Electroconvulsive therapy alters serum cytokine levels and correlates with symptom improvement in patients with acute schizophrenia

Abstract

BACKGROUND

Neuroinflammation is strongly implicated in the pathophysiology of schizophrenia. Key inflammatory markers including tumor necrosis factor-alpha (TNF-α), which modulates neuronal survival and synaptic transmission; interleukin (IL)-8, a neutrophil chemoattractant involved in synapse modulation; and IL-18, which regulates neuronal plasticity and cognitive processes, show distinct alterations in acute schizophrenia. Electroconvulsive therapy (ECT) demonstrates efficacy in acute schizophrenia, yet its effects on these specific inflammatory pathways remain unclear.

AIM

To investigate the effects of ECT on serum cytokine levels and their association with clinical symptoms in acute schizophrenia.

METHODS

Seventy-seven patients with acute schizophrenia (first-episode or relapsed after 4 weeks medication discontinuation, diagnosed per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) receiving antipsychotic treatment and 55 well-matched healthy controls were recruited. Groups were matched for age, sex, smoking status, and body mass index. Serum TNF-α, IL-8, and IL-18 were measured using Luminex technology. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Both PANSS and cytokines were remeasured after 8-10 ECT treatments at 48-hour intervals.

RESULTS

Compared to controls, patients exhibited significantly higher serum concentrations of TNF-α (t = 5.445, P < 0.001) and IL-8 (t = 9.612, P < 0.001) but lower IL-18 (t = -10.007, P < 0.001). ECT resulted in significant elevation of IL-8 and IL-18 levels (t = -3.188, P = 0.002; t = -4.682, P < 0.001, respectively), while TNF-α showed no significant change (t = -1.830, P = 0.071). Before ECT, the serum TNF-α concentration positively correlated with the PANSS general psychopathology score (r = 0.251, P = 0.028) and that of IL-8 negatively correlated with the PANSS negative symptom score (r = -0.250, P = 0.028). However, after ECT, the serum IL-8 concentration negatively correlated with the PANSS general psychopathology score (r = -0.320, P = 0.005). In ECT responders, the post-ECT serum IL-8 concentration positively correlated with a reduced PANSS positive symptom score (r = 0.414, P = 0.001).

CONCLUSION

ECT may mitigate the clinical symptoms of acute schizophrenia through modulation of inflammatory signaling.

Keywords: Electroconvulsive therapy; Schizophrenia; Tumor necrosis factor-α; Interleukin-8; Interleukin-18; Treatment response

Core Tip: Compared to healthy controls, acute schizophrenia patients exhibited significantly higher serum tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-8 levels but lower IL-18 levels. After electroconvulsive therapy (ECT), serum IL-8 and IL-18 concentrations increased significantly, while TNF-α remained unchanged. Before ECT, TNF-α positively correlated with Positive and Negative Syndrome Scale general psychopathology scores, while IL-8 negatively correlated with negative symptom scores. After ECT, IL-8 negatively correlated with general psychopathology scores. In ECT responders, post-treatment IL-8 levels positively correlated with improvements in positive symptoms. The study suggests ECT may ameliorate clinical symptoms of acute schizophrenia by modulating inflammatory signaling pathways, particularly IL-8 signaling.