Improving Early Recognition and Intervention in At-risk Stages of Bipolar Disorders

Study Overview
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Brief Summary
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Prospective multicentre observational study for treatment approaches in at-risk individuals. Furthermore the purpose of this study is to test feasibility of a clinical staging model and validate diagnostic tools to identify individuals at risk state for the development of BD.

Detailed Description
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This project is one out of nine projects and four translational platforms forming the core of an interdisciplinary consortium to research on the most important areas of uncertainties and unmet needs in early recognition and diagnostic assessment, prevention of relapse, and therapeutic strategies of BD. Within this project, currently used diagnostic tools for subthreshold bipolar symptoms (BPSS-P, EPIbipolar, BAR criteria) will be deployed within the first 24 months in defined risk groups. Predictive power of individual risk factors/risk constellations will be determined regarding the manifestation and prodromal development of BD within ≥24 months (follow-up every 6 months). Potential resilience factors are ascertained. Additionally, the diagnostic tools will be used in a representative cohort (IMAGEN, to ascertain the prevalence of clinical/neurobiological at-risk constellations in non-selected youth and young adults, data from previous follow-ups will be used, suffering/help-seeking behavior will be assessed). Regarding treatment, at-risk subjects identified will be staged according to a pilot staging model. Treatment guidance is provided linked to the model, however, the naturalistic setting allows for individual decision making. Reasons for decisions will be ascertained, efficacy will be assessed with respect to symptomatology, psychosocial functioning and conversion to full BD, tolerability/safety will be assessed according to research standard. Outcomes will be assessed within ≥ 24 months. Using the results, the clinical staging model & guidance will be refined. The long-term goal is to provide a model for research and clinical initiatives. Synopsis of study goals: Determination of the predictive power of individual risk factors and risk constellations in defined risk groups for BD, Identification of resilience factors, Integration of results for further development of diagnostic tools and harmonization of the diagnostic process across centers, Investigation of the process of treatment decision making, efficacy (acute/preventive effects) and tolerability/safety in at-risk subjects in a naturalistic setting, testing the feasibility of a pilot clinical staging model with treatment guidance, Refinement of the staging model and guidance.

Official Title
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Improving Early Recognition and Intervention in At-risk Stages of Bipolar Disorders

Conditions
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Bipolar Disorder

Intervention / Treatment
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* Other: ≥ 1 potential risk factor for BD
* Other: depressive syndrome
* Other: ADHD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Risk group I: help-seeking persons consulting collaborating Early Recognition Centers presenting hints for ≥ 1 potential risk factor for BD (e.g. (sub)threshold affective symptomatology, anxiety, sleep disturbances, family history of bipolar disorder, episodic substance misuse, depressive syndrome) Risk group II: in- and outpatients with depressive syndrome (SCID) from the network sites Risk group III: in- and outpatients with ADHD already cared for in the Dept. of Child and Adolescent as well as Adult psychiatry in Würzburg Representative population cohort: IMAGEN study participants Exclusion Criteria: bipolar disorder schizaffective disorder schizophrenia dominating anxiety disorder, obsessive-compulsive disorder dominating substance-related disorder

