Circadian Rhythm Dysregulation in Offspring of Parents With Bipolar Disorder

• Conditions: Bipolar Disorder

• Registration Number: NCT03656302
• Lead Sponsor: Chinese University of Hong Kong

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.

Study Timeline

• Study Start: 2017-02-11
• Study First Submitted: 2018-07-05
• Status Verified: 2018-08
• Study First Submitted QC: 2018-08-31
• Last Update Submitted: 2018-08-31
• Study First Posted: 2018-09-04
• Last Update Posted: 2018-09-04
• Primary Completion: 2020-02-28
• Study Completion: 2020-06-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Dim light melatonin onset (DLMO, free day)	9 hours	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.

Secondary Outcome Measures

Name	Time	Method
The rates of chronotype and sleep disorders	nearly one hour	Chronotype will be estimated by the Morningness-eveningness Questionnaire (MEQ) or the Children's ChronoType Questionnaire (CCTQ). Sleep disorders, such as insomnia and delayed sleep phase disorder, will be also determined by the Diagnostic Interview for Sleep Patterns and Disorders (DISP).
Actigraphy and sleep diary	one week	One-week Actigraphy (GENEActiv) and sleep diary will be employed to continuously measure sleep/wake patterns and physical activity.
Sleep macroarchitecture by polysomnography	One-night (nearly 8 hours)	One-night polysomnographic assessment will be measured to document the sleep architecture, together with DLMO measure. The recordings include electro-oculogram (EOG), electroencephalogram (EEG), electromyogram (EMG; monitoring over chin and bilateral anterior tibialis muscles), electrocardiogram (ECG), nasal-oral airflow and respiratory movements. The PSG data will be scored according to the most updated scoring manual of the American Academy of Sleep Medicine.
Body temperature	one week	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.
Circadian rhythm pattern of salivary cortisol (free day)	24 hours	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.
24-Hour Urinary 6-sulphatoxymelatonin (aMT6s) Assessment	24 hours	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.

Trial Locations

Locations (1)

Department of psychiatry, Faculty of Medicine, The Chinese University of Hong Kong; 🇭🇰 Hong Kong, Hong Kong