Active and Past Studies

EPICAL: Early Psychosis Intervention in California

Based on an average incidence of psychotic illness of 272 per 100,000 people each year, approximately 107,000 California residents are estimated to experience a first psychotic episode each year. California currently has 30 active programs providing Early Psychosis (EP) services across 26 counties. However, these programs are not identical. They offer different services, follow different treatment models, and measure treatment impact differently.

EPI-CAL aims to improve the quality of services and measure the impact of treatment. To do this, we have created a learning health care network (LHCN) of California EP programs. The goal of this network is to standardize practice and support knowledge-sharing. To make evaluation of these different EP programs possible, network members have agreed to gather the same information across the same timeframe. Clients, families, and providers will provide information by answering surveys at regular intervals throughout treatment. Surveys will be offered in 13 different languages to meet the needs the diverse communities represented in the LHCN. Surveys will ask about how clients are doing at work or school, how their social life is, and how they feel about their future.

The technology used by the LHCN will bring the information provided by clients and families back into their care. The providers will have access to their clients’ data to use as part of their regular appointments with clients and families. This may empower clients to use their own data in care decisions.

EPI-CAL will also allow programs to learn from their own data and from each other. Program management will have access to all of the survey data from their program. They can compare their whole clinic to the network as a whole. They can use this group data to evaluate the impact of program services and look for areas of strength or for improvement.

EPI-CAL started as a collaboration between California counties (Los Angeles, San Diego, Orange, Solano, and Napa) and One Mind to develop a Learning Health Care Network for the EP programs of those counties. A grant from NIH brought the California LHCN into the national network of EP programs, EPINET. This grant also made it possible to add additional county and university EP programs into the LHCN. Being a part of EPINET gives clients and programs the opportunity to contribute to the national conversation on how to inform and improve care for individuals with early psychosis across the US.

Duration of Untreated Psychosis (DUP)

Our team is working on developing and validating a novel DUP measure for use in community settings. We hypothesize this new measure will demonstrate inter-rater reliability (IRR) between coordinated specialty care (CSC) providers and a central assessor, with an intra-class coefficient (ICC) of at least .80 for days from initial assessment to DUP start point, days from assessment to DUP end point, and days from start point to end point DUP (total DUP). Additionally, we hypothesize predictive validity, defined by significant relationships between shorter DUP and greater improvements in functioning and quality of life at six months, as well as feasibility and acceptability to early psychosis (EP) providers and clients, with a mean administration time of less than 40 minutes.

The measure is currently being piloted at six sites, where we are actively collecting data to assess its reliability, validity, and feasibility in real-world settings.

County Data 

Our aim is to conduct preliminary evaluation of cost-effectiveness and impact of Early Psychosis (EP) program participation in community settings. The goal of this study is to produce a multi-county integrated analysis including data from both the early psychosis programs compared to regular outpatient treatment as usual for clients in the following counties: San Diego, Los Angeles, Solano, Orange, Napa, and Stanislaus. [We hypothesize that cost of care for individuals enrolled in EP programs will be lower than CG program participants, and participation in EP program services will be positively associated with improved outcomes.]  

The proposed analysis is based on pilot work conducted in Sacramento County, scaled to multiple counties (Niendam et al., 2016). It focuses on consumer-level data related to program service utilization, other outpatient services utilization, crisis/ED utilization, and psychiatric hospitalization and costs associated with these utilization domains during the time period of January 1st, 2017-June 30th, 2022.   

Training and Technical Assistance (TTA) 

The Early Psychosis Training and Technical Assistance Center (TTA) was developed by UC Davis in collaboration with UC San Francisco and Stanford University to support the implementation and sustainability of EP programs across California. Our goal is to support the provision of high quality early psychosis care to all Californians and to promote recovery and better outcomes through a learning healthcare network approach. 

As part of our program, we provide a suite of training modules designed to aid programs in developing or sustaining their EP programs in accordance with the Coordinated Specialty Care (CSC) model. Participating EP programs are offered ongoing consultation with TTA staff to provide program management guidance, connect programs with resources needed to reach fidelity, track training progress, and troubleshoot obstacles toward TTA goals.

