Repeated Low-Grade Infections Predict Antidepressant-Resistant Depression: A Nationwide Population-Based Cohort Study.

BACKGROUND: The relationship between severe inflammation and clinical depression in the context of major medical illnesses has been addressed, but the relationship between inflammation caused by mild infections and clinical depression is unclear. We aimed to examine whether a history of repeated low-grade infections (RLGI) in medically healthy subjects (MHS) could increase their vulnerability to major depressive disorder (MDD) (ICD-9-CM) and whether RLGI could be associated with higher resistance to antidepressants in those developing MDD. METHOD: A nationwide, population-based cohort study (January 1996 to December 2011) was conducted for MHS with and without a history of RLGI. The rates of MDD during an up to 8-year follow-up period were compared between the 2 groups in 2 independent cohorts. The stratified responses to adequate antidepressant trials, including easy-to-treat (ETT) and difficult-to-treat (DTT) responses, were also compared in the MDD patients. RESULTS: During the follow-up, the 2 cohorts consistently revealed that the RLGI(+) (ie, high-inflammation; n = 727) group had a significantly higher chance of developing MDD over time than the RLGI(-) (ie, low-inflammation; n = 443) group: Cox proportional hazards regression models showed that the hazard ratio associated with a history of RLGI was 1.369 to 1.911 (P < .001), after adjusting for confounding factors. The RLGI(+) group was consistently associated with a higher likelihood of DTT responses than was the RLGI(-) group (Cohort-2002: 11.5% vs 7.6%; Cohort-2004: 11.8% vs 4.3%; P < .05 by Wald χ² tests in both cohorts). CONCLUSIONS: This is the first large-scale retrospective cohort study to report a reliable temporal association between a history of RLGI and subsequent diagnosis of MDD and poor responses to antidepressants in 2 independent cohorts. Our data support the view that repeated mild infections play a role in the pathophysiology of MDD and antidepressant-resistant depression.

Risk of developing obstructive sleep apnea among women with polycystic ovarian syndrome: a nationwide longitudinal follow-up study.

BACKGROUND: Previous cross-sectional studies have suggested a comorbid relationship between polycystic ovarian syndrome (PCOS) and obstructive sleep apnea (OSA). However, the temporal association between these two distinct diseases has not yet been investigated. METHODS: Using the Taiwan National Health Insurance Research Database, 4595 women with PCOS and 4595 (1:1) age-/sex-matched controls were enrolled into the present study between 1998 and 2009, and followed to the end of 2011. Those who developed OSA during the follow-up were identified. RESULTS: Women with PCOS had a greater incidence of developing OSA (1.71 vs 0.63 1000 person-years, p < 0.001) than those without PCOS. The Cox regression analysis after adjusting for demographic data and medical comorbidities showed that women with PCOS had an elevated likelihood of subsequent OSA (hazard ratio: 2.63, 95% CI 1.57-4.04) during the follow-up compared to the controls. DISCUSSION: Women with PCOS were associated with an increased risk of developing OSA in later life. Further studies would be required to investigate the underlying pathophysiology between PCOS and OSA, and to clarify whether prompt intervention for PCOS would reduce the risk of OSA.

High dosage of hypnotics predicts subsequent sleep-related breathing disorders and is associated with worse outcomes for depression.

OBJECTIVES: The rates of sleep related breathing disorders (SRBD) and treatment outcomes of depression were compared among insomnia patients who had stratified levels of hypnotic use during a 10-year follow-up (2001-2010). DESIGN: A nationwide population-based cohort study. SETTING: A nationally representative cohort of 1,000,000 enrollees. PARTICIPANTS: Data were collected from patients with major depressive disorder (MDD) and comorbid insomnia during January 2001 to December 2003 (study cohort N = 3,235). The mean dosage of hypnotics at baseline in the study cohort was calculated, and this information was used to categorize the cohort into three equal-sized groups based on levels of hypnotic dosage. MAIN OUTCOME MEASURES: Patient response to antidepressants during a period that extended from 1 year before to 1 year after the study (short-term outcome) and patient psychiatric and non-psychiatric visits and hospitalizations during follow-up (long-term outcome) were analyzed. RESULTS: High-dosage patients presented the highest rates of subsequent SRBD diagnosis (3.9%), compared to medium-dosage patients (2.2%) and low-dosage patients (2.0%) (P = 0.011). Significantly more patients in the high-dosage group were difficult to treat with antidepressants compared to the other 2 groups (8.7% vs. 4.1% vs. 3.0%, P < 0.001), and their long-term depression outcome was worse for most parameters. Logistic regression showed that high-dosage hypnotics predicted the development of SRBD later (OR 1.678 [CI, 1.051 to 2.680], P = 0.030). CONCLUSIONS: There is a reliable association between a history of high dosages of hypnotics, subsequent diagnosis of sleep related breathing disorder, and worse depression outcomes.