National Institute of Mental Health Support for Cognitive Treatment Development in Schizophrenia: A Narrative Review.

For several decades the National Institute of Mental Health (NIMH) has supported basic and translational research into cognitive impairment in schizophrenia. This article describes the Institute's ongoing commitment to cognitive assessment and intervention research, as reflected by three signature initiatives-Measurement and Treatment Research to Improve Cognition in Schizophrenia; Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia; and Research Domain Criteria-and related funding announcements that span basic experimental studies, efficacy and comparative effectiveness trials, and implementation research designed to promote cognitive healthcare in real-world treatment settings. We discuss how trends in science and public health policy since the early 2000s have influenced NIMH treatment development activities, resulting in greater attention to (1) inclusive teams that reflect end-user perspectives on the utility of proposed studies; (2) measurement of discrete neurocognitive processes to inform targeted interventions; (3) clinical trials that produce useful information about putative illness mechanisms, promising treatment targets, and downstream clinical effects; and (4) "productive urgency" in pursuing feasible and effective cognitive interventions for psychosis. Programs employing these principles have catalyzed cognitive measurement, drug development, and behavioral intervention approaches that aim to improve neurocognition and community functioning among persons with schizophrenia. NIMH will maintain support for innovative and impactful investigator-initiated research that advances patient-centered, clinically effective, and continuously improving cognitive health care for persons with psychotic disorders.

Public Sector Learning Health Care Systems-Improving Patient Experience, Workforce Well-Being, and Recovery Outcomes.

This Viewpoint discusses the need for integrating basic, clinical, and epidemiological science into behavioral health care delivery to develop more scalable and sustainable learning health care systems and improve population health and patient experience, reduce costs, and promote the well-being of the health care workforce.

Trends in Children's Mental Health Services Research Funding: Response to Hoagwood and Colleagues' Commentary.

In their recent JAACAP Commentary, Hoagwood et al.1 examined data extracted from the National Institutes of Health Research Portfolio Online Reporting Tools (RePORT) and concluded there has been a decrease in National Institute of Mental Health (NIMH) funding for child and adolescent services and intervention research during the 10-year period from 2005 to 2015. They eloquently argued for the importance of research that can guide practice and inform the organization and delivery of children's mental health services in the current context of unmet need and the state of mental health service delivery.

Twelve-Month Health Care Use and Mortality in Commercially Insured Young People With Incident Psychosis in the United States.

Objective: To assess 12-month mortality and patterns of outpatient and inpatient treatment among young people experiencing an incident episode of psychosis in the United States. Method: Prospective observational analysis of a population-based cohort of commercially insured individuals aged 16-30 receiving a first observed (index) diagnosis of psychosis in 2008-2009. Data come from the US Department of Health and Human Services' Multi-Payer Claims Database Pilot. Outcomes are all-cause mortality identified via the Social Security Administration's full Death Master File; and inpatient, outpatient, and psychopharmacologic treatment based on health insurance claims data. Outcomes are assessed for the year after the index diagnosis. Results: Twelve-month mortality after the index psychosis diagnosis was 1968 per 100000 under our most conservative assumptions, some 24 times greater than in the general US population aged 16-30; and up to 7372 per 100000, some 89 times the corresponding general population rate. In the year after index, 61% of the cohort filled no antipsychotic prescriptions and 41% received no individual psychotherapy. Nearly two-thirds (62%) of the cohort had at least one hospitalization and/or one emergency department visit during the initial year of care. Conclusions: The hugely elevated mortality observed here underscores that young people experiencing psychosis warrant intensive clinical attention-yet we found low rates of pharmacotherapy and limited use of psychosocial treatment. These patterns reinforce the importance of providing coordinated, proactive treatment for young people with psychosis in US community settings.

Functional Capacity Assessed by the Map Task in Individuals at Clinical High-Risk for Psychosis.

OBJECTIVES: Recent studies have recognized that signs of functional disability in schizophrenia are evident in early phases of the disorder, and, as a result, can potentially serve as vulnerability markers of future illness. However, functional measures in the psychosis prodrome have focused exclusively on real-world achievements, rather than on the skills required to carry-out a particular real-world function (ie, capacity). Despite growing evidence that diminished capacity is critical to the etiology of the established disorder, virtually no attention has been directed towards assessing functional capacity in the pre-illness stages. In the present study, we introduce the Map task, a measure to assess functional capacity in adolescent and young-adult high-risk populations. METHODS: The Map task was administered to 609 subjects at Clinical High-Risk (CHR) for psychosis and 242 Healthy Controls (HCs) participating in the North American Prodrome Longitudinal Study (NAPLS2). Subjects were required to efficiently complete a set of specified errands in a fictional town. RESULTS: CHR participants showed large impairments across major indices of the Map task, relative to the HCs. Most importantly, poor performance on the Map task significantly predicted conversion to psychosis, even after adjusting for age, IQ, clinical state, and other potential confounders. CONCLUSIONS: To the best of our knowledge, the Map task is one of the first laboratory-based measures to assess functional capacity in high-risk populations. Functional capacity deficits prior to the onset of psychosis may reflect a basic mechanism that underlies risk for psychosis. Early intervention targeting this domain may help to offset risk and independently improve long-term outcome.

Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program.

OBJECTIVE: The primary aim of this study was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for implementation in the U.S. health care system, with community care on quality of life. METHOD: Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and ≤6 months of antipsychotic treatment (N=404) were enrolled and followed for ≥2 years. The primary outcome was the total score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in regular activities. RESULTS: The 223 recipients of NAVIGATE remained in treatment longer, experienced greater improvement in quality of life and psychopathology, and experienced greater involvement in work and school compared with 181 participants in community care. The median duration of untreated psychosis was 74 weeks. NAVIGATE participants with duration of untreated psychosis of <74 weeks had greater improvement in quality of life and psychopathology compared with those with longer duration of untreated psychosis and those in community care. Rates of hospitalization were relatively low compared with other first-episode psychosis clinical trials and did not differ between groups. CONCLUSIONS: Comprehensive care for first-episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes. Effects are more pronounced for those with shorter duration of untreated psychosis.

Specificity of Incident Diagnostic Outcomes in Patients at Clinical High Risk for Psychosis.

It is not well established whether the incident outcomes of the clinical high-risk (CHR) syndrome for psychosis are diagnostically specific for psychosis or whether CHR patients also are at elevated risk for a variety of nonpsychotic disorders. We collected 2 samples (NAPLS-1, PREDICT) that contained CHR patients and a control group who responded to CHR recruitment efforts but did not meet CHR criteria on interview (help-seeking comparison patients [HSC]). Incident diagnostic outcomes were defined as the occurrence of a SIPS-defined psychosis or a structured interview diagnosis from 1 of 3 nonpsychotic Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) groups (anxiety, bipolar, or nonbipolar mood disorder), when no diagnosis in that group was present at baseline. Logistic regression revealed that the CHR vs HSC effect did not vary significantly across study for any emergent diagnostic outcome; data from the 2 studies were therefore combined. CHR (n = 271) vs HSC (n = 171) emergent outcomes were: psychosis 19.6% vs 1.8%, bipolar disorders 1.1% vs 1.2%, nonbipolar mood disorders 4.4% vs 5.3%, and anxiety disorders 5.2% vs 5.3%. The main effect of CHR vs HSC was statistically significant (OR = 13.8, 95% CI 4.2-45.0, df = 1, P < .001) for emergent psychosis but not for any emergent nonpsychotic disorder. Sensitivity analyses confirmed these findings. Within the CHR group emergent psychosis was significantly more likely than each nonpsychotic DSM-IV emergent disorder, and within the HSC group emergent psychosis was significantly less likely than most emergent nonpsychotic disorders. The CHR syndrome is specific as a marker for research on predictors and mechanisms of developing psychosis.

Duration of Untreated Psychosis in Community Treatment Settings in the United States.

OBJECTIVE: This study is the first to examine duration of untreated psychosis (DUP) among persons receiving care in community mental health centers in the United States. METHODS: Participants were 404 individuals (ages 15-40) who presented for treatment for first-episode psychosis at 34 nonacademic clinics in 21 states. DUP and individual- and site-level variables were measured. RESULTS: Median DUP was 74 weeks (mean=193.5±262.2 weeks; 68% of participants had DUP of greater than six months). Correlates of longer DUP included earlier age at first psychotic symptoms, substance use disorder, positive and general symptom severity, poorer functioning, and referral from outpatient treatment settings. CONCLUSIONS: This study reported longer DUP than studies conducted in academic settings but found similar correlates of DUP. Reducing DUP in the United States will require examination of factors in treatment delay in local service settings and targeted strategies for closing gaps in pathways to specialty FEP care.

Stress exposure and sensitivity in the clinical high-risk syndrome: initial findings from the North American Prodrome Longitudinal Study (NAPLS).

