Clinical trial NCT03984084: Biological Classification of Mental Disorders
Official title: The Biological Classification of Mental Disorders Study: Towards a New Taxonomy of Mental Disorders
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Mental Disorder
Depressive Disorder
Anxiety
Trauma and Stressor Related Disorders
Keywords: biomarkers
translational medical research
psychiatry
Research Domain Criteria (RDoC)
omics
neuroimaging
taxonomy
Lead sponsor: Max-Planck-Institute of Psychiatry
Sponsor class: OTHER
First posted: 2019-06-12
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: individuals with varying degrees and a broad range of mental disorders from the anxiety and depression spectrum

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Identification of data-driven biologically-informed categories ("biotypes") of anxiety, depressive and stress-related mental disorders
timeFrame: cross-sectional (baseline)
measure: Comparison of the new biotypes (biological classification approach) to traditional symptom-based diagnostic categories (DIA-X/M-CIDI)
timeFrame: cross-sectional (baseline)
Secondary outcomes:
Other outcomes:
measure: Stability/change in methylation over time
timeFrame: baseline and at days 14, 28 and 56 after baseline
measure: Stability/change in body mass index (BMI) over time
timeFrame: baseline and at day 56 after baseline
measure: Stability/change in blood pressure over time
timeFrame: baseline and at days 14, 28 and 56 after baseline
measure: Stability/change in gene expression over time
timeFrame: baseline and at days 14, 28 and 56 after baseline
measure: Stability/change in BDI-II (Beck-Depression-Inventory-II) sum score
timeFrame: baseline and every follow-up assessment: day 14, 28 and 56 as well as 4 and 12 months after baseline)
measure: Stability/change in the Montgomery Asberg Depression Scale (MADRS) sum score
timeFrame: baseline and every follow-up assessment: day 14, 28 and 56 as well as 4 and 12 months after baseline)
measure: Stability/change in the state scale of the Spielberger State-Trait Anxiety Inventory (STAI)
timeFrame: baseline and every follow-up assessment: day 14, 28 and 56 as well as 4 and 12 months after baseline)
measure: Stability/change in the Panic and Agoraphobia Scale (PAS) score over time
timeFrame: baseline and every follow-up assessment: day 14, 28 and 56 as well as 4 and 12 months after baseline)
Locations:
city: Munich
country: Germany
facility: Max Planck Institute of Psychiatry
state: Bavaria
Study officials:
affiliation: Max-Planck-Institute of Psychiatry
name: Elisabeth B Binder, Prof. Dr. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bruckl TM, Spoormaker VI, Samann PG, Brem AK, Henco L, Czamara D, Elbau I, Grandi NC, Jollans L, Kuhnel A, Leuchs L, Pohlchen D, Schneider M, Tontsch A, Keck ME, Schilbach L, Czisch M, Lucae S, Erhardt A, Binder EB. The biological classification of mental disorders (BeCOME) study: a protocol for an observational deep-phenotyping study for the identification of biological subtypes. BMC Psychiatry. 2020 May 11;20(1):213. doi: 10.1186/s12888-020-02541-z.