Research Domain Criteria (rdoc): Toward a New Classification Framework for Research on Mental Disorders.

Back to table of contents Previous article Next article CommentaryFull AccessResearch Domain Criteria (RDoC): Toward a New Classification Framework for Research on Mental DisordersThomas Insel, M.D., Bruce Cuthbert, Ph.D., Marjorie Garvey, M.B., B.CH., Robert Heinssen, Ph.D., Daniel S. Pine, M.D., Kevin Quinn, Ph.D., Charles Sanislow, Ph.D., and Philip Wang, M.D., DR.P.H.Thomas Insel, M.D., Bruce Cuthbert, Ph.D., Marjorie Garvey, M.B., B.CH., Robert Heinssen, Ph.D., Daniel S. Pine, M.D., Kevin Quinn, Ph.D., Charles Sanislow, Ph.D., and Philip Wang, M.D., DR.P.H.Published Online:1 Jul 2010https://doi.org/10.1176/appi.ajp.2010.09091379AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Current versions of the DSM and ICD have facilitated reliable clinical diagnosis and research. However, problems have increasingly been documented over the past several years, both in clinical and research arenas (e.g., 1, 2). Diagnostic categories based on clinical consensus fail to align with findings emerging from clinical neuroscience and genetics. The boundaries of these categories have not been predictive of treatment response. And, perhaps most important, these categories, based upon presenting signs and symptoms, may not capture fundamental underlying mechanisms of dysfunction. One consequence has been to slow the development of new treatments targeted to underlying pathophysiological mechanisms.History shows that predictable problems arise with early, descriptive diagnostic systems designed without an accurate understanding of pathophysiology. Throughout medicine, disorders once considered unitary based on clinical presentation have been shown to be heterogeneous by laboratory tests—e.g., destruction of islet cells versus insulin resistance in distinct forms of diabetes mellitus. From infectious diseases to subtypes of cancer, we routinely use biomarkers to direct distinct treatments. Conversely, history also shows that syndromes appearing clinically distinct may result from the same etiology, as in the diverse clinical presentations following syphilis or a range of streptococcus-related disorders.While the potential advantages of a neuroscience-based approach to psychiatric classification are widely appreciated (3), no consensus exists about how to achieve this goal. The problem is not new. Four decades ago, Robins and Guze suggested five criteria for validating diagnosis (clinical description, laboratory tests, delimitation, follow-up studies, and family data), where the goal was specifying prognosis (4). Reminiscent of the rationale for developing the Research Diagnostic Criteria in the 1970s that led to the innovative DSM-III for clinical use, the question now becomes one of when and how to build a long-term framework for research that can yield classification based on discoveries in genomics and neuroscience as well as clinical observation, with a goal of improving treatment outcomes. As the major federal research agency funding mental health research in the United States, the National Institute of Mental Health (NIMH) believes the time has arrived to begin moving in such a new direction.The NIMH is launching the Research Domain Criteria (RDoC) project to create a framework for research on pathophysiology, especially for genomics and neuroscience, which ultimately will inform future classification schemes. The RDoC project is intended to be the next step in a long journey, one that continues the process begun in the 1970s of ensuring diagnosis that has both reliability and validity. While the focus of this journey over the past 30 years has been on refinements in clinically based classification, the time has come to lay the groundwork for the next step in this process: incorporating data on pathophysiology in ways that eventually will help identify new targets for treatment development, detect subgroups for treatment selection, and provide a better match between research findings and clinical decision making.RDoC classification rests on three assumptions. First, the RDoC framework conceptualizes mental illnesses as brain disorders. In contrast to neurological disorders with identifiable lesions, mental disorders can be addressed as disorders of brain circuits. Second, RDoC classification assumes that the dysfunction in neural circuits can be identified with the tools of clinical neuroscience, including electrophysiology, functional neuroimaging, and new methods for quantifying connections in vivo. Third, the