Clinical trial NCT03656302: Circadian Rhythm Dysregulation in Offspring of Parents With Bipolar Disorder
Official title: Circadian Rhythm Dysregulation in Offspring of Parents With Bipolar Disorder
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Bipolar Disorder
Keywords: Bipolar disorder
Circadian Rhythm Disorders
High-risk offspring
Endophenotypes
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Kowloon Hospital
name: The Affiliated Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital)
name: Shenzhen Nanshan Center for Chronic Disease Control
name: Shenzhen Baoan Center for Chronic Disease Control
name: Shenzhen Longgang Center for Chronic Disease Control
name: Shenzhen Futian Center for Chronic Disease Control
First posted: 2018-09-04
Enrollment: 1000
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with BD will be recruited from psychiatry outpatient clinics in Hong Kong and mainland China. Healthy parents will be recruited from our on-going community-based projects. In addition, the investigators will also recruit subjects through public advertisement through various media such as Facebook, poster, and emails. In view of the potential sex differences in these circadian rhythms indicators of interest, the adolescent offspring of healthy parents will be age- and sex-matched to the adolescent offspring of BD parents.

Brief summary: This study aims to 1) investigate the differences and variances in circadian rhythms at several levels, including physical activity, dim light melatonin onset, diurnal patterns of cortisol, and body temperature between the offspring of patients with bipolar disorder (BD) and offspring of healthy parents by using a high-risk study design; and 2) determine whether these indicators correlate with psychopathological symptoms as measured by the psychometric measurements.

Detailed description: Bipolar disorder (BD), characterized by episodes of mania or hypomania with frequent depressive episodes, is commonly found in the general population with a lifetime prevalence of 1-2% in the world. The morbidities and mortality associated with bipolar disorder are huge and the repercussion on their family members is considerate. Nonetheless, there is no existing well-established prevention strategy that may prevent this distressing mental disorder. A major reason is that there was limited understanding of the prodromal phase of BD. On the other hand, the genetic background determines about 60-85% of risk variance of BD. In other words, the offspring carries significant risk and propensity to develop future BD. Limited existing studies suggested that offspring of patients with BD have a higher rate of sleep and circadian disturbances and mental disorders than those offspring of parents without BD. Nonetheless, it is still unclear whether sleep and circadian disturbances are prodromal markers or risk factors for the development of bipolar disorder in this high-risk population.

In light of our research and other studies' preliminary findings on the relationship between circadian rhythms dysregulation and BD and robust heritability in BD, we hypothesize that

1. Circadian rhythm dysregulations are prodromal features and endophenotypes of BD. The offspring of BD parents will have more circadian rhythm dysregulations than those offspring of healthy controls;
2. The biologic indices of circadian rhythm dysregulations will be correlated with subsyndromal psychopathology.

Eligibility criteria: 1. Case offspring

Inclusion criteria:

1) aged 6-21 years old; 2) having at least one biological parent with a lifetime or current diagnosis of bipolar disorder; 3) being able to read, write and understand Chinese; 4) both the offspring and her/his parent(s) agree to sign the informed consent form

Exclusion criteria:

1) having lifetime history or current diagnosis of bipolar disorder; 2) having no good ability to attend this project, such as patients with dementia and mental retardation.

2. Control offspring

Inclusion criteria:

1) aged 6-21 years old; 2) having no biological parent(s) with lifetime or current diagnosis of mood disorders. 3) being able to read, write and understand Chinese; 4) both the offspring and her/his parent(s) agree to sign the informed consent form.

Exclusion criteria:

1) having lifetime history or current diagnosis of bipolar disorder. 2) having no good ability to attend this project, such as patients with dementia and mental retardation.

Primary outcomes:
measure: Dim light melatonin onset (DLMO, free day)
timeFrame: 9 hours
Secondary outcomes:
measure: Actigraphy and sleep diary
timeFrame: one week
measure: Body temperature
timeFrame: one week
measure: Circadian rhythm pattern of salivary cortisol (free day)
timeFrame: 24 hours
measure: 24-Hour Urinary 6-sulphatoxymelatonin (aMT6s) Assessment
timeFrame: 24 hours
measure: Sleep macroarchitecture by polysomnography
timeFrame: One-night (nearly 8 hours)
measure: The rates of chronotype and sleep disorders
timeFrame: nearly one hour
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Department of psychiatry, Faculty of Medicine, The Chinese University of Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: Jihui Zhang, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese University of Hong Kong
name: Yun Kwok Wing, MBChB
role: STUDY_CHAIR
affiliation: Shatin Hospital
name: Siu Ping Lam
role: STUDY_DIRECTOR
affiliation: Hong Kong University
name: Shirley Xin Li, PhD
role: STUDY_DIRECTOR
affiliation: Kowloon Hospital
name: Roger Man Kin Ng, PhD
role: STUDY_DIRECTOR
References: