Interrelationships among oxidative stress, niacin response, cognition, and symptoms in chronic schizophrenia: a case-control study

Abstract

Background

A growing body of evidence implicates oxidative stress in the pathophysiology of schizophrenia. This study aimed to analyze the pairwise correlations among the four variables in patients with schizophrenia: oxidative stress (lipid peroxidation), the niacin skin response, cognitive function, and clinical symptoms.

Methods

This cross-sectional observational case-control study included 40 patients with chronic schizophrenia and 40 matched healthy controls. Plasma lipid peroxidation (LPO) levels, the niacin skin flush response, and cognitive function were assessed in all participants. Symptom severity in patients was evaluated using the Positive and Negative Syndrome Scale (PANSS). Regression analyses were conducted to examine the relationships among LPO levels, the niacin skin response, clinical symptoms, and cognitive function.

Results

Plasma LPO levels were significantly higher in the patient group than in the healthy controls, whereas cognitive function and the niacin skin flush response were significantly reduced. Within the patient group, correlation analysis revealed that LPO levels were negatively associated with the total flush area at concentrations 1 and 2 measured at 5 min. Furthermore, significant negative correlations were observed between cognitive function and clinical symptoms across multiple dimensions (all P < 0.05).

Conclusion

Patients with chronic schizophrenia exhibited elevated oxidative stress (LPO), impaired cognitive function, and attenuated niacin skin flush response. Importantly, oxidative stress showed a negative correlation with the niacin response, while cognitive performance was also negatively correlated with clinical symptom severity. These findings suggest that oxidative stress may be involved in the pathophysiological process of schizophrenia, and that the attenuated niacin skin response could serve as a measurable marker of dysfunction in the peripheral inflammation-oxidative stress axis.

Clinical trial

Not applicable.

Introduction

Schizophrenia, a severe mental disorder, affects approximately 1% of the global population—equivalent to around 24 million individuals—and is ranked among the 25 most disabling conditions worldwide, with largely consistent incidence and prevalence across different countries [1]. Currently, diagnosis relies primarily on clinical assessment, including symptom presentation, degree of social functioning impairment, and duration of illness. Cognitive impairment is widely recognized as a core symptom of schizophrenia and a major contributor to functional disability; however, existing treatments show limited efficacy in improving cognitive function. Patients exhibit significant overall cognitive deficits, with average scores approximately two standard deviations below those of healthy controls [2]. Cognitive function is directly associated with real-world social outcomes [3, 4], and patients with cognitive impairment demonstrate lower treatment adherence, higher rates of rehospitalization, and longer hospital stays [5, 6]. The validity and reliability of schizophrenia diagnosis remain incompletely resolved, current research remains largely conceptual and theoretical, and the underlying pathophysiological mechanisms are still unclear, which contributes to limitations in clinical intervention.

Research indicates that the etiology of schizophrenia involves multiple factors, such as genetic and environmental components [7, 8], Oxidative stress is also widely recognized as playing a significant role in the pathophysiology of brain disorders. Substantial evidence shows that patients with schizophrenia—including those who have never been treated with antipsychotics—exhibit abnormalities in reactive oxygen species and inflammatory processes [9, 10]. Under normal physiological conditions, the body maintains a balance between oxidation and antioxidant defenses; however, oxidative stress occurs when the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) exceeds the capacity of the antioxidant defense system. A post-mortem anatomical study of individuals with schizophrenia identified alterations in the expression of multiple mitochondrial genes across several independent cohorts. In particular, mitochondrial dysfunction in oligodendrocytes may contribute to myelin pathology and underlie impaired brain connectivity [11]. Lipid peroxidation (LPO)—regarded as a downstream product of oxidative stress—results from the reaction of unsaturated fatty acid chains with free radicals or ROS, leading to the formation of lipid peroxides [12]. Under normal conditions, LPO levels remain very low; however, under pathological conditions, enhanced lipid peroxidation can elevate LPO concentrations, thereby disrupting the structural and functional integrity of cells and cell membranes, exacerbating pathological damage, and even leading to cell death.

