A Genetic Family Cohort Study of Bipolar Disorder in Chinese Han Population

Bipolar Disorder Clinical Trial

Official title:

A Genetic Family Cohort Study of Bipolar Disorder in Chinese Han Population

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04024553
• Other study ID #: CRC2018ZD02
• Status: Enrolling by invitation
• Start date: March 28, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: June 2019
• Source: Shanghai Mental Health Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study intends to find out the pathogenic genes of bipolar disorder by collecting the two-phase family of Chinese Han population with the large sample using a family cohort study design, combined with the new generation of high-throughput sequencing technology and Genome-Wide Association Studies (GWAS), Proteomics, bioinformatics analysis, etc., which is expected to be clarified at the genetic level. The pathogenesis of bipolar disorder. At the same time, the investigators will conduct a five-year follow-up of cognitive function, brain function imaging and other major clinical symptoms in patients with bipolar disorder in the core family, and to explore familial bipolar disorder and sporadic biphasic. Differences in the clinical features of the disorder, in order to explore sensitive and specific biomarkers from a multidimensional perspective (cognitive function, brain imaging, genetic features, clinical features, etc.), which may contribute to bipolar disorder in the future. Accurate diagnosis and early identification and prevention have important scientific significance and clinical diagnosis and treatment significance.

Description:

Bipolar disorder (BD) is a serious, complex, family-grafting mental illness. Studies have shown that genetic factors may be the dominant factor in the pathogenesis of bipolar disorder, thus, it is worth looking forward to getting started and clarifying the etiology of bipolar disorder from a genetic perspective. However, earlier genetic studies such as linkage analysis, genetic mutation detection (preferred candidate genes), and recent genetic studies (no need to presuppose candidate genes) such as Whole Genome Sequencing (WGS), whole genome GWAS and Whole-exome sequencing (WES) failed to identify any biogenic disorder gene or chromosomal region that plays a major role in, which may be related to the synergy of population heterogeneity, insufficient sample size or coordination effect caused by common mutations.

As a familial, highly heritable psychiatric disease, the literature suggests that the pathogenic genes of bipolar disorder may be directly derived from the intergenerational transmission of rare mutations in family members, and these rare variants are more likely to be predicated from the family. It has been found that the family has a higher frequency and is more susceptible to detecting susceptibility genes for bipolar disorder. Therefore, the family research design combined with WGS, GWAS and other advanced genetic research methods can reduce the unnecessary sample size, eliminate the confounding factors of the population, and more easily capture the potential genes of bipolar disorder.

However, at present, there are few reports of foreign bipolar disorder family and the results are not consistent. There is no research report on the large sample family of Chinese Han population in China. Therefore, it is necessary to expand the family sample size and combine with new genetic research methods in the Han population. explore. Therefore, this study intends to find out the pathogenic genes of bipolar disorder by collecting the two-phase family of Chinese Han population with the large sample using a family cohort study design, combined with the new generation of high-throughput sequencing technology and GWAS, Proteomics, bioinformatics analysis, etc., which is expected to be clarified at the genetic level. The pathogenesis of bipolar disorder. At the same time, the investigators will conduct a five-year follow-up of cognitive function, brain function imaging and other major clinical symptoms in patients with bipolar disorder in the core family, and to explore familial bipolar disorder and sporadic biphasic. Differences in the clinical features of the disorder, in order to explore sensitive and specific biomarkers from a multidimensional perspective (cognitive function, brain imaging, genetic features, clinical features, etc.), which may contribute to bipolar disorder in the future. Accurate diagnosis and early identification and prevention have important scientific significance and clinical diagnosis and treatment significance.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 2520
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• BD patients from BD family:

1. Meets the diagnostic criteria of BD in DSM-IV-TR, does not limit subtypes and current disease status;

2. age = 15 years old;

3. Han nationality;

4. There are enough audition levels to complete the necessary examinations for the study;

5. Understand the research content and sign the informed consent form. If the patient is unable to sign the informed consent form due to the young age, senior age, low education level or other reasons, they can be signed by their relatives or signed by their guardian.

• Healthy menbers from BD family:

1. age = 15 years old;

2. Han nationality;

3. biological parents or compatriots of the proband, cousins;

4. There are enough audition levels to complete the necessary examinations for the study;

5. Understand the research content and sign the informed consent form. If the patient is unable to sign the informed consent form due to the young age, senior age, low education level or other reasons, they can be signed by their relatives or signed by their guardian.

