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Persons diagnosed with schizophrenia (SCZ) or bipolar I disorder (BPI) are at high risk for self-injurious behavior, suicidal ideation, and suicidal behaviors (SB). Characterizing associations between diagnosed health problems, prior pharmacological treatments, and polygenic scores (PGS) has potential to inform risk stratification. We examined self-reported SB and ideation using the Columbia Suicide Severity Rating Scale (C-SSRS) among 3,942 SCZ and 5,414 BPI patients receiving care within the Veterans Health Administration (VHA). These cross-sectional data were integrated with electronic health records (EHRs), and compared across lifetime diagnoses, treatment histories, follow-up screenings, and mortality data. PGS were constructed using available genomic data for related traits. Genome-wide association studies were performed to identify and prioritize specific loci. Only 20% of the veterans who reported SB had a corroborating ICD-9/10 EHR code. Among those without prior SB, more than 20% reported new-onset SB at follow-up. SB were associated with a range of additional clinical diagnoses, and with treatment with specific classes of psychotropic medications (e.g., antidepressants, antipsychotics, etc.). PGS for externalizing behaviors, smoking initiation, suicide attempt, and major depressive disorder were associated with SB. The GWAS for SB yielded no significant loci. Among individuals with a diagnosed mental illness, self-reported SB were strongly associated with clinical variables across several EHR domains. Analyses point to sequelae of substance-related and psychiatric comorbidities as strong correlates of prior and subsequent SB. Nonetheless, past SB was frequently not documented in health records, underscoring the value of regular screening with direct, in-person assessments, especially among high-risk individuals.
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BACKGROUND: Cognition in MCI has responded poorly to pharmacological interventions, leading to use of computerized training. Combining computerized cognitive training (CCT) and functional skills training software (FUNSAT) produced improvements in 6 functional skills in MCI, with effect sizes >0.75. However, 4% of HC and 35% of MCI participants failed to master all 6 tasks. We address early identification of characteristics that identify participants who do not graduate, to improve later interventions. METHODS: NC participants (n = 72) received FUNSAT and MCI (n = 92) participants received FUNSAT alone or combined FUNSAT and CCT on a fully remote basis. Participants trained twice a week for up to 12 weeks. Participants "graduated" each task when they made one or fewer errors on all 3-6 subtasks per task. Tasks were no longer trained after graduation. RESULTS: Between-group comparisons of graduation status on baseline completion time and errors found that failure to graduate was associated with more baseline errors on all tasks but no longer completion times. A discriminant analysis found that errors on the first task (Ticket purchase) uniquely separated the groups, F = 41.40, p < .001, correctly classifying 94% of graduators. An ROC analysis found an AUC of .83. MOCA scores did not increase classification accuracy. CONCLUSIONS: More baseline errors, but not completion times, predicted failure to master all FUNSAT tasks. Accuracy of identification of eventual mastery was exceptional. Detection of risk to fail to master training tasks is possible in the first 15 minutes of the baseline assessment. This information can guide future enhancements of computerized training.
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INTRODUCTION: This study derived composite scores for two novel cognitive measures, the No Practice Effect (NPE) battery and the Miami Computerized Functional Skills Assessment and Training system for use in early-stage Alzheimer's disease (AD) clinical trials. Their psychometric properties and associations with AD risk markers were compared to those of well-established measures. METHODS: For 291 older adults with healthy cognition or early mild cognitive impairment, Exploratory factor analyses were used to identify the factor structure of the NPE. Factor and total scores were examined for their psychometric properties and associations with AD risk biomarkers. RESULTS: Composite scores from the novel cognitive and functional measures demonstrated better psychometric properties (distribution and test-retest reliability) and stronger associations with AD-related demographic, genetic, and brain risk markers than well-established measures, DISCUSSION: These novel measures have potential for use as primary cognitive and functional outcomes in early-stage AD clinical trials. HIGHLIGHTS: Well-established cognitive tests may not accurately detect subtle cognitive changes. No Practice Effect (NPE) and Computerized Functional Skills Assessment and Training are novel measures designed to have improved psychometric properties. NPE had Executive Function, Cognitive Control/Speed, and Episodic Memory domains. Novel measures had better psychometric properties compared to established measures. Significant associations with Alzheimer's disease biomarkers were found with novel measures.