It has been proposed that the niacin skin flush test, which may indirectly reflect cell membrane fatty acid composition, could serve as a potential indicator for various outcome measures in schizophrenia [13, 14]. The mechanism underlying the niacin-induced skin flush involves a coupled process of polyunsaturated fatty acid metabolism and inflammatory signaling. The intensity of the flush response is directly dependent on the total amount of releasable arachidonic acid in cell membranes: an adequate fatty acid reserve facilitates a strong flush, whereas a deficiency results in a diminished response. Additionally, abnormalities in the associated signaling pathways can also lead to altered niacin skin flush reactivity [15]. Niacin, also known as vitamin B3, has been shown to play key roles in multiple metabolic pathways as a precursor of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) [16]. Its derivatives are essential for various detoxification processes, DNA repair, and steroid hormone synthesis. The biochemical action of niacin is mediated through its binding to specific receptors on skin macrophages and epidermal Langerhans cells [17, 18]. Across studies involving different disease stages, phases, and severity levels, patients with schizophrenia consistently exhibit an attenuated cutaneous flushing response to niacin [18–20]. Reduced niacin sensitivity has been associated with greater functional impairment in schizophrenia [21] and has also been linked to altered protein activation, modified protein expression, and inflammatory dysregulation [22]. Research by Yang et al. suggests that abnormalities in arachidonic acid hydrolysis and an imbalance in the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are related to both the pathogenesis of schizophrenia and the attenuated niacin flush response [23]. These findings suggest that a diminished niacin skin flush response may represent an endophenotype in schizophrenia, and could potentially help differentiate schizophrenia from other psychiatric conditions such as depression [17], bipolar disorder [24, 25], and generalized social phobia [26].

Building upon the aforementioned research, we hypothesize that abnormal oxidative stress in patients with schizophrenia may contribute to the emergence of clinical symptoms and cognitive deficits, while the niacin skin flush test could reveal another facet of the disease’s pathological mechanisms. To test this, we recruited patients with chronic schizophrenia to conduct the present study, which aimed to investigate: (1) whether differences exist between patients with schizophrenia and healthy controls in plasma LPO levels, cognitive function, and the niacin skin flush response; (2) whether LPO levels, the intensity of the niacin skin flush response, and cognitive function correlate with the severity of clinical symptoms; and (3) whether LPO levels are correlated with the niacin skin flush response. This study provides preliminary evidence concerning the relationships among the oxidative stress marker LPO, clinical symptom severity, cognitive function, and the niacin skin flush response in patients with chronic schizophrenia.

Subjects and methods

Subjects and assessments

This cross-sectional randomized controlled study recruited participants between November 2021 and May 2022 through advertisement and screening of long-term inpatients from psychiatric hospital. All participants were informed of the study purpose and procedures and provided written informed consent for the use of their data in the research. Sociodemographic and medical history data were collected via face-to-face interviews with participants or their guardians. The patient group consisted of 40 clinically stable patients with chronic schizophrenia who had been hospitalized at Suzhou Guangji Hospital for more than one year, with a total illness duration exceeding two years, and who met the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). General information including sex, age, body mass index (BMI), and medication use was collected through questionnaires; antipsychotic dosages were converted to chlorpromazine-equivalent doses. The severity of clinical symptoms was assessed by two experienced psychiatrists using the Positive and Negative Syndrome Scale (PANSS), with an inter-rater correlation coefficient (r) exceeding 0.8.

Inclusion criteria for the patient group were as follows: (1) age 18–70 years, of Han Chinese ethnicity, and right-handed; (2) hospitalization for more than two years; (3) currently receiving antipsychotic medication with clinical stability maintained for at least 12 months; (4) no use of steroidal or non-steroidal anti-inflammatory drugs within two weeks prior to study initiation; and (5) completion of at least primary education and possession of adequate comprehension ability to respond to questions posed by the researchers.

Exclusion criteria for all included patients were as follows: (1) presence of severe somatic diseases; (2) history of major neurological disorders or intellectual disability; (3) diagnosis of other psychiatric disorders as screened by the Mini-International Neuropsychiatric Interview (MINI); (4) pregnancy or lactation; (5) receipt of electroconvulsive therapy within the six months prior to the study; (6) history of drug, alcohol, or other substance dependence or abuse; and (7) presence of intracranial metal implants.

Forty healthy controls residing in Suzhou were recruited via advertisements and matched to the patient group for age, sex, ethnicity, and body mass index (BMI). All control participants had completed at least primary education and reported no severe systemic illnesses, neurological disorders, learning disabilities, or psychiatric history. Additional exclusion criteria included pregnancy or lactation, use of non-steroidal or steroidal anti-inflammatory drugs within two weeks prior to the study, any history of substance dependence or abuse, and the presence of intracranial metal implants.