As the TTA Assessment Training team leads, our UCSF team supports the TTA by carrying out fidelity assessments, providing consultation in evidence-based assessment, and developing assessment training materials. Group and individual consultation is provided in the use of gold standard, trauma-informed evaluation of psychosis, common diagnostic differential considerations, and the integration of brief, low-burden screening tools for community based settings to enhance efficiency of service delivery.

COTES: Community-Based Cognitive Training in Early Schizophrenia

The study is a double-blind randomized controlled trial performed in 4 Early Intervention Services (EIS) community mental health clinics.  195 young patients (125 expected to provide complete data) with recent-onset (RO) schizophrenia will be stratified by education and symptom severity and randomly assigned to 1 of 3 groups:  1) iPad application consisting of targeted cognitive training (TCT, 30 hours total, ~10 weeks) developed by Brain Plasticity Institute, this consists of an auditory/verbal processing training module which will be applied for 20 hours, and a social cognition training module, which will be applied for 10 hours; 2) iPad application consisting of general cognitive exercises focusing on executive dysfunction (GCE) (30 hours total, ~10 weeks) developed by Brain Plasticity Institute, which will target executive functioning, general intelligence, and spatial navigation; or 3) Treatment-as-usual group (TAU) who will continue treatment as usual in the EIS program, but not participate in cognitive training.  The GCE and TAU participants will be offered access to the TCT training after completion of the follow-up assessment.  Subjects will undergo standardized clinical and cognitive assessments at baseline, after 30 hours (~10 weeks) of intervention, and at a 6 month follow-up.  The study procedure diagram is attached.

Additionally, participants who have been randomized to either training condition and who are over 18 will have the option to participante in a brief semi-structured interview that assesses the barriers and facilitators to implementation of remote cognitive training in early psychosis.

Additionally, participants will have the option to include a family member or friend to attend a meeting in which the participant, a research assistant, and the family member/friend discuss motivation and support strategies that the family member/friend may offer during the participants time in the study.

ENRS: Equity in Narrative Recovery Stories

The study will examine the lived experience of people who identify as racial, ethnic, gender, and/or sexual orientation minorities and who are in recovery from psychosis. The researcher will conduct (1) confidential one-on-one interviews that will be recorded for qualitative analysis, and (2) non-confidential interviews that will comprise a video collection to be shared publicly with training and professional audiences, with community groups, at schools, and/or through digital media. The purpose is to learn about the intersectionality of mental health conditions and minority status as it pertains to stigma that impacts one’s pathway to care and recovery, as well as to contribute to the destigmatization of psychosis. We will conduct a qualitative analysis to describe the potential roles of cultural factors, oppression, racism and/or bias in participants’ pathways to care and recovery journeys. The video collection will feature the voices and perspectives of individuals from historically marginalized communities.

PART: Clinical and Neurocognitive Assessment in Adolescents and Young Adults at Risk for Serious Psychiatric Disorders

The primary purpose of this study is to assess longitudinal changes in symptoms, risk factors, psychosocial and emotional functioning, neurocognitive features, blood biomarkers, structural and functional brain characteristics, stress responsivity and genetics in adolescents and young adults who are at very high risk for developing schizophrenia or other serious psychiatric disorders, as well as those with recent-onset schizophrenia.  This includes individuals who are showing high-risk features, sometimes termed “Prodromal” symptoms, consisting of cognitive difficulties, social withdrawal, and attenuated positive psychotic symptoms.  Subjects will be assessed at study entry, and then at multiple follow-up points during the following 2 years, which represents the period of highest risk for conversion to psychosis, with assessments at 6, 12, 18, and 24 months.  Measures of brain structural integrity are derived from magnetic resonance imaging (MRI) and brain functional integrity measures are derived from both functional MRI (fMRI) and electroencephalography (EEG).

