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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.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.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.

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.

In the endocrine pancreas, growth hormone (GH) is known to promote pancreatic islet growth and insulin secretion. In this study, we show that GH receptor (GHR) loss in the germline and in adulthood impacts islet mass in general but more profoundly in male mice. GHR knockout (GHRKO) mice have enhanced insulin sensitivity and low circulating insulin. We show that the total cross-sectional area of isolated islets (estimated islet mass) was reduced by 72% in male but by only 29% in female GHRKO mice compared with wild-type controls. Also, islets from GHRKO mice secreted ∼50% less glucose-stimulated insulin compared with size-matched islets from wild-type mice. We next used mice with a floxed Ghr gene to knock down the GHR in adult mice at 6 mo of age (6mGHRKO) and examined the impact on glucose and islet metabolism. By 12 mo of age, female 6mGHRKO mice had increased body fat and reduced islet mass but had no change in glucose tolerance or insulin sensitivity. However, male 6mGHRKO mice had nearly twice as much body fat, substantially reduced islet mass, and enhanced insulin sensitivity, but no change in glucose tolerance. Despite large losses in islet mass, glucose-stimulated insulin secretion from isolated islets was not significantly different between male 6mGHRKO and controls, whereas isolated islets from female 6mGHRKO mice showed increased glucose-stimulated insulin release. Our findings demonstrate the importance of GH to islet mass throughout life and that unique sex-specific adaptations to the loss of GH signaling allow mice to maintain normal glucose metabolism. NEW & NOTEWORTHY Growth hormone (GH) is important for more than just growth. GH helps to maintain pancreatic islet mass and insulin secretion throughout life. Sex-specific adaptations to the loss of GH signaling allow mice to maintain normal glucose regulation despite losing islet mass.

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.

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.

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.

It has been suggested that a shift in diet is one of the key adaptations that distinguishes the genus Homo from earlier hominins, but recent stable isotopic analyses of fossils attributed to Homo in the Turkana Basin show an increase in the consumption of C4 resources circa 1.65 million years ago, significantly after the earliest evidence for Homo in the eastern African fossil record. These data are consistent with ingesting more C4 plants, more animal tissues of C4 herbivores, or both, but it is also possible that this change reflects factors unrelated to changes in the palaeobiology of the genus Homo. Here we use new and published carbon and oxygen isotopic data (n = 999) taken from large-bodied fossil mammals, and pedogenic carbonates in fossil soils, from East Turkana in northern Kenya to investigate the context of this change in the isotope signal within Homo. By targeting taxa and temporal intervals unrepresented or undersampled in previous analyses, we were able to conduct the first comprehensive analysis of the ecological context of hominin diet at East Turkana during a period crucial for detecting any dietary and related behavioural differences between early Homo (H. habilis and/or H. rudolfensis) and Homo erectus. Our analyses suggest that the genus Homo underwent a dietary shift (as indicated by δ13Cena and δ18Oena values) that is (1) unrelated to changes in the East Turkana vegetation community and (2) unlike patterns found in other East Turkana large mammals, including Paranthropus and Theropithecus. These data suggest that within the Turkana Basin a dietary shift occurred well after we see the first evidence of early Homo in the region. Carbon and oxygen isotope analysis of sediments and soils from hominin locales in Kenya coupled with results from hominin taxa suggest that a dietary shift from C3 to C4 resources occurred in the genus Homo circa 1.65 million years ago despite palaeoenvironmental continuity.

We explore how hallucinations might be studied within the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) framework, which asks investigators to step back from diagnoses based on symptoms and focus on basic dimensions of functioning. We start with a description of the objectives of the RDoC project and its domains and constructs. Because the RDoC initiative asks investigators to study phenomena across the wellness spectrum and different diagnoses, we address whether hallucinations experienced in nonclinical populations are the same as those experienced by people with psychotic diagnoses, and whether hallucinations studied in one clinical group can inform our understanding of the same phenomenon in another. We then discuss the phenomenology of hallucinations and how different RDoC domains might be relevant to their study. We end with a discussion of various challenges and potential next steps to advance the application of the RDoC approach to this area of research.

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.

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 amongst 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.

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.

Current diagnostic systems for mental disorders were established before the tools of neuroscience were available, and although they have improved the reliability of psychiatric classification, progress toward the discovery of disease etiologies and novel approaches to treatment and prevention may benefit from alternative conceptualizations of mental disorders. The Research Domain Criteria (RDoC) initiative is the centerpiece of NIMH's effort to achieve its strategic goal of developing new methods to classify mental disorders for research purposes. The RDoC matrix provides a research framework that encourages investigators to reorient their research perspective by taking a dimensional approach to the study of the genetic, neural, and behavioral features of mental disorders, RDoCs integrative approach includes cognition along with social processes, arousal/regulatory systems, and negative and positive valence systems as the major domains, because these neurobehavioral systems have all evolved to serve the motivational and adaptive needs of the organism. With its focus on neural circuits informed by the growing evidence of the neurodevelopmental nature of many disorders and its capacity to capture the patterns of co-occurrence of behaviors and symptoms, the RDoC approach holds promise to advance our understanding of the nature of mental disorders.

Previous research has demonstrated deficits in pre-response motor activity in schizophrenia, as evidenced by a reduced lateralized readiness potential (LRP). The LRP deficit could be due to increased activation of the incorrect response (e.g., failure to suppress competition) or to reduced activation of the correct response (e.g., a low-level impairment in response preparation). To distinguish these possibilities, we asked whether the LRP impairment is increased under conditions of strong response competition. We manipulated the compatibility of stimulus-response mappings (Experiment 1) and the compatibility of the target with flankers (Experiment 2). In both experiments, the patient LRP was reduced as much under conditions of low response competition as under high competition. These results are incompatible with a failure of patients to suppress competition and are instead consistent with a deficit in activating the correct response.

