A pro-inflammatory phenotype has been related to psychotic disorders. The neutrophil-lymphocyte ratio (NLR) is an accessible biomarker that could be helpful to characterize this systemic inflammation state. This study evaluated the NLR in a cohort of 310 subjects with a first episode of psychosis (FEP) and a matched group of 215 healthy controls, recruited in 16 Spanish centers participating in the PEPs Project. We investigated the NLR measures over 2 years in a prospective, naturalistic study. At baseline, the FEP group showed a significant higher mean NLR compared to the control group (1.96 ± 1.11 vs 1.72 ± 0.74, P = 0.03). These ratio differences between groups grew at the 24 months follow-up visit (2.04 ± 0.86 vs 1.65 ± 0.65, P < 0.001). Within the FEP group, there were no significant differences in NLR across the follow-up visits, between genders or diagnosis groups (affective vs nonaffective). NLR values did not correlate with the Positive and Negative Symptoms Scale scores. The group of patients who did not reach remission criteria at the end of the study showed a significant higher NLR than those who remitted (2.1896 ± 0.85 vs 1.95 ± 0.87, P = 0.042). A significant correlation between antipsychotic doses and NLR was found at the two-years follow-up visit (r=0.461, P < 0.001). Our results highlight the existence of an underlying predisposition of FEP patients to present an increased mean NLR. The use of NLR in clinical practice could be helpful to identify this inflammatory imbalance.

There is some consistency in previous EEG findings that patients with schizophrenia have increased resting-state cortical activity. Furthermore, in previous work, we have provided evidence that there is a deficit in the modulation of bioelectrical activity during the performance of a P300 task in schizophrenia. Our hypothesis here is that a basal hyperactivation would be related with altered ability to change or modulate cortical activity during a cognitive task. However, no study so far, to the best of our knowledge, has studied the association between resting-state activity and task-related modulation. With this aim, we used a dual EEG paradigm (resting state and oddball task for elicitation of the P300 evoked potential) in a sample of patients with schizophrenia (n = 100), which included a subgroup of patients with first episode psychosis (n = 30), as well as a group of healthy controls (n = 93). The study measures were absolute power for resting-state; and spectral entropy (SE) and connectivity strength (CS) for P300-task data, whose modulation had been previously found to be altered in schizophrenia. Following the literature on P300, we focused our study on the theta frequency band. As expected, our results showed an increase in resting state activity and altered task-related modulation. Moreover, we found an inverse relationship between the amount of resting-state activity and modulation of task-related activity. Our results confirm our hypothesis and support the idea that a greater amount of resting theta-band synchrony could hamper the modulation of signal regularity (quantified by SE) and activity density (measured by CS) during the P300 task performance. This association was found in both patients and controls, suggesting the existence of a common mechanism and a possible ceiling effect in schizophrenia patients in relation to a decreased inhibitory function that limits their cortical reactivity to the task.

C-reactive protein (CRP) and inflammatory ratios have been proposed to study immune dysregulation in schizophrenia. Nevertheless, links between CRP and inflammatory ratios in acute SCZ inpatients have been understudied. This study investigated the relationship between CRP and inflammatory ratios (Neutrophil-Lymphocyte Ratio [NRL], Platelet-Lymphocyte Ratio [PLR], Monocyte-Lymphocyte ratio [MLR] and Basophil-Lymphocyte Ratio [BLR]) in a total of 698 acute SCZ inpatients; and analysed how this relationship is affected by sex and type of episode. CRP correlated with NLR (r_s = 0.338, p < 0.001), PLR (r_s = 0.271, p < 0.001) and MLR (r_s = 0.148, p < 0.001) but not with BLR (r_s = 0.059, p = 0.121). Multiple lineal regression analysis showed that high levels of NLR, MLR and PLR but not BLR were independently associated with high CRP levels. No sex-related variations were found. Significant associations were maintained for NLR and MLR in first-episode and multiepisode SCZ, although the strength of the association was stronger in multiepisode SCZ. Again, no sex-related differences were found in these associations. In conclusion, inflammatory ratios were low to moderately associated with CRP in acute SCZ inpatients. NLR and multiepisode SCZ showed the highest associations with CRP. Future studies should consider inflammatory ratios not as a substitute for CRP but as a complementary biomarker.