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May 17, 2018 by Megan Brooks | Medscape

Disrupted Body Clock Linked to Mental Illness

(Medscape) – Disruption of normal daily circadian rhythms can take a toll on a persons’ mental health and well-being, results from a large observational study show.

Investigators found that disturbances in the body’s internal clock, characterized by increased activity during rest periods or inactivity during the day, were associated with increased susceptibility to depression, bipolar disorder, and other problems.

“Our findings indicate an association between altered daily circadian rhythms and mood disorders and well-being,” Laura Lyall, PhD, from the Institute of Health and Wellbeing, University of Glasgow, Scotland, said in a statement.

The study was published online May 15 in Lancet Psychiatry.

Depression, Bipolar Disorder

Previous research has shown associations between circadian disruption and poor mental health, but these studies were typically based on self-reports of activity and sleep patterns, had small sample sizes, or adjusted for few potential confounders, Lyall noted in a journal podcast.

To address these methodologic problems, the investigators analyzed objective accelerometry-based rest and activity data for 91,105 participants (median age at baseline, 62 years) from the UK Biobank database.

All participants wore accelerometers for 7 days between 2013 and 2015. The researchers used the data to derive a circadian relative amplitude, a measure of the extent to which circadian rhythmicity of rest-activity cycles is disrupted.

They then examined cross-sectional associations between low relative amplitude (reflecting greater activity during rest periods and/or daytime inactivity) and lifetime risk for mood disorder. Well-being and cognitive function were also examined.

The investigators report that a one-quintile reduction in relative amplitude was associated with increased risk for major depressive disorder and bipolar disorder, as well as greater mood instability, higher neuroticism, more feelings of loneliness, lower happiness, lower health satisfaction, and slower reaction times (a crude measure of cognitive function).

Major depressive disorder OR, 1.06; 95% CI, 1.04 – 1.08 P < .0001
Bipolar disorder OR 1.11; 95% CI, 1.03 – 1.20 P = .007
Mood instability OR 1.02; 95% CI, 1.01 – 1.04 P = .004
Neuroticism IRR 1.01; 95% CI, 1.01 – 1.02 P < .0001
Happiness OR 0.91; 95% CI, 0.90 – 0.93 P < .0001
Health satisfaction OR 0.90; 95% CI, 0.89 – 0.91 P < .0001
Loneliness OR 1.09; 95% CI, 1.07 – 1.11) P < .0001
Reaction time LRC 1.75; 95% CI, 1.05 – 2.45) P < .0001
OR, odds ratio; 95% CI, 95% confidence interval; IRR, incidence rate ratio; LRC, linear regression coefficient

“These associations were independent of wide range of potential confounders,” said Lyall, including age, sex, lifestyle, education, and socioeconomic status.

Directionality Unclear

The researchers note that this study provides the first direct evidence of associations between objectively measured circadian disruption and neuroticism and mood instability, both of which have been consistently linked to increased risk for mood disorders. However, the effect sizes for mood instability and neuroticism were small, so the clinical relevance of these associations is unclear, they point out.

The researchers also acknowledge that this cross-sectional study cannot provide insights on causality.

“It could be that there is a direct causal link where circadian disruption causes impaired subjective well-being and increases risk of mood disorder. Or it could be the opposite, that this circadian disruption is a consequence of mood disorder and its associated risk factors,” said Lyall.

Despite these limitations, the researchers say accelerometry-derived relative amplitude is “relatively cheaply and easily measured and might be useful for identifying people at greater risk of major depressive disorder or bipolar disorder, or subgroups of patients who might benefit from therapies aimed at improving circadian rhythmicity.”

Writing in a linked comment, Aiden Doherty, PhD, from University of Oxford, United Kingdom, notes that although the UK Biobank is “one of the most important medical resources worldwide, the study population (median age at baseline of 62 years, IQR 54-68 years) is not ideal to examine the causes of mental health, given that 75% of disorders start before the age of 24 years.”

The circadian system, he points out, “undergoes developmental changes during adolescence, which is also a common time for the onset of mood disorders. It might be that the UK Biobank provides the template and impetus for a resource of a similar scale in adolescents and younger adults to help transform our understanding of the causes and consequences, prevention, and treatment of mental health disorders,” says Doherty.

The study was funded by the Lister Institute for Preventive Medicine. Dr Lyall and Dr Doherty have disclosed no relevant financial relationships.

Lancet Psychiatry. Published online May 15, 2018. AbstractComment


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