Peripheral blood complement factor C3 as a biomarker of clinical efficacy in patients with first-episode schizophrenia before and after treatment

doi:10.21203/rs.3.rs-4680675/v1

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Peripheral blood complement factor C3 as a biomarker of clinical efficacy in patients with first-episode schizophrenia before and after treatment

https://doi.org/10.21203/rs.3.rs-4680675/v1

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Objective

To observe the changes of serum complement factor before and after treatment in patients with first-episode schizophrenia, the main purpose is to find the biomarkers of clinical efficacy based on serum complement factor.

Methods

A total of forty patients with first-episode schizophrenia from Hefei Fourth People's Hospital from July 2022 to December 2023 were selected as the study group after being treated with a single anti-schizophrenia drug aripiprazole for 4 weeks. The study group consisted of a before treatment group and a after treatment group. 40 healthy volunteers in physical examination center were selected as control group. The levels of serum complement factors C1, C2, C3, C4 and CH50 in the study group and the control group were detected. Patients in the study group were evaluated with positive and negative Symptom scales (PANSS). Pearson's correlation test was used to assess the relationships the levels of serum complement factors C1, C2, C3, C4 and CH50 and the reduction rate of PANSS score.

Results

Compared with before treatment group, the PANSS total score, positive symptom score and negative symptom score were decreased after treatment group, and the difference was statistically significant (P < 0.05). The levels of serum C1, C2, C3, C4 and CH50 in control group were lower than those in before treatment group, with statistical significance (P < 0.05). After treatment with aripiprazole, the serum levels of C1, C2, C3 and C4 were significantly lower than those in the before treatment group, but the level of CH50 was significantly increased. Pearson correlation analysis showed that the serum C3 level was negatively correlated with the reduction rate of PANSS total score, the reduction rate of positive symptoms score and the reduction rate of negative symptoms score in the before treatment group (r=-0.467, -0.476, -0.367, all P < 0.05). The change of serum C3 level before and after treatment was negatively correlated with the reduction rate of PANSS total score, the reduction rate of positive symptom score and the reduction rate of negative symptom score (r=-0.458, -0.435, -0.420, all P < 0.05).

Conclusion

The serum levels of C1, C2, C3, C4 and CH50 in patients with first-episode schizophrenia are higher than those in healthy patients. After aripiprazole treatment, the serum levels of C1, C2, C3 and C4 are decreased, and the CH50 level is further increased. Changes in serum C3 levels before and after treatment in patients with first-episode schizophrenia can be used as a biomarker to predict clinical efficacy.

First episode schizophrenia

Aripiprazole

Before and after treatment

Serum complement factor

PANSS

Efficacy

schizophrenia (SCZ) is a serious mental disorder with high disability rate and high social burden. The disease has a long course and is prone to relapse, which causes a heavy burden to the family and society[1, 2]. According to the World Health Organization, the burden of mental illness will rise to a quarter of the total burden of disease by 2020, and its lifetime prevalence will be close to 1%[3, 4]. At present, the pathogenesis of schizophrenia has not been fully elucidated, and one of the new theories proposes that the immune dysfunction of the central nervous system may be related to the occurrence of the disease[5, 6].

In recent years, more and more studies have shown that immune dysfunction may be one of the important pathogenesis of schizophrenia[7, 8]. At the same time, some scholars have shown that there are disorders of the complement system in patients with schizophrenia[9]. The complement system is an important part of the immune system and is involved in the neurodevelopmental process of the brain[10]. Complement factors C1, C2, C3, and C4 play key roles in promoting the solubility and clearance of immune complexes[11]. Importantly, there is growing evidence that dysregulation of C1, C2, C3, and C4 is one of the risk factors for SCZ[12]. In addition, serum 50% hemolytic complement (CH50) activity is the most commonly used method for screening patients for the functional activity of serum classical complement pathways[13].At present, there is no uniform conclusion on the changes in the levels of complement factors C1, C2, C3, C4 and CH50 in patients with schizophrenia[14, 15]. Whether these complement factors can be used as objective and reliable biological indicators for the diagnosis, prognosis, and clinical efficacy assessment of patients with schizophrenia remains unclear.

Therefore, we investigated the changes of serum complement factors C1, C2, C3, C4 and CH50 levels in patients with first-episode schizophrenia before and after treatment, with the aim to discover and identify serum complement factor-based biomarkers of clinical efficacy based on serum complement.

