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.

Schizophrenia, as currently operationalized, is a serious public health concern everywhere in the globe. Occurring at a rate of approximately 4.6 per 1000 population at any point of observation and between 3.0 and 6.0 per 1000 over the lifetime, the condition is responsible for 7% of disability adjusted live years caused by mental and substance use disorders. The impact of the disorder on affected persons and communities across the world is thus considerable. In Africa, where schizophrenia is seen as the prototypical “mental disorder” by the lay public, it constitutes a major cause of human rights abuses as well as experienced stigma and discrimination. The delineation of the disorder, including its construct validity and cultural applicability, is of interest not only to researchers but also to mental health practitioners and policy makers. Studies conducted on the continent have demonstrated that the construct of schizophrenia, as described in the global classificatory systems, is recognizable and applicable in the African settings. But such studies have been largely designed from an etic perspective leaving open the question of whether the diagnostic construct has sufficient cultural and social fit as well as salience to African populations. This commentary seeks to highlight ways in which existing gap in knowledge can be addressed in providing an African perspective on the future status of schizophrenia as a diagnostic construct and as a descriptive label of a clinical state.

The integration of developmental processes is essential for a full understanding of psychopathology. The National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) provide a scaffold on which to organize the components and processes of psychopathology and to detail behavioral and biological disruptions in developmental processes gone awry. This special section on Integrating Developmental Psychopathology With the RDoC Framework provides the opportunity to comment on five extraordinary developmental psychopathology articles that report results and theory integral to RDoC. An introductory overview provides context for RDoC's approach to developmental issues. This is followed by brief summaries of each article and points regarding its particularly salient aspects, and concludes with broader comments about the import of the articles as a set. Collectively, the work by these eminent translational scholars illustrates how to conduct significant research on developmental psychopathology using RDoC, and simultaneously raises important questions and future directions to integrate development and environment in RDoC-framed research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

BACKGROUND:In 2013, a few years after the launch of the National Institute of Mental Health's Research Domain Criteria (RDoC) initiative, Cuthbert and Insel published a paper titled "Toward the future of psychiatric diagnosis: the seven pillars of RDoC." The RDoC project is a translational research effort to encourage new ways of studying psychopathology through a focus on disruptions in normal functions (such as reward learning or attention) that are defined jointly by observable behavior and neurobiological measures. The paper outlined the principles of the RDoC research framework, including emphases on research that acquires data from multiple measurement classes to foster integrative analyses, adopts dimensional approaches, and employs novel methods for ascertaining participants and identifying valid subgroups.DISCUSSION:To mark the first decade of the RDoC initiative, we revisit the seven pillars and highlight new research findings and updates to the framework that are related to each. This reappraisal emphasizes the flexible nature of the RDoC framework and its application in diverse areas of research, new findings related to the importance of developmental trajectories within and across neurobehavioral domains, and the value of computational approaches for clarifying complex multivariate relations among behavioral and neurobiological systems.CONCLUSION:The seven pillars of RDoC have provided a foundation that has helped to guide a surge of new studies that have examined neurobehavioral domains related to mental disorders, in the service of informing future psychiatric nosology. Building on this footing, future areas of emphasis for the RDoC project will include studying central-peripheral interactions, developing novel approaches to phenotyping for genomic studies, and identifying new targets for clinical trial research to facilitate progress in precision psychiatry.

