Assessing social connection for long-term care home residents: Systematic review using COnsensus-based Standards for the selection of health Measurement INstruments guidelines.

Social connection is important for long-term care (LTC) residents' quality of life and care. However, there is a lack of consensus on how to measure it and this limits ability to find what improves and impairs social connection in LTC homes. We therefore aimed to systematically review and evaluate the measurement properties of existing measures of social connection for LTC residents, to identify which, if any, measures can be recommended. We searched eight electronic databases from inception to April 2022 for studies which reported on psychometric properties of a measure of any aspect(s) of social connection (including social networks, interaction, engagement, support, isolation, connectedness, and loneliness) for LTC residents. We used COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines to evaluate the measurement properties reported for each identified measure and make recommendations. We identified 62 studies reporting on 38 measures; 21 measured quality of life, well-being or life satisfaction and included a social connection subscale or standalone items and 17 measures specifically targeted social connection. We found there was little high-quality evidence on psychometric properties such as sufficient content validity (n = 0), structural validity (n = 3), internal consistency (n = 3), reliability (n = 1), measurement error (n = 0), construct validity (n = 4), criterion validity (n = 0) and responsiveness (n = 0). No measures demonstrated satisfactory psychometric properties on all these aspects, so none could be recommended for use. Thirty-four measures have the potential to be recommended but require further research to assess their quality and the remaining four are not recommended for use. Our review therefore found that no existing measures have sufficient evidence to be recommended for assessment of social connection in residents of LTC homes. Further validation and reliability studies of existing instruments or the development of new measures are needed to enable accurate measurement of social connection in LTC residents for future observational and interventional studies. Highlights: Social connection is fundamental to person-centered care in long-term care homes.There is insufficient evidence for the reliability and validity of existing measures.No current measures can be recommended for use based on existing evidence.A reliable and valid measure of social connection is needed for future research.

Characterization of Effects of mTOR Inhibitors on Aging in Caenorhabditis elegans.

Pharmacological inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway with rapamycin can extend lifespan in several organisms. Although this includes the nematode Caenorhabditis elegans, effects in this species are relatively weak and sometimes difficult to reproduce. Here we test effects of drug dosage and timing of delivery to establish the upper limits of its capacity to extend life, and investigate drug effects on age-related pathology and causes of mortality. Liposome-mediated rapamycin treatment throughout adulthood showed a dose-dependent effect, causing a maximal 21.9% increase in mean lifespan, but shortening of lifespan at the highest dose, suggesting drug toxicity. Rapamycin treatment of larvae delayed development, weakly reduced fertility and modestly extended lifespan. By contrast, treatment initiated later in life robustly increased lifespan, even from Day 16 (or ~70 years in human terms). The rapalog temsirolimus extended lifespan similarly to rapamycin, but effects of everolimus were weaker. As in mouse, rapamycin had mixed effects on age-related pathologies, inhibiting one (uterine tumor growth) but not several others, suggesting a segmental antigeroid effect. These findings should usefully inform future experimental studies with rapamycin and rapalogs in C. elegans.

Mitochondrial clearance and increased HSF-1 activity are coupled to promote longevity in fasted Caenorhabditis elegans.

Fasting has emerged as a potent means of preserving tissue function with age in multiple model organisms. However, our understanding of the relationship between food removal and long-term health is incomplete. Here, we demonstrate that in the nematode worm Caenorhabditis elegans, a single period of early-life fasting is sufficient to selectively enhance HSF-1 activity, maintain proteostasis capacity and promote longevity without compromising fecundity. These effects persist even when food is returned, and are dependent on the mitochondrial sirtuin, SIR-2.2 and the H3K27me3 demethylase, JMJD-3.1. We find that increased HSF-1 activity upon fasting is associated with elevated SIR-2.2 levels, decreased mitochondrial copy number and reduced H3K27me3 levels at the promoters of HSF-1 target genes. Furthermore, consistent with our findings in worms, HSF-1 activity is also enhanced in muscle tissue from fasted mice, suggesting that the potentiation of HSF-1 is a conserved response to food withdrawal.

How can care home activities facilitate social connection in residents? A qualitative study.