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Hallucinogens , Humans , Aged , Hallucinogens/pharmacology , Age Factors , Aging/drug effects , Aging/psychologyABSTRACT
Background and Objectives: The performance of everyday technology-based tasks, such as online banking or shopping, can be challenging for older adults, especially those with a cognitive impairment. Technology-based tasks are cognitively demanding and require learning new skills. This study explored the efficacy of a technology-based functional skills assessment and training program (FUNSAT) among aging adults with and without mild cognitive impairment (MCI) in home settings. Research Design and Methods: One hundred and eighty-four racially/ethnically diverse male and female adults aged 65+ participated in the study. The sample included 75 noncognitively impaired (NC) older adults and 109 older adults with MCI. The FUNSAT program includes medication and money management, transportation, and shopping tasks. The MCI participants were randomized to the FUNSAT training or FUNSAT training combined with computer-based cognitive training (FUNSAT/CCT). The nonimpaired adults received the FUNSAT training only. Using alternative forms of the assessment component of the FUNSAT program, assessments occurred at baseline, post-training, and 1- and 3-month post-training. This paper reports the post-training results. Results: The findings indicated that the performance of both the nonimpaired and MCI participants improved significantly for all 6 tasks post-training. Specifically, training resulted in improvements in task completion time and task errors. Participants also reported greater confidence when performing the tasks in the real world. Discussion and Implications: Nonimpaired aging adults and those with MCI can learn to perform technology-based everyday tasks. Further, home-based technology training protocols are feasible for aging adults with and without a cognitive impairment. Clinical Trial Registration: NCT0467944 1.
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BACKGROUND: Patients with schizophrenia suffer from physical health conditions, culminating in reduced physical functioning with enormous costs for patients and society. Although aerobic endurance and skeletal muscle strength, typically reduced in this population, relate to cognition and function, no study has explored their respective contributions to performance of functional skills and everyday tasks. METHODS: In a cross-sectional study, 48 outpatients (28/20 men/women; 35 ± 11(SD) years) with schizophrenia spectrum disorders (ICD-10; F20-25) were administered the UCSD Performance-based Skills Assessment-Brief (UPSA-B; functional skills), Specific Level of Functioning (SLOF; functional performance) and the Positive and Negative Syndrome (PANSS) scale. Peak oxygen uptake (VÌO2peak) was assessed along with leg press maximal muscle strength (1RM) and mechanical power. RESULTS: UPSA-B performance was associated with VÌO2peak (r = 0.28,p < 0.05), accounting for 8 % (p < 0.05) of shared variance, but was unrelated to 1RM and mechanical power. The SLOF physical functioning domain was associated with VÌO2peak (r = 0.30,p < 0.05) and 1RM (r = 0.24,p < 0.05), while SLOF personal care (r = 0.27,p < 0.05) and activities (r = 0.30,p < 0.05) were related only to VÌO2peak. Hierarchical regression analyses revealed that while VÌO2peak and age combined to account for 20 % (p < 0.05) of the variance in physical functioning, the contribution of 1RM was eliminated after adjusting for age. VÌO2peak and negative symptoms combined predicted 24 % and 35 % of the variance in personal care and activities, respectively. UPSA-B scores did not add to the prediction of SLOF scores. CONCLUSIONS: Although VÌO2peak and 1RM both relate to functional outcomes, the combination of VÌO2peak, age, and negative symptoms exert the greatest detrimental influence on functional performance beyond skills deficits.