RDoC framework assumes that data from genetics and clinical neuroscience will yield biosignatures that will augment clinical symptoms and signs for clinical management. Examples where clinically relevant models of circuitry-behavior relationships augur future clinical use include fear/extinction, reward, executive function, and impulse control. For example, the practitioner of the future could supplement a clinical evaluation of what we now call an "anxiety disorder" with data from functional or structural imaging, genomic sequencing, and laboratory-based evaluations of fear conditioning and extinction to determine prognosis and appropriate treatment, analogous to what is done routinely today in many other areas of medicine.Clearly, this is a vision for the future, given the rudimentary nature of data relating measures of brain function to clinically relevant individual differences in genomics, pathophysiology, and behavior. In the near-term, RDoC may be most useful for researchers mapping brain-behavior relationships as well as genomic discoveries in human and non-human animal studies. For example, within the broad domain of developmental neuroscience, the emerging fields of imaging genomics and early life programming have already begun to clarify factors that shape the development of select neural circuits (5, 6). But the findings of developmental neuroscience have not yet proven useful for clinicians, often because the results are relevant to broad domains of function such as temperament rather than specific diagnoses. And the recent discovery of structural changes in the genome (copy number variations) associated with psychopathology already suggest the power of modern genomics for psychiatry, but the phenotypes associated with genomic variation do not align with current classifications of autism or schizophrenia or bipolar disorder. RDoC are intended to ultimately provide a framework for classification based on empirical data from genetics and neuroscience. Indeed, in 2010, we do not know how many different disorders are embedded in the current diagnosis of schizophrenia or autism or other current categories that share clinical features. Our expectation, based on experience in cancer, heart disease, and infectious diseases, is that identifying syndromes based on pathophysiology will eventually be able to improve outcomes (e.g., 7, 8).Research approaches for the RDoC project will differ from current practice, which typically constrains study designs not only to a single DSM/ICD patient group but also to particular clinical features. The primary focus for RDoC is on neural circuitry, with levels of analysis progressing in one of two directions: upwards from measures of circuitry function to clinically relevant variation, or downwards to the genetic and molecular/cellular factors that ultimately influence such function. From this perspective, research for RDoC can be conceived as a matrix in which the rows represent various constructs grouped hierarchically into broad domains of function (e.g., negative emotionality, cognition). The columns of the matrix denote different levels of analysis, from genetic, molecular, and cellular levels, proceeding to the circuit-level (which, as suggested above, is the focal element of the RDoC organization), and on to the level of the individual, family environment, and social context. Importantly, all of these levels are seen as affecting both the biology and psychology of mental illness. With the RDoC approach, independent variables for classification might be specified from any of these levels of analysis, with dependent variables chosen from one or more other columns. Notably, samples might include patients spanning multiple DSM diagnoses. For instance, a study of working memory might recruit patients from a psychotic disorders clinic, with the independent variable a genetic polymorphism and dependent variables comprising cognitive performance and neuroimaging of dorsolateral prefrontal cortex activation. A study of fear circuitry might include all patients presenting at an anxiety clinic, with an independent variable of defense-system reactivity (e.g., fear-potentiated startle) and dependent variables comprising scores on fear, distress, and symptom measures. While maintaining a clear focus on overt psychopathology, investigators will be encouraged to explicate the full range of a given dimension to develop thresholds for different types of interventions and identify early opportunities for preventive interventions.How will RDoC alter clinical practice? The