Somatoform disorders are a broad group of illnesses that have bodily signs and symptoms that can suggest major medical diseases yet have no associated serious and demonstrable organic disorder. In particular, undifferentiated somatoform disorder (USD) is one subgroup of somatoform disorders which is characterized by one or more unexplained physical complaints lasting for at least 6 months and is below the threshold for diagnosing somatization disorder (Guggenheim, 2000). The prevalence of USD is known to be quite high, ranging from 10.2% to 30.6% (De Waal et al., 2004, Chang et al., 2005 and LeiKeiknes et al., 2007).
Somatoform disorders may involve a variety of neuronal pathways (Guggenheim, 2000). In a study using functional magnetic resonance imaging (fMRI), somatoform pain disorder patients showed increased activation in the amygdala, parahippocampal gyrus, anterior/mid-insula, primary and secondary somatosensory cortex and inferior parietal cortex, in comparison to healthy controls (Gundel et al., 2008). The changes in pain memory observed in phantom and chronic pain conditions are also known to be modulated by fronto-medial, fronto-lateral, parietal, insular and anterior cingulate activation which can influence pain perception (Rainville et al., 1997, Wager et al., 2004, Schreckenberger et al., 2005 and Treede, 2006). Moreover, limbic connections may bind stress-regulating and pain-processing systems together, resulting in pain perception triggered by stress without specific noxious stimuli (LeDoux, 2000, Price, 2000 and Sandkuhler, 2000).
It has been reported that the activity of cytokines, such as interleukins, tumor necrosis factor, and interferon, is likely to be altered in somatization disorder (Kaplan and Sadock, 1998). In particular, proinflammatory cytokines may not only regulate the mounting of the adaptive immune responses that involve T and B lymphocytes but also trigger a brain–cytokine system that organizes the sickness response (Dantzer, 2005). Therefore, alteration of T cells as well as proinflammatory cytokines can be anticipated in patients with somatoform disorders, who often show sickness behavior (Dantzer, 2005). However, studies that have examined immune activity in somatoform disorder patients are sparse in comparison with those in depressive disorder (Kronfol et al., 1983, Kronfol and House, 1984, Krueger et al., 1984 and Andreoil et al., 1990) and anxiety disorder patients (Brambilla et al., 1992, La Via et al., 1996, Koh and Lee, 1998, Rapaport, 1998 and Koh and Lee, 2004).
Immune functions may be influenced by cerebral asymmetry. Direct evidence for the existence of a connection between cerebral asymmetry and the immune system has been provided by animal studies in which the effects of unilateral cortical lesions on immune response were evaluated (Renoux et al., 1983, Neveu et al., 1986, Barneoud et al., 1987 and Neveu, 1988). Renoux et al. (1983) showed that partial ablation of the left frontoparietal cerebral cortex of mice, resulting in relative right-sided activation, decreased immune responses, whereas comparable lesions in the right cortex either had no effect or increased immune responses. In humans, some of the previous studies (Kang et al., 1991 and Davidson et al., 1999) found that individual differences in measures of prefrontal activation asymmetry in healthy individuals were related to basal natural killer (NK) cell function, with left-activated subjects exhibiting higher levels of NK cell function than right-activated subjects. In addition, changes in lymphocyte proliferation and NK cell activity have been associated with negative life events only among individuals with greater left frontal cortical activation (Liang et al., 1997).
Taken together, the above-reviewed findings suggest the possibility that somatoform disorders are closely related to both the brain and the immune system. However, few studies have specifically examined the relationship between brain system activity and immune function in somatoform disorders. Lymphocyte proliferative responses to phytohemagglutinin (PHA) were chosen as a measure of cell-mediated immunity because T lymphocytes are one of the sources of lymphokines having some links to the brain (Rohatiner et al., 1983, Ballieux and Heijnen, 1989 and Mefford and Heyes, 1990), and alterations of T cells can be anticipated in patients with somatoform disorders (Dantzer, 2005). Therefore, the objective of this study was to examine the relationship between brain activity and immune function in somatoform disorder patients.
