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ImportanceImproved understanding of the boundaries and connections between positive symptoms, negative symptoms, and role functioning in schizophrenia is critical, given limited empirical support for clear distinctions among these... more
ImportanceImproved understanding of the boundaries and connections between positive symptoms, negative symptoms, and role functioning in schizophrenia is critical, given limited empirical support for clear distinctions among these clinical areas. This study’s use of network psychometrics to investigate differential associations and structural overlap between positive symptoms, negative symptoms, and functional domains in schizophrenia may contribute to such understanding.ObjectiveTo apply network analysis and community detection methods to examine the interplay and structure of positive symptoms, negative symptoms, and functional domains in individuals with schizophrenia.Design, Setting, and ParticipantsCross-sectional study in 5 geographically distributed research centers in the US as part of the Consortium on the Genetics of Schizophrenia-2 from July 1, 2010, through January 31, 2014. Data were analyzed from November 2021 to June 2022. Clinically stable outpatients with schizophre...
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OBJECTIVE Veterans with psychotic disorders often experience employment difficulties. Job tenure is highly variable with shorter tenure frequently tied to interpersonal difficulties in the workplace. The present study sought to address... more
OBJECTIVE Veterans with psychotic disorders often experience employment difficulties. Job tenure is highly variable with shorter tenure frequently tied to interpersonal difficulties in the workplace. The present study sought to address this problem by examining the efficacy of social cognition skills training (SCST) and social problem solving skills training (SPSST) interventions, implemented sequentially, and added to usual VA employment services (augmented vocational rehabilitation [VR]). METHOD Participants were 91 Veterans with schizophrenia and other psychotic disorders who were recently enrolled in one of three types of VA employment services (incentive therapy, transitional work, supported employment), and randomized 1:1 to augmented VR versus control VR. Training for the augmented VR group included 12 weeks of SCST plus 6 weeks of work-related SPSST; training for the control VR group included a control intervention (symptom management training) matched in instructional format and length of training to the SCST and SPSST interventions. All participants received baseline and posttraining measures of social cognition. For those who got jobs, the primary work outcome measures were social skills work behavior and job tenure. RESULTS Results showed a significant group x time interaction favoring the augmented VR group on measures of social cognition and social skills work behavior, but there were no significant differences in job tenure. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE The findings for workplace social skills support a promising new direction for enhancing work outcomes in this population; the null effect on job tenure may have been due to high job retention rates across the three types of employment service programs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Black Americans are overrepresented in Veteran and non-Veteran homeless populations. Community integration remains a problem for many Veterans after they obtain housing, and Black Veterans may encounter additional difficulties due to... more
Black Americans are overrepresented in Veteran and non-Veteran homeless populations. Community integration remains a problem for many Veterans after they obtain housing, and Black Veterans may encounter additional difficulties due to systemic racism. However, no prior study has specifically examined whether there are racial differences in community integration; similarly, no study has considered racial differences in psychosocial correlates of community integration in homeless Veterans. Knowledge of these factors could inform the development of culturally congruent rehabilitative interventions for Black Veterans. Semi-structured clinical interviews were administered to Black (N = 99) and White (N = 49) homeless Veterans to examine relations among psychiatric symptoms, motivation, and community integration domains (e.g., social integration, work productivity, and independent living). There were no significant racial differences in independent living or work productivity. Black Veterans had better social integration with family compared to White Veterans. In addition, psychiatric symptoms were more strongly correlated with social integration for Black than White Veterans. The association between motivation and work productivity was also stronger for Black Veterans. Recovery-oriented interventions could harness family connections and better target psychiatric symptoms to improve community integration for Black Veterans. Work productivity may improve from interventions aimed at enhancing motivation for Black Veterans.
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BackgroundThe aggregation of neurocognitive deficits among the non-psychotic first-degree relatives of adult- and childhood-onset schizophrenia patients suggests that there may be a common etiology for these deficits in childhood- and... more
BackgroundThe aggregation of neurocognitive deficits among the non-psychotic first-degree relatives of adult- and childhood-onset schizophrenia patients suggests that there may be a common etiology for these deficits in childhood- and adult-onset illness. However, there is considerable heterogeneity in the presentation of neurobiological abnormalities, and whether there are differences in the extent of familial transmission for specific domains of cognitive function has not been systematically addressed.MethodsWe employed variance components analysis, as implemented in SOLAR-Eclipse, to evaluate the evidence of familial transmission for empirically derived composite scores representing attention, working memory, verbal learning, verbal retention, and memory for faces. We contrast estimates for adult- and childhood-onset schizophrenia families and matched community control pedigrees, and compare our findings to previous reports based on analogous neurocognitive assessments.ResultsWe ...
