In recent years, the complex interplay between the immune system and psychiatric disorders has garnered significant attention, unveiling potential pathways that may contribute to symptom manifestation and disease progression. Among psychiatric illnesses, schizophrenia—a condition marked by profound disturbances in thought, perception, and behavior—has particularly intrigued researchers exploring the immune system’s role. A groundbreaking study published in BMC Psychiatry in 2025 sheds new light on this dynamic, focusing on the sex-specific associations between inflammatory markers and symptom severity in schizophrenia.
This innovative research centers around two inflammatory indices: the Neutrophil-Percentage-to-Albumin Ratio (NPAR) and the Neutrophil-to-Lymphocyte Ratio (NLR). Both markers, derived from routine blood tests, reflect systemic inflammation and have been linked to various medical conditions, including psychiatric disorders. What sets this study apart is its investigation into how these markers relate differently to the positive and negative symptoms of schizophrenia in males and females, a nuance often overlooked in prior research.
The background of this study highlights the biological principle that sex differences significantly influence immune responses. Males and females exhibit divergent immunological profiles, which may impact how systemic inflammation interacts with brain function and psychiatric symptoms. Given this context, the authors hypothesized that NPAR and NLR would demonstrate differential associations with the severity of schizophrenia symptoms based on sex—a hypothesis that their findings strongly support.
Data for the study were meticulously gathered from 217 patients with schizophrenia of Han Chinese ethnicity, comprising 108 males and 109 females admitted between January 2023 and March 2025. This retrospective design enabled the collection of comprehensive clinical and laboratory data, including neutrophil percentages, absolute neutrophil and lymphocyte counts, and albumin levels. These parameters were instrumental in calculating the NPAR and NLR scores for each patient.
Symptom severity was evaluated using two well-established scales: the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS). Positive symptoms include hallucinations and delusions, whereas negative symptoms reflect deficits such as emotional withdrawal and lack of motivation. These measures provided a robust framework for correlating inflammatory markers with clinical manifestations.
Strikingly, the results revealed a sex-dependent pattern of association. In male patients, the NLR was positively correlated with the intensity of positive symptoms, suggesting that heightened neutrophil activity relative to lymphocytes may exacerbate psychotic features such as delusions and hallucinations. Conversely, in female patients, the NPAR demonstrated a significant positive association with negative symptoms—implying that the balance between neutrophil percentage and albumin levels might influence the severity of emotional and motivational deficits uniquely in women.
Further analysis uncovered significant interaction effects between sex and the inflammatory markers on the severity of both symptom domains. This suggests that the immune-inflammatory axis’s influence on schizophrenia symptomatology is modulated by biological sex, underscoring the necessity of sex-specific considerations in both research and clinical practice.
This pioneering study’s implications are profound for the future of personalized psychiatry. The distinct inflammatory profiles linked to symptom type and sex could pave the way for individualized treatment strategies, potentially leveraging anti-inflammatory interventions tailored differently for males and females. Moreover, routine blood tests assessing NPAR and NLR could become valuable biomarkers in monitoring disease severity and treatment response.
Beyond clinical applications, the research points to the broader importance of understanding neuroimmune interactions in psychiatric disorders. The immune system’s bidirectional communication with the brain involves complex mechanisms that influence neurodevelopment, neurotransmission, and behavioral outputs. Unraveling sex-specific pathways in this communication enhances our comprehension of schizophrenia’s heterogeneity.
The choice of focusing on NPAR and NLR presents practical advantages. These markers are easily accessible, inexpensive, and routinely measured in clinical settings, making them feasible tools for widespread use. Their incorporation into psychiatric assessments could augment traditional clinical observations with objective biological data, ultimately improving diagnostic accuracy and therapeutic monitoring.
Despite its retrospective nature, the study’s well-defined ethnic cohort and rigorous methodology lend credibility to its findings. Future investigations are warranted to validate these results across different ethnic groups and prospective designs, as well as to elucidate the molecular mechanisms underpinning these sex-specific immune interactions.
In summary, this landmark study published in BMC Psychiatry illuminates the nuanced relationships between systemic inflammation markers and schizophrenia symptoms, contingent upon biological sex. It challenges the convention by emphasizing that males and females may experience and biologically respond to schizophrenia differently, urging the psychiatric community to integrate sex as a critical factor in research and treatment paradigms.
As the understanding of psychiatric disorders evolves beyond neurotransmitter dysfunction alone, studies like this spotlight the immune system’s vital role and open avenues for innovative approaches to mental health disorders. The journey toward personalized psychiatry is complex, but integrating immunological insights holds promising potential to transform outcomes for millions affected by schizophrenia worldwide.
Subject of Research:
Sex-specific associations between inflammatory markers, specifically Neutrophil-Percentage-to-Albumin Ratio (NPAR) and Neutrophil-to-Lymphocyte Ratio (NLR), and the severity of positive and negative symptoms in schizophrenia patients.
Article Title:
Sex-specific associations between Neutrophil-Percentage-to-Albumin Ratio(NPAR) and Neutrophil-to-Lymphocyte Ratio (NLR) with positive and negative symptoms in schizophrenia
Article References:
Zhu, Y., Ren, J. & Fu, Z. Sex-specific associations between Neutrophil-Percentage-to-Albumin Ratio(NPAR) and Neutrophil-to-Lymphocyte Ratio (NLR) with positive and negative symptoms in schizophrenia. BMC Psychiatry 25, 873 (2025). https://doi.org/10.1186/s12888-025-07373-3
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