OBJECTIVES: Good social connection is associated with better physical and mental health but care home residents experience barriers to social connection. Activities present a potential avenue for improving social connection in care homes but residents often experience loneliness despite access to activity programmes. We therefore aimed to identify what aspects of activities facilitate social connection in care home residents. METHOD: Qualitative study using semi-structured interviews that were analysed using Thematic Analysis. A purposive sample of 35 participants, including 12 residents, 10 family caregivers, nine care home staff and four clinicians, recruited from UK care homes. RESULTS: We found four main themes describing features of activities important for facilitating social connection: (1) personalisation with respect to residents' interests, social preferences, and cognitive ability; (2) activities which foster a sense of community; (3) finding and emphasising things in common that residents share; and (4) facilitating a sense of involvement with others. CONCLUSION: We identified the key aspects of activities which facilitate social connection in care homes. These findings can be applied to a range of existing and newly designed activities in care homes and inform the development and testing of psychosocial interventions aiming to improve social connection.

Characteristics Associated With Recurrent Urinary Tract Infections: A Case-Control Study.

IMPORTANCE: Recurrent urinary tract infections (rUTIs) affect 2-10% of adult women and are associated with a significant effect on quality of life, daily activities, and mental health. OBJECTIVE: The aim of this study was to identify clinical characteristics associated with rUTIs among women seeking care for pelvic floor disorders at an academic tertiary urogynecology clinic. STUDY DESIGN: A retrospective case-control study of women presenting to an academic tertiary urogynecology clinic was conducted. Cases were women with rUTIs, defined as ≥2 UTIs in 6 months or ≥3 within 1 year. Controls were women with no culture documented UTIs. Cases were matched 2:1 to controls by age and body mass index. Demographic and clinical characteristics were compared between cases and controls, and bivariate characteristics with P values ≤0.2 were assessed for an independent association with rUTIs by multivariable logistic regression. RESULTS: A total of 285 cases with rUTIs were identified, and 150 matched controls had a mean (SD) age of 72 (11.8) years and a body mass index of 29.6 (6.7; calculated as weight in kilograms divided by height in meters squared). Multivariable analysis revealed that prolapse beyond the introitus (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.13-0.60), parity (OR, 1.33; 95% CI, 1.08-1.64), Charlson Comorbidity Index (OR, 1.66; 95% CI, 1.37-2.03), and postvoid residual volume ≥100 mL (OR, 4.05; 95% CI, 2.01, 8.18) were associated with rUTIs. CONCLUSIONS: In this ambulatory urogynecologic population, prolapse through the introitus was negatively associated with rUTIs, whereas parity, increased medical comorbidities, and elevated postvoid residual volume were positively associated with rUTI. Future research should seek an increased understanding of these factors associated with rUTI to implement effective preventive strategies.

Treatment of Cervical Cancer Complicated by Advanced Pelvic Organ Prolapse: A Case Report.

ABSTRACT: Concurrent cervical cancer with advanced pelvic organ prolapse is rare: there are no well-established treatment recommendations. It is hypothesized that chronic irritation, as with long-standing pelvic organ prolapse, may lead to dysplasia and human papillomavirus-independent carcinoma, which represents only 5% of cervical cancers. Two patients with complete uterine procidentia were referred to gynecologic oncology with cervical squamous cell carcinoma; both were clinically staged as International Federation of Gynaecology and Obstetrics IB3. Treatment planning was complicated by procidentia in both cases. Standard definitive treatment of locally advanced cervical cancer is radiation therapy and concurrent chemotherapy; however, the mobility and externalization of the target lesion raised concerns regarding anatomic reproducibility during radiation treatment. After multidisciplinary team discussion (gynecologic oncology, urogynecology, radiation oncology), surgical resection and co-management with gynecologic oncology and urogynecology were successfully performed for definitive management for both patients. Although rare, this case study demonstrates the importance of multidisciplinary coordination in these complex clinical scenarios.

Colony level fitness analysis identifies a trade-off between population growth rate and dauer yield in Caenorhabditis elegans.

