severity (primary outcomes) and neuropsychological performance, functional capacity, social skills performance, and self-reported functional ability/everyday functioning, psychiatric symptom severity, and motivation (secondary outcomes) were administered at baseline, mid-treatment, post-treatment, and 6-month follow-up.ResultsMixed-effects models using baseline, mid-treatment, and post-treatment data demonstrated significant CBSST-CCT-associated effects on negative symptom severity, as assessed by the Scale for the Assessment of Negative Symptoms (p = .049, r = 0.22), with improvements in diminished motivation driving this effect (p = .037, r = 0.24). The CBSST-CCT group also demonstrated improved verbal learning compared to SC participants (p = .026, r = 0.36). The effects of CBSST-CCT appeared to be durable at 6-month follow-up.ConclusionsCBSST-CCT improved negative symptom severity and verbal learning in high-negative-symptom individuals relative to SC. CBSST-CCT warrants larger investigations to examine its efficacy in treating negative symptoms, along with other symptoms, cognition, and, ultimately, real-world functional outcomes. Clinical Trial registration number NCT02170051.

Sedentary behavior contributes to a shortened life expectancy in individuals with schizophrenia-spectrum disorders (SSDs), highlighting the need for effective interventions to improve health. This study examined whether reduced ecological momentary assessment (EMA) measures of sedentary activities were observed in individuals with SSDs who participated in a 24-week randomized trial of cognitive behavioral social skills training (CBSST) and either intranasal oxytocin or placebo (NCT01752712). Participants (n = 57) were prompted with EMA surveys seven times per day for seven days during the baseline, 12-week, and 24-week timepoints to sample sedentary behavior ratings, positive and negative affect, interpersonal interactions, and interpersonal interaction appraisals. Results revealed that sedentary behavior and social interactions did not significantly change over the 24-week clinical trial; however, positive and negative affect and defeatist interaction appraisals improved with treatment, and oxytocin produced modest additional improvements in these EMA outcomes. Greater momentary positive affect was significantly associated with greater activity and greater frequency of interactions. Overall, CBSST was effective at improving functioning, momentary affect, and defeatist interaction appraisals, although it did not reduce sedentary behavior; therefore, targeting these factors is not sufficient to reduce sedentary behavior, and adjunct interventions are needed.

BackgroundAdaptation of interventions is inevitable during translation to new populations or settings. Systematic approach to adaptation can ensure that fidelity to core functions of the intervention are preserved while optimizing implementation feasibility and effectiveness for the local context. In this study, we used an iterative, mixed methods, and stakeholder-engaged process to systematically adapt Collaborative Decision Skills Training for Veterans with psychosis currently participating in VA Psychosocial Rehabilitation and Recovery Centers.MethodsA modified approach to Intervention Mapping (IM-Adapt) guided the adaptation process. An Adaptation Resource Team of five Veterans, two VA clinicians, and four researchers was formed. The Adaptation Resource Team engaged in an iterative process of identifying and completing adaptations including individual qualitative interviews, group meetings, and post-meeting surveys. Qualitative interviews were analyzed using rapid matrix analysis. We used the modified, RE-AIM enriched expanded Framework for Reporting Adaptations and Modifications to Evidence-based interventions (FRAME) to document adaptations. Additional constructs included adaptation size and scope; implementation of planned adaptation (yes-no); rationale for non-implementation; and tailoring of adaptation for a specific population (e.g., Veterans).ResultsRapid matrix analysis of individual qualitative interviews resulted in 510 qualitative codes. Veterans and clinicians reported that the intervention was a generally good fit for VA Psychosocial Rehabilitation and Recovery Centers and for Veterans. Following group meetings to reach adaptation consensus, 158 adaptations were completed. Most commonly, adaptations added or extended a component; were small in size and scope; intended to improve the effectiveness of the intervention, and based on experience as a patient or working with patients. Few adaptations were targeted towards a specific group, including Veterans. Veteran and clinician stakeholders reported that these adaptations were important and would benefit Veterans, and that they felt heard and understood during the adaptation process.ConclusionsA stakeholder-engaged, iterative, and mixed methods approach was successful for adapting Collaborative Decision Skills Training for immediate clinical application to Veterans in a psychosocial rehabilitation center. The ongoing interactions among multiple stakeholders resulted in high quality, tailored adaptations which are likely to be generalizable to other populations or settings. We recommend the use of this stakeholder-engaged, iterative approach to guide adaptations.