• Healthy control enrollment criteria without family history:

1. age = 15 years old;

2. Han nationality;

3. gender matches the patient group in the family;

4. There are enough audition levels to complete the necessary examinations for the study;

5. Understand the research content and sign the informed consent form. If the patient is unable to sign the informed consent form due to his or her age, advanced age, low education level or other reasons, he or she may be entrusted to sign by his or her relatives or signed by his guardian;

Exclusion Criteria:

• BD patients from BD family:

1. There is a DSM-IV-TR axis II disease (mental retardation, etc.) that significantly affects the patient's current state of mind;

2. There are serious physical diseases, it is difficult to complete the necessary examinations, including history of brain trauma or cerebrovascular disease, severe cirrhosis, acute and chronic failure, severe diabetes, aplastic anemia, moderate to severe malnutrition and other serious nerves, heart, Physical diseases such as liver, kidney, endocrine, and blood system or diseases that may interfere with the test evaluation (the abnormal index is more than 2 times higher than the normal value).

• Healthy menbers from BD family and healthy control enrollment criteria without family history::

1. with a mental disorder that meets the diagnostic criteria for DSM-IV-TR axis I or who have suspected psychosis but do not meet the diagnostic criteria;

2. There are DSM-IV-TR axis II diseases (mental retardation, etc.) that significantly affect the patient's current mental state;

3. There are serious physical illnesses, and it is difficult to complete the necessary examinations.

Related Conditions & MeSH terms

• Bipolar Disorder
• Disease

Locations

Country	Name	City	State
China	Shanghai Mental Health Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Mental Health Center

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Potential risk genes	The investigators will collect peripheral blood samples of patients and healthy controls during the baseline period, and blood samples from family members during follow-up period. The blood will be used for WGS, GWAS, WES to get candidate genes. Reported high risk genes such as CACNA1C?DTNA?FOXP1 and so on are the focus.	at december 2022
Secondary	HAMD-17 scores of patients and high-risk subjects	Hamilton depression scale is used to assess subjects at the baseline and every follow-up point(health controls are assessed only at baseline). HAMD is the most commonly used scale for clinically assessed depression. Total score < 7 points means normal; total scores in 7~17 points indicates that there may be depression; total scores in 17~24 points shows that there must be depression; total score >24 points means major depression.	by december 2022
Secondary	Onset age of BD subjects	Data of onset age will be record since the subjects join this peoject, and the invetigators will continue recording especially at each follow-up point.	by december 2022
Secondary	Wisconsin Card Sorting Test results	The family members will be tested at baseline and 5 follow-up periods, totally 6 times. The healthy control will be tested once at baseline. Wisconsin Card Sorting Test (WCST) reflects congnitive function, which includes 13 indexes. Higher scores indicate better congnition.	by december 2022
Secondary	Characteristic changes of electroencephalogram	In this study the investigators use EEG equipment from BrainProducts of Germany. The sampling frequency is 1000hz. Detection items include gamma resonance, mismatched negative wave MMN, auditory event related potential P300, visual event related potential P300, and resting EEG. Family members were tested for the baseline period and subsequent annual follow-up period, a total of 6 times. Healthy controls test once at the baseline period.	by december 2022
Secondary	YMRS scores of patients and high-risk subjects	Young's Mania Rating Scale is used to assess subjects at the baseline and every follow-up point(health controls are assessed only at baseline). It is mainly used to assess the symptoms and severity of mania, which includes 11 items. Total scores range from 0 to 60, higher scores means the symptoms are more severe.	by december 2022
Secondary	Course of disease of BD subjects	Disease course will be record since the subjects join this peoject, and until the end of this study.	by december 2022
Secondary	Treatment plan of BD subjects	Treatment of BD patients will be record since the subjects join this peoject, and the invetigators will continue recording especially at each follow-up point.	by december 2022
Secondary	STROOP test results	The family members will be tested at baseline and 5 follow-up periods, totally 6 times. The healthy control will be tested once at baseline. STROOP test is a Cognitive psychology test, which is also called color word conflict test. In the randomly appearing text combinations, subjects are supposed to quickly read out names of colors according to the color of the text, and then the reading time is compared in this study.	by december 2022
Secondary	Repetitive Neuropsychological Status test (RBANS) results	The family members will be tested at baseline and 5 follow-up periods, totally 6 times. The healthy control will be tested once at baseline. RBANS is a test for subjects' neuropsychological state. It has 12 tasks. The original score will be converted to a standard score with a total score of 100 points. Higher scores means better congnitive function.	by december 2022