The biological classification of mental disorders (BeCOME) study: a protocol for an observational deep-phenotyping study for the identification of biological subtypes

Abstract

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 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, social reward learning task) are applied to stimulate a response in a basic system of human functioning (e.g., acute threat response, reward processing, stress response or social reward learning) 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 genetic, molecular, cellular, 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.

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. We 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.

Trial registration: Retrospectively registered on June 12, 2019 on ClinicalTrials.gov (TRN: NCT03984084).

Keywords: Anxiety; Biology-based taxonomy; Depression; Neuroimaging; Omics; Psychiatry; Research domain criteria (RDoC); Stress; Transdiagnostic; Translational.

Fig. 1

BeCOME schedule and assessment domains. Legend: DIA-X/M-CIDI, lifetime and 12-month version of the computer-assisted Munich-Composite International Diagnostic Interview; BDI-II, Beck Depression Inventory Second Edition; MADRS, Montgomery-Asberg Depression Rating Scale; STAI, State-Trait-Anxiety Inventory; ACQ, Agoraphobic Cognitions Questionnaire; BSQ, Body Sensations Questionnaire; IUS, Intolerance-of-Uncertainty Scale: PAS, Panic and Agoraphobia Scale; TPQ, Tridimensional Personality Questionnaire; ADP-IV, Assessment of DSM-IV Personality Disorders; IE-4; Internal-External Locus of Control Scale; BIS/BAS, Behavioral Inhibition and Behavioral Approach System Scales; RSQ, Relationship Scales Questionnaire; EQ, Empathy Quotient; AQ, Autism Quotient; SNQ, Social Network Questionnaire; ACIPS, Anticipatory and Consummatory Interpersonal Pleasure Scale; CTQ, Childhood Trauma Questionnaire; KIFTL, short inventory for the assessment of early traumatic life events; SVF78, German stress coping questionnaire – 78 items version; RS-11, resilience scale 11 items version

Fig. 2

Overview of neuroimaging procedures in BeCOME. Legend: ^#indices refer to Table 2