Plasma CRP levels in premenopausal women with major depression: a 12-month controlled study

Abstract

C-reactive protein (CRP), an inflammatory marker of cardiovascular risk, is often elevated in major depressive disorder (MDD). The magnitude and consistency of this elevation have not been previously characterized in premenopausal women with MDD. The aim of the study was to prospectively assess plasma CRP levels, body composition, endocrine and metabolic parameters, and depressive status in premenopausal women with MDD (n=77) and controls (n=41), aged 21 to 45. Women were enrolled in a 12-month, controlled study of bone turnover, the P.O.W.E.R. ( Premenopausal, Osteoporosis, Women, Al Endronate, Dep Ression) Study. Blood samples were taken at Baseline, Month 6, and Month 12. Most subjects with MDD were in clinical remission. These women tended to have consistently higher CRP levels than controls over 12 months (p=0.077). BMI was positively related to log[CRP] in women with MDD only. Nine women with MDD had CRP levels greater than 10 mg/l, a value associated with a very high cardiovascular risk. This subset was obese and had significantly higher triglycerides, total cholesterol, LDL-cholesterol, fasting insulin, and HOMA-IR than the rest of women with MDD. The variations in CRP levels over time were high (intra- and inter-individual coefficients of variations of approximately 30-50% and approximately 70-140%, respectively). No control had CRP levels greater than 10 mg/l. Depression was associated with increased plasma CRP in women with MDD. The clinical significance of abnormal plasma CRP for cardiovascular risk needs to be assessed in large prospective studies of women with depression.

Fig. 1

Analysis of baseline CRP levels in women with MDD and healthy control women. A. Box plots showing median, quartiles, and extreme values. The box represents the values between the 25^th and 75^th percentiles. The horizontal bar across each box represents the median value. Asterisks represent extreme values (values more than 3 box lengths from the upper edge of box). Open circles represent outliers (values between 1.5 and 3 box lengths from upper edge of box). One depressed subject with high CRP levels (29.3 mg/l) had reported recovery from an acute infection at the time of visit and was therefore excluded from the analyses. B. Percentile distribution of CRP values. CRP values for select percentiles are shown in the inset table. At the uppermost percentile (75^th), women with MDD have CRP levels over twice as high as control women. The dashed line marks the CRP level of 10 mg/l above which there are only MDD subjects.

Fig. 2

Individual plots of CRP values at Baseline, Month 6, and Month 12. Only subjects with at least 2 prospective measurements of CRP are plotted. Heavy lines indicate beginning of moderate (> 1–3 mg/l) and high (>3 mg/l) cardiovascular risk CRP levels.

Fig. 3

Regression analysis of BMI versus CRP baseline levels in control women and in women with MDD. BMI was related to CRP in women with depression (R² = 0.39; p < 0.0001) but not in control subjects. Three women with MDD had CRP values greater than 14 mg/l and these values were equated to 14 mg/l for graphical reasons. Results were similar at Month 6 and Month 12 (data not shown)