Most life-long drug addiction begins during adolescence. Important structural and functional changes in brain occur during adolescence and developmental differences in forebrain dopamine systems could mediate a biologic vulnerability to drug addiction during adolescence. Studies investigating age differences in psychostimulant responses have yielded mixed results, possibly because of different mechanisms for increasing extracellular dopamine. Recent research from our laboratory suggests that adolescent dopamine systems may be most affected by selective dopamine uptake inhibitors. We investigated age-related behavioral responses to acute administration of several dopamine uptake inhibitors [methylphenidate, 1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl)piperazine (GBR12909), and nomifensine] and releasing agents [amphetamine and methylenedioxymethamphetamine (MDMA)] in adolescent and adult male rats. Methylphenidate and amphetamine effects on stimulated dopamine efflux were determined using fast-scan cyclic voltammetry in vivo. Dopamine uptake inhibitors but not dopamine releasing agents induced more locomotion and/or stereotypy in adolescent relative to adult rats. MDMA effects were greater in adults at early time points after dosing. Methylphenidate but not amphetamine induced much greater dopamine efflux in periadolescent relative to adult rats. Periadolescent male rats are particularly sensitive to psychostimulants that are DAT inhibitors but are not internalized and do not release dopamine. Immaturity of DAT and/or DAT associated signaling systems in adolescence specifically enhances behavioral and dopaminergic responses in adolescence.

There is considerable interest in cognitive remediation for schizophrenia, but its essential components are still unclear. The goal of the current study was to develop a broadly targeted computer-assisted cognitive remediation program and conduct a rigorous clinical trial in a large group of schizophrenia patients.Sixty-nine people with schizophrenia or schizoaffective disorder were randomly assigned to 36 sessions of computer-assisted cognitive remediation or an active control condition. Remediation broadly targeted cognitive and everyday performance by providing supportive, graduated training and practice in selecting, executing, and monitoring cognitive operations. It used engaging computer-based cognitive exercises and one-on-one training. A total of 61 individuals (34 in remediation group, 27 in control group) engaged in treatment, completed posttreatment assessments, and were included in intent-to-treat analyses. Primary outcomes were remediation exercise metrics, neuropsychological composites (episodic memory, working memory, attention, executive functioning, and processing speed), and proxy measures of community functioning.Regression modeling indicated that performance on eight of 10 exercise metrics improved significantly more in the remediation condition than in the control condition. The mean effect size, favoring the remediation condition, was 0.53 across all 10 metrics. However, there were no significant benefits of cognitive remediation on any neuropsychological or functional outcome measure, either immediately after treatment or at the 3-month follow-up.Cognitive remediation for people with schizophrenia was effective in improving performance on computer exercises, but the benefits of training did not generalize to broader neuropsychological or functional outcome measures. The evidence for this treatment approach remains mixed.

Presenters Oberg and Morris described the current environment in two major private libraries, highlighting both the similarities and differences with typical nonprofit libraries. Their special environment demands accountability from their library divisions, often expressed in terms of financial return on investment, and can be instructive for librarians in other types of libraries.

Anyone who needs to get an electronic resource management (ERM) system up and running needed this session! Moderated by Ted Fons of Innovative Interfaces, Inc., “Real ERM Implementations: Notes from the Field,” included panelists Jeff Daniels of Grand Valley State University (GVSU), Karl Maria Fattig of Bowdoin College, Toni Katz of Colby College, Jeanne Langendorfer of Bowling Green State University (BGSU), and Paul Moeller of the University of Colorado at Boulder (UCB). Each panelist is at various stages of implementing an ERM at his or her library. By telling their stories, including their challenges, regrets, failures, and solutions, the panelists hoped they might help other libraries survive the same process. From the nuts-and-bolts details to tips on better serving users, this session was a road map for any other library trying to navigate a similar path.

Presenters Susan Davis of the University at Buffalo, State University of New York, and Sarah E. Morris of Reed Smith, LLP, led an informal discussion of past and future trends in serials librarianship. By comparing their perspectives as new and mid-career librarians, they illuminated various topics related to work with serials and electronic resources, including the skill sets required for e-resource management, users' demands for online access, and generational attitudes within the profession.

The panel at this strategy session was composed of three distinguished women from technical services who currently hold leadership positions. The session topic was divided into two sections: 1) What is leadership?; and 2) How can technical services help you be a leader? Each panelist spoke to the first topic and then reversed order to explore the second. The panelists all spoke to a definition of leadership based on the personal, social, and professional skills possessed by leaders. The panel concurred that technical services staff are uniquely prepared for leadership for a variety of reasons because the personal, social, and professional skills discussed by the panel in the first half of the session are prevalent in technical services departments.

In this study, the authors sought to determine whether abnormalities exhibited by schizophrenia patients in event-related potentials associated with self-monitoring--the error-related negativity (ERN) and the correct response negativity (CRN)--persist under conditions that maximize ERN amplitude and to examine relationships between the ERN and behavior in schizophrenia. Participants performed a flanker task under 2 contingencies: one encouraging accuracy and another emphasizing speed. Compared with healthy participants, in schizophrenia patients the ERN was reduced in the accuracy condition, and the CRN was enhanced in the speed condition. The amplitude of a later ERP component, the error positivity, did not differ between groups in either task condition. Reduced self-correction and increased accuracy following errors were associated with larger ERNs in both groups. Thus, ERN generation appears to be abnormal in schizophrenia patients even under conditions demonstrated to maximize ERN amplitude; however, functional characteristics of the ERN appear to be intact.

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.