Biological Classification of Mental Disorders

Anxiety Clinical Trial

— BeCOME  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03984084
• Other study ID #: 350-14
• Status: Recruiting
• Start date: June 9, 2015
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2023
• Source: Max-Planck-Institute of Psychiatry
• Contact: Elisabeth B Binder, Prof. Dr. Dr.
• Phone: +49 (0) 89-30622-586
• Email: binder[@]psych.mpg.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anxiety
• Depressive Disorder
• Mental Disorder
• Mental Disorders
• Psychotic Disorders
• Trauma and Stressor Related Disorders

Intervention

Other:
• no intervention
no intervention

Locations

Country	Name	City	State
Germany	Max Planck Institute of Psychiatry	Munich	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
Max-Planck-Institute of Psychiatry

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Stability/change in methylation over time	longitudinal analysis only in patients who are treated at the MPIP (group 2), DNA extraction from blood for the determination of epigenetic markers (DNA methylation) for the determination of the stability of methylation patterns from baseline up to study day 56.	baseline and at days 14, 28 and 56 after baseline
Other	Stability/change in body mass index (BMI) over time	longitudinal analysis only in patients who are treated at the MPIP (group 2), comparison of body mass index (BMI, calculated as kg/m^2) at study day 56 to body mass index at baseline	baseline and at day 56 after baseline
Other	Stability/change in blood pressure over time	longitudinal analysis only in patients who are treated at the MPIP (group 2), changes of blood pressure between baseline and study day 56.	baseline and at days 14, 28 and 56 after baseline
Other	Stability/change in gene expression over time	longitudinal analysis only in patients who are treated at the MPIP (group 2), messenger RNA extraction from blood for the determination of changes in gene expression from study day 1 up to study day 56.	baseline and at days 14, 28 and 56 after baseline
Other	Stability/change in BDI-II (Beck-Depression-Inventory-II) sum score	longitudinal analysis only in patients who are treated at the MPIP (group 2), Beck depression inventory, revised version (BDI-II) will be used for the assessment of changes in depression severity (indicated by the sum score, range from 0 to 63) from study day 1 up to 12 months after study day 1	baseline and every follow-up assessment: day 14, 28 and 56 as well as 4 and 12 months after baseline)
Other	Stability/change in the Montgomery Asberg Depression Scale (MADRS) sum score	longitudinal analysis only in patients who are treated at the MPIP (group 2), the observer-based Montgomery Asberg Depression Scale (MADRS) will be used for the assessment of changes in MADRS depression sum score (range from 0 to 60) from study day 1 up to 12 months after study day 1	baseline and every follow-up assessment: day 14, 28 and 56 as well as 4 and 12 months after baseline)
Other	Stability/change in the state scale of the Spielberger State-Trait Anxiety Inventory (STAI)	longitudinal analysis only in patients who are treated at the MPIP (group 2), the sum score of the state scale of the STAI (range from 20 to 80) will be used for the assessment of changes in state anxiety from study day 1 up to 12 months after study day 1	baseline and every follow-up assessment: day 14, 28 and 56 as well as 4 and 12 months after baseline)
Other	Stability/change in the Panic and Agoraphobia Scale (PAS) score over time	longitudinal analysis only in patients who are treated at the MPIP (group 2), the sum score of Panic and Agoraphobia Scale (PAS), range from 0 to 65, will be used for the assessment of changes in the severity of panic and agoraphobia.	baseline and every follow-up assessment: day 14, 28 and 56 as well as 4 and 12 months after baseline)
Primary	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)
Primary	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)