Dialogues in Clinical Neuroscience最新文献

The Research Domain Criteria (RDoC) project constitutes a translational framework for psychopathology research, initiated by the National Institute of Mental Health in an attempt to provide new avenues for research to circumvent problems emerging from the use of symptom-based diagnostic categories in diagnosing disorders. The RDoC alternative is a focus on psychopathology based on dimensions simultaneously defined by observable behavior (including quantitative measures of cognitive or affective behavior) and neurobiological measures. Key features of the RDoC framework include an emphasis on functional dimensions that range from normal to abnormal, integration of multiple measures in study designs (which can foster computational approaches), and high priority on studies of neurodevelopment and environmental influences (and their interaction) that can contribute to advances in understanding the etiology of disorders throughout the lifespan. The paper highlights key implications for ways in which RDoC can contribute to future ideas about classification, as well as some of the considerations involved in translating basic behavioral and neuroscience data to psychopathology.
.

Ever since psychiatry emerged as a clinical discipline and field of scientific inquiry in the late 18th century, debates about diagnosis have been at its very heart. Considered by many a requirement for clinical communication as well as for systematic study, others have critiqued psychiatric diagnosis for being modeled on a medical conception of disease that is ill-suited to the specific nature of mental disorders. Based on a review of seminal positions in the conceptual history of psychiatry and an examination of their epistemological underpinnings, we propose to consider diagnosis as dialogue. Such understanding, we argue, can serve as a meta-framework that provides a conceptual and practical umbrella to encourage open-minded conversation across the diverse conceptual and experiential frameworks that are characteristic of psychiatry. In this perspective psychopathology will also reinforce the interpersonal realm as a necessary element of any clinical encounter, be it diagnostic in purpose or otherwise. Current challenges to traditional diagnostic systems like Research Domain Criteria (RDoC) and Hierarchical Taxonomy of Psychopathology (HiTOP) are discussed in light of these considerations.
.

The traditional categorical classification system and new diagnostic systems will be discussed in this issue.
.

While the ICD-DSM paradigm has been a major advance in clinical psychiatry, its usefulness for biological psychiatry is debated. By defining consensus-based disorders rather than empirically driven phenotypes, consensus classifications were not an implementation of the biomedical paradigm. In the field of endogenous psychoses, the Wernicke-Kleist-Leonhard (WKL) pathway has optimized the descriptions of 35 major phenotypes using common medical heuristics on lifelong diachronic observations. Regarding their construct validity, WKL phenotypes have good reliability and predictive and face validity. WKL phenotypes come with remarkable evidence for differential validity on age of onset, familiality, pregnancy complications, precipitating factors, and treatment response. Most impressive is the replicated separation of high- and low-familiality phenotypes. Created in the purest tradition of the biomedical paradigm, the WKL phenotypes deserve to be contrasted as credible alternatives with other approaches currently under discussion.
.

This article describes the history of the diagnostic class of neurodevelopmental disorders (NDDs) up to DSM-5. We further analyze how the development of genetics will transform the classification and diagnosis of NDDs. In DSM-5, NDDs include intellectual disability (ID), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Physicians in German-, French- and English-speaking countries (eg, Weikard, Georget, Esquirol, Down, Asperger, and Kanner) contributed to the phenomenological definitions of these disorders throughout the 18th and 20th centuries. These diagnostic categories show considerable comorbidity and phenotypic overlap. NDDs are one of the chapters of psychiatric nosology most likely to benefit from the approach advocated by the National Institute of Mental Health's Research Domain Criteria project. Genetic research supports the hypothesis that ID, ASD, ADHD, schizophrenia, and bipolar disorder lie on a neurodevelopmental continuum. The identification of recurrently observed copy number variants and disruptive gene variants in ASD (eg, CDH8, 16p11.2, SCN2A) led to the adoption of the genotype-first approach to characterize individuals at the etiological level.
.

This article provides a brief overview of the changes from ICD-10 to ICD-11 regarding the classification of mental, behavioral, or neurodevelopmental disorders. These changes include a new chapter structure, new diagnostic categories, changes in diagnostic criteria, and steps towards dimensionality. Additionally, we review evaluative field studies of ICD-11, which provide preliminary evidence for higher reliability and clinical utility of ICD-11 compared with ICD-10. Despite the extensive revision process, changes from ICD-10 to ICD-11 were relatively modest in that both systems are categorical, classifying mental phenomena based on self-reported or clinically observable symptoms. Other recent approaches to psychiatric nosology and classification (eg, neurobiology-based or hierarchical) are discussed. To meet the needs of different user groups, we propose expanding the stepwise approach to diagnosis introduced for some diagnostic categories in ICD-11, which includes categorical and dimensional elements.
.

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical structural model of psychological symptoms formulated to improve the reliability and validity of clinical assessment. Neurobiology can inform assessments of early risk and intervention strategies, and the HiTOP model has greater potential to interface with neurobiological measures than traditional categorical diagnoses given its enhanced reliability. However, one complication is that observed biological correlates of clinical symptoms can reflect various factors, ranging from dispositional risk to consequences of psychopathology. In this paper, we argue that the HiTOP model provides an optimized framework for conducting research on the biological correlates of psychopathology from an ontogenetic perspective that distinguishes among indicators of liability, current symptoms, and consequences of illness. Through this approach, neurobiological research can contribute more effectively to identifying individuals at high dispositional risk, indexing treatment-related gains, and monitoring the consequences of mental illness, consistent with the aims of the HiTOP framework.
.

Development and regulatory approval of psychotropic drugs targets individuals with syndromes described in the current Diagnostic and Statistical Manual of Mental Disorders (DSM). This helps drug developers and regulators to communicate with prescribers, and prescribers to match a specific psychotropic with the individual patient(s) most likely to benefit from it. However, this practice has been criticized on the grounds that DSM syndromes are too heterogenous biologically, and the effects of psychotropics are too nonspecific to allow for an effective match. This review considers the advantages and disadvantages of the current practice and the possible alternatives. It concludes that efforts should be made to explore psychotropic development transdiagnostically, free of the DSM boundaries. However, currently there exists no alternative diagnostic system that is clearly superior to the DSM in terms of communications between the stakeholders in drug development.
.

Depression is a devastating psychiatric disorder caused by a combination of genetic predisposition and life events, mainly exposure to stress. Early life stress (ELS) in particular is known to "scar" the brain, leading to an increased susceptibility to developing depression later in life via epigenetic mechanisms. Epigenetic processes lead to changes in gene expression that are not due to changes in DNA sequence, but achieved via modulation of chromatin modifications, DNA methylation, and noncoding RNAs. Here we review common epigenetic mechanisms including the enzymes that take part in reading, writing, and erasing specific epigenetic marks. We then describe recent developments in understanding how ELS leads to changes in the epigenome that are manifested in increased susceptibility to depression-like abnormalities in animal models. We conclude with highlighting the need for future studies that will potentially enable the utilisation of the understanding of epigenetic changes linked to ELS for the development of much-needed novel therapeutic strategies and biomarker discovery.
.