PRODROMAL QUESTIONNAIRE

This study aims to establish preliminary validity of the Prodromal Questionnaire (PQ), a 92-item self-report screening measure for prodromal and psychotic symptoms. Adolescents and young adults (N = 113) referred to a prodromal psychosis research clinic completed the PQ and the Structured Interview for Prodromal Syndromes (SIPS [Miller, T.J., McGlashan, T.H., Woods, S.W., Stein, K., Driesen, N., Corcoran, C.M., Hoffman, R., Davidson, L., 1999. Symptom assessment in schizophrenic prodromal states. Psychiatric Quarterly 70(4), 273-287]), an interview with established validity for predicting future psychosis. When maximizing selection of true positive cases, scores on a subset of PQ items that assess positive symptoms predicted a concurrent prodromal or psychotic SIPS diagnosis with 90% sensitivity and 49% specificity. The PQ shows good preliminary validity in detecting individuals with an interview-diagnosed prodromal or psychotic syndrome, but it is less sensitive to the threshold between prodromal and full-blown psychosis.

STANLEY: Randomized clinical trial of intensive computer-based cognitive remediation in recent-onset schizophrenia

The aim of this study is to investigate the efficacy of neuroscience-guided computerized cognitive training exercises on the remediation of cognitive deficits and symptoms associated with recent-onset schizophrenia and prodromal schizophrenia, and to examine the influence of subject characteristics, brain structure and function, and pharmacotherapy on the response to remediation.  Training exercises will be based on the principles of the self-adjusted psychophysical training tools developed by Merzenich et al. (1996a-c). Exercises will directly target a core domain of neurocognitive impairment in schizophrenia-- verbal and visuo-spatial processing efficiency-- which is known to be relevant to clinical and psychosocial outcome, while secondarily training two other functionally important cognitive skills, attention and executive control. The study is a randomized controlled clinical trial comparing the neuroscience-guided cognitive remediation exercises with a control condition (enjoyable computer games). There is also a comparison condition for recent-onset patients where there is no training done between pre and post testing.

Subjects in the active condition will complete a total of 40 hours of the targeted cognitive training (TCT) module (auditory processing). We will monitor the changes in neurocognitive functioning before and after training. In addition to the TCT, subjects will undergo pre- and post-TCT electroencephalogram (EEG) and magnetic resonance imaging (MRI) to examine any changes in brain structure or function.

Recent-onset participants who are eligible for the study but not interested in participating in the full cognitive training will be asked to complete assessments and imaging at baseline and then again in 13 weeks, in order to provide a follow-along comparison group.  We will also see these participants again in 6 months.

The general study design will be a controlled clinical trial in which volunteer subjects with schizophrenia will be paired according to IQ (< 100 vs. >100), baseline symptom severity (PANSS rating < 2.0 vs. >2.0), and gender (male vs. female),with one member of each pair randomly assigned to training exercises that use a neuroadaptive training procedure, and the other matched subject assigned to a control intervention (commercially available enjoyable computer games). UHR subjects will also be paired according to IQ (< 100 vs. >100), baseline symptom severity (positive symptom ratings from the SIPS (< 2.0 vs. >2.0)and gender (male vs. female). As subjects enter the study, they will be categorized using a 2 x 3 classification (high/low IQ, high/low symptoms, and gender male/female), with cut-points at IQ >100 and mean PANSS >2.0 if they are a subject with schizophrenia. Pairs of subjects with the same IQ and symptom-severity classification will be randomly assigned to active treatment (TCT) or placebo (CG). For UHR subjects, they will be categorized using a 2x3 classification (high/low IQ, high/low symptoms, gender male/female). Healthy Controls will be matched to the UHR subjects according to age, gender and IQ. There will also be some schizophrenia subjects who choose not to do training.