BACKGROUND: In the evolution from unicellular to multicellular life forms, natural selection favored reduced cell proliferation and even programmed cell death if this increased organismal fitness. Could reduced individual fertility or even programmed organismal death similarly increase the fitness of colonies of closely-related metazoan organisms? This possibility is at least consistent with evolutionary theory, and has been supported by computer modelling. Caenorhabditis elegans has a boom and bust life history, where populations of nematodes that are sometimes near clonal subsist on and consume food patches, and then generate dauer larva dispersal propagules. A recent study of an in silico model of C. elegans predicted that one determinant of colony fitness (measured as dauer yield) is minimization of futile food consumption (i.e. that which does not contribute to dauer yield). One way to achieve this is to optimize colony population structure by adjustment of individual fertility. RESULTS: Here we describe development of a C. elegans colony fitness assay, and its use to investigate the effect of altering population structure on colony fitness after population bust. Fitness metrics measured were speed of dauer production, and dauer yield, an indirect measure of efficiency of resource utilization (i.e. conversion of food into dauers). We find that with increasing founder number, speed of dauer production increases (due to earlier bust) but dauer yield rises and falls. In addition, some dauer recovery was detected soon after the post-colony bust peak of dauer yield, suggesting possible bet hedging among dauers. CONCLUSIONS: These results suggest the presence of a fitness trade-off at colony level between speed and efficiency of resource utilization in C. elegans. They also provide indirect evidence that population structure is a determinant of colony level fitness, potentially by affecting level of futile food consumption.

Association of quality of prenatal care with contraceptive planning in a United States population: a retrospective cohort study.

BACKGROUND: Understanding how prenatal care influences planned postpartum contraception can help guide shared decision-making. This study looks to examine the association of the quality of prenatal care with planned postpartum contraception. METHODS: This is a retrospective cohort study conducted in a single tertiary, academic urban institution in the southwest United States. The institutional review board (IRB) for human research at Valleywise Health Medical Center approved this study. Using a validated measure of prenatal care, the Kessner index, prenatal care was classified as adequate, intermediate, or inadequate. The World Health Organization (WHO) protocol for contraceptive effectiveness was used to classify contraceptives as very effective, effective, and less effective. The planned contraceptive choice was determined at the time of hospital discharge after delivery by discharge summary. Chi-squared testing and logistic regression were used to measure associations between the adequacy of prenatal care and contraceptive planning. RESULTS: This study included 450 deliveries, 404 (90%) patients with adequate prenatal care, and 46 (10%) patients without adequate (intermediate or inadequate) prenatal care. There was not a statistically significant difference in planning for very effective or effective methods of contraception at hospital discharge between adequate (74%) and non-adequate (61%) prenatal care groups (p = 0.06). There was no association between the adequacy of prenatal care and the effectiveness of contraceptive planning after controlling for age and parity (aOR = 1.7, 95% CI 0.89-3.22). CONCLUSIONS: Many women chose very effective and effective methods of postpartum contraception; however, there was no statistically significant association between the quality of prenatal care and planned contraception at hospital discharge.

The impact of depression on opioid withdrawal symptoms among smokers with opioid use disorder receiving medication-assisted opioid detoxification.

Individuals with opioid use disorder (OUD) endorse high rates of combustible smoking (Zale et al., 2015) which is associated with poorer outcomes (e.g., opioid craving and lower detoxification completion rates) among individuals receiving medications for opioid use disorder (MOUD; Mannelli et al., 2013) and lower smoking cessation rates (Okoli et al., 2010). The complex pharmacological relationship between opioids and nicotine may help explain these findings (Kohut, 2017); however, little is known about psychosocial variables that influence MOUD processes among combustible smokers with OUD. The present study sought to expand upon prior work (Mannelli et al., 2013) by examining the impact of psychological factors and smoking-related variables on opioid withdrawal symptoms among smokers with OUD receiving Suboxone at an inpatient substance use treatment facility. Current smokers with OUD (N = 64) completed a battery of psychological measures examining depression, anxiety, and smoking constructs. The present study tested the influence of daily smoking rate, nicotine dependence, smoking urges, anxiety, and depression on opioid withdrawal symptoms through a hierarchical multiple regression. Findings revealed that smoking urges (p = .003) predicted severity of opioid withdrawal symptoms while controlling for race, daily smoking rate, and nicotine dependence. Depression (p = .000), however, explained variance in severity of opioid withdrawal symptoms above and beyond all smoking-related variables and anxiety. Results highlight the importance of considering psychological factors, specifically depression, which impact treatment processes among smokers with OUD to help inform the development of effective treatment interventions for both OUD and smoking cessation among individuals with OUD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Loss of MTCH-1 suppresses age-related proteostasis collapse through the inhibition of programmed cell death factors.

