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Abstract
Cross-sectional data show elevated levels of circulating cytokines in psychiatric patients. The literature is divided concerning anti-inflammatory drugs' ability to relieve symptoms, questioning a causal link between inflammatory pathways and psychiatric conditions. We hypothesised that the development of circulating cytokine levels is related to mental distress, and that this relationship is affected by the use of anti-inflammatory drugs. The study was a longitudinal assessment of 12-week inpatient treatment at Modum Bad Psychiatric Center, Norway. Sera and self-reported Global Severity Index (GSI) scores, which measure psychological distress, were collected at admission (T0), halfway (T1) and before discharge (T2). Other variables known to distort the neuroimmune interplay were included. These were age, gender, diagnosis of PTSD, antidepressants and anti-inflammatory drugs. A total of 128 patients (92 women and 36 men) were included, and 28 were using anti-inflammatory medication. Multilevel modelling was used for data analysis. Patients with higher levels of IL-1RA and MCP-1 had higher GSI scores (p = 0.005 and p = 0.020). PTSD patients scored higher on GSI than non-PTSD patients (p = 0.002). These relationships were mostly present among those not using anti-inflammatory drugs (n = 99), with higher levels of IL-1RA and MCP-1 being related to higher GSI score (p = 0.023 and 0.018, respectively). Again, PTSD patients showed higher GSI levels than non-PTSD patients (p = 0.014). Cytokine levels were associated with level of mental distress as measured by the GSI scores, but this relationship was not present among those using anti-inflammatory drugs. We found no association between cytokine levels and development of GSI score over time.
Highlights
Several studies have found an association between cytokine levels and severity of mental distress (Maes, 1995; Furtado & Katzman, 2015; Miller & Raison, 2016; Dalton et al, 2018)
Cytokines, such as interleukin (IL)-1, IL-6, and tumour necrosis factor-alpha (TNF-α), are significantly elevated in depressed individuals as well as in a broad spectre of other psychiatric diagnoses compared to healthy controls (Dowlati et al, 2010; Passos et al, 2015; Dalton et al, 2018)
When stratifying according to the use of anti-inflammatory drugs during treatment, we found associations between levels of cytokines and Global Severity Index (GSI) only among those not using anti-inflammatory drugs
Summary
Several studies have found an association between cytokine levels and severity of mental distress (Maes, 1995; Furtado & Katzman, 2015; Miller & Raison, 2016; Dalton et al, 2018). Cytokines, such as interleukin (IL)-1, IL-6, and tumour necrosis factor-alpha (TNF-α), are significantly elevated in depressed individuals as well as in a broad spectre of other psychiatric diagnoses compared to healthy controls (Dowlati et al, 2010; Passos et al, 2015; Dalton et al, 2018). We have previously found both higher levels and a distinct escalation during treatment of pro-inflammatory and anti-inflammatory cytokines in patients with posttraumatic stress disorder (PTSD), but not for other psychiatric disorders (Toft et al, 2018). There is, evidence of an opposite direction, that is, mental distress preceding an inflammatory response (Wang et al, 2017)
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