Contextual influences on social behavior and affective dynamics are not well understood in schizophrenia. We examined the role of social context on emotions, and the motivation to interact in the future, using dynamic network analysis of ecological momentary assessment (EMA) data. Participants included 105 outpatients with schizophrenia or schizoaffective disorder (SZ) and 76 healthy comparators (HC) who completed 7 days, 7 times a day of EMA. Dynamic networks were constructed using EMA data to visualize causal interactions between emotional states, motivation, and context (e.g., location, social interactions). Models were extended to include the type and frequency of interactions and the motivation to interact in the near future. Results indicated SZ networks were generally similar to HC but that contextual influences on emotion and social motivation were more evident in SZ. Further, feedback loops in HC were likely adaptive (e.g., positive emotions leading to social motivation), but most were likely maladaptive in SZ (e.g., sadness leading to reduced happiness leading to increased sadness). Overall, these findings indicate that network analyses may be useful in specifying emotion regulation problems in SZ and that instability related to contextual influences may be a central aspect of aberrant regulation.

Author(s): Maj-Brit Nørregaard Kjær [sup.1] [sup.2], Tine Sylvest Meyhoff [sup.1] [sup.2], Praleene Sivapalan [sup.1] [sup.2], Anders Granholm [sup.1] [sup.2], Peter Buhl Hjortrup [sup.1] [sup.3], Martin Bruun Madsen [sup.1] [sup.3], Morten [...], Purpose To assess long-term outcomes of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock included in the European Conservative versus Liberal Approach to Fluid Therapy in Septic Shock in Intensive Care (CLASSIC) trial. Methods We conducted the pre-planned analyses of mortality, health-related quality of life (HRQoL) using EuroQol (EQ)-5D-5L index values and EQ visual analogue scale (VAS), and cognitive function using Mini Montreal Cognitive Assessment (Mini MoCA) test at 1 year. Deceased patients were assigned numerical zero for HRQoL as a state equal to death and zero for cognitive function outcomes as worst possible score, and we used multiple imputation for missing data on HRQoL and cognitive function. Results Among 1554 randomized patients, we obtained 1-year data on mortality in 97.9% of patients, HRQoL in 91.3%, and cognitive function in 86.3%. One-year mortality was 385/746 (51.3%) in the restrictive-fluid group versus 383/767 (49.9%) in the standard-fluid group, absolute risk difference 1.5%-points [99% confidence interval (CI) - 4.8 to 7.8]. Mean differences were 0.00 (99% CI - 0.06 to 0.05) for EQ-5D-5L index values, - 0.65 for EQ VAS (- 5.40 to 4.08), and - 0.14 for Mini MoCA (- 1.59 to 1.14) for the restrictive-fluid group versus the standard-fluid group. The results for survivors only were similar in both groups. Conclusions Among adult ICU patients with septic shock, restrictive versus standard IV fluid therapy resulted in similar survival, HRQoL, and cognitive function at 1 year, but clinically important differences could not be ruled out.

BACKGROUND: People with psychotic disorders are at an increased risk of suicide, but there is little understanding of suicidal ideation (SI) in this population. The Interpersonal Psychological Theory of Suicide posits that perceived burdensomeness (PB) and thwarted belonginess (TB) contribute to SI. To our knowledge there are no studies using ecological momentary assessment (EMA) to assess these interpersonal risk factors in a sample of individuals with psychotic disorders. This study investigated the validity and variability of PB and TB, and whether SI, EMA-measured psychotic symptoms, mood, and social context relate to PB and TB. METHOD: Ninety-six participants with a psychotic disorder, including mood disorders with psychosis completed in-lab assessments of current SI, and then EMA surveys on a smartphone 3×/day for 10 days, answering questions about burdensomeness, belongingness, symptoms (i.e., hearing voices, experiencing suspiciousness), mood (i.e., happy, sad), and social context. RESULTS: Burdensomeness varied within-participants less than belongingness (t (95) = -3.74, p=< .001). Participants with SI had higher mean burdensomeness ratings (t (94) = -2.70, p < .01) and lower mean belongingness ratings (t (94) = 3.68, p < .001) than did participants without SI. Being with others, greater psychotic experiences, less happiness, and greater sadness related to greater burdensomeness. SI status, being alone, greater psychotic experiences, less happiness, and greater sadness related to less belongingness. CONCLUSIONS: This study examined the real-time influences of SI and psychotic symptoms on burdensomeness and belongingness. Hearing voices, suspiciousness, mood, and SI are related to interpersonal suicide-related risk factors. In this sample, social context had a differential effect on burdensomeness and belongingness.

IntroductionThe locus coeruleus (LC) undergoes extensive neurodegeneration in early Alzheimer's disease (AD). The LC is implicated in regulating the sleep-wake cycle, modulating cognitive function, and AD progression.MethodsParticipants were 481 men (ages 62 to 71.7) from the Vietnam Era Twin Study of Aging. LC structural integrity was indexed by neuromelanin-sensitive magnetic resonance imaging (MRI) contrast-to-noise ratio (LCCNR ). We examined LCCNR , cognition, amnestic mild cognitive impairment (aMCI), and daytime dysfunction.ResultsHeritability of LCCNR was .48. Participants with aMCI showed greater daytime dysfunction. Lower LCCNR was associated with poorer episodic memory, general verbal fluency, semantic fluency, and processing speed, as well as increased odds of aMCI and greater daytime dysfunction.DiscussionReduced LC integrity is associated with widespread differences across cognitive domains, daytime sleep-related dysfunction, and risk for aMCI. These findings in late-middle-aged adults highlight the potential of MRI-based measures of LC integrity in early identification of AD risk.

