Inflammation: a linking mechanism between psychiatric and somatic health?
In modern society, disease burden of depression and anxiety, obesity, diabetes and cardiovascular
disease is increasing alarmingly worldwide. Moreover, there is an enormous amount of literature
demonstrating high comorbidity between depression and anxiety disorders with cardiovascular risk
factors and disease. Gaining insight into the underlying mechanisms to comorbidity between mental
and somatic health could greatly help in preventing and treating these diseases, which might have
major public health impact.
Chronic low-grade inflammation, indicated by high levels of inflammatory cytokines, is
fundamentally implicated in a multitude of somatic conditions and diseases, such as obesity, metabolic
syndrome, diabetes and cardiovascular disease, but also rheumatic disease, cancer and pain.
Growing evidence suggests that inflammatory processes play a role in depression as well, as
depressed persons are found to have higher levels of C-reactive protein (CRP), interleukin (IL)-1 and
IL-6. Some evidence also exists for an association between inflammation and anxiety. Recent studies,
therefore, have suggested inflammation as a pathophysiological pathway explaining the link between
affective disorders and somatic disease, especially cardiovascular disease. Only very little studies
have tried to directly test this hypothesis.
It is yet unclear how inflammation is exactly involved in the comorbidity between mental and
somatic health. Bidirectional associations between depression and inflammatory markers have been
suggested (see Figure 1). Depression could bring about disturbances in important stress systems of
the human body, i.e. the hypothalamus-pituitary-adrenal (HPA)-axis and the autonomic nervous
system (ANS), which in turn might stimulate production of cytokines.
On the other hand, administration of
Other pathophysiological
processes
Depression & Anxiety
pro-inflammatory cytokines (for instance
(e.g. HPA-axis, ANS)
in cancer or hepatitis C treatment) has
consistently been shown to induce
depression in about a third of patients.
Metabolic syndrome
Inflammation
Inflammation
Similarly, inflammation might increase
Obesity
genes
the risk of cardiovascular and related
diseases through the process of
atherosclerosis, but these chronic
Diabetes
Cardiovascular disease
conditions in itself could again stimulate
Other somatic diseases
cytokine production. Very few studies
(e.g. rheumatic arthritis,
cancer)
have longitudinally examined the
Figure 1. Research model for the associations between
direction of the association between
inflammation, mental and somatic health.
depression and anxiety and
inflammation.
Genetic factors may play a role as well. A genetic predisposition to elevated production of
inflammatory markers might increase the risk of both mental and somatic disease. Several
inflammatory genes (e.g. TNFA, MEF2A, IL-6, ICAM-1) have been implicated in cardiovascular
disease, but only few have been examined in relation to depression or anxiety. Moreover, it has not
been studied whether inflammation genes could (partly) explain the link between psyche and soma.
Furthermore, the influence of genetic factors may alter over the life course, as is illustrated by the
study finding that depression at young age is associated with a family history of depression, while
depression at old age with a family history of vascular disease (Kendler et al., 2009; Biol Psychiatry).
Also, inflammation increases with aging and is for that reason a more important somatic health aspect
in older persons. Therefore, it is important to take age into account when studying inflammation
(genes) as possible mediator between depression and anxiety and cardiovascular and other somatic
diseases. Comparing the importance of pathophysiological pathways between mental and somatic
health across younger and older populations has not been done frequently.
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Figure 1 (see above) summarizes the model for the present research proposal which will be used
to test hypotheses on the associations between depression and anxiety, inflammation (genes),
obesity, metabolic syndrome, diabetes and cardiovascular disease. Investigating the involvement of
other pathophysiological processes and other somatic diseases will not be the aim of the present
proposal, but will be included in a subsequent grant application. Specifically, within the present
proposal, the following hypotheses will be tested: 1) The longitudinal relationship between depression
and anxiety and inflammation is bidirectional; 2) The association between depression/anxiety and
obesity, metabolic syndrome, diabetes and cardiovascular disease is (partly) mediated by
inflammation (genes); 3) Inflammation markers and genes are more strongly involved in the
association between depression/anxiety and obesity, metabolic syndrome, diabetes and
cardiovascular disease in older persons with late-life mental disorders than in younger persons who
have early-life mental disorders.
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