Abstract
Total white blood cell count (TWBCC) and percentage (%) composition of lymphocytes (PL) or neutrophils (PN) are linked to mid- and late-life depression, though sex-specific temporal relationships between those inflammatory markers and depressive symptoms remain unclear. The association between inflammation and depressive symptoms in longitudinal data on ethnically and socioeconomically diverse urban adults was examined with two hypotheses. In hypothesis 1, we examined the relationship between TWBCC, PL and PN with change in level of depressive symptoms from baseline to follow-up, stratifying by sex. In hypothesis 2, we examined reverse causality, by testing the relationship of depressive symptoms with change in TWBCC, PL and PN. Multiple linear mixed-effects regression models were performed to examine both the hypotheses. The sample sizes of participants (n) and repeated observations (n') were: Hypothesis 1 (n=2009; n'=3501); Hypothesis 2 (n=2081; n'=3560). Among key findings (Hypothesis 1), in women, higher TWBCC was linked to a faster increase in depressive symptom total score (γ1112±s.e.: +0.81±0.28, P=0.003), with a slower increase over time in the positive affect subdomain coupled with faster increases in depressed affect and somatic complaints. Among women, baseline score on somatic complaints was positively associated with low PN (γ01a=+1.61±0.48, P<0.001) and high PL (γ01a=+1.16±0.45, P=0.011), whereas baseline score on positive affect was inversely related to higher PL (γ01a=−0.69±0.28, P=0.017). Results among men indicated that there was a positive cross-sectional relationship between low TWBCC and depressive symptoms, depressed affect and an inverse cross-sectional relationship with positive affect. However, over time, a low TWBCC in men was linked to a higher score on positive affect. There was no evidence of a bi-directional relationship between WBC parameters and depressive symptoms (Hypothesis 2). In sum, TWBCC and related markers were linked to depressive symptoms, mostly among women. Further longitudinal studies are needed to replicate this sex-specific association.
Highlights
Several studies included in metaanalyses found an association of elevated depressive symptoms with WBC-related markers of inflammation including increased absolute leukocyte levels (that is, total white blood cell count (TWBCC)), reduced percentage lymphocytes (PL) out of total leukocytes or lymphopenia, and increased percentage neutrophils (PN) or neutrophilia
3720 participants were recruited (Sample 1), Center for Epidemiologic Studies-Depression (CES-D) data were available for N = 2725 participants at baseline and N = 2258 at wave 3; while wave 1 Total white blood cell count (TWBCC), PN and PL were available for N = 2744–2745 participants and wave 3 TWBCC, PN and PL were available for N = 2254–2266
PN was higher in women who were more likely to be in the o 10th percentile of the distribution (9.9% vs 5.9%, P = 0.002), when elevated depressive symptoms (EDS)+ vs EDS−
Summary
Unipolar depression is a chronic condition[1,2] accounting for a major part of the health care system,[3] with a lifetime prevalence among American adults of ~ 12% in men and ~ 21% in women.[3]. As reverse causality cannot be ruled out, bi-directional associations between white blood cell (WBC)-related markers (TWBCC, PN and PL) and depressive symptoms in populations are under-studied, in terms of sex-specific longitudinal changes in one as predicted by the baseline value of the other.[24,28]. The first objective (Objective 1) was to assess the cross-sectional (that is, baseline vs baseline) and bi-directional longitudinal (that is, baseline vs rate of change) relationships of WBC-related markers (that is, high/low TWBCC, high/low PN, high/ low PL; high: 490th percentile, low: o10th percentile) with depressive symptoms, while the second objective (Objective 2) was to assess the cross-sectional and longitudinal relationships of WBC-related markers with specific domain of depressive symptomatology. Two longitudinal relationships were tested: Hypothesis 1: baseline WBC-related markers predict rate of change in depressive symptoms and Hypothesis 2: baseline depressive symptoms predict WBC-related markers
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