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Activities of Daily Living , Muscle Strength , Schizophrenia , Humans , Male , Female , Schizophrenia/physiopathology , Muscle Strength/physiology , Adult , Cross-Sectional Studies , Middle Aged , Oxygen Consumption/physiology , Physical Endurance/physiology , Muscle, Skeletal/physiopathology , Muscle, Skeletal/physiology , Psychiatric Status Rating Scales , Young AdultABSTRACT
Background: Paranoia is a spectrum of fear-related experiences that spans diagnostic categories and is influenced by social and cognitive factors. The extent to which social media and other types of media use are associated with paranoia remains unclear. Objective: We aimed to examine associations between media use and paranoia at the within- and between-person levels. Methods: Participants were 409 individuals diagnosed with schizophrenia spectrum or bipolar disorder. Measures included sociodemographic and clinical characteristics at baseline, followed by ecological momentary assessments (EMAs) collected 3 times daily over 30 days. EMA evaluated paranoia and 5 types of media use: social media, television, music, reading or writing, and other internet or computer use. Generalized linear mixed models were used to examine paranoia as a function of each type of media use and vice versa at the within- and between-person levels. Results: Of the 409 participants, the following subgroups reported at least 1 instance of media use: 261 (63.8%) for using social media, 385 (94.1%) for watching TV, 292 (71.4%) for listening to music, 191 (46.7%) for reading or writing, and 280 (68.5%) for other internet or computer use. Gender, ethnoracial groups, educational attainment, and diagnosis of schizophrenia versus bipolar disorder were differentially associated with the likelihood of media use. There was a within-person association between social media use and paranoia: using social media was associated with a subsequent decrease of 5.5% (fold-change 0.945, 95% CI 0.904-0.987) in paranoia. The reverse association, from paranoia to subsequent changes in social media use, was not statistically significant. Other types of media use were not significantly associated with paranoia. Conclusions: This study shows that social media use was associated with a modest decrease in paranoia, perhaps reflecting the clinical benefits of social connection. However, structural disadvantage and individual factors may hamper the accessibility of media activities, and the mental health correlates of media use may further vary as a function of contents and contexts of use.
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Bipolar Disorder , Ecological Momentary Assessment , Paranoid Disorders , Schizophrenia , Social Media , Humans , Female , Male , Bipolar Disorder/psychology , Bipolar Disorder/epidemiology , Adult , Schizophrenia/epidemiology , Schizophrenia/diagnosis , Social Media/statistics & numerical data , Middle Aged , Paranoid Disorders/psychology , Paranoid Disorders/epidemiologyABSTRACT
People with schizophrenia-spectrum and bipolar disorders have difficulty accurately estimating their abilities and skills (impaired introspective accuracy [IA]) and tend to over- or underestimate their performance. This discrepancy between self-reported and objective task performance has been identified as a significant predictor of functional impairment. Yet, the factors driving this discrepancy are currently unclear. To date, the relationships between sleep quality and IA have not been examined. The current study aimed to explore the relationships between sleep quality and IA in participants diagnosed with schizophrenia (SCZ; n = 36), schizoaffective disorder (SCZ-A; n = 55), and bipolar disorder with psychotic features (BP; n = 87). Participants completed tasks of emotion recognition, estimated their performance on the tasks (used to calculate IA), and provided confidence ratings for their accuracy judgments. Participants also self-reported their sleep quality. These results suggest significantly greater discrepancies between self-reported and actual task scores for those with SCZ and SCZ-A compared to participants with BP. For those with SCZ, lower confidence on the tasks and underestimation of abilities were associated with lower sleep quality, while for those with SCZ-A, lower sleep quality was associated with higher confidence and overestimation of performance. Results suggest differential relationships between diagnostic groups. Future research is needed to further explore the factors driving these differing relationships, particularly the contrasting relationships between SCZ and SCZ-A.
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Excessive placebo response rates have long been a major challenge for central nervous system (CNS) drug discovery. As CNS trials progressively shift toward digitalization, decentralization, and novel remote assessment approaches, questions are emerging about whether innovative technologies can help mitigate the placebo response. This article begins with a conceptual framework for understanding placebo response. We then critically evaluate the potential of a range of innovative technologies and associated research designs that might help mitigate the placebo response and enhance detection of treatment signals. These include technologies developed to directly address placebo response; technology-based approaches focused on recruitment, retention, and data collection with potential relevance to placebo response; and novel remote digital phenotyping technologies. Finally, we describe key scientific and regulatory considerations when evaluating and selecting innovative strategies to mitigate placebo response. While a range of technological innovations shows potential for helping to address the placebo response in CNS trials, much work remains to carefully evaluate their risks and benefits.