The age-related loss of protein homeostasis (proteostasis) is at the heart of numerous neurodegenerative diseases. Therefore, finding ways to preserve proteome integrity in aged cells may be a powerful way to promote long-term health. Here, we show that reducing the activity of a highly conserved mitochondrial outer membrane protein, MTCH-1/MTCH2, suppresses age-related proteostasis collapse in Caenorhabditis elegans without disrupting development, growth, or reproduction. Loss of MTCH-1 does not influence proteostasis capacity in aged tissues through previously described pathways but instead operates by reducing CED-4 levels. This results in the sequestration of HSP-90 by inactive CED-3, which in turn leads to an increase in HSF-1 activity, transcriptional remodeling of the proteostasis network, and maintenance of proteostasis capacity with age. Together, our findings reveal a role for programmed cell death factors in determining proteome health and suggest that inhibiting MTCH-1 activity in adulthood may safeguard the aging proteome and suppress age-related diseases.

Serum amyloid A and fibrinogen as markers for early detection of surgical site infection associated with internal fixation in the horse.

The objective of this study was to determine the diagnostic ability of serum amyloid A (SAA) and fibrinogen for early detection of surgical site infection (SSI) after equine internal fixation. Horses undergoing internal fixation for fracture, arthrodesis, or osteotomy with internal fixation for limb deformity were included in the study. SAA and fibrinogen were measured on blood samples preoperatively and on days 1, 3, 5, 7, 10, and 14 postoperatively. Statistical analysis included use of Spearman's rank correlation, logistic regression, and calculating the area under the receiver operating characteristic (ROC) curve. SAA and fibrinogen measurements were both associated with SSI, with SAA being considered an excellent marker (area under the ROC curve 0.8) and fibrinogen being considered acceptable (<0.8). As the amount of time postoperatively increased, SAA elevations indicated a higher likelihood of SSI (area under the ROC curve 0.8 compared with fibrinogen 0.7). SAA and fibrinogen were predictive markers of SSI and SAA is of greater diagnostic utility when compared with fibrinogen. Persistent elevations of SAA postoperatively are associated with the development of SSI. Serial monitoring of SAA can be used to help predict the development of SSI in horses undergoing internal fixation. This may lead to earlier suspicion, and therefore recognition and treatment of SSI.

Validation of accelerometry as a digital phenotyping measure of negative symptoms in schizophrenia.

Negative symptoms are commonly assessed via clinical rating scales; however, these measures have several inherent limitations that impact validity and utility for their use in clinical trials. Objective digital phenotyping measures that overcome some of these limitations are now available. The current study evaluated the validity of accelerometry (ACL), a passive digital phenotyping method that involves collecting data on the presence, vigor, and variability of movement. Outpatients with schizophrenia (SZ: n = 50) and demographically matched healthy controls (CN: n = 70) had ACL continuously recorded from a smartphone and smartband for 6 days. Active digital phenotyping assessments, including surveys related to activity context, were also collected via 8 daily surveys throughout the 6 day period. SZ participants had lower scores on phone ACL variables reflecting vigor and variability of movement compared to CN. ACL variables demonstrated convergent validity as indicated by significant correlations with active digital phenotyping self-reports of time spent in goal-directed activities and clinical ratings of negative symptoms. The discriminant validity of ACL was demonstrated by low correlations with clinical rating scale measures of positive, disorganized, and total symptoms. Collectively, findings suggest that ACL is a valid objective measure of negative symptoms that may complement traditional approaches to assessing the construct using clinical rating scales.

Ultrabrief Right Unilateral Electroconvulsive Therapy for the Treatment of the Neuropsychiatric Symptoms of Dementia with Lewy Bodies.