Study design and participants

In this study, patients with first-episode schizophrenia were selected from Hefei Fourth People's Hospital from July 2022 to December 2023. The following were the general requirements for inclusion: (1) meeting the diagnostic criteria for schizophrenia in the International Classification of Diseases 10th Edition (ICD-10); (2)There was no antipsychotic medication or physical therapy such as electro convulsion or transcranial magnetic stimulation before enrollment; (3) being between the ages of 18 and 65. The exclusion criteria were as follows: (1) Mental illness, drug or alcohol abuse, or other severe physical diseases; (2) Female pregnancy, lactation period; (3) In the case of tissue injury and acute inflammation, anti-inflammatory drugs and immunosuppressants are used. We also recruited 40 healthy controls at the same time, all of whom matched the patients in age, gender, and ethnicity in frequency. This study was approved by the Ethics Committee of Hefei Fourth People's Hospital, with registration number HFSY-IRB-PJXQR-2,022,001, and carried out in accordance with the Declaration of Helsinki. All participants provided signed informed consent.

Medication regimen

The first-episode schizophrenia patient was treated with antipsychotic drug aripiprazole (Shangyao Pharmaceutical, Shanghai, China, 5 mg, Lot number: C0612022017) after admission. The initial dose was 5mg/day, then gradually increased to 15-30mg/ day according to the patient's condition, and the dose was maintained for 6 weeks.

Clinical assessment

The improvement of schizophrenia symptoms before and after treatment was compared in patients with first-episode schizophrenia. Positive and negative Symptom Scale (PANSS) score was used to evaluate the patients' condition. The severity of psychiatric symptoms was measured by the Brief Psychiatric Rating Scale (BPRS) and the Negative/Positive Symptom Scale[16, 17]. The BPRS score consists of 18 items that are used to assess psychopathological variables. The negative symptom score provides a comprehensive assessment of negative SCZ symptoms, which includes 24 questions. The positive symptom score has 35 questions and is used to assess positive symptoms of SCZ[18]. The clinical effect was evaluated by the reduction rate of score before and after treatment. Reduction rate in score = (before treatment score − after treatment score)/ before treatment score X 100%, the response rate was defined as a reduction rate in score ≥ 30%[19].

Blood sample collection and measurement of serum complement factors

Blood collection before treatment and after 4 weeks of aripiprazole maintenance dose treatment. blood samples were taken from the participants' veins between 7am and 8am and immediately centrifuged at 1200g at 4°C for 10 minutes. Serum samples were extracted from the supernatant. All samples are stored at -80°C until tested. In addition, the timing of the collection of control samples matched that of the SCZ group as much as possible. Using commercially available enzyme-linked immunosorbent assay (ELISA) kit (Jianglai Bio, Shanghai, China), Serum complement factors C1(catalog number: JL24020003), C2(catalog number: JL24040001), C3(catalog number: JL23110001), C4(catalog number: JL24040001) and CH50(catalog number: JL24020001) were detected according to manufacturer's instructions.

Statistical analysis

SPSS (version 17.0; IBM Corp., Armonk, NY, USA) was used to analyze the data. The data are expressed as mean ± standard deviation (SD), and the P value for statistical significance was set at 0.05. The continuous variable normality distribution was derived from the one-sample Kolmogorov-Smirnov test. Differences in gender were determined using chi-square tests. The comparison of PANSS scale scores, age, BMI, and the levels of C1, C2, C3, C4 and CH50 between the two groups were conducted by independent sample t test. Pearson analyzed between serum levels of C1, C2, C3, C4, CH50 and the change value of C1, C2, C3, C4, CH50 level before and after treatment correlated with the reduction rate of PANSS score in patients with first-episode schizophrenia.

Differences in demographic and clinical characteristics of participants

There were no significant differences in age (t = 1.580, P = 0.118), sex (χ2 = 0.741, P = 0.389) and BMI (t = 0.856, P = 0.395) between patients with before treatment group and control group, as shown in Table 1. Compared with the before treatment group, the PANSS total score, positive symptom score, negative symptom score and BPRS symptom score of patients after treatment group all decreased, with statistical significance (Table 2, P < 0.05).

