Elevated CRP Linked to Depression, Psychological Distress

Deborah Brauser

December 27, 2012

Elevated levels of C-reactive protein (CRP), a biomarker commonly used to assess inflammation, may be associated with an increased risk for depression, new research suggests.

Data from 2 general population studies conducted in Denmark, which included a total of more than 73,000 adults, showed that those who had the highest levels of CRP were more than twice as likely to have psychological distress and depression than those with normal levels of CRP.

Increasing levels of CRP were also associated with an increased risk for hospitalization due to depression.

"Contrary to previous studies, these associations did not disappear when we adjusted for BMI [body mass index] or chronic disease," write Marie Kim Wium-Andersen, MD, from the Department of Clinical Biochemistry at Herlev Hospital and from the Copenhagen University Hospital in Denmark, and colleagues.

The investigators note that more research is now needed "to establish the direction of the association between CRP and depression" — especially because these studies were primarily cross-sectional.

"The results also support the initiation of intervention studies to examine whether adding anti-inflammatory drugs to antidepressants for treatment of depression will improve outcome," they write.

The study was published online December 24 in Archives of General Psychiatry.

Common Biomarker

According to the researchers, CRP is a commonly used marker of inflammation. And CRP levels that exceed 10 mg/L are associated with inflammatory disease.

Although past research has suggested that low-grade, systemic inflammation may also be a contributor to the development of depression, it has been unclear what role CRP levels may play.

For this study, the investigators evaluated data from 73,131 adults between the ages of 20 and 100 years from the Copenhagen General Population study and the Copenhagen City Heart study.

In these studies, elevated plasma levels of CRP were measured for all participants.

In addition, psychological distress related to depression was ascertained through a 2-item self-report questionnaire; and depression was determined though self-reported use of antidepressants, antidepressant prescriptions, and depression-related hospitalizations.

Increasing Risk

Results showed that increasing levels of CRP were associated with increasing risk for psychological distress and for depression.

For those who answered "yes" to the first survey question, which dealt with feelings of not having accomplished much, the age- and sex-adjusted odds ratio (OR) was 1.11 when CRP levels were between 1.01 and 3.00 mg/L compared with the lowest levels of 0.01 to 1.00 mg/L. The ORs increased to 1.80 for CRP levels of 3.01 to 10.00 mg/L and to 2.61 for levels greater than 10.00 mg/L.

For the second question, which dealt with wanting to give up, the corresponding ORs were 1.14, 1.79, and 2.30, respectively.

For the participants who reported using antidepressants, the adjusted ORs were 1.38 when their CRP levels were 1.01 to 3.00 mg/L, 2.02 for CRP levels of 3.01 to 10.00mg/L, and 2.70 for CRP levels greater than 10.00 mg/L compared with the lowest 0.01 to 1.00 mg/L levels.

The corresponding ratios went down slightly for prescriptions of antidepressants: OR, 1.08 for CRP levels of 1.01 to 3.00 mg/L; OR, 1.47 for CRP levels of 3.01 to 10.00mg/L; and OR, 1.77 for CRP levels greater than 10.00 mg/L.

For those who experienced hospitalizations, the ORs were 1.30, 1.84, and 2.27, respectively.

In prospective analyses, increasing CRP levels were also associated with increasing risk for hospitalization with depression: ORs, 1.04, 1.34, and 1.51, respectively.

"Depression is one of the leading contributors to the global burden of disease and the leading cause of disability measured by years living with disability," write the investigators.

"The main finding of this study consisted of an association of elevated CRP levels with an increased risk for psychological distress and depression in the general population."

They add that it will be important to further research the underlying mechanism between inflammation and depression.

The study was funded by Herlev Hospital, Copenhagen University Hospital, and the Danish Council for Independent Research, Medical Sciences. The study authors have disclosed no relevant financial relationships.

Arch Gen Psychiatry. Published online December 24, 2012. Abstract