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Preexposure prophylaxis (PrEP) has emerged as a human immunodeficiency virus (HIV) prevention tool for populations at highest risk for HIV infection. Current US Centers for Disease Control and Prevention (CDC) guidelines for identifying... more
Preexposure prophylaxis (PrEP) has emerged as a human immunodeficiency virus (HIV) prevention tool for populations at highest risk for HIV infection. Current US Centers for Disease Control and Prevention (CDC) guidelines for identifying PrEP candidates may not be specific enough to identify gay, bisexual, and other men who have sex with men (MSM) at the highest risk for HIV infection. We created an HIV risk score for HIV-negative MSM based on Syndemics Theory to develop a more targeted criterion for assessing PrEP candidacy. Behavioral risk assessment and HIV testing data were analyzed for HIV-negative MSM attending the Los Angeles LGBT Center between January 2009 and June 2014 (n = 9481). Syndemics Theory informed the selection of variables for a multivariable Cox proportional hazards model. Estimated coefficients were summed to create an HIV risk score, and model fit was compared between our model and CDC guidelines using the Akaike Information Criterion and Bayesian Information C...
Research Interests: Risk assessment, Medicine, Biological Sciences, Humans, United States, and 12 moreMale, Men who have Sex with Men, Adult, Akaike Information Criterion, Risk Assessment, Bayes Theorem, Pre exposure Prophylaxis, Sexually Transmitted Diseases, Precision Medicine, Proportional Hazards Models, Medical and Health Sciences, and HIV infections
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Research Interests: Pharmacology, Quality of life, Public Health, Ovarian Cancer, Medicine, and 15 moreHumans, Female, Method, Cluster Analysis, Data Clustering, Health Status, Aged, Middle Aged, Quality adjusted life years, Adult, Economic evaluation, Preference, Internet, Preference Elicitation, and Ovarian Neoplasms
Research Interests: Mathematics, Computer Science, Algorithms, Econometrics, Interaction, and 15 moreInference, Adolescent, Medicine, Software, Humans, Child, Female, Regression, Male, Missing Data, Public health systems and services research, Multiple Imputation, Bayes Theorem, Multivariate Normal Distribution, and Predictive value of tests
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When designing and interpreting results from clinical trials evaluating treatments for children on the autism spectrum, a complicating factor is that most children receive a range of concurrent treatments. Thus, it is important to better... more
When designing and interpreting results from clinical trials evaluating treatments for children on the autism spectrum, a complicating factor is that most children receive a range of concurrent treatments. Thus, it is important to better understand the types and hours of interventions that participants typically receive as part of standard of care, as well as to understand the child, family, and geographic factors that are associated with different patterns of service utilization. In this multi-site study, we interviewed 280 caregivers of 6-to-11-year-old school-aged children on the autism spectrum about the types and amounts of interventions their children received in the prior 6 weeks. Reported interventions were coded as "evidence-based practice" or "other interventions," reflecting the level of empirical support. Results indicated that children received a variety of interventions with varying levels of empirical evidence and a wide range of hours (0 to 79.3 hours/week). Children with higher autism symptom levels, living in particular states, and who identified as non-Hispanic received more evidence-based intervention hours. Higher parental education level related to more hours of other interventions. Children who were younger, had lower cognitive ability, and with higher autism symptom levels received a greater variety of interventions overall. Thus, based on our findings, it would seem prudent when designing clinical trials to take into consideration a variety of factors including autism symptom levels, age, cognitive ability, ethnicity, parent education and geographic location. Future research should continue to investigate the ethnic, racial, and socioeconomic influences on school-aged intervention services.