Table 1

Demographic comparison between before treatment group and control group (n = 40, ± s)
Variables	before treatment	control	t/χ²	P
Age	33.45 ± 11.92	37.43 ± 10.55	1.580	0.118
Sex (male/female)	13/27	12/28	0.741	0.389
BMI(kg/m²)	22.11 ± 3.66	22.77 ± 3.32	0.856	0.395

Table 2

Comparison of PANSS scores between before treatment group and after treatment group (n = 40, ± s)
Variables	before treatment	after treatment	t	P
PANSS total score	102.70 ± 31.63	46.88 ± 21.12	9.282	< 0.001
positive symptom score	27.73 ± 11.57	14.43 ± 8.98	5.743	< 0.001
negative symptom score BPRS symptom score	40.53 ± 22.86 34.45 ± 7.78	22.90 ± 14.46 9.55 ± 3.17	4.121 18.748	< 0.001 < 0.001

Comparative analysis of serum complement factors between patients with before treatment group and control group

Table 3 shows the serum complement factor levels of control group and before treatment group. Patients with before treatment group had higher levels of C1, C2, C3, C4, and CH50 than control group (Table 3, all P < 0.05).

Table 3

Comparative analysis of serum complement factors between control group and before treatment group (n = 40, ± s)
Variables	control	before treatment	t	P
C1 (mg/L)	128.16 ± 41.72	171.64 ± 59.82	-3.771	0.000
C2 (mg/L)	225.60 ± 45.19	271.81 ± 127.96	-2.153	0.036
C3 (mg/L)	472.67 ± 118.04	561.39 ± 201.64	-2.402	0.019
C4 (mg/L)	320.56 ± 70.69	371.50 ± 114.79	-2.390	0.020
CH50 (µg/L)	25.02 ± 6.83	43.60 ± 29.44	-3.887	0.000

Comparative analysis of serum complement factors between patients with after treatment group and control group

Table 4 shows that the levels of serum C1 and CH50 in the control group were lower than after treatment group (P < 0.05). The levels of serum C2, C3 and C4 in the control group were higher than after treatment group, and the differences in serum C2 and C3 levels were statistically significant (P < 0.05), while the differences in C4 levels were not statistically significant (P > 0.05). In conclusion, treatment with antipsychotic drug aripiprazole can reduce the levels of serum C1, C2, C3 and C4, and increase the levels of CH50.

Table 4

Comparative analysis of serum complement factors between control group and after treatment group (n = 40, ± s)
Variables	control	after treatment	t	P
C1 (mg/L)	128.16 ± 41.72	149.71 ± 36.99	2.445	0.017
C2 (mg/L)	225.60 ± 45.19	107.96 ± 24.79	-14.437	0.000
C3 (mg/L)	472.67 ± 118.04	388.65 ± 90.71	-3.569	0.001
C4 (mg/L)	320.56 ± 70.69	310.45 ± 74.94	-0.621	0.537
CH50 (µg/L)	25.02 ± 6.83	72.96 ± 28.68	10.284	0.000

Comparative analysis of serum complement factors between patients with before treatment group and after treatment group

Table 5 shows patients with after treatment group the levels of serum C1, C2, C3 and C4 were significantly decreased compared with that before treatment group, but the level of CH50 was significantly increased. Compared with the before treatment group, the levels of C2, C3, C4 and CH50 in the after treatment group were significantly different (P < 0.05). However, there was no significant difference in C1 level between the two groups (P > 0.05).

Table 5

Comparative analysis of serum complement factors between before treatment group and after treatment group (n = 40, ± s)
Variables	before treatment	after treatment	t	P
C1 (mg/L)	171.64 ± 59.82	149.71 ± 36.99	1.972	0.530
C2 (mg/L)	271.81 ± 127.96	107.96 ± 24.79	7.951	0.000
C3 (mg/L)	561.39 ± 201.64	388.65 ± 90.71	4.941	0.000
C4 (mg/L)	371.50 ± 114.79	310.45 ± 74.94	2.816	0.006
CH50 (µg/L)	43.60 ± 29.44	72.96 ± 28.68	-4.519	0.000

Comparison of serum complement levels in the study groups with different efficacies

In this study, 40 patients with first-episode schizophrenia were enrolled, and the clinical efficacy was assessed by the reduction rate of PANSS score in before and after treatment. The response rate was defined as a reduction rate in score ≥ 30%. After 4 weeks of aripiprazole treatment, 33 cases (82.50%) were effective and 7 cases (17.50%) were ineffective. The results showed that aripiprazole was effective in the treatment of patients with first-episode schizophrenia. The after treatment group serum C1, C2, C3 and C4 concentrations were lower in the effective group than in the before treatment group, and the difference was statistically significant (P < 0.05). The after treatment group serum CH50 concentrations were higher than in the before treatment group, and the difference was statistically significant (P < 0.05). Comparing serum C1, C2, C3, C4 and CH50 levels in the ineffective group before and after treatment, the difference was not statistically significant (P > 0.05).