All participants were fully informed of the study objectives and procedures and participated voluntarily. To ensure confidentiality, all collected research data were anonymized. The study protocol was approved by the Ethics Committee of Suzhou Guangji Hospital (Approval No. 2019-051), and written informed consent was obtained from all participants or their legal guardians.

Blood sampling and biochemical assays

All participants fasted overnight, and venous blood samples were collected from the antecubital vein between 7:00 and 8:00 a.m. the following morning prior to breakfast. After anticoagulation, the blood was centrifuged at 3000 rpm for 15 min to separate the plasma. The plasma supernatant was then aliquoted and stored at − 80 °C until subsequent batch analysis. Plasma levels of the oxidative stress marker LPO were quantified using a colorimetric assay (Kit No. A106-1, Nanjing Jiancheng Bioengineering Institute). The results are expressed in micromoles per liter (µmol/L).

Niacin skin flush test

The niacin skin response tester used to assess the niacin-induced flush response (Model: TY-Lab-01; Shanghai Tianyin Biotechnology Co., Ltd.) consists of three components: a six-well standard patch, an automatic imaging device, and intelligent image-recognition software (Patent No.: ZL 20211070775.0). Equal volumes of six different concentrations of methyl nicotinate solution (three-fold serial dilutions starting from 60 mmol/L: 60, 20, 6.67, 2.22, 0.74, and 0.25 mmol/L, corresponding to wells 1–6, respectively) were applied to the patch. The patch was placed on the distal part of the participant’s right forearm (well 1), with wells 2–6 aligned sequentially toward the proximal forearm. After 1 min of contact, the patch was removed, and the forearm was fixed in the test device. An automatic imaging system captured photographs of the forearm every 10 s for 10 min, yielding 60 images per participant. Using the intelligent image-recognition software, the area of skin in contact with the methyl nicotinate solution was identified in each image. The image taken at 10 s served as the baseline reference. A total of 59 subsequent images were analyzed for each participant, generating 354 erythema area measurements in total. The software identified and calculated the erythema area for each measurement time point, and the total erythema area across time points was subsequently summarized.

Statistical analysis

All data were analyzed using SPSS version 27.0. Sample size was calculated with GPower version 3.1.9.7, assuming a two-tailed test, an α level of 0.05, a power (1-β) of 0.8, and equal group sizes. Normality of data distribution was assessed using the Shapiro–Wilk test. Continuous variables conforming to a normal distribution are presented as mean ± standard deviation (x ± s) and were compared between groups using independent-samples t-tests; when covariates were included, analysis of covariance (ANCOVA) was applied. Continuous variables not normally distributed are reported as medians, and categorical variables were compared using the χ² test.

To identify independent associations among key variables, partial correlation analyses were performed for all predefined clinical and biological variable pairs, controlling for potential confounders (e.g.sex, years of education). To control for the risk of Type I error due to multiple testing, a strict Bonferroni correction was applied to the P-values of all partial correlation tests. For variable pairs that remained significant after correction, multiple linear regression models were further conducted to evaluate the robustness of the associations after adjusting for relevant confounders. Because these regression analyses were performed to test specific hypotheses derived from the initial stringent screening step, their P-values were not subjected to a second round of Bonferroni correction. All tests were two-tailed, and a P-value < 0.05 was considered statistically significant.

Results

Comparison of demographic and general clinical characteristics between schizophrenia patients and healthy controls

Table 1 presents the demographic and clinical characteristics of the schizophrenia patients and healthy controls. No significant differences were observed between the two groups in terms of sex distribution, age, or BMI; however, patients had significantly fewer years of education than controls. The mean PANSS total score in the patient group was 67.80 ± 14.66, with subscores of 14.45 ± 4.64 for positive symptoms, 18.85 ± 6.42 for negative symptoms, and 34.50 ± 7.36 for general psychopathology. The mean chlorpromazine-equivalent dose was 419.75 ± 163.31 mg.

Table 1.