BACKGROUND:Interesting data and theories have emerged regarding auditory hallucinations (AHs) in patients with schizophrenia. The possibility that these patients may have changes in the anatomy of the auditory cortex and/or subcortical structures of the central auditory nervous system and present with deficits on audiological tests is important information to the audiology community. However, it seems clear that, in general, audiologists are not sufficiently aware of these findings.PURPOSE:There are two main purposes of this article: (1) to educate audiologists about AHs related to schizophrenia and related issues, and (2) to encourage audiologists and hearing scientists to become involved in the evaluation and research of AHs. This fascinating disorder is one in which audiologists/hearing scientists are well suited to make a significant contribution.RESEARCH DESIGN:A review and synthesis of the literature was conducted. Relevant literature was identified through PubMed, Google Scholar, as well as independent book chapters and article searches. Keywords driving the searches were AHs, auditory illusions, verbal and musical hallucinations, schizophrenia, and central auditory disorders. Given the currency of the topic, the information collected was primarily between 1990 and 2020.STUDY SAMPLE:The review is organized around categorization, prevalence, models, mechanisms, anatomy, pathophysiology, and audiological correlates related to AHs.DATA COLLECTION AND ANALYSIS:Searches were conducted using well-known search engines and manual searches by each author. This information on AHs was then analyzed collectively by the authors for useful background and relevance, as well as important for the field of audiology.RESULTS:Several anatomical, physiological, and functional imaging studies have shown compromise of the auditory cortex in those with schizophrenia and AHs. Potentially related to this, are studies that demonstrated sub-par performance on behavioral audiologic measures for this unique clinical population. These findings align well with the kind of hearing disorder for which audiologists are well-trained to make significant contributions.CONCLUSION:Neurobiological and audiological evidence is accumulating on patients with schizophrenia and AH potentially rendering it as both an auditory and psychiatric disorder. Audiologists should consider expanding their horizon and playing a role in the clinical investigation of this disorder.

Several trends intersecting over the past two decades have generated increasing debate as to how the concepts of schizophrenia, the schizophrenia spectrum, and the psychotic disorders spectrum should be regarded. These trends are reflected in various areas of research such as genomics, neuroimaging, and data-driven computational studies of multiple response systems. Growing evidence suggests that schizophrenia represents a broad and heterogenous syndrome, rather than a specific disease entity, that is part of a multi-faceted psychosis spectrum. Progress in explicating these various developments has been hampered by the dependence upon sets of symptoms and signs for determining a diagnosis, and by the reliance on traditional diagnostic categories in reviewing clinical research grants. To address these concerns, the U.S. National Institute of Mental Health initiated the Research Domain Criteria (RDoC) project, a translational research program that calls for studies designed in terms of empirically-based functions (such as cognitive control or reward learning) rather than diagnostic groups. RDoC is a research framework rather than an alternative diagnostic system, intended to provide data that can inform future nosological manuals. This commentary includes a brief summary of RDoC as it pertains to schizophrenia and psychotic spectra, examples of recent data that highlight the utility of the approach, and conclusions regarding the implications for evolving conceptualizations of serious mental illness.

Understanding and treating psychotic-spectrum disorders presents a great challenge for psychiatry; such psychopathology is complex and involves disruptions that span basic neural mechanisms and higher order cognitive processes. That these disruptions can occur in many variations, over the course of development, and unfold with epigenetic variants interacting with environmental events, helps to define the scope of the substantial heterogeneity characteristic of psychosis syndromes. This chapter argues that the Research Domain Criteria (RDoC) offers an approach to facilitate progress by providing a framework to catalog and relate dimensional disruptions in neural systems, psychological processes, and behaviors relevant to understanding psychotic-spectrum psychopathology. It further argues that the “grain size” of the psychotic clinical syndromes is too large to deconstruct the heterogeneity of psychotic disorders as they are currently defined and reiterates defining principles of the RDoC that offer an alternative for researching psychosis.

The United States National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) initiative offers a framework to facilitate integrative research to clarify core mechanisms of human mental distress and dysfunction. The RDoC was developed to provide an alternative to research, designed around clinical syndromes based on descriptive diagnosis. Rather than beginning with a syndrome and then working ‘down’ to clarify mechanisms, the aim of the RDoC is to guide research that begins with disruptions in neurobiological and behavioural mechanisms, and then works across systems to clarify connections among such disruptions and clinical symptoms. The RDoC also departs from widely accepted categorical diagnoses, instead advocating a dimensional account of clinically significant variance in disrupted mechanisms and symptoms. The need for the RDoC stemmed from the realization that psychopathology research was not keeping pace with advances in clinical neuroscience and behavioural science, and the recognition that the cycle of scientific progress has been hampered by the instantiation of DSM diagnoses as the starting point of psychiatric research design. This chapter details the rationale and development of the RDoC and describes their structure. Some practical considerations and theoretical matters for implementing the RDoC alternative are considered.

