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Decreased Serum S100A10 Levels in Patients with Both Schizophrenia and Metabolic Syndrome

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Decreased Serum S100A10 Levels in Patients with Both Schizophrenia and Metabolic Syndrome Original Article Decreased Serum S100A10 Levels in Patients with Both Schizophrenia and Metabolic Syndrome Chin-Chuen Lin, M.D., Meng-Chang Tsai, M.D., Tiao-Lai Huang, M.D.* Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan Abstract Background: Brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of schizophrenia and metabolic syndrome. S100A10 is associated with the antidepressant effect of BDNF, and decreased S100A10 mRNA has also been found in schizophrenia. S100A10 also interacts with serotonin and annexin A2, both are associated with obesity. In this study, we intended to investigate the serum BDNF and S100A10 levels in patients with schizophrenia with and without metabolic syndrome. Methods: We recruited patients with schizophrenia, collected their demographic data, and measured their metabolic profiles, serum BDNF, and S100A10 levels. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale. Metabolic syndrome was determined using the criteria provided by the Ministry of Health and Welfare of Taiwan. Results: In this study, 38.7% of 93 participants had metabolic syndrome. No statistical significance was found in serum BDNF levels between patients with and without metabolic syndrome. Patients with metabolic syndrome had significantly lower S100A10 levels compared to those without (p < 0.01). Conclusion: Decreased serum S100A10 levels were found in patients with schizophrenia and metabolic syndrome compared to schizophrenic patients without. Those data suggested that serum S100A10 level could play a rôle in metabolic syndrome among patients with schizophrenia. Key words: brain-derived neurotrophic factor, energy metabolism, p11, positive and negative syndrome scale Taiwanese Journal of Psychiatry (Taipei) 2020; 34: 110-114 Introduction can be used to help identify individuals at risk of cardiovascular disease [10]. The prevalence of metabolic syndrome in patients Schizophrenia is a multifactorial disorder that involves with schizophrenia is about 35% in males and 50% in females, many pathways. Brain-derived neurotrophic factor (BDNF) both far greater than general population [11]. Many factors is involved in the growth, survival, differentiation, and such as the use of antipsychotic medications, lifestyle, social repair of neurons [1] and is found to be associated with economic status, and genetics, contribute to the increased neuropsychiatric disorders, such as schizophrenia and prevalence of metabolic syndrome among patients with mood disorder [2]. S100A10, also known as p11, is a schizophrenia [12]. member of the S100 family of calcium effector proteins [3]. Several members of S100 proteins are associated Antidepressant effect of BDNF has been shown to be closely with metabolic syndromes. In the rat model of metabolic related to S100A10 in primary neuronal cultures and syndrome, S100A3 gene expression is upregulated through transgenic mice [4]. In the peripheral blood mononuclear microarray [13]. Increased expression of S100A8 is found cell of patients with schizophrenia, S100A10 mRNA levels in the whole blood of Latinos with metabolic syndrome as are higher than the controls [5]. compared to those without [14]. Peripheral serum S100A8, Patients with schizophrenia tend to have higher mortality and shorter lifespan [6, 7]. Cardiovascular disease is found to be a major contributing factor to the increased mortality of patients *Corresponding author. No. 123, Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan. with schizophrenia [8, 9]. The diagnosis of metabolic syndrome E-mail: Tiao-Lai Huang <[email protected]> Received: Apr. 21, 2020 revised: Jun. 19, 2020 accepted: Jun. 22, 2020 date published: Sep. 28, 2020 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to Access this article online remix, tweak, and build upon the work non-commercially, as long as appropriate credit Quick Response Code: is given and the new creations are licensed under the identical terms. Website: For reprints contact: [email protected] www.e-tjp.org How to cite this article: Lin CC, Tsai MC, Huang TL. Decreased serum DOI: S100A10 levels in patients with both schizophrenia and metabolic syndrome. 