Demographics of patients with schizophrenia and healthy controls (mean ± SD)

	patients(n = 40)	controls(n = 40)	t/χ²	P
Gender (Male/Female)	21/19	14/26	2.489	0.115a
Age(years)	46.80 ± 7.68	44.45 ± 7.29	1.403	0.165b
BMI(kg/m2)	23.236 ± 1.99	22.754 ± 2.03	1.072	0.287 b
Education(years)	10.90 ± 2.24	13.30 ± 2.54	4.479	< 0.001b
Equivalent dose of chlorpromazine(mg/d)	419.75 ± 163.31
P subscores	14.45 ± 4.64
N subscores	18.85 ± 6.42
G subscores	34.50 ± 7.36
PANSS total score	67.80 ± 14.66

BMI, body mass index

PANSS, positive and negative syndrome scale

^aχ² test

^bStudent’s t-test

Comparison of LPO levels, cognitive function, and niacin skin flush response areas between schizophrenia patients and healthy controls

Because a significant difference in years of education was observed between the patient and control groups, analysis of covariance (ANCOVA) was performed with education as a covariate to control for its potential influence on cognitive scores. The results indicated that education had no significant main effect on any of the RBANS scores except for the language domain (P = 0.031). After adjustment, all cognitive function scores still differed significantly between the two groups (P < 0.05), as detailed in Table 2.

Table 2.

The levels of cognitive function between patients and healthy controls

Variables	patients		controls	t	P
Immediate Memory	75.00 ± 17.58	89.58 ± 14.93		-3.977a	<0.001**
Visuospatial	86.18 ± 16.96	99.23 ± 16.14		-3.526a	<0.001**
Language	85.68 ± 10.46	98.00 ± 8.67		-5.739a	<0.001**
Attention	86.65 ± 14.89	109.35 ± 13.15		-7.228a	<0.001**
Delayed Memory	84.88 ± 17.91	97.85 ± 12.09		-3.797a	<0.001**
RBANS total score	78.95 ± 13.01	98.18 ± 12.12		-6.837a	<0.001**

RBANS: Repeatable Battery for the Assessment of Neuropsychological Status;

^a: ANCOVA test

*: P<0.05;**:P<0.001;

Given that some participants exhibited extremely weak responses at concentration points 4, 5, and 6, making the measurement of erythema areas unfeasible, these values were treated as missing data. To ensure the integrity and accuracy of the quantitative analysis, the total areas corresponding to these three concentration points were excluded from further analysis, as detailed in Table 3.

Table 3.

The area of NSFT and LPO level between patients and healthy controls (x ± s)

Area of NSFT	time	patients	controls	t	P
Concentration 1	5 min	1131.73 ± 514.22	1584.29 ± 437.71	-2.55a	0.013*
	10 min	3378.83 ± 1089.75	4070.81 ± 822.53	-3.20a	0.002*
Concentration 2	5 min	929.39 ± 485.68	1172.17 ± 459.58	-2.29a	0.024*
	10 min	2734.20 ± 1169.64	3317.38 ± 817.92	-2.58a	0.012*
Concentration 3	5 min	638.97 ± 438.91	933.86 ± 483.69	-2.86a	0.06
	10 min	2068.58 ± 1077.85	2759.60 ± 970.91	-3.01a	0.003*
LPO(umol/L)	-	8.159 ± 2.191	4.582 ± 2.373	7.004	<0.001**

NSFT, niacin skin flush test

^a: Student’s t-test

*P<0.05;**P<0.001

Correlation analysis among LPO levels, cognitive function, clinical symptoms, and niacin skin flush area in the patient group

Partial correlation analysis

To examine the independent associations between cognitive function, clinical symptoms, niacin skin flush area, and LPO within the patient group, partial correlation analyses were conducted while controlling for the effects of sex, age, years of education, body mass index (BMI), and antipsychotic dose. As summarized in Table 4, the results revealed a significant negative correlation between the niacin skin response area and the oxidative damage marker (LPO). Additionally, a significant negative association was observed between cognitive function and psychopathological symptoms.

Table 4.

Results of partial correlation analyses among variables in the patient group

Variable 1	Variable 2	Partial r	P
SumArea-Conc1-5 min	LPO	-0.423	0.048*
SumArea-Conc2-5 min	LPO	-0.439	0.036*
Language	N subscores	-0.458	0.016*
RBANS total score	PANSS total score	-0.425	0.032*
RBANS total score	G subscores	-0.454	0.016*

*P<0.05

The analyses described above were performed only within the patient group. We also examined the correlation between LPO and the niacin skin flush area in the control group, and found no significant association (all P > 0.05); these results are not presented.