Correlation analysis of serum levels of C1, C2, C3, C4, CH50 and the reduction rate of PANSS score in first-episode schizophrenia

Pearson correlation analysis showed that the serum C2 level was negatively correlated with the reduction rate of positive symptoms score and the reduction rate of BPRS score in first-episode schizophrenia (r=-0.454, -0.365, P < 0.05). The serum C3 level of the first-episode schizophrenia was negatively correlated with the reduction rate of PANSS total score, the reduction rate of positive symptom score and the reduction rate of negative symptom score (r=-0.467, -0.476, -0.367, all P < 0.05). There was a positive correlation between serum CH50 level and reduction rate of BPRS score in first-episode schizophrenia (r = 0.439, P < 0.05). Serum C1, C4 levels were not correlated with reduction rate of PANSS total score, reduction rate of positive symptom score, reduction rate of negative symptom score and reduction rate of BPRS score in the first-episode schizophrenia (P > 0.05). The above results are shown in Fig. 1.

Pearson correlation analysis was performed on the changes of serum levels of C1, C2, C3, C4 and CH50 of the study group before and after treatment and the reduction rate of PANSS total score, reduction rate of positive symptom score, reduction rate of negative symptom score and reduction rate of BPRS score. Figure 2 shows that the change value of serum C2 level in the study group before and after treatment was negatively correlated with the reduction rate of positive symptoms score and the reduction rate of BPRS score (r=-0.434, -0.352, P < 0.05). The change of serum C3 level in the study group before and after treatment was negatively correlated with the reduction rate of PANSS total score, the reduction rate of positive symptom score and the reduction rate of negative symptom score (r=-0.458, -0.435, -0.420, all P < 0.05). The changes of serum C1, C4 and CH50 levels before and after treatment were not correlated with the reduction rate of PANSS total score, the reduction rate of positive symptoms score, the reduction rate of negative symptoms score and reduction rate of BPRS score (P > 0.05).

With the acceleration of social rhythm, people's life pressure increases, and the incidence of schizophrenia has been increasing year by year in recent years, and tends to be younger[20, 21]. Schizophrenia is a group of common serious mental diseases, most of which occur in young adults and seriously affect patients' social function and quality of life[22, 23]. Clinically, patients with schizophrenia are mainly treated with atypical antipsychotics, which requires long-term adherence to medication. Aripiprazole is an atypical antipsychotic drug, which is commonly used in the clinical treatment of schizophrenia, and can significantly improve the positive and negative mental symptoms of patients. The main findings of this study: (1) After 4 weeks of treatment with atypical antipsychotics aripiprazole, the PANSS total score, positive symptom score and negative symptom score were decreased, and the psychiatric symptoms were alleviated. (2) First-episode schizophrenia had higher levels of C1, C2, C3, C4, and CH50 than healthy controls. (3) After 4 weeks of treatment with aripiprazole, the serum levels of C1, C2, C3 and C4 were significantly lower than before treatment, but the level of CH50 was significantly higher than before treatment. (4) The serum C3 level of first-episode schizophrenia patients and the changes of C3 level before and after treatment were negatively correlated with the reduction rate of PANSS total score, the reduction rate of positive symptoms score and the reduction rate of negative symptoms score, suggesting that the serum C3 level before and after treatment can be used as a biomarker to predict clinical efficacy.