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| help-seekers at-risk<br>persons consulting collaborating Early Recognition Centers presenting with hints for ≥ 1 potential risk factor for BD (e.g. (sub)threshold affective symptomatology, anxiety, sleep disturbances, family history, episodic substance misuse, ADHD) anticipated n = 500 | Other: ≥ 1 potential risk factor for BD<br>* exposure to ≥ 1 potential risk factors for BD (e.g. (sub)threshold affective symptomatology, anxiety, sleep disturbances, family history, episodic substance misuse)<br>|
| patients with depressive syndrome<br>in- and outpatients with depressive syndrome (SCID) anticipated n = 500 | Other: depressive syndrome<br>* in- and outpatients with depressive syndrome<br>|
| patients with ADHD<br>in- and outpatients with Attention-Deficit/Hyperactivity-Disorder (ADHD) anticipated n = 150 | Other: ADHD<br>* in- and outpatients with ADHD<br>|
| representative population cohort<br>representative population cohort from the IMAGEN study anticipated n = 500 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prodromal Symptoms for bipolar development via BPSS-FP & EPIbipolar | Bipolar Prodrome Symptom Scale - Full Prospective - BPSS-FP describes and rates prodromal mania/depression and other symptoms that have occurred in the past month and in the past year; Early Phase Inventory for bipolar disorders - EPIbipolar describes and rates symptoms associated with BD in the early phase (past 12 months) as sleep and circadian rhythm, mood swings and neuroticism, anxiety, functioning and comorbidity in childhood and youth, substance use, development of symptomatic pattern | baseline | 
| Prodromal Symptoms for bipolar development via BPSS-FP & EPIbipolar | Bipolar Prodrome Symptom Scale - Full Prospective - BPSS-FP describes and rates prodromal mania/depression and other symptoms that have occurred in the past month and in the past year; Early Phase Inventory for bipolar disorders - EPIbipolar describes and rates symptoms associated with BD in the early phase (past 12 months) as sleep and circadian rhythm, mood swings and neuroticism, anxiety, functioning and comorbidity in childhood and youth, substance use, development of symptomatic pattern | 1-year follow-up | 
| Prodromal Symptoms for bipolar development via BPSS-FP & EPIbipolar | Bipolar Prodrome Symptom Scale - Full Prospective - BPSS-FP describes and rates prodromal mania/depression and other symptoms that have occurred in the past month and in the past year; Early Phase Inventory for bipolar disorders - EPIbipolar describes and rates symptoms associated with BD in the early phase (past 12 months) as sleep and circadian rhythm, mood swings and neuroticism, anxiety, functioning and comorbidity in childhood and youth, substance use, development of symptomatic pattern | 2-year follow-up | 
| Diagnostic Status: psychiatric disorders via SCID-I | Diagnostic Status: psychiatric disorders via SCID-I | baseline | 
| Diagnostic Status: psychiatric disorders via SCID-I | Diagnostic Status: psychiatric disorders via SCID-I | 1-year follow-up | 
| Diagnostic Status: psychiatric disorders via SCID-I | Diagnostic Status: psychiatric disorders via SCID-I | 2-year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychotic Prodrome via PQ-16 (SOPS, SPi-A) | Screening for psychotic prodrome using Prodromal Questionnaire - PQ-16 Assessing psychotic prodrome after positive screening via Structured Interview for Prodromal Syndroms - SOPS and Schizophrenia Proneness Instrument, Adult Version - SPi-A (german version) | baseline | 
| Personality disorder via SCID-II (screening) | self-report screening questionnaire for personality disorder via SCID-II Assessing personality disorder via SCID-II after positive screening | baseline | 
| Depressive Symptoms via Montgomery-Åsberg Depression Rating Scale (MADRS) | Clinician-rated severity of depressive symptoms over the past 7 days, 10 items, scoring 0-6 each, yielding a total between 0 and 60. | baseline | 
| Depressive Symptoms via Quick Inventory of Depressive Symptomatology (QIDS-SR16) | Self-rated severity of depressive symptoms over the past 7 days, 16 items, scoring 0-3 each, yielding a total between 0 and 48. | baseline | 
| Manic Symptoms via Young Mania Rating Scale (YMRS) | Clinician-rated severity of manic symptoms over the past 48 hours, 11 items, 7 items scoring 0-4 each,4 items scoring 0-8 each, yielding a total between 0 and 60. | baseline | 
| Manic Symptoms via Altman Self-Rating Mania Scale (ASRM) | Self-rated severity of manic symptoms over the past 7 days, 5 items, scoring 0-4 each (0=no difficulty, 3=severe difficulty), yielding a total between 0 and 50. | baseline | 
| Functional Impairment via Functioning Assessment Short Test (FAST) | Clinician-rated functional impairment over the past 48 hours, 24 items, scoring 0-3 each (0=no difficulty, 3=severe difficulty), yielding a total between 0 and 72. | baseline | 
| Functional Impairment via Functioning Assessment Short Test (FAST) | Clinician-rated functional impairment over the past 48 hours, 24 items, scoring 0-3 each (0=no difficulty, 3=severe difficulty), yielding a total between 0 and 72. | 1-year follow-up | 
| Functional Impairment via Functioning Assessment Short Test (FAST) | Clinician-rated functional impairment over the past 48 hours, 24 items, scoring 0-3 each (0=no difficulty, 3=severe difficulty), yielding a total between 0 and 72. | 2-year follow-up | 
| Functioning via GAF-scale | Clinician-rated global functioning at the present moment via Global Assessment of Functioning scale (GAF-scale), scoring between 1-100 (1=no difficulty, 100=Persistent danger of severely hurting self or others or persistent inability to maintain minimal personal hygiene or serious suicidal act with clear expectation of death) | baseline | 
| Functioning via GAF-scale | Clinician-rated global functioning at the present moment via Global Assessment of Functioning scale (GAF-scale), scoring between 1-100 (1=no difficulty, 100=Persistent danger of severely hurting self or others or persistent inability to maintain minimal personal hygiene or serious suicidal act with clear expectation of death) | 1-year follow-up | 
| Functioning via GAF-scale | Clinician-rated global functioning at the present moment via Global Assessment of Functioning scale (GAF-scale), scoring between 1-100 (1=no difficulty, 100=Persistent danger of severely hurting self or others or persistent inability to maintain minimal personal hygiene or serious suicidal act with clear expectation of death) | 2-year follow-up | 
| Impulsiveness via Barrat Impulsiveness Scale (BIS) | Self-rated measure of impulsiveness, 30 items, scoring 1-4 each (1=rarely/never, 4=almost always/always), yielding a total between 30 and 120. | baseline | 
| Traumatic life events in childhood via Childhood Trauma Questionnaire (CTQ-SF) | Retrospective self-report to identify adolescent and adult clients with histories of trauma, 28 items, scoring on a 5-point Likert-type scale according to the frequency with which experiences occurred (never true to very often true). | baseline | 
| Affective temperament via Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire version (TEMPS-A) | Self-rated assessment of five affective temperaments, 30 items, dichotomous scale 0=applies, 1= does not apply. | baseline | 
| Creativity via Barron Welsh Art Scale (BWAS) | Assessment of the aesthetic preference by scoring like or dislike for certain black-and-white figures (85 items). | baseline | 
| Creative Achievement via Creative Achievement Questionnaire (CAQ) | Self-report measure of creative achievements across 10 domains, 96 items. | baseline | 
| Chronic Stress via Trierer Inventar zum chronischen Stress (TICS) | Self-rated measure of chronic stress in the past 3 months, 57 items, scoring 0-4 each (1=never, 4=almost always), yielding a total between 0 and 228. | baseline | 
| Ressources and self-management via Fragebogen zur Erfassung von Ressourcen und Selbstmanagementfähigkeit (FERUS) | Self-rated measure of health related ressources and self-management ability in the past two to three weeks, 66 items, scoring 1-5 each (1=strongly disagree, 4=strongly agree), yielding a total between 66 and 330. | baseline | 
| Quality of life via WHOQOL-BREF | Self-rated measure to assess subjective quality of life in the past two weeks, 26 items, 5-point scale with varying verbal equivalents | baseline | 
| Quality of life via WHOQOL-BREF | Self-rated measure to assess subjective quality of life in the past two weeks, 26 items, 5-point scale with varying verbal equivalents | 1-year follow-up | 
| Quality of life via WHOQOL-BREF | Self-rated measure to assess subjective quality of life in the past two weeks, 26 items, 5-point scale with varying verbal equivalents | 2-year follow-up | 
| Sensitivity of Behavioral Inhibition System and Behavioral Activation System via BIS/BAS scales | Self-rated measure to assess Sensitivity of the Behavioral Inhibition System and the Behavioral Activation System, 24 items, scoring 1-4 each (1=strongly disagree, 4=strongly agree) yielding a total between 24 and 96. | baseline | 
| Life events and -changes via Life Events Questionnaire (LEQ) | Inventory to assess life events and -changes during the past year, 82 items, choosing applying life events from a list of 82 events, rating Type of effect (good vs bad) and effect of event on life (0=no effect, 3=great effect). | baseline | 
| Life events and -changes via Life Events Questionnaire (LEQ) | Inventory to assess life events and -changes during the past year, 82 items, choosing applying life events from a list of 82 events, rating Type of effect (good vs bad) and effect of event on life (0=no effect, 3=great effect). | 1-year follow-up | 
| Life events and -changes via Life Events Questionnaire (LEQ) | Inventory to assess life events and -changes during the past year, 82 items, choosing applying life events from a list of 82 events, rating Type of effect (good vs bad) and effect of event on life (0=no effect, 3=great effect). | 2-year follow-up |