Study of the Genetic and Environmental Factors of Vulnerability in Bipolar Disorders

Study Overview
=================
Brief Summary
-----------------
Bipolar disorder is a complex, multifactorial disorder with the intervention of genetic vulnerability factors. To help the identification of these genetic factors and to improve genotype-phenotype correlation, the identification of endophenotype through the exploration of vulnerability characteristics in unaffected first degree relatives have been recommended. For this purpose, the investigator include bipolar patients, unaffected first degree relatives and control subjects to perform genetic association studies and subphenotype analyses. In this study the investigator will focus on subgroups defined according to the existence of abnormal circadian rhythm (a major indicator of bipolar vulnerability). Lithium is the leading treatment of bipolar disorders but prophylactic lithium response is highly variable and difficult to predict due to lack of biomarkers of response. To explore lithium response variability and to identify biomarkers of response, the investigator characterise lithium response using ALDA scale to conduct pharmacogenetic studies and pharmacokinetic studies of lithium extended release, in the subpopulation of patients treated with lithium. As lithium is a circadian agent, the investigator will also explore the links between lithium response and circadian phenotypes. Finally, using Li7 magnetic spectroscopy, the investigator will compare lithium brain distribution in a small sample of good and partial responders to lithium.

Official Title
-----------------
Study of the Genetic and Environmental Factors of Vulnerability in Bipolar Disorders

Conditions
-----------------
Bipolar Disorder

Intervention / Treatment
-----------------
* Other: Blood sample
* Device: actometer


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with Bipolar I, II or Not Otherwise Specified (NOS) disorders Euthymic Age > 18 Affiliated to the French social health care system Somatic state compatible with a blood test Informed consent signed for the study European Exclusion Criteria: Patients major protected Patients adopted Geographical origin of grandparents unknown

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Main module<br>Blood sample | Other: Blood sample<br>* A blood sample is taken at inclusion of patients in the study to perform DNA analysis<br>Device: actometer<br>* To evaluate the quality of sleep, questionnaires are completed and patients wear an actometer for 21 days. They will also complete a sleep diary<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Allele frequencies |  | All genotyping will be performed after 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Activity (movement per minute) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Total time in bed (minutes) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Total time in bed with and without sleep (minutes) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Day to day Stability in Time to bed (ratio of minutes) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Day to day Stability in activity (ratio of minutes) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Sleep latency (minutes) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Total time awaken during the night (minutes) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Time awaken during the night (minutes) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Percentage of time sleeping (%) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Fragmentation index (ratio) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Total sleep time (minutes) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Activity during sleep (movement per minute) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Total activity amplitude (movement per minute) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Start L5: start of the 5 hours with the lowest activity period (hours:minutes) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Start M10: start of the 10 hours with the highest activity period (hours:minutes) | Variable recorded in the activity tracking module | End of participation of the activity tracking module : Day 21 | 
| Plasma and erythrocyte lithium concentration (Meq/L) at different times after inclusion |  | At inclusion : time 0, 1 hour, 4 hours and 8 hours - At Day 30 : Time 0 and 1 hour | 
| Lithium brain distribution using Li7 magnetic spectroscopy |  | Day 1 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bipolar disorders, Genetic, Biomarkers, Circadian rhythm