Repeated Low-Grade Infections Associated With Antidepressant-Resistant Depression

sad woman looking down
sad woman looking down
Investigators believe this is the first large-scale retrospective study to evaluate the association between history of low-grade infections and major depressive disorder.

According to the results of a recent study published in the Journal of Clinical Psychiatry, individuals with a history of repeated low-grade infections were at an increased risk for subsequent depression and were more likely to have difficult-to-treat depression.

In this nationwide population-based study, 2 independent cohorts of medically healthy participants from Taiwan were categorized by the presence of a history of repeated low-grade infections, which included common upper airway system diagnoses. One-third of each cohort with the highest frequency of infections was categorized as having repeated low-grade infections (RLGI) and the bottom third was considered a control group for medically healthy subjects (MHS). The incidence of major depressive disorder (MDD) and treatment outcomes were compared between groups. Depression was considered difficult-to-treat if patients failed to respond to at least two antidepressant trials within 2 years of diagnosis. Easy-to-treat depression was considered depression that required no antidepressants or a single antidepressant.

In both cohorts, a history of repeated low-grade infections was associated with an increased risk for depression after adjustment for demographics (hazard ratio [HR] 1.37-1.91; P <.001). Other factors that influenced the risk of depression were female gender (HR 1.745-1.892) and higher income (HR 0.567-0.839).

More patients without a history of repeated low-grade infection were considered easy-to-treat (75.9% and 83.5%) compared with patients with a history of repeated low-grade infections (67.2% and 67.5%). Depressed patients with a history of repeated low-grade infections were more likely to be considered difficult-to-treat in both cohorts (P <.05 for all).

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In an interview with Psychiatry Advisor, Cheng-Ta Li, MD, PhD, chief of the division of community & rehabilitation psychiatry at Taipei Veterans General Hospital in Taiwan, explained that patients with repeated infections may have had a “higher level of inflammation, which has been linked to depression.” He concluded that “repeated inflammation could serve as a reliable predictor for responses to antidepressants, for which there is currently no objective method.”


Jeng JS, Li CT, Chen MH, et al. Repeated low-grade infections predict antidepressant-resistant depression: a nationwide population-based cohort study. J Clin Psychiatry. 2017;79(1). doi:10.4088/JCP.17m11540