Psychobiological aspects of somatization syndromes: contributions of inflammatory cytokines and neopterin.

Previous research suggests a dysregulation of immune-to-brain communication in the pathophysiology of somatization syndromes (multiple somatoform symptoms). We compared blood levels of the inflammatory markers tumor necrosis factor-alpha (TNF-α), interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6) and neopterin between 23 patients with somatization syndromes (Somatoform Symptom Index-8, SSI-8), 23 age- and sex-matched healthy controls and 23 patients with major depression. No group differences were found for IL-1ra and IL-6. While TNF-α was increased in both clinical groups, neopterin was only increased in somatization syndromes. Correlational analyses revealed that neopterin tended to be related to somatoform pain complaints in patients with somatization syndromes. This study is the first to demonstrate increased levels of TNF-α and neopterin in patients with somatization syndromes without a diagnosis of depression, which may support a role of immune alterations in somatization syndromes. Neopterin is a reliable indicator for interferon-γ (IFN-γ) which was identified as the only cytokine that induces significant production of neopterin. Considering recent research indicating that IFN-γ can lead to increased neuronal responsiveness and body perceptions by reducing inhibitory tone in the dorsal horn, the observed association between somatization syndromes and neopterin might support the idea of central sensitization in the pathogenesis of somatoform symptoms.