Biological Classification of Mental Disorders

Study Overview
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Brief Summary
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BeCOME intends to include at least 1000 individuals with a broad spectrum of affective, anxiety and stress-related mental disorders as well as 500 individuals unaffected by mental disorders. After a screening visit, all participants undergo in-depth phenotyping procedures and omics assessments on two consecutive days. Several validated paradigms (e.g., fear conditioning, reward anticipation, imaging stress test) are applied to stimulate a response in a basic system of human functioning (e.g., acute threat response, reward processing, stress response) that plays a key role in the development of affective, anxiety and stress-related mental disorders. The response to this stimulation is then read out across multiple levels. Assessments comprise omics, physiological, neuroimaging, neurocognitive, psychophysiological and psychometric measurements. The multilevel information collected in BeCOME will be used to identify data-driven biologically-informed categories of mental disorders using cluster analytical techniques. A subgroup of affected individuals (patients of the outpatients clinic of the Max Planck Institute of Psychiatry) are longitudinally observed regarding the stability of omics markers, vital parameters and symptom severity.

Detailed Description
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Background: A major research finding in the field of Biological Psychiatry is that symptom-based categories of mental disorders map poorly onto dysfunctions in brain circuits or neurobiological pathways. Many of the identified (neuro)biological dysfunctions are transdiagnostic, meaning that they do not reflect diagnostic boundaries but are shared by different ICD/DSM diagnoses. The compromised biological validity of the current classification system for mental disorders impedes rather than supports the development of treatments that not only target symptoms but also the underlying pathophysiological mechanisms. The Biological Classification of Mental Disorders (BeCOME) study aims to identify biology-based classes of mental disorders that improve the translation of novel biomedical findings into tailored clinical applications. Methods: BeCOME intends to include at least 1000 affected individuals (recruited through advertisements/self-referral or visits in the institute's outpatient clinic or in collaborating practices) with a broad spectrum of affective, anxiety and stress-related mental disorders as well as 500 individuals unaffected by mental disorders (advertisements/self-referral). After a screening visit, all participants undergo in-depth phenotyping procedures and omics assessments on two consecutive days. Several validated paradigms (e.g., fear conditioning, reward anticipation, imaging stress test) are applied to stimulate a response in a basic system of human functioning (e.g., acute threat response, reward processing, stress response) that plays a key role in the development of affective, anxiety and stress-related mental disorders. The response to this stimulation is then read out across multiple levels. Assessments comprise omics, physiological, neuroimaging, neurocognitive, psychophysiological and psychometric measurements. The multilevel information collected in BeCOME will be used to identify data-driven biologically-informed categories of mental disorders using cluster analytical techniques. Moreover, the subgroup of patients from the outpatient clinic of the Max Planck Institute of Psychiatry is followed-up at study days 14, 28 and 56 as well as 4 and 12 months after baseline for changes in a subset of parameters (omics, vital parameters and selected psychometric measures). Discussion: The novelty of BeCOME lies in the dynamic in-depth phenotyping and omics characterization of individuals with mental disorders from the depression and anxiety spectrum of varying severity. The investigators believe that such biology-based subclasses of mental disorders will serve as better treatment targets than purely symptom-based disease entities, and help in tailoring the right treatment to the individual patient suffering from a mental disorder. BeCOME has the potential to contribute to a novel taxonomy of mental disorders that integrates the underlying pathomechanisms into diagnoses.

Official Title
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The Biological Classification of Mental Disorders Study: Towards a New Taxonomy of Mental Disorders

Conditions
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Mental Disorder, Depressive Disorder, Anxiety, Trauma and Stressor Related Disorders

Intervention / Treatment
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* Other: no intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of an affective, anxiety or stress-related mental disorder according to the criteria of DSM-IV or DSM-5 (Depressive disorders;Anxiety and obsessive-compulsive disorders: agoraphobia with and without panic disorder, panic disorder, social phobia, specific phobia, generalized anxiety disorder, obsessive compulsive disorder; Stress and trauma-associated mental disorders (e.g. posttraumatic stress disorder). or no mental disorder Exclusion Criteria: Intake of any psychotropic medication/substance for a minimum of 2 months before study day 1. Current illness in the field of organic mental disorders; Affective disorders caused by a medical condition Organic mental disorders (e.g. dementia) Current disorders of schizophrenia; Current eating disorder; Mental retardation and profound developmental disorders; Severe neurological or internal medical illness; Posttraumatic or post-ischemic brain damage or elapsed cerebral hemorrhage; Acute suicidality; Pregnancy and postpartum period; Magnetic resonance imaging contraindications (e.g. non-MR compatible metal implants including cardiac pacemakers, claustrophobia); Myopia <-6 D, which cannot be compensated by contact lenses or MR compatible glasses (Cambridge Research Systems, Rochester, UK); Current substance abuse; Current or past substance dependence; Risky alcohol consumption, screened with the Alcohol Use Disorder Identification Test - Consumption questions (AUDIT-C) and defined as score of ≥5 in males and of ≥4 in females.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| externally recruited participants<br>Self-referred affected and non-affected participants responding to advertisements | Other: no intervention<br>* no intervention<br>|
| In-house patients<br>Patients seeking treatment in the outpatient clinic of the Max-Planck-institute of Psychiatry | Other: no intervention<br>* no intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of data-driven biologically-informed categories (biotypes) of anxiety, depressive and stress-related mental disorders | The study is exploratory. Following an Research Domain Criteria (RDoC) approach, the study will use multi-level information for clustering of patients anxiety, depressive and stress-related mental disorders. | cross-sectional (baseline) | 
| Comparison of the new biotypes (biological classification approach) to traditional symptom-based diagnostic categories (DIA-X/M-CIDI) | Assessment of anxiety, depressive and stress-related disorders using the diagnostic interview (computerized Munich version of the Composite International Diagnostic Interview, DIA-X/M-CIDI) according to the traditional classification approach in order to assess the distribution of biotypes across traditional diagnostic categories of affective and anxiety disorders. | cross-sectional (baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biomarkers, translational medical research, psychiatry, Research Domain Criteria (RDoC), omics, neuroimaging, taxonomy