There is inconsistent evidence for increased stress exposure among individuals at clinical high risk (CHR) for psychosis. Yet similar to patients with a diagnosed psychotic illness, the preponderance of evidence suggests that CHR individuals tend to experience stressful life events (LE) and daily hassles (DH) as more subjectively stressful than healthy individuals. The present study utilizes data from the North American Prodrome Longitudinal Study Phase 2 (NAPLS-2) to test the hypotheses that (1) CHR individuals manifest higher self-reported stress in response to both LE and DH when compared to healthy controls (HC), (2) group differences in self-reported stress increase with age, (3) baseline self-reported stress is associated with follow-up clinical status, and (4) there is a sensitization effect of LE on the response to DH. In contrast to some previous research, the present findings indicate that the CHR group (N=314) reported exposure to more LE when compared to the HC group (N=162). As predicted, CHR participants rated events as more stressful, and those who progressed to psychosis reported a greater frequency of LE and greater stress from events compared to those whose prodromal symptoms remitted. There was also some evidence of stress-sensitization; those who experienced more stress from LE rated current DH as more stressful. The results indicate that the "prodromal" phase is a period of heightened stress and stress sensitivity, and elevated cumulative lifetime exposure to stressful events may increase reactions to current stressors.

Informed consent in the psychosis prodrome: ethical, procedural and cultural considerations.

Research focused on the prodromal period prior to the onset of psychosis is essential for the further development of strategies for early detection, early intervention, and disease pre-emption. Such efforts necessarily require the enrollment of individuals who are at risk of psychosis but have not yet developed a psychotic illness into research and treatment protocols. This work is becoming increasingly internationalized, which warrants special consideration of cultural differences in conceptualization of mental illness and international differences in health care practices and rights regarding research participation. The process of identifying and requesting informed consent from individuals at elevated risk for psychosis requires thoughtful communication about illness risk and often involves the participation of family members. Empirical studies of risk reasoning and decisional capacity in young people and individuals with psychosis suggest that most individuals who are at-risk for psychosis can adequately provide informed consent; however ongoing improvements to tools and procedures are important to ensure that this work proceeds with maximal consideration of relevant ethical issues. This review provides a discussion of these issues in the context of international research efforts.

A strategic approach for prioritizing research and action to prevent suicide.

It is time to strategically apply science and accountability to the public health problem of preventable suicide. U.S. suicide rates have remained stable for decades. More than 36,000 individuals now die by suicide each year. A public health-based approach to quickly and substantially reduce suicides requires strategic deployment of existing evidence-based interventions, rapid development of new interventions, and measures to increase accountability for results. The purpose of this Open Forum is to galvanize researchers to further develop and consolidate knowledge needed to guide these actions. As researchers overcome data limitations and methodological challenges, they enable better prioritization of high-risk subgroups for targeted suicide prevention efforts, identification of effective interventions ready for deployment, estimation of the implementation impact of effective interventions in real-world settings, and assessment of time horizons for taking implementation to scale. This new knowledge will permit decision makers to take strategic action to reduce suicide and stakeholders to hold them accountable for results.

Developing constructs for psychopathology research: research domain criteria.

There exists a divide between findings from integrative neuroscience and clinical research focused on mechanisms of psychopathology. Specifically, a clear correspondence does not emerge between clusters of complex clinical symptoms and dysregulated neurobiological systems, with many apparent redundancies. For instance, many mental disorders involve multiple disruptions in putative mechanistic factors (e.g., excessive fear, deficient impulse control), and different disrupted mechanisms appear to play major roles in many disorders. The Research Domain Criteria (RDoC) framework is a heuristic to facilitate the incorporation of behavioral neuroscience in the study of psychopathology. Such integration might be achieved by shifting the central research focus of the field away from clinical description to more squarely examine aberrant mechanisms. RDoC first aims to identify reliable and valid psychological and biological mechanisms and their disruptions, with an eventual goal of understanding how anomalies in these mechanisms drive psychiatric symptoms. This approach will require new methods to ascertain samples, relying on hypothesized psychopathological mechanisms to define experimental groups instead of traditional diagnostic categories. RDoC, by design, uncouples research efforts from clinically familiar categories to focus directly on fundamental mechanisms of psychopathology. RDoC proposes a matrix of domains and levels of analyses and invites the field to test and refine the framework. If RDoC is successful, the domains will ultimately relate to familiar psychopathologies in ways that promote new knowledge regarding etiology and more efficient development of new preventive and treatment interventions.

Person-centered psychiatric care: a tribute to Wayne S. Fenton, MD.

Wayne S. Fenton, MD, was an accomplished psychiatric researcher, but his colleagues knew him as an equally talented clinician. This memorial recognizes the personal qualities and professional skills that endeared Wayne Fenton to hundreds of mentally ill persons he treated over the course of his professional career. Among these attributes, deep compassion, sincere respect, and tremendous flexibility were hallmarks of an approach that emphasized collaborative, recovery-oriented therapy. Through his actions and writings, Wayne Fenton influenced a generation of mental health professionals who aspire to similar professional excellence in all aspects of clinical care.