Immune function might explain why women on hormonal contraception have increased risk of depression

Depressive disorders afflict almost 10 percent of the United States population, but the incidence of depression among women is about twice that of men. Now, a new study published in the scientific journal Brain, Behavior, and Immunity provides preliminary evidence that this difference is related to immune function.

The research also could help explain why women who use hormonal contraception face an increased risk of depression.

“Some molecules released in the brain in response to inflammation in the body can help protect neurons by promoting the health of these cells,” explained study author Jonathan Savitz, principal investigator at the Laureate Institute for Brain Research and a professor at the University of Tulsa. “These molecules are considered to be ‘neuroprotective’. However, other molecules produced by inflammation can have harmful effects, i.e. are ‘neurotoxic’.”

“Two different molecules produced by inflammation, kynurenic acid (KynA), which is neuroprotective, and quinolinic acid (QA), which is neurotoxic, have different effects at NMDA receptors in the brain,” Savitz said. “We have consistently found reduced concentrations of KynA in the serum of people with depression.”

“Further, greater levels of neurotoxic kynurenine metabolites were consistently associated with structural and functional brain abnormalities in individuals with depression. Thus, we and others have hypothesized that abnormal kynurenine metabolism may be a final common pathway through which inflammation leads to depression.”

“We found large sex differences, with lower levels of neuroprotective metabolites in females,” Savitz explained. “This is interesting given that females and males differ substantially in immune function and the incidence of depression is approximately twice as high in females versus males.”

In their new study of 130 men and 350 women, the researchers found that both the healthy and depressed women had significantly lower levels of kynurenic acid compared to men. In addition, women using oral contraceptives had a greater reduction in kynurenic acid compared to women who were not on any form of hormonal birth control.

“Historically, the greater rate of depression in females has been attributed to psychosocial and hormonal factors. However, given the significant differences in immune function between males and females (there are many papers on this topic), the immune system or an interaction between the immune system and other factors (e.g. hormonal) may partly explain sex differences in the epidemiology of depression.”

However, the design of the study prevents the researchers from making any conclusions about cause and effect.

“This was a cross-sectional study and thus the results are correlational, not necessarily causal,” Savitz said. “Second, we did not control for type of oral contraceptive or the length of time on oral contraceptives. Third, the sample size for the menstrual phase analysis was too small to draw any conclusions.”

But additional studies could help mental health professionals determine how immune function relates to depression.

“This is a finding worth following up on. Large scale epidemiological studies or prospective designs are needed to take this research further,” Savitz remarked.

The study, “Kynurenic acid is reduced in females and oral contraceptive users: Implications for depression“, was also co-authored by Timothy B. Meier, Wayne C. Drevets, T. Kent Teague, Brent E. Wurfel, Sven C. Mueller, Jerzy Bodurka and Robert Dantzer.