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INTRODUCTION: People with serious mental illness (SMI; schizophrenia, schizoaffective disorder, bipolar disorder) are at increased risk of suicidal ideation (SI). Over-attribution of social threat, or attributing threatening emotions to neutral faces, may contribute to social isolation through increased social avoidance and decreased social approach motivation. These factors are related to suicide, as well as perceived burdensomeness (PB) and thwarted belongingness (TB). This study examined how over-attribution of threat relates to PB, TB, and social motivations. METHOD: N = 273 participants with SMI were assessed for current SI and behavior, and were stratified into SI (N = 130) vs. non-SI (N = 143) groups. Participants completed smartphone surveys (via ecological momentary assessments [EMA]) 3×/day for 10 days. They also completed the Mobile Ecological Test of Emotion Recognition (METER) 1×/day. Linear mixed models and multi-level mediation tested the relationships between over-attribution of threat, METER performance, PB/TB, and social motivations. RESULTS: Participants with and without SI did not significantly differ in over-attribution of threat or METER performance. In separate models, there was a relationship of over-attribution of threat with increased PB (B = 1.00, SE = 0.21, t = 4.72, p < .001), reduced social approach motivation (B = -0.74, SE = 0.22, t = -3.33, p < .001), and increased social avoidance (B = 0.90, SE = 0.24, t = 3.70, p < .001), all significant when adjusting for facial affect recognition ability. A model examining social motivations as a mediator between over-attribution of threat and PB/TB was not significant. CONCLUSION: These results suggest that over-attribution of threat relates to interpersonal constructs related to SI irrespective of facial affect abilities. This study may inform understanding of social cognitive processes related to suicide in SMI.
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Psychotic Disorders , Suicide , Humans , Interpersonal Relations , Ecological Momentary Assessment , Suicide/psychology , Suicidal Ideation , Risk Factors , CognitionABSTRACT
With no pharmacological treatments for Mild Cognitive impairment (MCI), computerized training strategies have been attempted. A computerized skills training intervention, FUNSAT, previously produced training-related gains in cognition in MCI and in comparators with normal cognition (NC). A new remotely delivered version of FUNSAT was administered to a new sample of participants with NC and MCI. Outcomes measures included cognition (BAC) and functional capacity (VRFCAT) to examine training transfer. Participants with MCI (n = 92) and NC (n = 72) trained for up to 12 weeks on FUNSAT. Half the MCI participants started with 3 weeks of computerized cognitive training (CCT). Baseline, post-training, and 30-day follow-up scores on cognition and functional capacity were compared. Participants improved on both cognition (d = 0.80) and functional capacity (d = 0.64), with no differences in training gains across MCI and NC, although treatment with CCT in MCI was associated with similar gains with fewer FUNSAT training sessions. This is the first treatment study in MCI to demonstrate transfer to untrained measures of functional capacity. NC improved in cognition and functional capacity with skills training alone. These findings have implications for other conditions, such as schizophrenia, where functional capacity is a treatment target.
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Cognition , Cognitive Dysfunction , Humans , Aged , Cognitive Dysfunction/therapy , Health StatusABSTRACT
People with serious mental illness have challenged self-awareness, including momentary monitoring of performance. A core feature of this challenge is in the domain of using external information to guide behavior, an ability that is measured very well by certain problem-solving tasks such as the Wisconsin Card Sorting Test (WCST) . We used a modified WCST to examine correct sorts and accuracy decisions regarding the correctness of sort. Participants with schizophrenia (n = 99) or bipolar disorder (n = 76) sorted 64 cards and then made judgments regarding correctness of each sort prior to feedback. Time series analyses examined the course of correct sorts and correct accuracy decisions by examining the momentary correlation and lagged correlation on the next sort. People with schizophrenia had fewer correct sorts, fewer categories, and fewer correct accuracy decisions (all p<.001). Positive response biases were seen in both groups. After an incorrect sort or accuracy decision, the groups were equally likely to be incorrect on the next sort or accuracy decision. Following correct accuracy decisions, participants with bipolar disorder were significantly (p=.003) more likely to produce a correct sort or accuracy decision. These data are consistent with previous studies implicating failures to consider external feedback for decision making. Interventions aimed at increasing consideration of external information during decision making have been developed and interventions targeting use of feedback during cognitive test performance are in development.