answer depends on how well RDoC perform for research. Following Robins and Guze's postulates for the Research Diagnostic Criteria, the critical test is how well the new molecular and neurobiological parameters predict prognosis or treatment response. If a BDNF polymorphism identifies people with anxiety syndromes who do not respond to behavior therapy, if a copy number variant defines a form of psychosis with high remission rates, if neuroimaging yields a subtype of mood disorder that consistently responds to lithium, RDoC could provide a classification scheme that will improve outcomes. But we recognize that there are many "ifs" at this stage. We are still a long way from knowing if this approach will succeed.NIMH plans to maintain liaison with the American Psychiatric Association and the World Health Organization regarding mutual interests in psychiatric classification. As an initial step, representatives of the APA, WHO, and NIMH met in July 2009 to map out common ground. These organizations have also articulated the importance of adding molecular and neurobiological parameters to future diagnostic systems, but at our current state of knowledge this step seems more appropriate for research than for immediate clinical use. NIMH views RDoC as the beginning of a transformative effort that needs to succeed over the next decade and beyond to implement neuroscience-based psychiatric classification. We recognize that the creation of such a new approach is a daunting task, which will likely require several mid-course corrections and may ultimately fail to deliver the transformation we seek in clinical care. However, NIMH hopes that the scientific and clinical communities will recognize the importance of joining in constructive dialogue on efforts aiming to accelerate the pace of new clinical discoveries and improve clinical outcomes.National Institute of Mental Health, Bethesda, Md.Commentary accepted for publication April 2010. Address correspondence and reprint requests to Dr. Cuthbert, National Institute of Mental Health, 6001 Executive Blvd. (MSC 9632), Bethesda, MD 20892-9632; [email protected]nih.gov (e-mail).All authors report no financial relationships with commercial interests.References1 Regier DA , Narrow WE , Kuhl EA , Kupfer DJ : The conceptual development of DSM-V. Am J Psychiatry 2009; 166:1–7 Link, Google Scholar2 Hyman S : Can neuroscience be integrated into the DSM-V? Nat Rev Neurosci 2008; 8:725–732 Crossref, Google Scholar3 Charney D , Barlow D , Botteron K : Neuroscience research agenda to guide development of a pathophysiologically based classification system, in A Research Agenda for DSM-V. Edited by Kupfer DFirst MRegier D. Arlington, Va, American Psychiatric Association, 2002, pp 31–84 Google Scholar4 Robins E , Guze SB : Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia. Am J Psychiatry 1970; 126:983–987 Link, Google Scholar5 Meyer-Lindenberg A : Neural connectivity as an intermediate phenotype: brain networks under genetic control. Human Brain Mapping; 30:1938–1946 Crossref, Medline, Google Scholar6 Barker D , Osmond C , Forsèn T , Kajantie E , Eriksson J : Trajectories of growth among children who have coronary events as adults. N Engl J Med 2005; 353:1802–1809 Crossref, Medline, Google Scholar7 Stefansson H , Ophoff R , Steinberg S , Andreassen OA , Cichon S , Rujescu D , Werge T , Pietiläinen OP , Mors O , Mortensen PB , Sigurdsson E , Gustafsson O , Nyegaard M , Tuulio-Henriksson A , Ingason A , Hansen T , Suvisaari J , Lonnqvist J , Paunio T , Børglum AD , Hartmann A , Fink-Jensen A , Nordentoft M , Hougaard D , Norgaard-Pedersen B , Böttcher Y , Olesen J , Breuer R , Möller HJ , Giegling I , Rasmussen HB , Timm S , Mattheisen M , Bitter I , Réthelyi JM , Magnusdottir BB , Sigmundsson T , Olason P , Masson G , Gulcher JR , Haraldsson M , Fossdal R , Thorgeirsson TE , Thorsteinsdottir U , Ruggeri M , Tosato S , Franke B , Strengman E , Kiemeney LA Genetic Risk and Outcome in Psychosis (GROUP) , Melle I , Djurovic S , Abramova L , Kaleda V , Sanjuan J , de Frutos R , Bramon E , Vassos E , Fraser G , Ettinger U , Picchioni M , Walker N , Toulopoulou T , Need AC , Ge D , Yoon JL , Shianna KV , Freimer NB , Cantor RM , Murray R , Kong A , Golimbet V , Carracedo A , Arango C , Costas J , Jönsson EG , Terenius L , Agartz I , Petursson H , Nöthen MM , Rietschel M , Matthews PM , Muglia P , Peltonen L , St Clair D , Goldstein DB , Stefansson K , Collier DA : Common variants conferring risk of schizophrenia. Nature 2009; 460:744–747 Crossref, Medline, Google Scholar8 Losh M , Sullivan