Association of Serum SOCS3 and Inflammatory Marker Levels With Cognitive Function in First-Episode Schizophrenia

Accumulating evidence suggests that dysregulated inflammatory signalling pathway plays a crucial role in the development and pathogenesis of clinical features in schizophrenia. SOCS3, a key regulator of inflammatory signalling pathways, has been implicated in this process. However, the complicated association between SOCS3 function and clinical features in unmedicated first-episode schizophrenia (SCZ) remains poorly understood. While increased levels of systemic inflammatory markers, including C-reactive protein (CRP) and proinflammatory cytokines like IL-6 and IL-1β, have been negatively linked to severity of negative and mood symptoms in SCZ patients, the levels of systemic inflammatory markers cytokines levels neurocognitive function in SCZ warrants further investigation. The primary hypotheses of this study are as follows: (1) The levels of SOCS3 and systemic inflammatory cytokines levels could differentiate between individuals with first-episode SCZ and healthy controls. (2) Patients with first-episode SCZ exhibit significantly lower cognitive function and executive abilities compared to healthy controls. (3) Dysregulated SOCS3 pathways contribute to cognitive impairment in first-episode SCZ.

A total of 93 patients diagnosed with first-episode SCZ and 60 healthy controls were recruited for the current study. The serum levels of CRP, IL-6, IL-1β and SOCS3 were determined with ELISA. Clinical symptoms in SCZ patients were evaluated using the PANSS scale and Stroop test, while cognitive function in the healthy control group were assessed solely using the Stroop test. Statistical analyses were performed with adjustments for age and gender as covariates.

Compared to healthy controls, individuals with first-episode SCZ exhibited significantly decreased serum SOCS3 levels (p < 0.05) and elevated IL-6 levels (p < 0.05), while no significant differences in CRP or IL-1β levels (p > 0.05) were observed between the two groups. In the Stroop test, the SCZ group demonstrated prolonged response times (One word time, One colour time, word-Color time and Color-Word time) and increased error rates (One word errors, One colour errors, Word-Colour errors and Colour-Word errors) compared to healthy controls, with all differences reaching statistical significance (p < 0.05). Serum SOCS3 levels were negatively correlated with PANSS cognitive subscale scores in the SCZ group, whereas IL-6 levels showed a positive correlation with one-colour time and one-colour errors in the Stroop test. The predictive value of serum SOCS3 for SCZ was determined by an AUC of 0.832, surpassing that of IL-6 (AUC = 0.789).

The current findings along with previous studies support the immune dysfunction plays a potential role in development of SCZ. Notably, alteration in peripheral levels of SOCS3 and IL-6 highlighting their potential application for early intervention for first episode SCZ and these changes are further associated with cognitive dysfunction. Moreover, SOCS3 demonstrated superior sensitivity in predicting SCZ, underscoring the importance of further investigating its role in SCZ pathogenesis and exploring novel therapeutic interventions.