scholarly journals Chronic Stress in Adolescents and Its Neurobiological and Psychopathological Consequences: An RDoC Perspective

2017 ◽  
Vol 1 ◽  
pp. 247054701771564 ◽  
Author(s):  
Chandni Sheth ◽  
Erin McGlade ◽  
Deborah Yurgelun-Todd
Keyword(s):  
Psychiatric Disorders ◽  
Chronic Stress ◽  
Neural Circuits ◽  
Environmental Influence ◽  
Research Domain Criteria ◽  
Psychiatric Illnesses ◽  
Orthogonal Dimension ◽  
Induced Changes ◽  
Behavioral Constructs ◽  
Research Domain

The Research Domain Criteria (RDoC) initiative provides a strategy for classifying psychopathology based on behavioral dimensions and neurobiological measures. Neurodevelopment is an orthogonal dimension in the current RDoC framework; however, it has not yet been fully incorporated into the RDoC approach. A combination of both a neurodevelopmental and RDoC approach offers a multidimensional perspective for understanding the emergence of psychopathology during development. Environmental influence (e.g., stress) has a profound impact on the risk for development of psychiatric illnesses. It has been shown that chronic stress interacts with the developing brain, producing significant changes in neural circuits that eventually increase the susceptibility for development of psychiatric disorders. This review highlights effects of chronic stress on the adolescent brain, as adolescence is a period characterized by a combination of significant brain alterations, high levels of stress, and emergence of psychopathology. The literature synthesized in this review suggests that chronic stress-induced changes in neurobiology and behavioral constructs underlie the shared vulnerability across a number of disorders in adolescence. The review particularly focuses on depression and substance use disorders; however, a similar argument can also be made for other psychopathologies, including anxiety disorders. The summarized findings underscore the need for a framework to integrate neurobiological findings from disparate psychiatric disorders and to target transdiagnostic mechanisms across disorders.

scholarly journals Research Domain Criteria: cognitive systems, neural circuits, and dimensions of behavior

2012 ◽  
Vol 14 (1) ◽  
pp. 29-37 ◽  
Keyword(s):  
Mental Disorders ◽  
Neural Circuits ◽  
Integrative Approach ◽  
Research Domain Criteria ◽  
Diagnostic Systems ◽  
Research Perspective ◽  
Treatment And Prevention ◽  
Regulatory Systems ◽  
Positive Valence ◽  
Research Domain

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.

scholarly journals P2X7R antagonists in chronic stress-based depression models: a review

2021 ◽  
Author(s):  
Iven-Alex von Muecke-Heim ◽  
Clemens Ries ◽  
Lidia Urbina ◽  
Jan M. Deussing
Keyword(s):  
Chronic Stress ◽  
Chronic Mild Stress ◽  
Purinergic Signalling ◽  
Mild Stress ◽  
Research Domain Criteria ◽  
Application Timing ◽  
Study Planning ◽  
Level Increase ◽  
Immune Changes ◽  
Research Domain

AbstractDepression affects around 320 million people worldwide. Growing evidence proposes the immune system to be the core interface between psychosocial stress and the neurobiological and behavioural features of depression. Many studies have identified purinergic signalling via the P2X7 receptor (P2X7R) to be of great importance in depression genesis yet only a few have evaluated P2X7R antagonists in chronic stress-based depression models. This review summarizes their findings and analyses their methodology. The four available studies used three to nine weeks of unpredictable, chronic mild stress or unpredictable, chronic stress in male mice or rats. Stress paradigm composition varied moderately, with stimuli being primarily psychophysical rather than psychosocial. Behavioural testing was performed during or after the last week of stress application and resulted in depressive-like behaviours, immune changes (NLRP3 assembly, interleukin-1β level increase, microglia activation) and neuroplasticity impairment. During the second half of each stress paradigm, a P2X7R antagonist (Brilliant Blue G, A-438079, A-804598) was applied. Studies differed with regard to antagonist dosage and application timing. Nonetheless, all treatments attenuated the stress-induced neurobiological changes and depressive-like behaviours. The evidence at hand underpins the importance of P2X7R signalling in chronic stress and depression. However, improvements in study planning and reporting are necessary to minimize experimental bias and increase data purview. To achieve this, we propose adherence to the Research Domain Criteria and the STRANGE framework.

scholarly journals Targeting Endocannabinoid Signaling in the Lateral Habenula as an Intervention to Prevent Mental Illnesses Following Early Life Stress: A Perspective