P , Trembath D , Piven J : Current developments in the genetics of autism: from phenome to genome. J Neuropathol Exp Neurol 2008; 67:829–837 Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byPathobiology of CNS human immunodeficiency virus infectionDimensions of childhood maltreatment and adult risky behaviors: Differential affective and inhibitory control mechanismsChild Abuse & Neglect, Vol. 134The (un)learning of social functions and its significance for mental healthClinical Psychology Review, Vol. 98Psychopathological knowledge and methodically sound diagnostics are core elements of forensic psychiatryForensic Science International: Mind and Law, Vol. 3Examining patterns of executive functioning across dimensions of psychopathologyJournal of Behavior Therapy and Experimental Psychiatry, Vol. 77Molecular mechanisms underlying the N-methyl-d-aspartate receptor antagonists: Highlighting their potential for transdiagnostic therapeuticsProgress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 119Effects of comorbid posttraumatic stress disorder on cognitive dysfunction in Chinese male methamphetamine patientsProgress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 119Charting the neural circuits disruption in inhibitory control and its subcomponents across psychiatric disorders: A neuroimaging meta-analysisProgress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 119Individualized prediction of future cognition based on developmental changes in cortical anatomyNeuroimage: Reports, Vol. 2, No. 4The effects of lisdexamfetamine dimesylate on eating behaviour and homeostatic, reward and cognitive processes in women with binge-eating symptoms: an experimental medicine study10 January 2022 | Translational Psychiatry, Vol. 12, No. 1Characterizing mood disorders in the AFFECT study: a large, longitudinal, and phenotypically rich genetic cohort in the US25 March 2022 | Translational Psychiatry, Vol. 12, No. 1Developing symptom clusters: linking inflammatory biomarkers to depressive symptom profiles31 March 2022 | Translational Psychiatry, Vol. 12, No. 1Application of positron emission tomography in psychiatry—methodological developments and future directions14 June 2022 | Translational Psychiatry, Vol. 12, No. 1Relating psychiatric symptoms and self-regulation during the COVID-19 crisis11 July 2022 | Translational Psychiatry, Vol. 12, No. 1Transdiagnostic connectome signatures from resting-state fMRI predict individual-level intellectual capacity6 September 2022 | Translational Psychiatry, Vol. 12, No. 1Quantitative trait locus analysis for endophenotypes reveals genetic substrates of core symptom domains and neurocognitive function in autism spectrum disorder24 September 2022 | Translational Psychiatry, Vol. 12, No. 1Depressive symptoms reduce when dorsolateral prefrontal cortex-precuneus connectivity normalizes after functional connectivity neurofeedback16 February 2022 | Scientific Reports, Vol. 12, No. 1Grey matter correlates of affective and somatic symptoms of premenstrual dysphoric disorder9 April 2022 | Scientific Reports, Vol. 12, No. 1Self-esteem depends on beliefs about the rate of change of social approval22 April 2022 | Scientific Reports, Vol. 12, No. 1An electroencephalography connectome predictive model of major depressive disorder severity26 April 2022 | Scientific Reports, Vol. 12, No. 1Establishing the transdiagnostic contextual pathways of emotional outbursts6 May 2022 | Scientific Reports, Vol. 12, No. 1EEG time–frequency analysis reveals blunted tendency to approach and increased processing of unpleasant stimuli in dysphoria17 May 2022 | Scientific Reports, Vol. 12, No. 1An evaluation of Internet searches as a marker of trends in population mental health in the US27 May 2022 | Scientific Reports, Vol. 12, No. 1Multiscale neural gradients reflect transdiagnostic effects of major psychiatric conditions on cortical morphology27 September 2022 | Communications Biology, Vol. 5, No. 1Psychiatrically relevant signatures of domain-general decision-making and metacognition in the general population30 August 2022 | npj Mental Health Research, Vol. 1, No. 1Transdiagnostic alterations in neural emotion regulation circuits – neural substrates of cognitive reappraisal in patients with depression and post-traumatic stress disorder8 March 2022 | BMC Psychiatry, Vol. 22, No. 1The mood disorder spectrum vs. schizophrenia decision tree: EDIPHAS research into the childhood and adolescence of 205 patients18 March 2022 | BMC Psychiatry, Vol. 22, No. 1Feasibility and acceptability of a novel