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Neurobiol Stress. 2016 Oct;4:55-61.

Association between serum C-reactive protein and DSM-IV generalized anxiety disorder in adolescence: Findings from the ALSPAC cohort.

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Department of Psychiatry, University of Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
Centre for Mental Health, Addiction and Suicide Research, School of Social and Community Medicine, University of Bristol, UK; Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, UK.
Division of Psychiatry, University College London, UK.



Animal studies suggest a role of inflammation in the pathophysiology of anxiety, but human studies of inflammatory markers and anxiety disorders are scarce. We report a study of serum C-reactive protein (CRP) and generalised anxiety disorder (GAD) from the general population-based ALSPAC birth cohort.


DSM-IV diagnosis of GAD was obtained from 5365 cohort members during face-to-face clinical assessment at age 16 years, of which 3392 also provided data on serum high sensitivity CRP levels. Logistic regression calculated odds ratio (OR) for GAD among individuals in top and middle thirds of CRP distribution compared with the bottom third. Effect of comorbid depression was assessed. Age, sex, body mass, ethnicity, social class, maternal education, maternal age at delivery, and family history of inflammatory conditions were included as potential confounders.


Forty participants met DSM-IV criteria for GAD (0.74%). CRP levels were higher in GAD cases compared with the rest of the cohort (P = 0.005). After adjusting for potential confounders, participants in the top third of CRP values compared with the bottom third were more likely to have GAD; adjusted OR 5.06 (95% CI, 1.31-19.59). The association between CRP and GAD was consistent with a linear dose-response relationship. The pattern of association between CRP and GAD remained unchanged after excluding cases with co-morbid depression.


The findings are consistent with a role of inflammation in anxiety disorders. Longitudinal studies of inflammatory markers, subsequent anxiety taking into account current and past psychological stress are required to understand this association further.


Biological markers; Birth cohort study; C-reactive protein; Generalized anxiety disorder; Systemic inflammation

Conflict of interest statement

Declaration of interest The authors have no conflicts of interest to disclose. PBJ received an honorarium, that he donated to his department, from Roche for taking part in an advisory board to advise on education about schizophrenia for psychiatrists.

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