Abstract
Although anxiety disorders, like depression, are increasingly being associated with metabolic and cardiovascular burden, in contrast with depression, the role of inflammation in anxiety has sparsely been examined. This large cohort study examines the association between anxiety disorders and anxiety characteristics with several inflammatory markers. For this purpose, persons (18–65 years) with a current (N=1273) or remitted (N=459) anxiety disorder (generalized anxiety disorder, social phobia, panic disorder, agoraphobia) according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and healthy controls (N=556) were selected from the Netherlands Study of Depression and Anxiety. In addition, severity, duration, age of onset, anxiety subtype and co-morbid depression were assessed. Inflammatory markers included C-reactive protein (CRP), interleukin (IL)-6 and tumor-necrosis factor (TNF)-α. Results show that after adjustment for sociodemographics, lifestyle and disease, elevated levels of CRP were found in men, but not in women, with a current anxiety disorder compared with controls (1.18 (s.e.=1.05) versus 0.98 (s.e.=1.07) mg l−1, P=0.04, Cohen's d=0.18). No associations were found with IL-6 or TNF-α. Among persons with a current anxiety disorder, those with social phobia, in particular women, had lower levels of CRP and IL-6, whereas highest CRP levels were found in those with an older age of anxiety disorder onset. Especially in persons with an age of onset after 50 years, CRP levels were increased compared with controls (1.95 (s.e.=1.18) versus 1.27 (s.e.=1.05) mg l−1, P=0.01, Cohen's d=0.37). In conclusion, elevated inflammation is present in men with current anxiety disorders. Immune dysregulation is especially found in persons with a late-onset anxiety disorder, suggesting the existence of a specific late-onset anxiety subtype with a distinct etiology, which could possibly benefit from alternative treatments.
Highlights
Anxiety disorders are among the most prevalent and disabling mental disorders.[1,2] Increasing evidence links anxiety to cardiovascular risk factors and diseases such as atherosclerosis,[3] metabolic syndrome,[4] and coronary heart disease.[5,6] As low-grade systemic inflammation is clearly involved in the etiology of these somatic conditions,[7,8,9] it has been hypothesized that inflammation has a role in anxiety disorders and may form the link between anxiety disorders and cardiovascular burden.[10]
The results show that men with a current anxiety disorder have somewhat increased levels of C-reactive protein (CRP), even after taking a large set of lifestyle and disease factors into account
Our study adds to the literature by showing that elevated CRP levels can be found among several common anxiety disorders in a relatively large cohort of anxious persons and controls, in those with a later onset of the anxiety disorder
Summary
Anxiety disorders are among the most prevalent and disabling mental disorders.[1,2] Increasing evidence links anxiety to cardiovascular risk factors and diseases such as atherosclerosis,[3] metabolic syndrome,[4] and coronary heart disease.[5,6] As low-grade systemic inflammation is clearly involved in the etiology of these somatic conditions,[7,8,9] it has been hypothesized that inflammation has a role in anxiety disorders and may form the link between anxiety disorders and cardiovascular burden.[10]. Two recent studies have correlated anxiety symptoms with increased cytokine levels, in particular C-reactive protein (CRP).[14,15] With regard to anxiety disorders, research has mainly focused on posttraumatic stress disorder, in which high levels of inflammatory markers have been found.[16,17] Sparse evidence from relatively small clinical studies (nE100) suggests increased inflammatory activation in patients with panic disorder[18] and generalized anxiety disorder,[19] which seems to be independent of co-morbid depression
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