Abstract Background Days alive without life support (DAWOLS) and similar outcomes that seek to summarise mortality and non-mortality experiences are increasingly used in critical care research. The use of these outcomes is challenged by different definitions and non-normal outcome distributions that complicate statistical analysis decisions. Methods We scrutinized the central methodological considerations when using DAWOLS and similar outcomes and provide a description and overview of the pros and cons of various statistical methods for analysis supplemented with a comparison of these methods using data from the COVID STEROID 2 randomised clinical trial. We focused on readily available regression models of increasing complexity (linear, hurdle-negative binomial, zero–one-inflated beta, and cumulative logistic regression models) that allow comparison of multiple treatment arms, adjustment for covariates and interaction terms to assess treatment effect heterogeneity. Results In general, the simpler models adequately estimated group means despite not fitting the data well enough to mimic the input data. The more complex models better fitted and thus better replicated the input data, although this came with increased complexity and uncertainty of estimates. While the more complex models can model separate components of the outcome distributions (i.e., the probability of having zero DAWOLS), this complexity means that the specification of interpretable priors in a Bayesian setting is difficult. Finally, we present multiple examples of how these outcomes may be visualised to aid assessment and interpretation. Conclusions This summary of central methodological considerations when using, defining, and analysing DAWOLS and similar outcomes may help researchers choose the definition and analysis method that best fits their planned studies. Trial registration COVID STEROID 2 trial, ClinicalTrials.gov: NCT04509973, ctri.nic.in: CTRI/2020/10/028731.

BACKGROUND: A significant proportion of people with schizophrenia are characterized by impaired ability to socially engage with others. The development of effective interventions for social functioning remains a central therapeutic challenge. Cognitive-behavioral social skills training (CBSST) has been found to improve social functioning in schizophrenia, but with only medium effect sizes. Intranasal oxytocin also has prosocial effects, but also only with modest effect sizes. This study assessed whether the addition of intranasal oxytocin to CBSST can strengthen their impact on social function. METHODS: Participants (N = 62) with schizophrenia or schizoaffective disorder entered a 24-week, double-blind, placebo-controlled, randomized clinical trial with a 3-month follow-up evaluation at 2 sites: Maryland and San Diego. Participants were randomized to either intranasal oxytocin 36 IU (3 sprays) twice a day (n = 31) or intranasal placebo-oxytocin (3 sprays) twice a day (n = 31). All participants received CBSST plus a social cognition skills training module (48 total sessions). RESULTS: There were no significant treatment group differences in social functioning, positive symptoms, negative symptoms, defeatist beliefs, or asocial beliefs. The interpretation of treatment effects was complicated by site effects, whereby participants in San Diego began the trial with greater severity of impairments and subsequently showed greater improvements compared with participants in Maryland. CONCLUSIONS: The results did not support the utility of add-on intranasal oxytocin to psychosocial rehabilitation interventions like CBSST for improvement in social function (ClinicalTrials.gov trial number: NCT01752712).

BACKGROUND: Collaborative decision-making is an innovative decision-making approach that assigns equal power and responsibility to patients and providers. Most veterans with serious mental illnesses like schizophrenia want a greater role in treatment decisions, but there are no interventions targeted for this population. A skills-based intervention is promising because it is well-aligned with the recovery model, uses similar mechanisms as other evidence-based interventions in this population, and generalizes across decisional contexts while empowering veterans to decide when to initiate collaborative decision-making. Collaborative Decision Skills Training (CDST) was developed in a civilian serious mental illness sample and may fill this gap but needs to undergo a systematic adaptation process to ensure fit for veterans. METHODS: In aim 1, the IM Adapt systematic process will be used to adapt CDST for veterans with serious mental illness. Veterans and Veterans Affairs (VA) staff will join an Adaptation Resource Team and complete qualitative interviews to identify how elements of CDST or service delivery may need to be adapted to optimize its effectiveness or viability for veterans and the VA context. During aim 2, an open trial will be conducted with veterans in a VA Psychosocial Rehabilitation and Recovery Center (PRRC) to assess additional adaptations, feasibility, and initial evidence of effectiveness. DISCUSSION: This study will be the first to evaluate a collaborative decision-making intervention among veterans with serious mental illness. It will also contribute to the fields understanding of perceptions of collaborative decision-making among veterans with serious mental illness and VA clinicians, and result in a service delivery manual that may be used to understand adaptation needs generally in VA PRRCs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04324944.