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Bipolar Disorder , Schizophrenia , Humans , Wisconsin Card Sorting Test , Self-Assessment , CognitionABSTRACT
BACKGROUND: Despite high rates of suicide among people with psychosis, relatively little is known about the mechanisms underlying the transition from suicidal ideation to behavior in this population. The Interpersonal Psychological Theory of Suicide (IPTS) proposes that fearlessness about death (FAD) may play a role in this relationship. The present study tested whether constructs of the IPTS [thwarted belongingness (TB), perceived burdensomeness (PB), and FAD] were associated with the severity of suicidal ideation in a sample of adults with histories of psychosis. METHOD: 261 adults with histories of psychosis completed measures of IPTS constructs, current severity of suicidal ideation, and history of suicidal attempts. We examined differences between those with past suicide attempts and those without and conducted regression analyses to evaluate the associations among TB, PB, FAD and severity of current suicidal ideation. RESULTS: Contrary to expectations, a history of suicidal behavior was not uniquely associated with FAD. Regression analyses revealed TB × PB and FAD × PB interactions emerged as significant correlates of the severity of suicidal ideation, with the relationship between PB and suicidal ideation more pronounced at higher levels of FAD and TB. Interestingly, positive symptoms of psychosis were positively associated with PB. IMPLICATIONS: This study provides support for broadening the investigation of FAD as a contributor to suicidal ideation in individuals with psychotic symptoms. Future research investigating the role of other contributors that may influence capability for suicide (e.g., impulsivity) may add additional understanding of suicide in this population.
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Fear , Psychotic Disorders , Suicidal Ideation , Humans , Male , Psychotic Disorders/psychology , Female , Adult , Middle Aged , Young Adult , Attitude to Death , Suicide, Attempted/psychology , AdolescentABSTRACT
Roluperidone, a 5-HT2A, sigma2, and É1A-adrenergic receptor antagonist, has proven efficacious for treating negative symptoms of schizophrenia in phase 2b and phase 3 clinical trials. Using network analysis, we demonstrated that the improvements observed in the phase 2b trial resulted from targeting avolition which was highly central and spurred a cascading effect of global negative symptom reductions when successfully treated. The current study aims to replicate these network findings using the phase 3 roluperidone clinical trial data. Participants included 496 schizophrenia patients with moderate to severe negative symptoms who were randomized to either roluperidone 32 mg/day (n =167), 64 mg/day (n = 162), or placebo (n = 167). Negative symptoms were assessed at baseline and weeks 2,4,8, and 12. Network intervention analysis (NIA) evaluated treatment-induced symptom changes over time to identify direct and indirect treatment effects. This analytic approach extends prior work by determining whether the symptoms with highest centrality have causal effects on the entire negative symptom construct and directly lead to symptom improvement. NIA indicated that the efficacious 64 mg/day dose of roluperidone had a direct effect on avolition, suggesting that changes in avolition propels treatment effects across the entire negative symptom constellation. These phase 3 findings replicated the phase 2b findings, indicating that from a network perspective, roluperidone achieves its effect by influencing the extent to which avolition drives other negative symptoms. These findings are relevant for understanding negative symptoms and how to treat them in neuropsychiatric disorders.
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Negative symptoms are a source of disability in schizophrenia, but criteria for identifying patients for clinical trials are in flux. Minimum severity for negative symptoms is paired with a definition of minimal psychosis to identify predominant negative symptoms. Two previous successful negative symptoms treatment studies used very different severity and selection criteria. We compared the prevalence of participants meeting those two criteria in a large outpatient sample of participants with schizophrenia. Data from 867 outpatients with schizophrenia who participated in one of four NIMH-funded studies were analyzed. Common data elements included diagnoses, the PANSS, and an assessment of everyday functioning. We compared previous criterion for premoninant negative symptoms based on low levels of agitation and psychosis and different cut-offs for negative symptoms severity. 57 % of the participants met the agitation-based criteria for low scores and 33 % met the psychosis-based criteria. 18 % met total PANSS score ≥ 20 and 8 % met ≥24 prominent negative symptoms criteria. 14 % met low agitation and PANSS≥20 and 2 % met the low psychosis and negative symptoms ≥24 criteria. Participants who met all predominant criteria had more impairments in social functioning (all p < .001, all d > 0.37). Criteria for predominant negative symptoms from previous clinical trials identify widely different numbers of cases, with criteria for negative symptom severity and low symptoms both impacting. All criteria yield the expected profile of relatively specific social deficits. Even in unselected populations who participated in complex research protocols, 14 % meet low- agitation based criteria for predominant negative symptoms and many more participants would be expected to meet criteria with enrichment for the presence of negative symptoms.
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Response times (RTs) to ecological momentary assessment (EMA) items often decrease after repeated EMA administration, but whether this is accompanied by lower response quality requires investigation. We examined the relationship between EMA item RTs and EMA response quality. In one data set, declining response quality was operationalized as decreasing correspondence over time between subjective and objective measures of blood glucose taken at the same time. In a second EMA study data set, declining response quality was operationalized as decreasing correspondence between subjective ratings of memory test performance and objective memory test scores. We assumed that measurement error in the objective measures did not increase across time, meaning that decreasing correspondence across days within a person could be attributed to lower response quality. RTs to EMA items decreased across study days, while no decrements in the mean response quality were observed. Decreasing EMA item RTs across study days did not appear problematic overall.
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Cognitive deficits are a core impairment across the range of schizophrenia (SZ) spectrum disorders, including schizotypal personality disorder (SPD). The MATRICS Consensus Cognitive Battery (MCCB) was developed to be a robust, specific, and valid cognitive assessment battery to assess cognition in clinical trials for treating cognitive impairments in SZ. Despite the similarity of cognitive impairments shown in SPD and SZ and the clear relevance of uniform assessment across a diagnostic spectrum, the MCCB has yet to be validated in SPD. As such, this is the first study to evaluate the sensitivity of the MCCB for the assessment of cognitive function in individuals with SPD. Participants were 30 individuals with SPD and 54 healthy controls (HC) assessed with the MCCB and supplemental neurocognitive assessments (Trails B, DOT test, Paced Auditory Serial Addition Test (PASAT), AX Continuous Performance Task (AX-CPT), and N-back). Individuals with SPD performed worse than HC participants on all MCCB subtests, as well as on converging supplemental tasks including Trails B, DOT test, PASAT, AX-CPT, and N-back. These results indicate that the MCCB was sensitive to cognitive impairment in SPD compared to controls. SPD participants demonstrate impairments similar to data of SZ participants within the literature, although to a slightly lesser degree of severity. Taken together, these results highlight the generalizability of using the MCCB across SZ spectrum diagnostic groups to assess cognition. Such findings allow for further comparison across disorders, greater understanding of the cognitive characteristics in the spectrum, and use of uniform assessment within cognitive intervention research.
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Cognitive Dysfunction , Neuropsychological Tests , Schizotypal Personality Disorder , Humans , Male , Female , Schizotypal Personality Disorder/diagnosis , Schizotypal Personality Disorder/physiopathology , Schizotypal Personality Disorder/complications , Adult , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Neuropsychological Tests/standards , Young Adult , Middle AgedABSTRACT
Background: Standardized definitions of suicidality phenotypes, including suicidal ideation (SI), attempt (SA), and death (SD) are a critical step towards improving understanding and comparison of results in suicide research. The complexity of suicidality contributes to heterogeneity in phenotype definitions, impeding evaluation of clinical and genetic risk factors across studies and efforts to combine samples within consortia. Here, we present expert and data-supported recommendations for defining suicidality and control phenotypes to facilitate merging current/legacy samples with definition variability and aid future sample creation. Methods: A subgroup of clinician researchers and experts from the Suicide Workgroup of the Psychiatric Genomics Consortium (PGC) reviewed existing PGC definitions for SI, SA, SD, and control groups and generated preliminary consensus guidelines for instrument-derived and international classification of disease (ICD) data. ICD lists were validated in two independent datasets (N = 9,151 and 12,394). Results: Recommendations are provided for evaluated instruments for SA and SI, emphasizing selection of lifetime measures phenotype-specific wording. Recommendations are also provided for defining SI and SD from ICD data. As the SA ICD definition is complex, SA code list recommendations were validated against instrument results with sensitivity (range = 15.4% to 80.6%), specificity (range = 67.6% to 97.4%), and positive predictive values (range = 0.59-0.93) reported. Conclusions: Best-practice guidelines are presented for the use of existing information to define SI/SA/SD in consortia research. These proposed definitions are expected to facilitate more homogeneous data aggregation for genetic and multisite studies. Future research should involve refinement, improved generalizability, and validation in diverse populations.