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

2016 ◽  
Vol 28 (4pt1) ◽  
pp. 1089-1101 ◽  
Author(s):  
Ian R. Gizer

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.

2017 ◽  
Vol 1 ◽  
pp. 247054701771564 ◽  
Author(s):  
Chandni Sheth ◽  
Erin McGlade ◽  
Deborah Yurgelun-Todd

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.


2017 ◽  
Vol 35 (2) ◽  
pp. 89-94 ◽  
Author(s):  
J. R. Kelly ◽  
G. Clarke ◽  
J. F. Cryan ◽  
T. G. Dinan

The biological mechanisms underlying psychiatric diagnoses are not well defined. Clinical diagnosis based on categorical systems exhibit high levels of heterogeneity and co-morbidity. The Research Domain Criteria (RDoC) attempts to reconceptualize psychiatric disorders into transdiagnostic functional dimensional constructs based on neurobiological measures and observable behaviour. By understanding the underlying neurobiology and pathophysiology of the relevant processes, the RDoC aims to advance biomarker development for disease prediction and treatment response. This important evolving dimensional framework must also consider environmental factors. Emerging evidence suggests that gut microbes (microbiome) play a physiological role in brain diseases by modulating neuroimmune, neuroendocrine and neural signalling pathways between the gut and the brain. The integration of the gut microbiome signature as an additional dimensional component of the RDoC may enhance precision psychiatry.


2017 ◽  
Vol 1 ◽  
pp. 247054701769446 ◽  
Author(s):  
Shariful A. Syed ◽  
Charles B. Nemeroff

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.


2017 ◽  
Vol 225 (3) ◽  
pp. 189-199 ◽  
Author(s):  
Tina B. Lonsdorf ◽  
Jan Richter

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.


2017 ◽  
Vol 225 (3) ◽  
pp. 175-188 ◽  
Author(s):  
Peter J. Lang ◽  
Lisa M. McTeague ◽  
Margaret M. Bradley

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.


2016 ◽  
Vol Ano 6 ◽  
pp. 38-42
Author(s):  
Andrea Feijó Mello ◽  
Euthymia B. Almeida Prado

O presente artigo discorre sobre a comorbidade entre transtorno bipolar (TB) e transtorno de estresse póstraumático (TEPT) e questiona sobre certos casos serem melhor avaliados à luz das novas teorias do Research Domain Criteria (RDoC), principalmente aqueles quadros de TEPT com sintomas disfóricos que podem ser classificados como TB, apesar de não preencherem critérios para tal. Nesse caso, questiona-se a comorbidade e propõe-se um aprofundamento da fisiopatologia dessa sintomatologia que está sobreposta. Clinicamente, esse olhar poderá facilitar o manejo farmacológico de pacientes graves com histórico de trauma.


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