telepsychiatry-delivered precision prescribing intervention for anxiety and depression19 July 2022 | BMC Psychiatry, Vol. 22, No. 1Building a neurocognitive profile of suicidal risk in severe mental disorders26 September 2022 | BMC Psychiatry, Vol. 22, No. 1Training for Awareness, Resilience and Action (TARA) for medical students: a single-arm mixed methods feasibility study to evaluate TARA as an indicated intervention to prevent mental disorders and stress-related symptoms28 February 2022 | BMC Medical Education, Vol. 22, No. 1Clinical research diagnostic criteria for bipolar illness (CRDC-BP): rationale and validity13 October 2022 | International Journal of Bipolar Disorders, Vol. 10, No. 1Challenges and opportunities for precision medicine in neurodevelopmental disordersAdvanced Drug Delivery Reviews, Vol. 191Using causal methods to map symptoms to brain circuits in neurodevelopment disorders: moving from identifying correlates to developing treatments12 March 2022 | Journal of Neurodevelopmental Disorders, Vol. 14, No. 1Cognitive, emotional, and social functioning of preschoolers with attention deficit hyperactivity problems1 February 2022 | BMC Psychiatry, Vol. 22, No. 1Clusters, lines and webs—so does my patient have psychosis? reflections on the use of psychiatric conceptual frameworks from a clinical vantage point14 February 2022 | Philosophy, Ethics, and Humanities in Medicine, Vol. 17, No. 1Machine learning of language use on Twitter reveals weak and non-specific predictions25 March 2022 | npj Digital Medicine, Vol. 5, No. 1The Role of the Posterior Cerebellum in Dysfunctional Social Sequencing12 October 2021 | The Cerebellum, Vol. 21, No. 6Symptoms of depression together with trait anxiety increase the ability to predict alpha power change between attention and resting statesInternational Journal of Psychophysiology, Vol. 182Task-related neural activation abnormalities in patients with remitted major depressive disorder: A coordinate-based meta-analysisNeuroscience & Biobehavioral Reviews, Vol. 143Resting-state EEG functional connectivity predicts post-traumatic stress disorder subtypes in veterans9 November 2022 | Journal of Neural Engineering, Vol. 19, No. 6Protracted abstinence in males with an opioid use disorder: partial recovery of nucleus accumbens function26 February 2022 | Translational Psychiatry, Vol. 12, No. 1Evaluating the validity of animal models of mental disorder: from modeling syndromes to modeling endophenotypes10 November 2022 | History and Philosophy of the Life Sciences, Vol. 44, No. 4Accommodating site variation in neuroimaging data using normative and hierarchical Bayesian modelsNeuroImage, Vol. 264Coordinated cortical thickness alterations across six neurodevelopmental and psychiatric disorders11 November 2022 | Nature Communications, Vol. 13, No. 1Anticipatory and consummatory pleasure in eating disorders12 November 2022 | Journal of Eating Disorders, Vol. 10, No. 1A longitudinal resource for studying connectome development and its psychiatric associations during childhood14 June 2022 | Scientific Data, Vol. 9, No. 1How well do Cognitive Behavioural Therapy and Behavioural Activation for depression repair anhedonia? A secondary analysis of the COBRA randomized controlled trialBehaviour Research and Therapy, Vol. 159Linking Individual Differences in Personalized Functional Network Topography to Psychopathology in YouthBiological Psychiatry, Vol. 92, No. 12Putamen Structure and Function in Familial Risk for Depression: A Multimodal Imaging StudyBiological Psychiatry, Vol. 92, No. 12The association of glutamate level in pregenual anterior cingulate, anhedonia, and emotion-behavior decoupling in patients with major depressive disorderAsian Journal of Psychiatry, Vol. 78Conceptualizing the Role of Parent and Child Emotion Regulation in the Treatment of Early-Onset Behavior Disorders: Theory, Research, and Future Directions17 November 2022 | Clinical Child and Family Psychology Review, Vol. 56Translational models of addiction phenotypes to advance addiction pharmacotherapy17 November 2022 | Annals of the New York Academy of Sciences, Vol. 22Negative valence system as a relevant domain in compulsivity: review in a preclinical model of compulsivity15 November 2022 | Emerging Topics in Life Sciences, Vol. 33Temporal predictions of negative anxiety response styles in depression risk12 November 2022 | Current Psychology, Vol. 96Neural activation, cognitive control, and attention deficit hyperactivity disorder: Evaluating three competing etiological models8 November 2022 | Development