Depression affects an estimated 15% of adults in high-income nations, and a growing body of research suggests that it is associated with several lifestyle and dietary factors such as physical activity, smoking, alcohol intake, and consumption of coffee and tea — the most commonly consumed beverages worldwide besides water.

Experts propose that caffeine facilitates the transmission of serotonin and dopamine, which contribute to depression. While some studies have found an inverse relationship between coffee or caffeine intake and depression, others have found no beneficial effect.

Researchers at Qingdao University Medical College in China conducted the first meta-analysis of observational studies to examine the link between depression risk in adults and consumption of coffee and caffeine, seeking to clarify the link by conducting a dose-response analysis of “all available data of observational studies to derive a quantitative estimation of the association between coffee or caffeine intake and depression.”

The analysis covered 15 case-control, cohort, and cross-sectional studies that included a cumulative 330 677 participants for the coffee-depression association and 38 223 participants for the caffeine-depression association.

The researchers found a linear relationship between coffee consumption and depression risk, with a dose-response relationship of 8% reduced risk for each cup consumed per day.

Additionally, they observed a nonlinear relationship between caffeine intake and depression risk, in which “the risk of depression decreased faster and the association became significant when the caffeine consumption was above 68 mg/day and below 509 mg/day.”

Although researchers are not certain about the mechanisms driving the link between depression and coffee or caffeine consumption, several potential explanations have emerged. Previous findings have implicated inflammation and oxidative stress in the pathophysiology of depression, and one possibility is that the various chemicals present in coffee in significant amounts — including chlorogenic acid, nicotinic acid, trigonelline, quinolinic acid, tannic acid, pyrogallic acid — have anti-inflammatory and antioxidant effects that impact depression.

“Second, caffeine, as a nonspecific adenosine A1/ A2A receptor antagonist, generates psychostimulant effects through modulating dopaminergic transmission… and major metabolites of caffeine act on adenosine receptors in the brain,” the researchers wrote. This may help explain the reduced risk of depression associated with coffee intake.

Some of the limitations of the study included high between-study heterogeneity, the use of different methods across studies to assess caffeine intake, and the possibility of confounding by certain side effects. For example, if patients with depression avoid or minimize caffeine consumption because of its anxiogenic effects, “then there would appear to be a correlation between greater caffeine intake and less depression, especially in the cross-sectional studies,” the authors wrote.

Although these findings provide promising results, further investigation is needed to elucidate underlying mechanisms in the relationship between depression risk and coffee or caffeine intake.