All subjects will receive a baseline evaluation of clinical, neurocognitive, and functional measures.  All subjects will have blood drawn to assay DNA and biomarkers relevant to schizophrenia (e.g. BDNF, hormones, neuropeptides, cytokines) at baseline, two weeks into the training, post training, and 6 months later.  Subjects will also undergo electroencephalogram (EEG) and magnetic resonance imaging (MRI) at baseline. Note: baseline assessments will be conducted unless data has already been gathered from another study titled “Clinical and Neurocognitive Assessment in Adolescents and Young Adults at Risk for Serious Psychiatric Disorder”, IRB Number:  10-00610 within 2 months of the start of TCT. Subjects will complete either the intensive, computer-based cognitive training exercises (targeted cognitive training group, TCT), performing the exercises for 60 minutes per day, five days per week, until completion (40 hours of training/8 weeks participation), or will perform a control graphics-based computer games (CG) intervention at an equivalent frequency and intensity and for an equivalent period of time. Subjects’ participation will be monitored by the TCT program, and this information will be uploaded from their laptop, home computer, or computer in the lab every two weeks.  After the intervention, subjects will undergo a second evaluation of clinical, neurocognitive, and functional outcome measures. At the conclusion of training, blood will be drawn.  A second set of EEG and MRI measures will occur at this time.  Independent personnel unaware of subjects’ group status will perform the assessments. Subjects with schizophrenia who have not done training will complete all of these assessments, except blood samples, EEG and MRI, 13 weeks after completing baseline assessments and again 6 months later.

In order to determine stability of training effects six months after completion of the intervention, each subject will be asked to return to the laboratory for a re-evaluation of clinical, neuropsychological, and functional outcome measures.

Recent Onset subjects will be informed of which condition (control or active) they were assigned to at the end of their 6 month follow up appointments.  The subjects (if adults) will then be offered an opportunity to participate in another section of the research in which they will get an active condition program (Targeted Affective Remediation Approach; TARA) that focuses on social cognition.  Subjects who continue on to this part of the study will complete pre-assessments, 24 hours of training, followed by post-assessments.  Former CG subjects who complete TARA (or choose not to), will then be offered the active training (TCT).

In addition, subjects from a parallel study of TCT vs CG in adult schizophrenia subjects(Study Number 10-02727 Neuroscience guided remediation of cognitive deficits in schizophrenia), on which Dr. Sophia Vinogradov is the PI, will be offered participation in the TARA arm of this study after they complete either an active or control condition for that study.

We will also recruit directly into the TARA arm for individuals who are eligible but cannot complete the main study due to not being able to complete the MRI, not able to complete the full one year of participation, etc.

UHR subjects will be seen 6 and 12 months after training.  At the 12 month post training evaluation, the individuals in the control condition will be informed that they were in the control condition and will be offered the active condition TCT software so that they can complete the training on their own.  Individuals in the TCT condition will be seen again 18 and 24 months after training and will complete the clinical and neuropsychological assessments at each of these time points.

If imaging is done at a later time point than baseline due to imaging being unavailable or subject choosing to do imaging at a later time point, we will image the subject as soon as possible and then after training or 6 months later depending on the time that the baseline imaging is completed.

If a UHR subject has a psychotic episode (converts) during participation in the study, we will meet with them for a clinical assessment to confirm their diagnosis and they will complete an EEG and MRI. If this occurs during the cognitive training, they will resume training once they are clinically stable. If this occurs during the follow-up phase of the study, and they meet criteria for a ‘psychotic syndrome’ on the SIPS, but do not meet criteria for schizophrenia, schizophreniform or schizoaffective disorder, they will complete a clinical assessment every 6 months until they meet criteria for one of those diagnoses or until they reach the end of the 24 month study, whichever comes first. Once they meet criteria for one of those diagnoses, they will stop participating in the study.

Feedback will be provided to all subjects regarding the results of the study eligibility evaluation.  This will occur either directly after the evaluation or at a separatly scheduled appointment.  UHR subjects will receive feedback after each follow-up time point as well.

Multisite details: Procedures described above will take place at UCSF, UCD, and First Hope in Contra Costa County, CA. Although Dr. Carter will assume primary responsibility for the research at UCD, Dr. Vinogradov will have overall responsibility for the project at all sites.