Exploratory analysis: bidirectional associations between variables

Given the cross-sectional design of this study, the causal direction between the niacin skin response and LPO levels, as well as between cognitive function and clinical symptom severity, cannot be determined. Therefore, exploratory bidirectional regression analyses were performed to examine the robustness of these associations (Table 5). When LPO levels were treated as the dependent variable (Model A), the niacin skin response was a significant independent negative predictor. Conversely, when the niacin skin response served as the dependent variable (Model B), LPO levels also showed a significant negative predictive effect. These mutually consistent results strongly support the existence of a stable negative covariation between the two measures, independent of the included covariates. Furthermore, a significant association was also observed between cognitive function and clinical symptoms in the analyses. Detailed results are presented in Table 5.

Table 5.

Exploratory regression analysis of bidirectional associations between variables

Model Specification (DV ~ IV)	β	t	P	R²/Adj.R2
A: LPO ~ SumArea-Conc1-5 min	-0.360	-2.405	0.022	0.331/0.254
B: SumArea-Conc1-5 min ~ LPO	-0.394	-2.405	0.022	0.266/0.182
A: LPO ~ SumArea-Conc2-5 min	-0.383	-2.501	0.017	0.338/0.263
B: SumArea-Conc2-5 min ~ LPO	-0.396	-2.501	0.017	0.317/0.239
A: Language ~ N subscores	-0.478	-3.219	0.003	0.255/0.170
B: N subscores ~ Language	-0.478	-3.219	0.003	0.255/0.169
A: RBANS total score ~ PANSS total score	-0.461	-2.825	0.008	0.221/0.132
B: PANSS total score ~ RBANS total score	-0.403	-2.825	0.008	0.318/0.240
A: RBANS total score ~ G subscores	-0.508	-3.206	0.003	0.260/0.176
B: G subscores ~ RBANS total score	-0.447	-3.206	0.003	0.350/0.276

DV = Dependent Variable; IV = Independent Variable

Adjusted for age, sex, BMI, years of education, and antipsychotic dose

Discussion

This study demonstrates that patients with chronic schizophrenia exhibit three distinct pathological phenotypes: elevated levels of oxidative stress products (LPO), multi‑domain cognitive impairment, and an attenuated niacin skin flush response. These findings are consistent with a substantial body of previous studies on oxidative stress [27–30], cognitive function [31–33], and niacin response [34–36]. The core discovery of this work lies in revealing two specific internal associations within the same patient cohort: first, a significant negative correlation between the degree of oxidative damage (LPO levels) and the intensity of the niacin‑induced skin flush response (area at 5 min for concentrations 1 and 2); second, a significant negative correlation between cognitive function (RBANS total score, verbal subset) and the severity of clinical symptoms (PANSS total score, negative symptoms, and general psychopathology score). It must be clearly stated that this study did not find a direct association between the oxidative stress marker (LPO) and cognitive function, suggesting that these may represent relatively independent pathological dimensions in this sample.

This study identified a negative correlation between peripheral oxidative stress levels and niacin skin response intensity in patients with chronic schizophrenia. Our results suggest that the attenuated niacin response is related to systemic redox imbalance, a viewpoint consistent with the finding by Yang et al. that a weakened niacin response is associated with antioxidant deficiency [37]. Previous research has shown that niacin can inhibit vascular inflammation by reducing the generation of reactive oxygen species in vascular endothelial cells, thereby decreasing low‑density lipoprotein oxidation and the production of inflammatory cytokines [38]. Moreover, niacin significantly suppresses H₂O₂‑induced upregulation of IL‑6 mRNA, directly blocking the propagation of inflammatory signals in the brain and mitigating local inflammatory damage to neurons. Consequently, the anti‑inflammatory mechanism of niacin is also relevant to the pathological processes of neurodegenerative diseases in the brain [39]. The association observed in our study supports the possibility that the attenuation of the niacin skin response may reflect insufficient efficacy of the endogenous anti‑inflammatory and antioxidant defense system when confronting oxidative stress. The brain meets 90% of its energy demand through aerobic metabolism and is rich in oxidizable unsaturated lipids, rendering it highly sensitive to oxidative stress. Growing evidence indicates that abnormally elevated oxidative stress is associated with neurodegeneration, impaired information processing, cognitive decline, and behavioral abnormalities [38, 40, 41]. Such dysregulation of oxidative stress may play a role in the pathophysiological mechanisms of schizophrenia, and the present study provides further supporting evidence for these conclusions.

The results of this study reconfirm a certain degree of covariation between cognitive deficits and psychopathological symptoms. This association has been widely validated across different research contexts: it has been reported in first‑episode, medication‑naïve patients [42], in patients across clinical subtypes [43], and in studies encompassing both first‑episode and chronic patients [44]. The manifestation of cognitive impairment may evolve with disease stage, presenting as widespread deficits at first episode [45], tending toward relative stability in the chronic phase [46], yet potentially exhibiting accelerated decline in specific domains such as verbal memory in older age [47]. Furthermore, research suggests that alexithymia may mediate the pathway from cognitive deficits to negative symptoms [48]. These findings collectively indicate that the cognition‑symptom relationship is complex and multifactorial, and its specific mechanisms require further in‑depth exploration.

It is noteworthy that, unlike some previous studies, this research did not find a significant correlation between the niacin skin flush response and clinical symptoms. Prior studies have indicated that reduced niacin sensitivity is significantly associated with greater overall functional impairment in schizophrenia [21]; Sui et al. [49]found a negative correlation between niacin‑induced skin flush sensitivity and PANSS total score; Ju et al. [50] also observed that the subtype with an attenuated niacin response in first‑episode psychosis presented with more severe negative symptoms and cognitive impairment. Our findings are closer to the report by Tavares et al. [51], which may reflect heterogeneity in study populations, illness duration, and measurement methodologies.

Synthesizing the data from this study, we propose that in chronic schizophrenia, the association between niacin response and LPO and the association between cognitive function and clinical symptoms may represent two pathological dimensions that are internally closely linked but lack direct correlational data with each other. Both dimensions may be driven by earlier‑stage or higher‑order pathological processes. According to the neurodevelopmental hypothesis of schizophrenia, abnormalities during critical early‑life stages (e.g., impaired myelination, synaptic pruning) may establish a vulnerability foundation for the disorder [10]. The brain is highly sensitive to oxidative damage due to its high metabolic rate and lipid‑rich composition, and excessive oxidative damage can also interfere with neurodevelopment and plasticity, affecting higher‑order functions [52]. Therefore, oxidative stress may be an important node in the pathological network of schizophrenia; however, data from this study suggest that it may not be the direct pathway linking peripheral inflammatory abnormalities to central cognitive symptoms.

This study has several limitations. First, the included patients were in the chronic stage of illness, differing from those with acute or first‑episode schizophrenia. The clinical symptoms and oxidative stress levels in chronic patients may be influenced by various factors such as age, duration of hospitalization, diet, and long‑term medication. Future research needs to include more individuals at different stages of schizophrenia for comparative analysis. Second, this study examined a limited number of oxidative stress markers; future analyses should incorporate more oxidative stress biomarkers or cytokines. Third, the cross‑sectional design cannot establish causal relationships between oxidative stress markers and PANSS scores or niacin indicators; longitudinal studies are needed to further explore this possibility.

Conclusion

In summary, our preliminary findings indicate that cognitive function correlates with the severity of clinical symptoms in patients with schizophrenia, and that the oxidative stress marker LPO is associated with the niacin skin flush area. These results further support the view that oxidative stress may be involved in the abnormal niacin skin flush response in schizophrenia, suggesting a potential link between oxidative stress and the pathophysiological processes of the disorder. Future research should validate these findings by expanding sample sizes, including more oxidative stress markers, and enrolling patients at different stages of disease progression. We also hope this study holds clinical application value, contributing to the improvement of treatment and rehabilitation for patients with schizophrenia.

Author contributions

Lihua Chen wrote the manuscript; Xiaobin Zhang was responsible for study design; Jiyong He and Ying Yuan performed the statistical analysis; Qing Tian was responsible for performing the clinical rating; Lihua Chen and Chao Sun were responsible for recruiting the patients and collecting the samples. All authors have contributed to and have approved the final manuscript.

Funding

The study was financially supported by the Suzhou Clinical Medical Center for Mood Disorders (grant no. Szlcyxzx202109), Suzhou Key Laboratory (grant no. SZS2024016), Suzhou Multicenter Clinical Research Project on Major Diseases (grant no. DZXYJ202413, MR-32-25-054378),Suzhou Municipal Key Project for Applied Basic Research in Medical and Health Sciences(SYW2025022). The funding sources of this study had no role in study design, data collection and analysis, decision to publish, or preparation of the article.

Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethical approval and consent to participate

We declare that all experiments on human subjects were conducted in accordance with the Declaration of Helsinki and that all procedures were carried out with the adequate understanding and written consent of the subjects. All experimental protocols were approved by the Ethics Committee of The Affiliated Guangji Hospital of Soochow University. Informed consent was obtained from all the participants and/or their legal guardians. All methods were carried out in accordance with relevant guidelines and regulations.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.