Investigation of the relationship between neurocognitive and social cognitive functions and peripheral inflammatory markers in patients with schizophrenia

Introduction

Schizophrenia is a chronic neuropsychiatric disorder characterized by multifaceted impairments in thought, perception, and behavior, leading to profound functional disability (1). Beyond classical positive and negative symptoms, neurocognitive and social cognitive deficits are now recognized as core, intrinsic features of the illness. Meta-analytic evidence confirms that these impairments emerge from the earliest stages and constitute a stable component of its pathology (2, 3). Recent research underscores that both neurocognitive and social cognitive abilities are robust predictors of long-term functional outcomes. Emerging evidence suggests that peripheral inflammation—reflected by markers such as the Neutrophil-to-Lymphocyte Ratio (NLR)—may play a role in modulating these cognitive processes (4). However, systematic investigations examining the relationship between systemic inflammatory markers and distinct social cognitive domains, such as Theory of Mind (ToM) and facial emotion recognition, remain scarce (5).

Aims

The primary aim of this study is to evaluate the predictive impact of peripheral inflammatory markers—specifically the Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Monocyte-to-Lymphocyte Ratio (MLR)—on neurocognitive and social cognitive performance in clinically stable patients diagnosed with schizophrenia.

Methods

This cross-sectional study is being conducted at Marmara University Pendik Training and Research Hospital, targeting a sample of at least 52 clinically stable volunteers (aged 18–65) diagnosed with schizophrenia according to DSM-5 criteria. To ensure data reliability, exclusion criteria include active infection within the last month, chronic inflammatory/autoimmune diseases, malignancy, hematological disorders, recent use of steroids or immunosuppressants, clozapine treatment, and recent substance use. Neurocognitive functions are assessed using the Montreal Cognitive Assessment (MoCA). Social cognitive performance is evaluated through a battery consisting of the Reading the Mind in the Eyes Test (RMET), the Dokuz Eylül Theory of Mind Scale (DEZİKÖ), and the Facial Emotion Recognition Test. Clinical symptom severity is documented via PANSS, while inflammatory parameters are calculated from synchronized complete blood count (CBC) results.

Results

Data collection is currently active and ongoing; therefore, findings are categorized as preliminary protocol observations rather than conclusive data. Following the completion of data collection for the target sample size, multiple linear regression analyses will be performed to examine the associations between inflammatory markers and cognitive scores. The analysis plan will control for confounding variables, including age, smoking status, and body mass index, to isolate the specific impact of markers such as NLR on the social cognitive domain.

Conclusions

The outcomes of this research are expected to contribute significantly to understanding the biological underpinnings of cognitive deterioration in schizophrenia. Identifying links between measurable inflammatory markers and cognitive decline may facilitate the development of novel monitoring parameters. This protocol highlights the importance of integrating immunological assessment into psychiatric evaluation to guide personalized treatment strategies and highlight the immune system as a potential therapeutic target.

References

1)Owen MJ, et al. Schizophrenia. Lancet. 2016. 2)Green MF, et al. Nat Rev Neurosci. 2015. 3)Mesholam-Gately RI, et al. Neuropsychology. 2009. 4)Zhou X, et al. Front Psychiatry. 2020. 5)Karahan A, et al. Int J Psychiatry Med. 2024.