2021 ◽  
Vol 13 ◽  
Author(s):  
Ryan D. Shepard ◽  
Fereshteh S. Nugent
Keyword(s):  
Psychiatric Disorders ◽  
Life Stress ◽  
Early Life ◽  
Neural Circuits ◽  
Treatment Strategies ◽  
Early Life Stress ◽  
Mental Illnesses ◽  
Lateral Habenula ◽  
Psychiatric Illnesses ◽  
New Research

Adverse events and childhood trauma increase the susceptibility towards developing psychiatric disorders (substance use disorder, anxiety, depression, etc.) in adulthood. Although there are treatment strategies that have utility in combating these psychiatric disorders, little attention is placed on how to therapeutically intervene in children exposed to early life stress (ELS) to prevent the development of later psychopathology. The lateral habenula (LHb) has been a topic of extensive investigation in mental health disorders due to its prominent role in emotion and mood regulation through modulation of brain reward and motivational neural circuits. Importantly, rodent models of ELS have been shown to promote LHb dysfunction. Moreover, one of the potential mechanisms contributing to LHb neuronal and synaptic dysfunction involves endocannabinoid (eCB) signaling, which has been observed to critically regulate emotion/mood and motivation. Many pre-clinical studies targeting eCB signaling suggest that this neuromodulatory system could be exploited as an intervention therapy to halt maladaptive processes that promote dysfunction in reward and motivational neural circuits involving the LHb. In this perspective article, we report what is currently known about the role of eCB signaling in LHb function and discuss our opinions on new research directions to determine whether the eCB system is a potentially attractive therapeutic intervention for the prevention and/or treatment of ELS-associated psychiatric illnesses.

scholarly journals The Neurobiology of Panic: A Chronic Stress Disorder

2017 ◽  
Vol 1 ◽  
pp. 247054701773603 ◽  
Author(s):  
Andrew W. Goddard
Keyword(s):  
Mental Health ◽  
Risk Factors ◽  
Panic Disorder ◽  
Chronic Stress ◽  
Stress Disorder ◽  
Mental Health Research ◽  
Research Domain Criteria ◽  
Neuroimaging Data ◽  
Potential Impact ◽  
Research Domain

Panic disorder is an often chronic and impairing human anxiety syndrome, which frequently results in serious psychiatric and medical comorbidities. Although, to date, there have been many advances in the diagnosis and treatment of panic disorder, its pathophysiology still remains to be elucidated. In this review, recent evidence for a neurobiological basis of panic disorder is reviewed with particular attention to risk factors such as genetic vulnerability, chronic stress, and temperament. In addition, neuroimaging data are reviewed which provides support for the concept of panic disorder as a fear network disorder. The potential impact of the National Institute of Mental Health Research Domain Criteria constructs of acute and chronic threats responses and their implications for the neurobiology of panic disorder are also discussed.

scholarly journals Molecular genetic approaches to understanding the comorbidity of psychiatric disorders

2016 ◽  
Vol 28 (4pt1) ◽  
pp. 1089-1101 ◽  
Author(s):  
Ian R. Gizer
Keyword(s):  
Psychiatric Disorders ◽  
Present Report ◽  
Molecular Genetic ◽  
Population Level ◽  
Epidemiologic Studies ◽  
Research Domain Criteria ◽  
Comorbid Conditions ◽  
Biological Mechanisms ◽  
Different Levels ◽  
Research Domain

AbstractEpidemiologic studies demonstrating high rates of co-occurrence among psychiatric disorders at the population level have contributed to large literatures focused on identifying the causal mechanisms underlying the patterns of co-occurrence among these disorders. Such efforts have long represented a core focus of developmental psychopathologists and have more recently been supported by the Research Domain Criteria initiative developed by the NIMH, which provides a further framework for how the hypothesized mechanisms can be studied at different levels of analysis. The present overview focuses on molecular genetic approaches that are being used currently to study the etiology of psychiatric disorders, and how these approaches have been applied in efforts to understand the biological mechanisms that give rise to comorbid conditions. The present report begins with a review of molecular genetic approaches used to identify individual variants that confer risk for multiple disorders and the intervening biological mechanisms that contribute to their comorbidity. This is followed by a review of molecular genetic approaches that use genetic data in aggregate to examine these questions, and concludes with a discussion of how developmental psychopathologists are uniquely positioned to apply these methods in a way that will further our understanding of the causal factors that contribute to the development of comorbid conditions.