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Key points This work confirms previous reports that CM4620, a small molecule inhibitor of Ca2+ entry via store operated Ca2+ entry (SOCE) channels formed by stromal interaction molecule 1 (STIM1)/Orai complexes, attenuates acinar cell... more
Key points This work confirms previous reports that CM4620, a small molecule inhibitor of Ca2+ entry via store operated Ca2+ entry (SOCE) channels formed by stromal interaction molecule 1 (STIM1)/Orai complexes, attenuates acinar cell pathology and acute pancreatitis in mouse experimental models. Here we report that intravenous administration of CM4620 reduces the severity of acute pancreatitis in the rat, a hitherto untested species. Using CM4620, we probe further the mechanisms whereby SOCE via STIM1/Orai complexes contributes to the disease in pancreatic acinar cells, supporting a role for endoplasmic reticulum stress/cell death pathways in these cells. Using CM4620, we show that SOCE via STIM1/Orai complexes promotes neutrophil oxidative burst and inflammatory gene expression during acute pancreatitis, including in immune cells which may be either circulating or invading the pancreas. Using CM4620, we show that SOCE via STIM1/Orai complexes promotes activation and fibroinflammat...
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Research Interests: Genetics, Neuroscience, Mathematics, Computer Science, Artificial Intelligence, and 15 moreEconometrics, Statistics, Machine Learning, Mental Health, Cancer, EEG, Electroencephalography, Infectious Diseases, Inference, Medicine, Cluster Analysis, Synchronicity, Pooling, Spectral Clustering, and Consensus clustering
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Research Interests: Cognitive Science, Neuroimaging, Bipolar Disorder, Magnetic Resonance Imaging, Medicine, and 15 moreLinear models, Mood, Brain Mapping, Hippocampus, Humans, Mania, Female, Male, Amygdala, Clinical Sciences, Middle Aged, Adult, Neurosciences, Psychiatric Status Rating Scales, and Medical and Health Sciences
Research Interests: Neuroscience, Psychology, Computer Science, Bipolar Disorder, Magnetic Resonance Imaging, and 13 moreMedicine, Prefrontal Cortex, Brain Mapping, Humans, Mania, Functional Magnetic Resonance Imaging, Female, Neuroimage, Male, Amygdala, Adult, Psychology and Cognitive Sciences, and Medical and Health Sciences
Clinical research in neurodevelopmental disorders remains reliant upon clinician and caregiver measures. Limitations of these approaches indicate a need for objective, quantitative, and reliable biomarkers to advance clinical research.... more
Clinical research in neurodevelopmental disorders remains reliant upon clinician and caregiver measures. Limitations of these approaches indicate a need for objective, quantitative, and reliable biomarkers to advance clinical research. Extant research suggests the potential utility of multiple candidate biomarkers; however, effective application of these markers in trials requires additional understanding of replicability, individual differences, and intra-individual stability over time. The Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is a multi-site study designed to investigate a battery of electrophysiological (EEG) and eye-tracking (ET) indices as candidate biomarkers for autism spectrum disorder (ASD). The study complements published biomarker research through: inclusion of large, deeply phenotyped cohorts of children with autism spectrum disorder (ASD) and typical development; a longitudinal design; a focus on well-evidenced candidate biomarkers harmonized with a...
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Recent proposals have suggested the potential for neural biomarkers to improve clinical trial processes in neurodevelopmental conditions; however, few efforts have identified whether chronological age-based adjustments will be necessary... more
Recent proposals have suggested the potential for neural biomarkers to improve clinical trial processes in neurodevelopmental conditions; however, few efforts have identified whether chronological age-based adjustments will be necessary (as used in standardized behavioral assessments). Event-related potentials (ERPs) demonstrate early differences in the processing of faces vs. objects in the visual processing system by 4 years of age and age-based improvement (decreases in latency) through adolescence. Additionally, face processing has been proposed to be related to social skills as well as autistic social-communication traits. While previous reports suggest delayed latency in individuals with autism spectrum disorder (ASD), extensive individual and age based heterogeneity exists. In this report, we utilize a sample of 252 children with ASD and 118 children with typical development (TD), to assess the N170 and P100 ERP component latencies (N170L and P100L, respectively), to upright ...