and Psychopathology, Vol. 10A more holistic approach to autism using the International Classification of Functioning: The why, what, and how of functioning4 November 2022 | Autism, Vol. 43Error‐related brain activity: A time‐domain and time‐frequency investigation in pediatric obsessive–compulsive disorder4 November 2022 | PsychophysiologyEveryday Conflict in Families at Risk for Violence Exposure: Examining Unique, Bidirectional Associations with Children’s Anxious- and Withdrawn-Depressed Symptoms4 November 2022 | Research on Child and Adolescent Psychopathology, Vol. 32Is the serotonin hypothesis dead? If so, how will clinical psychology respond?3 November 2022 | Frontiers in Psychology, Vol. 13Associations of Parental Depression with Children’s Internalizing and Externalizing Problems: Meta-Analyses of Cross-Sectional and Longitudinal Effects24 October 2022 | Journal of Clinical Child & Adolescent Psychology, Vol. 51, No. 6Early hypervigilance and later avoidance: Event-related potentials track the processing of threatening stimuli in anxietyBehaviour Research and Therapy, Vol. 158Increased immuno-inflammatory mediators in women with post-traumatic stress disorder after sexual assault: 1-Year follow-upJournal of Psychiatric Research, Vol. 155Clenbuterol attenuates immune reaction to lipopolysaccharide and its relationship to anhedonia in adolescentsBrain, Behavior, and Immunity, Vol. 106Drift-Diffusion Model Reveals Impaired Reward-Based Perceptual Decision-Making Processes Associated with Depression in Late Childhood and Early Adolescent Girls9 June 2022 | Research on Child and Adolescent Psychopathology, Vol. 50, No. 11Theory of Mind and social functioning among neuropsychiatric disorders: A transdiagnostic studyEuropean Neuropsychopharmacology, Vol. 64The neurobiological reward system and binge eating: A critical systematic review of neuroimaging studies15 July 2022 | International Journal of Eating Disorders, Vol. 55, No. 11Symptom-Based Profiling and Multimodal Neuroimaging of a Large Preteenage Population Identifies Distinct Obsessive-Compulsive Disorder–like Subtypes With Neurocognitive DifferencesBiological Psychiatry: Cognitive Neuroscience and Neuroimaging, Vol. 7, No. 11THE TRANSLATIONAL GENETICS OF ADHD AND RELATED PHENOTYPES IN MODEL ORGANISMSNeuroscience & Biobehavioral Reviews, Vol. 5Relations of gray matter volume to dimensional measures of cognition and affect in mood disordersCortex, Vol. 156The miR-124-AMPAR pathway connects polygenic risks with behavioral changes shared between schizophrenia and bipolar disorderNeuron, Vol. 349Modern views of machine learning for precision psychiatryPatterns, Vol. 3, No. 11Boosting psychological change: Combining non-invasive brain stimulation with psychotherapyNeuroscience & Biobehavioral Reviews, Vol. 142A Critical Review of Multimodal-multisensor Analytics for Anxiety Assessment3 November 2022 | ACM Transactions on Computing for Healthcare, Vol. 3, No. 4A network analysis of anxiety, depressive, and psychotic symptoms and functioning in children and adolescents at clinical high risk for psychosis28 October 2022 | Frontiers in Psychiatry, Vol. 13Psychotic Symptom, Mood, and Cognition-associated Multimodal MRI Reveal Shared Links to the Salience Network Within the Psychosis Spectrum Disorders28 October 2022 | Schizophrenia Bulletin, Vol. 360Transdiagnostic Patterns of Sensory Processing in Autism and ADHD28 October 2022 | Journal of Autism and Developmental Disorders, Vol. 173Deep learning in neuroimaging data analysis: Applications, challenges, and solutions26 October 2022 | Frontiers in Neuroimaging, Vol. 1The neuropsychological correlates of (sluggish) cognitive tempo scales in school-aged children25 October 2022 | Child Neuropsychology, Vol. 60Profiles of executive functioning and neuroticism in emerging adulthood: Concurrent associations with psychopathology and health-related quality of life24 October 2022 | Journal of American College Health, Vol. 2A call for renewed attention to construct validity and measurement in psychopathology research21 October 2022 | Psychological Medicine, Vol. 3Pathways to depression: Dynamic associations between neural responses to appetitive cues in the environment, stress, and the development of illness18 October 2022 | Psychophysiology, Vol. 30Subjective reward processing and catechol-O- methyltransferase Val158Met polymorphism as potential research domain criteria in addiction: A pilot study14 October 2022 | Frontiers in Psychiatry, Vol. 13A Predictive Biomarker Model Using Quantitative Electroencephalogra