10.4103/TPSY.TPSY_28_20 Taiwan J Psychiatry 2020;34:110-4. © 2020 Taiwanese Journal of Psychiatry (Taipei) | Published by Wolters Kluwer - Medknow 110 © 2020 Taiwanese Journal of Psychiatry (Taipei) | Published by Wolters Kluwer - Medknow Lin, et al.: p11 and metabolic syndrome in schizophrenia A9, and A12 mRNA levels are closely associated with insulin • iWaist circumference 90 cm in males or 80 cm in resistance and inflammation [15]. Lower serum S100A1 females, or body mass index (BMI) 27 kg/m2 levels and higher serum S100B levels have been found in • Systolic BP 130 mgHg≧ or diastolic BP 85≧ mmHg patients with metabolic syndrome than those in healthy • Fasting blood sugar 110 mg/dL ≧ controls [16, 17]. S100A10 protein has close interactions • LTG 150 mg/dL≧ ≧ with serotonin receptors and annexin A2. S100A10 increases • LHDL < 40 mg/dL in≧ males or < 50 mg/dL in females. ≧ localization of serotonin 1B (5-HT1B) receptors at the cell Patients were considered to have metabolic syndrome if surface [18]. While CNS serotonin inhibits appetite, peripheral they met three or more of those five criteria. serotonin synthesis is associated with obesity, and inhibition The above criteria were modified from the U.S. National of peripheral serotonin can reduce obesity [19]. In adipose Cholesterol Education Program Adult Treatment Panel III tissues, annexin A2 contributes to glucose and fatty acid (2001). The most notable difference is in the definition of transport [20]. Those data suggest that S100 proteins play a central obesity (waist circumference 100 cm or 40 inches rôle in the energy metabolism. in male or 88 cm or 35 inches in female). In this study, we intended to investigate the relationship ≧ between serum BDNF levels, serum S100A10 levels, and Statistical≧ analysis metabolic syndrome in patients with schizophrenia. We described results as mean ± standard deviation. Chi-square was used to analyze the distribution of metabolic Methods syndrome among male and female samples. Independent t-test and analysis of variance (ANOVA) were used to compare Participants serum BDNF and S100A10 levels between patients with and From July 2016 to June 2018, we recruited patients without metabolic syndrome, as well as demographic data with schizophrenia at the Chang Gung Memorial Hospital. between the two groups. We used Pearson correlation to assess Schizophrenia was diagnosed by a psychiatrist using the the relationship with the associated parameters. criteria of the Diagnostic and Statistical Manual of Mental Data analysis was done using Statistical Package of Social Disorders, Fourth Edition (DSM-IV) [21]. Clinical symptoms Science software version 19 (Chicago, Illinois, U.S.A.). The were evaluated using Positive and Negative Syndrome Scale differences were considered significant ifp -values were smaller (PANSS). We also collected demographic data, blood pressure than 0.05. (BP), and waist circumference. Written informed consent was provided by all participants after the content of the study Results was fully explained. The institutional review board of Chang A total of 93 patients with schizophrenia were recruited, Gung Memorial Hospital approved the study designs (protocol including 41 males and 52 females. Their ages were ranged number = IRB 201600266A3, and date of approval = May from 20.8 to 78.1 years, with the mean of 45.8 ± 11.3 years. 11, 2016; IRB 201600266A3C101, and date of approval Illness duration was ranged from 0.9 to 48.2 years, with the June 29, 2017). mean of 20.4 ± 9.4 years. PANSS scores were ranged from 32 Laboratory data to 131, with the mean of 81.7 ± 27.5. Six (6.5%) patients met zero criteria of metabolic syndrome, Venous blood was drawn from each participant in the 25 (26.9%) met one criteria; 26 (28.0%) met two criteria, 26 morning following a six-hour fast. Serum levels of fasting (28.0%) met three criteria, 7 (7.5%) met four criteria, and blood sugar, triglyceride (TG), and high-density lipoprotein three (3.2%) met all criteria. Overall, 36 (38.7%) patients had cholesterol (HDL) were measured in the hospital laboratory. metabolic syndrome. Among them, 19 of 41 (46.3%) male and Serum BDNF protein levels were measured using a 17 of 52 (32.7%) female patients had metabolic syndrome. commercially available ELISA kit of the sandwich type, i.e., The male and female distribution of metabolic syndrome was BDNF Emax Immunoassay System (Promega Corporation, not significant. Using ATP III criteria, 15 (16.1%) patients Madison, Wisconsin, USA). Each system contained anti-BDNF met zero criteria of metabolic syndrome, 23 (24.7%) met one mAb, Block&Sample 5X buffer, BDNF standard, antihuman criteria, 22 (23.7%) met two criteria, 23 (24.7%) met three BDNF pAb, anti-IgY HRP, TMB solution, peroxidase substrate, criteria, 7 (7.5%) met four criteria, and three (3.2%) met all and protocol. We measured serum S100A10 protein levels with criteria. Overall, 33 (35.5%) patients had metabolic syndrome. a commercially available ELISA kit, i.e., CircuLex S100A10 Using independent t-test, no statistical significance was ELISA Kit (CycLex Company, Ltd., Taipei), which employs found in BDNF levels
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