scholarly journals Early Life Stress, Mood, and Anxiety Disorders

2017 ◽  
Vol 1 ◽  
pp. 247054701769446 ◽  
Author(s):  
Shariful A. Syed ◽  
Charles B. Nemeroff
Keyword(s):  
Psychiatric Disorders ◽  
Life Stress ◽  
Early Life ◽  
Wide Spectrum ◽  
Early Life Stress ◽  
Research Domain Criteria ◽  
Long Term Effects ◽  
Research Perspective ◽  
Discrete Domains ◽  
Research Domain

Early life stress has been shown to exert profound short- and long-term effects on human physiology both in the central nervous system and peripherally. Early life stress has demonstrated clear association with many psychiatric disorders including major depression, posttraumatic stress disorder, and bipolar disorder. The Diagnostic and Statistics Manuel of Mental Disorders (DSM) diagnostic categorical system has served as a necessary framework for clinical service, delivery, and research, however has not been completely matching the neurobiological research perspective. Early life stress presents a complex dynamic featuring a wide spectrum of physiologic alterations: from epigenetic alterations, inflammatory changes, to dysregulation of the hypothalamic pituitary axis and has further added to the challenge of identifying biomarkers associated with psychiatric disorders. The National Institute of Mental Health’s proposed Research Domain Criteria initiative incorporates a dimensional approach to assess discrete domains and constructs of behavioral function that are subserved by identifiable neural circuits. The current neurobiology of early life stress is reviewed in accordance with dimensional organization of Research Domain Criteria matrix and how the findings as a whole fit within the Research Domain Criteria frameworks.

Challenges of Fear Conditioning Research in the Age of RDoC

2017 ◽  
Vol 225 (3) ◽  
pp. 189-199 ◽  
Author(s):  
Tina B. Lonsdorf ◽  
Jan Richter
Keyword(s):  
Fear Conditioning ◽  
Clinical Diagnosis ◽  
Research Domain Criteria ◽  
Major Focus ◽  
The Future ◽  
Definition Of ◽  
Methodological Considerations ◽  
Research Domain

Abstract. As the criticism of the definition of the phenotype (i.e., clinical diagnosis) represents the major focus of the Research Domain Criteria (RDoC) initiative, it is somewhat surprising that discussions have not yet focused more on specific conceptual and procedural considerations of the suggested RDoC constructs, sub-constructs, and associated paradigms. We argue that we need more precise thinking as well as a conceptual and methodological discussion of RDoC domains and constructs, their interrelationships as well as their experimental operationalization and nomenclature. The present work is intended to start such a debate using fear conditioning as an example. Thereby, we aim to provide thought-provoking impulses on the role of fear conditioning in the age of RDoC as well as conceptual and methodological considerations and suggestions to guide RDoC-based fear conditioning research in the future.

The Psychophysiology of Anxiety and Mood Disorders

2017 ◽  
Vol 225 (3) ◽  
pp. 175-188 ◽  
Author(s):  
Peter J. Lang ◽  
Lisa M. McTeague ◽  
Margaret M. Bradley
Keyword(s):  
Mental Health ◽  
Heart Rate ◽  
Brain Function ◽  
Physiological Reactivity ◽  
Research Domain Criteria ◽  
Diagnostic Systems ◽  
Psychophysiological Reactivity ◽  
Diagnostic Categories ◽  
New Research ◽  
Research Domain

Abstract. Several decades of research are reviewed, assessing patterns of psychophysiological reactivity in anxiety patients responding to a fear/threat imagery challenge. Findings show substantive differences in these measures within principal diagnostic categories, questioning the reliability and categorical specificity of current diagnostic systems. Following a new research framework (US National Institute of Mental Health [NIMH], Research Domain Criteria [RDoC]; Cuthbert & Insel, 2013 ), dimensional patterns of physiological reactivity are explored in a large sample of anxiety and mood disorder patients. Patients’ responses (e.g., startle reflex, heart rate) during fear/threat imagery varied significantly with higher questionnaire measured “negative affect,” stress history, and overall life dysfunction – bio-marking disorder groups, independent of Diagnostic and Statistical Manuals (DSM). The review concludes with a description of new research, currently underway, exploring brain function indices (structure activation, circuit connectivity) as potential biological classifiers (collectively with the reflex physiology) of anxiety and mood pathology.

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