Schizophrenia is a chronic mental illness of unknown etiology. A growing and compelling body of evidence implicates immunologic dysfunction as the key element in its pathomechanism. Cytokines, whose altered levels have been increasingly reported in various patient populations, are the major mediators involved in the coordination of the immune system. The available literature reports both elevated levels of proinflammatory as well as reduced levels of anti-inflammatory cytokines, and their effects on clinical status and neuroimaging changes. There is evidence of at least a partial genetic basis for the association between cytokine alterations and schizophrenia. Two other factors implicated in its development include early childhood trauma and disturbances in the gut microbiome. Moreover, its various subtypes, characterized by individual symptom severity and course, such as deficit schizophrenia, seem to differ in terms of changes in peripheral cytokine levels. While the use of a systematic review methodology could be difficult due to the breadth and diversity of the issues covered in this review, the applied narrative approach allows for a more holistic presentation. The aim of this narrative review was to present up-to-date evidence on cytokine dysregulation in schizophrenia, its effect on the psychopathological presentation, and links with antipsychotic medication. We also attempted to summarize its postulated underpinnings, including early childhood trauma and gut microbiome disturbances, and propose trait and state markers of schizophrenia.

Background: Studies have shown that there are deviations in the results of peripheral blood counts, which lead to increased values of the neutrophils-to-lymphocytes ratio (NLR) in schizophrenia. Antipsychotic drugs have proven to lower the levels of pro-inflammatory cytokines and a growing number of studies indicate a similar effect on NLR values. Methods: We identified inpatients with schizophrenia and collected data of NLR at the beginning (NLR₁) and end (NLR₂) of hospitalization, the status of antipsychotic medication on admission and potential confounding factors. In the statistical analysis, we applied a linear mixed model. Results: After the inclusion and exclusion process the records of 40 patients (n_p = 40) and 71 hospitalizations (n_h = 71) were analyzed. We found that in the group of antipsychotics-naive patients, the NLR₁ were significantly higher than the NLR₂ values. Such a difference did not occur in the case of non-antipsychotics-naïve patients. Age and the diagnosis of hypothyroidism influenced the value of change in NLR from the beginning to the end of hospitalization in a given patient (ΔNLR). Conclusions: The study confirmed the lowering effect of antipsychotics on NLR values in psychosis. The NLR may potentially be a tool for assessing response to treatment with antipsychotics.

Background/Objectives: Borderline personality disorder (BPD) is a serious psychiatric condition characterized by affective instability, impulsivity, and self-harming behaviors. Increasing evidence suggests that epigenetic mechanisms, especially DNA methylation, may mediate the interaction between genetic susceptibility and adverse environmental factors. This systematic review aimed to synthesize available findings on DNA methylation in BPD, including candidate gene studies and epigenome-wide association studies (EWAS). Methods: We conducted a systematic search of PubMed, Embase, and Scopus databases following PRISMA guidelines. Eligible studies (N = 19) included original research examining DNA methylation in individuals with BPD, assessed either through candidate gene approaches or genome-wide platforms. Data were extracted regarding study design, sample characteristics, psychometric instruments, genes, CpG sites analyzed, and main findings. Results: Inconsistent associations were found between BPD and altered methylation of several candidate genes, such as NR3C1, FKBP5, BDNF, DRD2, HTR2A, and COMT. Differential methylation was often linked to early-life adversities and symptom severity. EWAS also identified new loci, including APBA3, MCF2, PXDN, and OPRK1. Across studies, methodological heterogeneity and small sample sizes limited definitive conclusions. Conclusions: Evidence for DNA methylation alterations in BPD is mixed, and current findings do not allow firm conclusions about their mechanisms or clinical relevance. Larger and longitudinal studies are required to clarify whether these epigenetic changes contribute meaningfully to BPD.