The complement system is the inflammatory activated part of the innate immune system, and some studies mainly focus on the status of the complement system in patients with SCZ[24]. There are some differences in the reports on the levels of complement factors C1, C2, C3, C4 and CH50[25, 26]. It has been reported that the classical complement C1, C3, C4 and CH50 have increased hemolytic activity in patients with schizophrenia[27]. This conclusion is consistent with the results of this study, the levels of serum C1, C2, C3, C4 and CH50 in the first-episode schizophrenia patients were higher than those in the healthy control group. Complement components C3 and C4 play a central role in the complement cascade[28]. It has been reported that C3 levels in peripheral blood of patients with SCZ are elevated compared to healthy controls[29]. Regarding C4[26, 30], recent studies have found that plasma C4 levels in patients with SCZ are elevated during the acute phase of the disease and can be reduced by treatment with antipsychotic drugs. Studies have shown [31]that CH50 in patients with schizophrenia in remission is significantly increased, and a few studies have suggested that the hemolytic activity of CH50 in patients with schizophrenia has a certain trend of increase after treatment with antipsychotic drugs, which is consistent with the conclusion in this study. However, previous studies on complement factor levels were not comprehensive enough. In this study, 40 first-episode schizophrenia after aripiprazole treatment for 4 weeks, the serum levels of C1, C2, C3 and C4 were significantly reduced compared with before treatment, but the level of CH50 was significantly increased compared with before treatment. It is suggested that aripiprazole has a certain trend of increasing CH50 level in schizophrenia, which may be related to the different disease stages of enrolled patients (such as acute or chronic stage), and the specific mechanism needs to be further studied. Taken together, these findings will provide additional data reference for linking the complement system with SCZ.

The PANSS scale score is the most widely used interview scale to assess the severity of psychiatric symptoms. Therefore, in this study, PANSS scale score[32] was used to evaluate the severity of psychiatric symptoms in patients with SCZ, and the score reduction rate was used as the clinical efficacy evaluation index. Several studies have explored the relationship between the severity of psychiatric symptoms and the complement system in patients with SCZ[18]. Studies have shown a significant positive correlation between the C4/C3 ratio and the positive symptom score in psychiatric patients[33]. Another study found that increases in C3 and C4 were associated with lower PANSS total scores[34]. In this study, the serum C3 level of patients with first-episode schizophrenia and the change value of C3 level before and after treatment were negatively correlated with the reduction rate of PANSS total score, the reduction rate of positive symptoms score and the reduction rate of negative symptoms score, suggesting that the serum C3 level before and after treatment may be one of the indicators to predict drug efficacy. The reason for these relationships between the severity of psychiatric symptoms and the complement system is unclear. In light of the relatively small sample size and the single-center design of this study, further multicentric studies are needed to confirm these findings, and the specific mechanisms underlying these relationships require further investigation.

There are some limitations of this study that need to be considered. First, the sample size of this study was small and could be expanded for future studies. Second, this study was a single-center design and there is a possibility of sampling bias, which could be further investigated through multicenter. Third, there was no causal relationship between psychiatric symptoms and the complement system in this cross-sectional study. Fourth, not all complement factors were analyzed due to financial constraints.

In conclusion, this study showed that serum levels of C1, C2, C3, C4 and CH50 were higher in patients with first-episode schizophrenia than in healthy individuals, and that serum levels of C1, C2, C3, and C4 decreased and CH50 increased after aripiprazole treatment. Serum C3 levels before and after treatment in patients with first-episode schizophrenia can be used as a biomarker to predict clinical efficacy.

the reduction rate of PANSS total score

RRPTS

the reduction rate of positive symptoms score

RRPSS

the reduction rate of negative symptoms score

RRNSS

the reduction rate of BPRS score

RRBS.

Acknowledgements

We thank all clinical psychiatrists, nurses, and patients who participated in the study

Author contributions

Yin Cao, Jun Liang, and Qingrong Xia were involved in the conception and design of the study. Yin Cao, Jun Liang, Biao Dai, and Feng Shan were responsible for data collection and statistical analysis. Yin Cao constructed a draft of the manuscript. Qingrong Xia have provided relevant feedback and critical revisions of the manuscript. The authors read and approved the final manuscript.

Ethics approval and consent to participate

This procedure was approved by the ethics committee of the Hefei Fourth People's Hospital (registration number HFSY-IRB-PJ-XQR-2022001) and was conducted according to the principles of the Declaration of Helsinki. Written informed consent was obtained from all patients.

Consent to Publish declaration

Not applicable

Disclosure

The authors report no conflicts of interest in this work.

Funding

This study was provided by the Research Fund Project of Anhui Medical University (Project No: 2021xkj113), Research Fund Project of Hefei Fourth People’s Hospital (Project No: HFSY202109), Hefei Seventh cycle Key Medical Specialty, and Anhui Province Medical and Health Key Specialty Construction Project.

