Disease Outcome, Alexithymia and Depression are Differently Associated with Serum IL-18 Levels in Acute Stroke

Abstract

Stroke has been shown to lead to depressive disorders, anxiety disorders and other emotional consequences. Although the cause of these disorders is a subject of debate, stroke has clearly been shown to lead to the production of pro-inflammatory cytokines, which we hypothesized to play a role in the production of post-stroke emotional disorders. Thus we investigated here whether acute stroke might be associated with changes in the normal serum levels of IL-18 and if these changes were related to stroke severity, as well as to the presence and severity of alexithymia and depression. Thirty patients with a first-ever symptomatic ischemic stroke were included. Alexithymia (Toronto Alexithymia Scale; TAS-20), depression (Hamilton Depression Rating Scale; HDRS-17) and serum IL-18 were assessed. Stroke patients showed serum levels of IL-18 significantly related to stroke severity. Furthermore, a strong positive correlation was observed between IL-18 levels and severity of alexithymia, particularly among patients with right-hemisphere lesions. Specifically, circulating concentrations of IL-18 were significantly increased in patients with categorical alexithymia (TAS-20 score 61), as compared with both non alexithymic patients and control subjects. In addition, stroke was more severe in alexithymic patients, as compared to non alexithymic patients. Following multivariate regression, serum IL-18 levels appeared to be specifically associated with alexithymia rather than with stroke severity in patients with right-hemisphere lesions only. These results suggest that IL-18 might be specifically implicated in the pathogenesis of post-stroke alexithymia, ultimately contributing to impaired recovery from stroke.

IL-18 Serum Levels and Variants of the Serotonin Transporter Gene Are Related to Awareness of Emotions in Healthy Subjects: A Preliminary Study

“…Therefore, we feel that findings from this research provide an interesting initial insight into the role of serotonin transmission in the relationship between IL-18 and alexithymia, identifying a novel interaction between cytokine serum levels and 5-HTT gene variants, both of which are involved in the alexithymic construct specifically related to difficulty identifying feelings and influenced by gender. In fact, our result is in line with other studies, which described the same positive association of TAS-20 F1 with IL-18 [16] and with the LL genotype [26], even if the exact mechanisms of such an interaction remain to be elucidated.…”

“…Accordingly, in this study male LL carriers had the highest levels of IL-18 among all of the genotyped groups and showed a significant correlation between IL-18 levels and the alexithymia F1 subscore. The latter is the second main finding of this study, in line with our previous data reporting that in poststroke patients IL-18 serum levels were positively associated with the alexithymia score and significantly related to disease severity [16]. The link between IL-18 and alexithymia would be more evident in pathological conditions where IL-18 elevation may be caused by the disease, while in health it may be observable when cytokine levels are physiologically higher, but in the absence of a real inflammatory status.…”

“…In addition, the mood state can regulate IL-18 levels in relation to central opioid neurotransmission [15], and, as previously observed in post-stroke patients, IL-18 may be a pathogenic mediator of emotional awareness disturbance, suggesting that IL-18-mediated mechanisms might underlie specific psychiatric modifications, including alexithymia [16]. Like IL-18, other proinflammatory cytokines, including IL-6, are also able to regulate the neuroendocrine system, affecting neuropsychological behavior and possibly playing a role in depression, anxiety, subjective stress, and alexithymia [5, 17-19].…”

Post-Stroke Depression: A Review

“…41 We have recently described that IL-18 peripheral levels are negatively correlated with depression severity in acute stroke survivors. 42 This may indicate that the inflammatory processes leading to PSD, just as laterality of lesion location, are time dependent. Thus mechanisms of depression in patients with acute and chronic stroke must be considered different and this may impact on future treatment interventions.…”

Possible Effectiveness of Collaboration between Occupational Therapists and Care Managers using the Management Tool for Daily Life Performance for Stroke Patients in Transitional Care

“…Self-rated health is well known to be an important indicator of QOL; it has also been reported to predict mortality [18−20] and the prognosis of stroke patients [21]. Stroke has been shown to lead to depressive and anxiety disorders and other emotional effects [22]. One-third of all stroke patients experience significant depressive symptoms after the onset of stroke [23].…”