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Research Interests: Psychiatry, Mental Health, Family, Adolescent, Medicine, and 15 moreNeurocognitive, Endophenotypes, Computers, Neurocognition, Humans, Clinical research, Aged, Middle Aged, Adult, Case Control, Neurosciences, Case Control Studies, Neuropsychological Tests, Brain Disorders, and Medical and Health Sciences
Research Interests: Psychology, Clinical Psychology, Coping Strategies, Schizophrenia, Adolescent, and 15 moreMedicine, Humans, Child, Female, Male, Risk factors, Social Adjustment, Clinical Sciences, Longitudinal Studies, Adult, Psychotic Disorders, Risk Factors, Cross Sectional Studies, Case Control Studies, and Prodromal Symptoms
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Functional brain imaging through electroencephalography (EEG) relies upon the analysis and interpretation of high-dimensional, spatially organized time series. We propose to represent time-localized frequency domain characterizations of... more
Functional brain imaging through electroencephalography (EEG) relies upon the analysis and interpretation of high-dimensional, spatially organized time series. We propose to represent time-localized frequency domain characterizations of EEG data as region-referenced functional data. This representation is coupled with a hierarchical regression modeling approach to multivariate functional observations. Within this familiar setting we discuss how several prior models relate to structural assumptions about multivariate covariance operators. An overarching modeling framework, based on infinite factorial decompositions, is finally proposed to balance flexibility and efficiency in estimation. The motivating application stems from a study of implicit auditory learning, in which typically developing (TD) children, and children with autism spectrum disorder (ASD) were exposed to a continuous speech stream. Using the proposed model, we examine differential band power dynamics as brain functio...
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We previously reported that donepezil, a central-type acetylcholinesterase inhibitor, showed neuroprotective action via alpha4-and alpha7-nicotinic acetylcholine receptors against glutamate neurotoxicity in rat cortical culture. The... more
We previously reported that donepezil, a central-type acetylcholinesterase inhibitor, showed neuroprotective action via alpha4-and alpha7-nicotinic acetylcholine receptors against glutamate neurotoxicity in rat cortical culture. The present study was performed to investigate whether the neuroprotective action of acetylcholinesterase inhibitors is accompanied by the alteration of expression and function of nicotinic receptors. Four days treatment with acetylcholinesterase inhibitors (10 microM) enhanced the nicotine-induced increase of the intracellular calcium concentration. Immunoblot analysis revealed that donepezil increased both alpha4 and alpha7 subunit proteins. Donepezil and galanthamine increased the number of cells expressing alpha4- and alpha7-nicotinic receptors in immunocytochemical analysis. We examined whether up-regulation of nicotinic receptors affected the neuroprotective action of acetylcholinesterase inhibitors. Under up-regulating conditions, donepezil and galanthamine exerted neuroprotective action at lower concentrations. These results suggest that donepezil and galanthamine up-regulate nicotinic receptors in cortical neurons, and that the up-regulation of nicotinic receptors may make cortical neurons more sensitive to the neuroprotective action of donepezil and galanthamine.
Research Interests: Calcium, Neuroprotection, Glutamate, Cerebral Cortex, Animals, and 15 moreNeurons, Cholinesterase inhibitors, European, Rats, Time Factors, Galantamine, Glutamic Acid, Intracellular Calcium, Piperidines, Immunoblotting, Indans, Psychology and Cognitive Sciences, reverse transcriptase polymerase chain reaction, Medical and Health Sciences, and Pharmacology and pharmaceutical sciences(Neurons, Cholinesterase inhibitors, European, Rats, Time Factors, Galantamine, Glutamic Acid, Intracellular Calcium, Piperidines, Immunoblotting, Indans, Psychology and Cognitive Sciences, reverse transcriptase polymerase chain reaction, Medical and Health Sciences, and Pharmacology and pharmaceutical sciences)
(Neurons, Cholinesterase inhibitors, European, Rats, Time Factors, Galantamine, Glutamic Acid, Intracellular Calcium, Piperidines, Immunoblotting, Indans, Psychology and Cognitive Sciences, reverse transcriptase polymerase chain reaction, Medical and Health Sciences, and Pharmacology and pharmaceutical sciences)
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Studies demonstrate that dynamic assessment (i.e., learning potential) improves the prediction of response to rehabilitation over static measures in individuals with schizophrenia. Learning potential is most commonly assessed using... more
Studies demonstrate that dynamic assessment (i.e., learning potential) improves the prediction of response to rehabilitation over static measures in individuals with schizophrenia. Learning potential is most commonly assessed using neuropsychological tests under a test-train-test paradigm to examine change in performance. Novel learning potential approaches using social cognitive tasks may have added value, particularly for the prediction of social functioning, but this area is unexplored. The present study is the first to investigate whether patients with schizophrenia demonstrate social cognitive learning potential across phase of illness. This study included 43 participants at clinical high risk (CHR), 63 first-episode, and 36 chronic schizophrenia patients. Assessment of learning potential involved test-train-test versions of the Wisconsin Card Sorting Test (non-social cognitive learning potential) and the Facial Emotion Identification Test (social cognitive learning potential)....
