Earlier Wake Up Time Reduces Risk of Depression

Iyas Daghlas, BS

An earlier wake up time could pay dividends in drastically cutting the risk of major depressive disorder (MDD), according to new research.

A team, led by Iyas Daghlas, BS, Broad Institute of MIT and Harvard, examined the association of genetically proxied morning diurnal preference with the risk of depression.

While morning diurnal preference is linked to a reduced risk of MDD, the causality of this association is not yet known. 

"We have known for some time that there is a relationship between sleep timing and mood, but a question we often hear from clinicians is: How much earlier do we need to shift people to see a benefit?" said senior author Celine Vetter, assistant professor of integrative physiology at CU Boulder, in a statement. "We found that even one-hour earlier sleep timing is associated with significantly lower risk of depression."

The Study Parameters

In the two-sample mendelian randomization study, the research team used summary-level genetic associations with diurnal preference and MDD of 697,828 participants of European ancestry. The investigators used up to 340 genetic loci associated with diurnal preference in a meta-analysis of the UK Biobank and 23andMe cohorts as genetic proxies for diurnal preference.

They also scaled the effect size of the variants by using genetic associations with accelerometer-based measurement of the sleep midpoint and obtained genetic associations with MDD from a meta-analysis of genome-wide association studies data derived from the Psychiatric Genomics Consortium and UK Biobank.

Using the inverse-variance weighted method, the investigators estimated the association of genetically proxied morning diurnal preference, corresponding to a one-hour earlier sleep midpoint with the risk of depression.

The investigators sought main outcomes of the risk of MDD, including self-reported and clinically diagnosed cases. This data was identified in meta-analyses of genome-wide association studies.

A total of 85,502 individuals in the UK Biobank cohort had measurements of the sleep midpoint and 170,756 participants had diagnosed MDD, with 329,443 participants serving as the control group. 

The Benefit of Optimal Sleep Timing

The researchers found genetically proxied earlier diurnal preference was linked with a 23% decrease in depression risk (OR per one-hour earlier sleep midpoint, 0.77; 95% CI, 0.63-0.94; P = 0.01).

There was a similar association after restricting the analysis to individuals with MDD as stringently defined by the Psychiatric Genomics Consortium (OR, 0.73; 95% CI, 0.54-1.00; P = 0.05).

However, this was not statistically significant when defined by hospital-based billing codes in the UK Biobank cohort (OR, 0.64; 95% CI, 0.39-1.06; P = 0.08).

The researchers found similar finding implementing sensitivity analyses examining potential biases because of pleiotropy or reverse causality (intercept [SE], 0.00 [0.001]; P = .66 by Egger intercept test).

“The results of this mendelian randomization study support a protective association of earlier diurnal preference with risk of MDD and provide estimates contextualized to an objective sleep timing measure,” the authors wrote. “Further investigation in the form of randomized clinical trials may be warranted.”

The study, “Genetically Proxied Diurnal Preference, Sleep Timing, and Risk of Major Depressive Disorder,” was published online in JAMA Psychiatry.