The main finding of this paper is that the temperament trait harm avoidance was positively, and the character trait self-directedness negatively, associated with CRP levels in a population-based cohort of women. In line with this outcome, an inverse correlation between harm avoidance and self-directedness has been observed by others [39
], and was confirmed by our data (not shown).
This is the first study examining CRP levels in subjects in which personality traits have been assessed using the TCI. Previous studies regarding personality traits, measured with other instruments, versus CRP levels, also are sparse. Proneness for anger and hostility has however been associated with elevated levels of CRP [4
]. Also, a study regarding fear for terror attacks revealed, in women but not in men, a positive association between fear and elevated CRP levels after adjustment for generalized anxiety, depressive symptoms and other confounding variables [43
Although the literature is not unanimous [44
], a large number of studies suggest that ongoing depression is associated with elevated levels of CRP [1
]. In line with this notion, women in our study reporting ongoing depression displayed elevated CRP levels. Since previous studies have shown that depression is often associated with high harm avoidance and low self-directedness state [51
], it might be suggested that the observed association between these personality traits and CRP merely reflects an underlying depression. However, the association between personality traits and CRP was found also in women denying ongoing depression, suggesting that these personality traits per se
are related to low-grade inflammation, irrespectively of an ongoing depression.
Different explanations for the relationship between high levels of CRP and depression have been put forward, including the possibility that depression influences the immune system, hence eliciting low-grade inflammation, and the alternative explanation that low-grade inflammation may cause depression. The present study, indicating that CRP may be associated with personality traits, assumed to be relatively stable throughout life, casts new light on this issue. Of interest in this context is however the fact that high harm avoidance and low self-directedness, i.e. the two traits displaying significant associations with CRP in this study, are important predictors of depression [29
]. One possibility would be that low-grade inflammation may be both the result of actual or perceived stress [55
] – and hence associated with certain personality traits – and a cause for depression, subjects with high harm avoidance and low self-directedness being characterized by low-grade inflammation that may trigger depressive episodes.
Notably, previous studies as well as our data suggest that levels of CRP are higher during an ongoing depression than after recovery, hence suggesting CRP to be a state dependent rather than a trait dependent marker of depression [47
]. On the other hand, the available data do not exclude the possibility that CRP levels are slightly elevated also after recovery, and between episodes in recurrent depression [1
Importantly, twin studies [56
] suggest the heritability of CRP levels to be considerable. This might reflect that the underlying determinants of CRP formation such as obesity or proneness to low-grade inflammation are hereditary, but may also be the result of a more direct influence of genes on CRP production. Several reports have thus shown that polymorphisms in the gene coding for CRP are associated with baseline levels of circulating CRP [57
]. These polymorphisms may hence be of possible importance for the inflammatory response [59
]. When discussing possible explanations for the association with personality traits and depressed mood on the one hand, and CRP levels on the other, in terms of causality, the possibility that certain genes may exert a parallel influence on CRP levels and on brain development and function should not be excluded. The fact that genes are important for personality traits, including those assessed by the TCI scale [37
], as well as for traits such as aggression and irritability [60
], is well established.
Previous studies have suggested that the apparent association between symptoms of depression and CRP may be partly due to a confounding variable, e.g. high BMI [44
]. It is hence important to note that the association between CRP and the traits harm avoidance and self-directedness was not weakened by correcting for BMI or smoking. On the other hand, it should be taken into consideration that we did not control for other factors that may influence CRP levels such as diet [61
], exercise [62
], and socioeconomic status [63
]. In order to exclude individuals with an acute infection or inflammation and avoid false high levels of CRP women with CRP levels exceeding 5 mg/L were excluded. However, the acute phase response is a continuum and no true normal range for CRP levels is established. It has been suggested that levels below approximately 3 mg/L represent "normal" values and CRP levels above 10 mg/L reflect a clinically significant inflammatory state [35
]. Since blood samples were obtained once only, it cannot be excluded that high levels in some subjects were the results of an ongoing infection or inflammation.
CRP being associated with certain personality traits, and, at the same time, being an important risk factor for cardiovascular disease, makes it tempting to suggest that it may serve as a mediator between these two variables. The TCI sub-dimensions that most clearly correlated with CRP, i.e. fatigability/asthenia and purposefulness, may be factors predisposing individuals to burnout, a state characterized by emotional exhaustion and feelings of inadequate control over one's job [for refs, see [65
]]. Burnout has been associated with microinflammation [66
] as well as with cardiovascular disease [67
] also after controlling for depression and other confounding variables. Interestingly, CRP has been suggested to directly influence atherosclerosis [22
]. A speculative interpretation of our study would be that women being confident, optimistic and self-sufficient, by displaying lower levels of CRP, also may exhibit a decreased risk for cardiovascular disease. This suggestion is well in line with previous studies [69
Limitations of this study are that the number of assessed subjects was relatively small, and that the presented associations, though significant, were modest in term of r
-values. The population was recruited by means of population register, but the fact that the participants had accepted to participate may render a group somewhat non-representative for the general population. A strength of the study is that all studied subjects were of the same gender and age, hence reducing age- and sex-related sources of variability, and that all blood samples taken for analyses of CRP levels were obtained in the same (follicular) phase of the menstrual cycle [72
]. At the same time, the homogeneity of the group with respect to sex and age obviously limits the possibility to draw more generalised conclusions from the results, and makes further studies investigating the relationship between levels of CRP and personality traits in women at other ages and in men highly warranted. Another important limitation of the study is that depression was not assessed using a structured interview, but only by means of a few questions. Previous studies however suggest that very brief depression questionnaires, comprising only a couple of questions, such as the one used in this trial, do display an acceptable sensitivity [73
]; there are hence reasons to believe that the observation of a relationship between personality traits and CRP in the non-depressed group is not largely influenced by the erroneous inclusion of depressed subjects in this analysis. Also, the self-reported rate of depression in this female population is well in line with other reports [75
]. This notwithstanding, the results should be regarded as preliminary until replicated in women evaluated by a more comprehensive depression questionnaire, or, preferably, by a structured interview.