Study Group Summary: Owing to the scarcity of women and underrepresented minorities in science especially in senior and leadership roles, diversity and inclusion are aspirational "buzzwords" that are used widely across institutions, organizational settings, and the scientific community.At federal, state and private sector levels, billions of dollars have been allocated to "fix" this longstanding systemic problem.Unfortunately, there remains no clear consensus on methods deemed effective to improve institutional diversity and inclusion.Moreover, those who are tasked with initiatives to create systemic change are often members of underrepresented groups who are given many responsibilities, but little to no authority or support.Consequently, these individuals often report feeling as though they are "preaching to the choir" and/or end up sustaining a career cost from engaging in such efforts.To create lasting change while minimizing burden on underrepresented individuals, it is important to ensure that efforts to promote diversity and inclusion are evidence-based and rely on methods with demonstrated positive transformation.Given that effective strategies are often based on social psychological and behavioral change theories tested with clinical trial methodology, it is particularly important for members of scientific societies, such as the American College of Neuropsychopharmacology (ACNP), to be aware of optimal practices in this area.The proposed study group will introduce specific methods, tailored towards fostering inclusion and diversity efforts in large scientific organizations and institutions.Drs.

The NIMH Research Domain Criteria (RDoC) can aid in the translation of integrative neuroscience. We argue that the RDoC framework, with its emphasis on integration across units of analysis, leveraged with computational approaches, can organize intermediary treatment targets and clinical outcomes, augmenting the translational stream.

BackgroundRecent theories suggest that poor working memory (WM) may be the cognitive underpinning of negative symptoms in people with schizophrenia. In this study, we first explore the effect of cognitive remediation (CR) on two clusters of negative symptoms (i.e. expressive and social amotivation), and then assess the relevance of WM gains as a possible mediator of symptom improvement.MethodData were accessed for 309 people with schizophrenia from the NIMH Database of Cognitive Training and Remediation Studies and a separate study. Approximately half the participants received CR and the rest were allocated to a control condition. All participants were assessed before and after therapy and at follow-up. Expressive negative symptoms and social amotivation symptoms scores were calculated from the Positive and Negative Syndrome Scale. WM was assessed with digit span and letter-number span tests.ResultsParticipants who received CR had a significant improvement in WM scores (d = 0.27) compared with those in the control condition. Improvements in social amotivation levels approached statistical significance (d = −0.19), but change in expressive negative symptoms did not differ between groups. WM change did not mediate the effect of CR on social amotivation.ConclusionsThe results suggest that a course of CR may benefit behavioural negative symptoms. Despite hypotheses linking memory problems with negative symptoms, the current findings do not support the role of this cognitive domain as a significant mediator. The results indicate that WM improves independently from negative symptoms reduction.

Aim Previous research indicates that preventive intervention is likely to benefit patients “at risk” of psychosis, in terms of functional improvement, symptom reduction and delay or prevention of onset of threshold psychotic disorder. The primary aim of the current study is to test outcomes of ultra high risk ( UHR ) patients, primarily functional outcome, in response to a sequential intervention strategy consisting of support and problem solving (SPS), cognitive‐behavioural case management and antidepressant medication. A secondary aim is to test biological and psychological variables that moderate and mediate response to this sequential treatment strategy. Methods This is a sequential multiple assignment randomised trial ( SMART ) consisting of three steps: Step 1: SPS (1.5 months); Step 2: SPS vs Cognitive Behavioural Case Management (4.5 months); Step 3: Cognitive Behavioural Case Management + Antidepressant Medication vs Cognitive Behavioural Case Management + Placebo (6 months). The intervention is of 12 months duration in total and participants will be followed up at 18 months and 24 months post baseline. Conclusion This paper reports on the rationale and protocol of the Staged Treatment in Early Psychosis ( STEP ) study. With a large sample of 500 UHR participants this study will investigate the most effective type and sequence of treatments for improving functioning and reducing the risk of developing psychotic disorder in this clinical population.