Nucifora FC Jr., Woznica E, Lee BJ, Cascella N, Sawa A. Treatment resistant schizophrenia: Clinical, biological, and therapeutic perspectives. Neurobiol Dis. 2019;131:104257.
Gosek P, Kotowska J, Rowinska-Garbien E, Bartczak D, Heitzman J. Treatment resistance and prolonged length of stay among schizophrenia inpatients in forensic institutions. Psychiatry Res. 2021;298:113771.
Yu H, Ni P, Tian Y, Zhao L, Li M, Li X, Wei W, Wei J, Wang Q, Guo W, et al. Association of elevated levels of peripheral complement components with cortical thinning and impaired logical memory in drug-naive patients with first-episode schizophrenia. Schizophrenia (Heidelb). 2023;9(1):79.
Charlson FJ, Ferrari AJ, Santomauro DF, Diminic S, Stockings E, Scott JG, McGrath JJ, Whiteford HA. Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study 2016. Schizophr Bull. 2018;44(6):1195–203.
Khandaker GM, Cousins L, Deakin J, Lennox BR, Yolken R, Jones PB. Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment. Lancet Psychiatry. 2015;2(3):258–70.
North HF, Weissleder C, Bitar M, Barry G, Fullerton JM, Webster MJ, Weickert CS. RNA-sequencing suggests extracellular matrix and vasculature dysregulation could impair neurogenesis in schizophrenia cases with elevated inflammation. Schizophrenia (Heidelb). 2024;10(1):50.
Muller N. Inflammation in Schizophrenia: Pathogenetic Aspects and Therapeutic Considerations. Schizophr Bull. 2018;44(5):973–82.
Prerna C, Gurjit K, Rajendra P, Harmanjit S. Pharmacotherapy of schizophrenia: immunological aspects and potential role of immunotherapy. Expert Rev Neurother 2021, 21(12).
Nimgaonkar VL, Prasad KM, Chowdari KV, Severance EG, Yolken RH. The complement system: a gateway to gene-environment interactions in schizophrenia pathogenesis. Mol Psychiatry. 2017;22(11):1554–61.
Lee JD, Coulthard LG, Woodruff TM. Complement dysregulation in the central nervous system during development and disease. Semin Immunol. 2019;45:101340.
Pouw RB, Ricklin D. Tipping the balance: intricate roles of the complement system in disease and therapy. Semin Immunopathol. 2021;43(6):757–71.
Magdalon J, Mansur F, Teles ESAL, de Goes VA, Reiner O, Sertie AL. Complement System in Brain Architecture and Neurodevelopmental Disorders. Front Neurosci. 2020;14:23.
Namatame C, Misu T, Takai Y, Nishiyama S, Nakashima I, Fujihara K, Aoki M. CH50 as a putative biomarker of eculizumab treatment in neuromyelitis optica spectrum disorder. Heliyon. 2021;7(1):e05899.
Baumeister D, Ciufolini S, Mondelli V. Effects of psychotropic drugs on inflammation: consequence or mediator of therapeutic effects in psychiatric treatment? Psychopharmacology. 2016;233(9):1575–89.
Kopczynska M, Zelek W, Touchard S, Gaughran F, Di Forti M, Mondelli V, Murray R, O'Donovan MC, Morgan BP. Complement system biomarkers in first episode psychosis. Schizophr Res. 2019;204:16–22.
Mohd Asyraf AJ, Nour El Huda AR, Hanisah MN, Norsidah KZ, Norlelawati AT. Relationship of selective complement markers with schizophrenia. J Neuroimmunol. 2022;363:577793.
Kangkang X, Jingli C, Yarui W, Yuan C, Shaoqiang H, Caihong W, Yong Z, Xueqin S, Jingliang C. Altered static and dynamic functional connectivity of habenula in first-episode, drug-naïve schizophrenia patients, and their association with symptoms including hallucination and anxiety. Front Psychiatry 2023, 14(0).
Cao Y, Xu Y, Xia Q, Shan F, Liang J. Peripheral Complement Factor-Based Biomarkers for Patients with First-Episode Schizophrenia. Neuropsychiatr Dis Treat. 2023;19:1455–62.
Zhao M, Qin B, Mao Y, Wang H, Wang A, Wang C. Efficacy and Safety of Low-Dose Brexpiprazole for Acute Schizophrenia: Meta-Analysis of Randomized Placebo-Controlled Trials. Neuropsychiatr Dis Treat. 2022;18:1705–13.
Clément D, Joshua TK, Alice M, Alice MS, Andrea B, Pejman S, Antigona M, Monica NOC, Daniel C. J: Early auditory processing dysfunction in schizophrenia: Mechanisms and implications. Neurosci Biobehav Rev 2023, 148(0).