OBJECTIVES: Dementia with Lewy bodies (DLB) is a debilitating disorder associated with a number of distressing neuropsychiatric symptoms. There is currently limited guidance regarding the most effective strategies of managing these symptoms, and both pharmacologic and nonpharmacologic strategies are often used. Electroconvulsive therapy (ECT) has been reported as a potential nonpharmacologic method to alleviate some of these debilitating neuropsychiatric symptoms. However, there remains a paucity of evidence in current literature. This report aims to add to existing literature regarding ECT in DLB by highlighting successful treatment in seven cases. METHODS: Our study is a retrospective case series of 7 patients with DLB who received treatment with ultrabrief (UB) right unilateral (RUL) ECT for the treatment of agitation and depressive symptoms. Participants included patients with a diagnosis of DLB who were admitted to Emory University Hospital at Wesley Woods from 2011 to 2020 presenting with agitation and/or depressive symptoms after failing pharmacologic intervention. Patients underwent UB RUL ECT administered by a board-certified psychiatrist. After treatment, Pittsburg Agitation Scale and Clinical Global Impression-Improvement scales were recorded as measures of agitation and clinical improvement, respectively. RESULTS: All 7 patients responded to UB RUL ECT with marked improvement in their presenting symptoms of agitation and/or depression without significant adverse effects from treatment. CONCLUSIONS: Ultrabrief RUL ECT seems to be a safe and effective treatment of the agitative and depressive features of DLB.

Digital phenotyping adherence, feasibility, and tolerability in outpatients with schizophrenia.

Digital phenotyping has potential for use as an objective and ecologically valid form of symptom assessment in clinical trials for schizophrenia. However, there are critical methodological factors that must be addressed before digital phenotyping can be used for this purpose. The current study evaluated levels of adherence, feasibility, and tolerability for active (i.e., signal and event contingent ecological momentary assessment surveys) and passive (i.e., geolocation, accelerometry, and ambulatory psychophysiology) digital phenotyping methods recorded from smartphone and smartband devices. Participants included outpatients diagnosed with schizophrenia (SZ: n = 54) and demographically matched healthy controls (CN: n = 55), who completed 6 days of digital phenotyping. Adherence was significantly lower in SZ than CN for active recordings, but not markedly different for passive recordings. Some forms of passive recordings had lower adherence (ambulatory psychophysiology) than others (accelerometry and geolocation). Active digital phenotyping adherence was predicted by higher psychosocial functioning, whereas passive digital phenotyping adherence was predicted by education, positive symptoms, negative symptoms, and psychosocial functioning in people with SZ. Both groups found digital phenotyping methods tolerable and feasibility was supported by low frequency of invalid responding, brief survey completion times, and similar impediments to study completion. Digital phenotyping methods can be completed by individuals with SZ with good adherence, feasibility, and tolerability. Recommendations are provided for using digital phenotyping methods in clinical trials for SZ.

Ultra-brief right unilateral electroconvulsive therapy for the treatment of late-life bipolar disorder.

BACKGROUND: Bipolar Affective Disorder (BPAD) accounts for 10-25% of all mood disorders in the geriatric population and 5% of all inpatient admissions to geropsychiatric units. Electroconvulsive therapy (ECT) is an effective treatment for all phases of BPAD, though only a few studies have focused on BPAD in the geriatric population. This study examines the safety and efficacy of ultra-brief right unilateral (UBRUL) ECT for patients with late-life bipolar depression (BD). METHODS: A retrospective chart review was conducted of patients with late-life BD who received UBRUL ECT treatments. Symptomatic response was measured using pre- and post-ECT Quick Inventory of Depressive Symptomatology (QIDS-SR16) and Beck Depression Inventory (BDI-II) scores. Clinical improvement and cognitive change were measured using Clinical Global Impression-Improvement (CGI-I) and Electroconvulsive Cognitive Assessment (ECCA) scores. RESULTS: Twenty-Seven elderly patients (mean age 69.1 ± 7.7 years) were included in the analysis. Baseline QIDS-SR16 was 17.3 ± 5.3 and BDI-II 30.0 ± 9.2. 80.0% (16/20) and 57.1% (4/7) of patients achieved response (50.0% decline) in their QIDS-SR16 and BDI-II scores, respectively. Remission rates in QIDS-SR16 (post-ECT scores ≤5) and BDI-II (post-ECT scores ≤12) were 65.0% (13/20) and 42.9% (3/7), respectively. Mean QIDS-SR16 and BDI-II scores were reduced by a statistically significant 68.2% and 50.5%, respectively (two-tailed, paired p-values <0.01) after ECT. CGI-I of ≤2 was attained by 85.2% (23/27) of patients. 85.7% (12/14) of patients saw no change or improvement in ECCA scores. LIMITATIONS: Inherent complications of chart review regarding quality, availability, and homogeny of data. CONCLUSIONS: UBRUL ECT is a safe and effective treatment for patients presenting with late-life BD.