Several factors have contributed to a renewed debate in recent years about the nature of schizophrenia. These include discussions about modifications to the diagnostic criteria for the DMS-5 and ICD-11 revisions, increasing data showing that schizophrenia and bipolar disorder do not “breed true,” GWAS findings of shared genetic risk among disorders, and endophenotype-based intermediate phenotypes that show considerable overlap across disorders. These factors accord with proposals that schizophrenia should be thought of not as a specific disease, but rather as a syndrome that represents one segment of a broad spectrum of serious mental illness. Testing such hypotheses requires a different approach to classification that transcends typical “disorder versus control” studies that preclude analysis of cross-cutting mechanisms. The NIMH Research Domain Criteria (RDoC) project was initiated to develop an experimental classification system based upon functional neurobehavioral domains that can be measured at various units of analysis. We provide an overview of the rationale and goals of the RDoC initiative and discuss examples from the recent schizophrenia literature that illustrate RDoC principles. These are intended to illustrate RDoC’s role in facilitating explorations of heterogeneity and co-morbidity that can lead to more precise diagnosis and treatment for psychotic disorders.

In the article "Conducting Psychopathology Prevention Research in the RDoC Era," Zalta and Shankman (2016) dispel the myth that it would be difficult to conduct prevention research within the bounds of the Research Domain Criteria (RDoC) initiative. Illustrating a strategy to align prevention science and RDoC, and introducing the notion of a " prevention-mechanism" trial, the authors provide guidance to the field that could stimulate novel intervention development research to prevent psychopathology. We build off of their ideas, further clarifying the intent and principles underlying the RDoC initiative. Risk factors for psychopathology can be nonspecific. Because of this, taking an approach to understanding illness trajectory that is free of the constraints of a categorical diagnostic system and that focuses on underlying processes may help strengthen our ability to preempt the development of psychopathology before it starts.

The current special issue, devoted to the Research Domain Criteria (RDoC) initiative of the US National Institute of Mental Health, showcases a variety of empirical and review articles that address issues related to this dimensional and multi-method approach to research on mental disorders. Here, we provide an integrative perspective on various aspects of these articles, focused around the primary principles of the RDoC approach and the practical and methodological issues related to conducting RDoC-informed research. The chief point we wish to highlight is that these articles demonstrate the ways in which the field of psychophysiology already thinks along the lines of RDoC in terms of using biobehavioral constructs, looking for convergence among constructs using various methodologies, and utilizing dimensional measurements in studies. In this sense, RDoC is not novel; however, by specifying a formal research platform it provides explicit encouragement and guidance for using such principles in understanding psychiatric phenomena, rather than continuing to focus research efforts on traditional diagnostic categories alone.

Recent research in neurodevelopment, neuroplasticity and genetics is providing new insights into the etiogenesis of psychopathology, but progress in treatment development has been hampered by reliance on diagnostic categories that are characterized by heterogeneity and based primarily on phenomenology. The NIMH Research Domain Criteria (RDoC) initiative seeks to provide a neuroscience-based nosological framework for future research on psychopathology, categorizing individuals for research purposes using a dimensional approach that capitalizes on advances in modern neuroscience. These scientific advances and new approaches to classification can inform the development of novel, circuit-based interventions and the personalization of treatment. In this paper, we review key advances areas in clinical neuroscience, describe the RDoC project and highlight some emerging treatment approaches that are consistent with these developments.