Zhuo C, Tian H, Song X, Jiang D, Chen G, Cai Z, Ping J, Cheng L, Zhou C, Chen C. Microglia and cognitive impairment in schizophrenia: translating scientific progress into novel therapeutic interventions. Schizophrenia (Heidelb). 2023;9(1):42.
Kristensen TD, Raghava JM, Skjerbaek MW, Dhollander T, Syeda W, Ambrosen KS, Bojesen KB, Nielsen MO, Pantelis C, Glenthoj BY, et al. Fibre density and fibre-bundle cross-section of the corticospinal tract are distinctly linked to psychosis-specific symptoms in antipsychotic-naive patients with first-episode schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2023;273(8):1797–812.
Aymen K, Laatabi A, Karroumi S, Adali I, Manoudi F. Quality of Life and C-Reactive Protein in Patients with Schizophrenia: A Cross-Sectional Study. Alpha Psychiatry 2024, 25(2).
Mustafa G, Hasan Mervan A, Oya G. Evaluation of Serum Complement Levels and Factors Affecting Treatment Resistance in Patients with Schizophrenia. Psychiatry Clin Psychopharmacol 2024, 33(2).
Guo W, Gu Y, Zhou J, Wang X, Sun Q. Characteristics and associated factors of violence in male patients with schizophrenia in China. Front Psychiatry. 2023;14:1106950.
Wesley MM, Danillo GA, Kristen JW, Jill AH. High-throughput complement component 4 genomic sequence analysis with C4Investigator. HLA 2023, 103(1).
Nis B-L, Zhihong Z, Esben A, Clara A, Michael EB, Beilei B, Anders DB, Cynthia MB, Goldtsche J-CP, Jakob D. G : The correlates of neonatal complement component 3 and 4 protein concentrations with a focus on psychiatric and autoimmune disorders. Cell Genom 2023, 3(12).
Chen Y, Zhao Z, Lin F, Wang L, Lin Z, Yue W. Associations Between Genotype and Peripheral Complement Proteins in First-Episode Psychosis: Evidences From C3 and C4. Front Genet. 2021;12:647246.
Ali FT, Abd El-Azeem EM, Hamed MA, Ali MAM, Abd Al-Kader NM, Hassan EA. Redox dysregulation, immuno-inflammatory alterations and genetic variants of BDNF and MMP-9 in schizophrenia: Pathophysiological and phenotypic implications. Schizophr Res. 2017;188:98–109.
Jingfeng S, Xia F, Kaiyuan C, Zeman F, Handi Z. Plasma complement component 4 alterations in patients with schizophrenia before and after antipsychotic treatment. Asian J Psychiatr 2022, 73(0).
Mayilyan KR, Weinberger DR, Sim RB. The complement system in schizophrenia. Drug News Perspect. 2008;21(4):200–10.
Zhao YJ, Ma T, Zhang L, Ran X, Zhang RY, Ku Y. Atypically larger variability of resource allocation accounts for visual working memory deficits in schizophrenia. PLoS Comput Biol. 2021;17(11):e1009544.
Laskaris L, Zalesky A, Weickert CS, Di Biase MA, Chana G, Baune BT, Bousman C, Nelson B, McGorry P, Everall I, et al. Investigation of peripheral complement factors across stages of psychosis. Schizophr Res. 2019;204:30–7.
Li H, Zhang Q, Li N, Wang F, Xiang H, Zhang Z, Su Y, Huang Y, Zhang S, Zhao G, et al. Plasma levels of Th17-related cytokines and complement C3 correlated with aggressive behavior in patients with schizophrenia. Psychiatry Res. 2016;246:700–6.

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Peripheral blood complement factor C3 as a biomarker of clinical efficacy in patients with first-episode schizophrenia before and after treatment

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Abstract

Objective

Methods

Results

Conclusion

Figures

Introduction

Materials and methods

Study design and participants

Medication regimen

Clinical assessment

Blood sample collection and measurement of serum complement factors

Statistical analysis

Results

Differences in demographic and clinical characteristics of participants

Comparative analysis of serum complement factors between patients with before treatment group and control group

Comparative analysis of serum complement factors between patients with after treatment group and control group

Comparison of serum complement levels in the study groups with different efficacies

Discussion

Abbreviations

Declarations

References

Additional Declarations

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Version 1