Circadian Rhythm Dysregulation in Offspring of Parents With Bipolar Disorder

Chinese University of Hong Kong1,000 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

1,000

Conditions

Bipolar Disorder

Eligibility

Sex: ALLMin age: 6 YearsMax age: 21 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Department of psychiatry, Faculty of Medicine, The Chinese University of Hong Kong

Hong Kong, Hong Kong

RECRUITING

Outcomes

Primary Outcomes

Dim light melatonin onset (DLMO, free day)

The subjects will be instructed to arrive at our sleep laboratory 9 hours before their usual bedtime. Saliva samples will be collected into clear sterile tubes every 30 minutes for eight hours, starting six hours before and 2 hours after individual's habitual bedtime. Subjects will be asked to stay in the light-controlled study room (\<30 lux in any direction of gaze) and remain awake and sit quietly.

Time frame: 9 hours

Secondary Outcomes

Actigraphy and sleep diary

One-week Actigraphy (GENEActiv) and sleep diary will be employed to continuously measure sleep/wake patterns and physical activity.

Time frame: one week

Body temperature

Consecutive one-week period Skin temperature will be measured by iButton DS1921H (Dallas, Maxim) at 3 places: right on the middle of the frontal aspect of the thigh, abdomen (1 cm above the navel), and the right infraclavicular area. It has been demonstrated that iButton has satisfactory validity, reliability, and utility in the measurements of circadian rhythms and sleep/wake cycles.

Time frame: one week

Circadian rhythm pattern of salivary cortisol (free day)

Subjects will be instructed to collect saliva samples using salivettes upon awakening (0 minute, 15 minutes, 30 minutes, and 45 minutes to measure cortisol awakening response) and then every 4 hours to measure the circadian rhythm patterns of cortisol secretion.

Time frame: 24 hours

24-Hour Urinary 6-sulphatoxymelatonin (aMT6s) Assessment

During the night of DLMO measure, all subjects will be instructed to collect a 24-h urinary samples (nearly 1000 mL) for the urinary 6-sulfatoxymelatonin assessment.

Time frame: 24 hours

Central Contacts

Jihui Zhang, PhD

CONTACT

(852) 39197647 jihui.zhang@cuhk.edu.hk

Data from ClinicalTrials.gov

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