Mutation of daf-2 extends lifespan via tissue-specific effectors that suppress distinct life-limiting pathologies.

In aging Caenorhabditis elegans, as in higher organisms, there is more than one cause of death. C. elegans exhibit early death with a swollen, infected pharynx (P death), and later death with pharyngeal atrophy (p death). Interventions that alter lifespan can differentially affect frequency and timing of each type of death, generating complex survival curve shapes. Here, we use mortality deconvolution analysis to investigate how reduction of insulin/IGF-1 signaling (IIS), which increases lifespan (the Age phenotype), affects different forms of death. All daf-2 insulin/IGF-1 receptor mutants exhibit increased lifespan in the p subpopulation (p Age), while pleiotropic class 2 daf-2 mutants show an additional marked reduction in P death frequency. The latter is promoted by pharyngeal expression of the IIS-regulated DAF-16 FOXO transcription factor, and at higher temperature by reduced pharyngeal pumping rate. Pharyngeal DAF-16 also promotes p Age in class 2 daf-2 mutants, revealing a previously unknown role for the pharynx in the regulation of aging. Necropsy analysis of daf-2 interactions with the daf-12 steroid receptor implies that previously described opposing effects of daf-12 on daf-2 longevity are attributable to internal hatching of larvae, rather than complex interactions between insulin/IGF-1 and steroid signaling. These findings support the view that wild-type IIS acts through multiple distinct mechanisms which promote different life-limiting pathologies, each of which contribute to late-life mortality. This study further demonstrates the utility of mortality deconvolution analysis to better understand the genetics of lifespan.

Delay discounting in youth at clinical high-risk for psychosis and adults with schizophrenia.

BACKGROUND: Schizophrenia (SZ) is typically preceded by a prodromal (i.e. pre-illness) period characterized by attenuated positive symptoms and declining functional outcome. Negative symptoms are prominent among individuals at clinical high-risk (CHR) for psychosis (i.e. those with prodromal syndromes) and highly predictive of conversion to illness. Mechanisms underlying negative symptoms in the CHR population are unclear. Two studies were conducted to evaluate whether abnormalities in a reward processing mechanism thought to be core to negative symptoms in SZ, value representation, also exist in CHR individuals and whether they are associated with negative symptoms transphasically. METHODS: Study 1 included 33 individuals in the chronic phase of illness who have been diagnosed with schizophrenia or schizoaffective disorder (SZ) and 40 healthy controls (CN). Study 2 included 37 CHR participants and 45 CN. In both studies, participants completed the delay discounting (DD) task as a measure of value representation and the Brief Negative Symptom Scale was rated to measure negative symptoms. RESULTS: Results indicated that patients with SZ had steeper discounting rates than CN, indicating impairments in value representation. However, CHR participants were unimpaired on the DD task. In both studies, steeper discounting was associated with greater severity of negative symptoms. CONCLUSIONS: These findings suggest that deficits in value representation are associated with negative symptoms transphasically.

The Latent Structure of Negative Symptoms in Individuals With Attenuated Psychosis Syndrome and Early Psychosis: Support for the 5 Consensus Domains.