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Electroencephalography (EEG) data possess a complex structure that includes regional, functional, and longitudinal dimensions. Our motivating example is a word segmentation paradigm in which typically developing (TD) children, and... more
Electroencephalography (EEG) data possess a complex structure that includes regional, functional, and longitudinal dimensions. Our motivating example is a word segmentation paradigm in which typically developing (TD) children, and children with autism spectrum disorder (ASD) were exposed to a continuous speech stream. For each subject, continuous EEG signals recorded at each electrode were divided into one-second segments and projected into the frequency domain via fast Fourier transform. Following a spectral principal components analysis, the resulting data consist of region-referenced principal power indexed regionally by scalp location, functionally across frequencies, and longitudinally by one-second segments. Standard EEG power analyses often collapse information across the longitudinal and functional dimensions by averaging power across segments and concentrating on specific frequency bands. We propose a hybrid principal components analysis for region-referenced longitudinal f...
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This report describes the first comparative double-blind, placebo-controlled trial of levothyroxine (L-T ) and triiodothyronine (T ) as adjunctive treatments in rapid cycling bipolar disorder. Thirty-two treatment-resistant, rapid cycling... more
This report describes the first comparative double-blind, placebo-controlled trial of levothyroxine (L-T ) and triiodothyronine (T ) as adjunctive treatments in rapid cycling bipolar disorder. Thirty-two treatment-resistant, rapid cycling patients who had failed a trial of lithium were randomized into three treatment arms: L-T , T , or placebo. They were followed for ≥4 months with weekly clinical and endocrine assessments. There were no statistically significant differences between the groups in age, gender, duration of illness, or thyroid status. Markov chain analyses were employed to assess treatment effects on cycling patterns among mood states (euthymia, depression, mania, and mixed). Within groups, post-treatment the L-T group spent significantly less time depressed or in a mixed state and greater time euthymic. The T and placebo groups did not differ significantly pre- and post-treatment in any mood state, although the pattern of effects was the same for the T group as for th...
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Researchers collected multiple measurements on patients with schizophrenia and their relatives, as well as control subjects and their relatives, to study vulnerability factors for schizophrenics and their near relatives. Observations... more
Researchers collected multiple measurements on patients with schizophrenia and their relatives, as well as control subjects and their relatives, to study vulnerability factors for schizophrenics and their near relatives. Observations across individuals from the same family are correlated, and also the multiple outcome measures on the same individuals are correlated. Traditional data analyses model outcomes separately and thus do not provide information about the interrelationships among outcomes. We propose a novel Bayesian family factor model (BFFM), which extends the classical confirmatory factor analysis model to explain the correlations among observed variables using a combination of family-member and outcome factors. Traditional methods for fitting confirmatory factor analysis models, such as full-information maximum likelihood (FIML) estimation using quasi-Newton optimization (QNO), can have convergence problems and Heywood cases (lack of convergence) caused by empirical under...
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Although evidence-based treatments for pediatric obsessive-compulsive disorder (OCD) exist, many youth fail to respond, and interventions tailored to the needs of specific subsets of patients are lacking. This study examines the efficacy... more
Although evidence-based treatments for pediatric obsessive-compulsive disorder (OCD) exist, many youth fail to respond, and interventions tailored to the needs of specific subsets of patients are lacking. This study examines the efficacy of a family intervention module designed for cases of OCD complicated by poor family functioning. Participants were 62 youngsters aged 8 to 17 years (mean age = 12.71 years; 57% male; 65% white) with a primary diagnosis of OCD and at least 2 indicators of poor family functioning. They were randomized to receive 12 sessions of individual child cognitive-behavioral therapy (CBT) plus weekly parent psychoeducation and session review (standard treatment [ST]) or the same 12 child sessions plus 6 sessions of family therapy aimed at improving OCD-related emotion regulation and problem solving (positive family interaction therapy [PFIT]). Blinded raters evaluated outcomes and tracked responders to 3-month follow-up. Compared to ST, PFIT demonstrated better...