Negative symptoms are prevalent in the prodromal and first-episode phases of psychosis and highly predictive of poor clinical outcomes (eg, liability for conversion and functioning). However, the latent structure of negative symptoms is unclear in the early phases of illness. Determining the latent structure of negative symptoms in early psychosis (EP) is of critical importance for early identification, prevention, and treatment efforts. In the current study, confirmatory factor analysis was used to evaluate latent structure in relation to 4 theoretically derived models: 1. a 1-factor model, 2. a 2-factor model with expression (EXP) and motivation and pleasure (MAP) factors, 3. a 5-factor model with separate factors for the 5 National Institute of Mental Health (NIMH) consensus development conference domains (blunted affect, alogia, anhedonia, avolition, and asociality), and 4. a hierarchical model with 2 second-order factors reflecting EXP and MAP, as well as 5 first-order factors reflecting the 5 consensus domains. Participants included 164 individuals at clinical high risk (CHR) who met the criteria for a prodromal syndrome and 377 EP patients who were rated on the Brief Negative Symptom Scale. Results indicated that the 1- and 2-factor models provided poor fit for the data. The 5-factor and hierarchical models provided excellent fit, with the 5-factor model outperforming the hierarchical model. These findings suggest that similar to the chronic phase of schizophrenia, the latent structure of negative symptom is best conceptualized in relation to the 5 consensus domains in the CHR and EP populations. Implications for early identification, prevention, and treatment are discussed.

Geolocation as a Digital Phenotyping Measure of Negative Symptoms and Functional Outcome.

OBJECTIVE: Negative symptoms and functional outcome have traditionally been assessed using clinical rating scales, which rely on retrospective self-reports and have several inherent limitations that impact validity. These issues may be addressed with more objective digital phenotyping measures. In the current study, we evaluated the psychometric properties of a novel "passive" digital phenotyping method: geolocation. METHOD: Participants included outpatients with schizophrenia or schizoaffective disorder (SZ: n = 44), outpatients with bipolar disorder (BD: n =19), and demographically matched healthy controls (CN: n = 42) who completed 6 days of "active" digital phenotyping assessments (eg, surveys) while geolocation was recorded. RESULTS: Results indicated that SZ patients show less activity than CN and BD, particularly, in their travel from home. Geolocation variables demonstrated convergent validity by small to medium correlations with negative symptoms and functional outcome measured via clinical rating scales, as well as active digital phenotyping behavioral indices of avolition, asociality, and anhedonia. Discriminant validity was supported by low correlations with positive symptoms, depression, and anxiety. Reliability was supported by good internal consistency and moderate stability across days. CONCLUSIONS: These findings provide preliminary support for the reliability and validity of geolocation as an objective measure of negative symptoms and functional outcome. Geolocation offers enhanced precision and the ability to take a "big data" approach that facilitates sophisticated computational models. Near-continuous recordings and large numbers of samples may make geolocation a novel outcome measure for clinical trials due to enhanced power to detect treatment effects.

Modeling perception and behavior in individuals at clinical high risk for psychosis: Support for the predictive processing framework.

Early intervention in psychotic spectrum disorders is critical for maximizing key clinical outcomes. While there is some evidence for the utility of intervention during the prodromal phase of the illness, efficacy of interventions is difficult to assess without appropriate risk stratification. This will require biomarkers that robustly help to identify risk level and are also relatively easy to obtain. Recent work highlights the utility of computer-based behavioral tasks for understanding the pathophysiology of psychotic symptoms. Computational modeling of performance on such tasks may be particularly useful because they explicitly and formally link performance and symptom expression. Several recent studies have successfully applied principles of Bayesian inference to understanding the computational underpinnings of hallucinations. Within this framework, hallucinations are seen as arising from an over-weighting of prior beliefs relative to sensory evidence. This view is supported by recently-published data from two tasks: the Conditioned Hallucinations (CH) task, which determines the degree to which participants use expectations in detecting a target tone; and a Sine-Vocoded Speech (SVS) task, in which participants can use prior exposure to speech samples to inform their understanding of degraded speech stimuli. We administered both of these tasks to two samples of participants at clinical high risk for psychosis (CHR; N = 19) and healthy controls (HC; N = 17). CHR participants reported both more conditioned hallucinations and more pre-training SVS detection. In addition, relationships were found between participants' performance on both tasks. On computational modeling of behavior on the CH task, CHR participants demonstrate significantly poorer recognition of task volatility as well as a trend toward higher weighting of priors. A relationship was found between this latter effect and performance on both tasks. Taken together, these results support the assertion that these two tasks may be driven by similar latent factors in perceptual inference, and highlight the potential utility of computationally-based tasks in identifying risk.