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Mikulic FL, Sagud M, Nikolac Perkovic M, Kudlek Mikulic S, Ganoci L, Bajs Janovic M, Janovic S, Filipcic Simunovic I, Mihaljevic Peles A, Bozicevic M, Bradas Z, Pivac N. Long-term effects of antipsychotics on serum BDNF levels in patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2025; 136:111240. [PMID: 39743169 DOI: 10.1016/j.pnpbp.2024.111240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 12/05/2024] [Accepted: 12/29/2024] [Indexed: 01/04/2025]
Abstract
Brain-derived neurotrophic factor (BDNF) is implicated in the etiology of schizophrenia, and peripheral BDNF levels are affected by the short-term antipsychotic treatment. However, the data on their long-term effects on BDNF levels are scarce, and there is no information whether BDNF levels change during sustained remission in relation to values in healthy individuals. The aim of the present study was to compare serum BDNF levels in patients in long-term remission and healthy controls. This study is an extension of our previous research on the effects of olanzapine and risperidone on serum BDNF in acute-episode patients with schizophrenia. Patients who remained in remission for at least 3 years on the same antipsychotic regimen (40 % of the initial cohort) were included. Symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). Serum BDNF levels were measured by ELISA in patients in remission (N = 20), evaluated at baseline, after 6 weeks of treatment and after 3 years of treatment, and in healthy individuals (N = 40). At baseline (p = 0.046) and after 6 weeks of treatment (p = 0.028), patients had significantly lower BDNF levels than controls. However, after 3 years of continuous antipsychotic maintenance treatment, serum BDNF levels were increased compared to baseline and values after 6 weeks of treatment in remitted patients, and were also significantly higher in patients than in healthy controls (p = 0.002). Antipsychotic medications appear to have distinct effects on serum BDNF levels in short-and long-term treatment. It remains to be determined if such finding may be related to potential neuroprotective effects of antipsychotic maintenance treatment.
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Affiliation(s)
- F L Mikulic
- University Hospital Centre Zagreb, Department of Emergency Medicine, Croatia
| | - M Sagud
- School of Medicine, University of Zagreb, Croatia; University Hospital Center Zagreb, Department of Psychiatry and Psychological Medicine, Zagreb, Croatia
| | - M Nikolac Perkovic
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia
| | - S Kudlek Mikulic
- University Hospital Center Zagreb, Department of Psychiatry and Psychological Medicine, Zagreb, Croatia
| | - L Ganoci
- University Hospital Centre Zagreb, Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, Zagreb, Croatia
| | - M Bajs Janovic
- School of Medicine, University of Zagreb, Croatia; University Hospital Center Zagreb, Department of Psychiatry and Psychological Medicine, Zagreb, Croatia
| | - S Janovic
- University Centre Varazdin, University North, Varazdin, Croatia
| | - I Filipcic Simunovic
- University Hospital Center Zagreb, Department of Psychiatry and Psychological Medicine, Zagreb, Croatia; Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - A Mihaljevic Peles
- School of Medicine, University of Zagreb, Croatia; University Hospital Center Zagreb, Department of Psychiatry and Psychological Medicine, Zagreb, Croatia
| | - M Bozicevic
- University Hospital Center Zagreb, Department of Psychiatry and Psychological Medicine, Zagreb, Croatia
| | - Z Bradas
- University Hospital Center Zagreb, Department of Psychiatry and Psychological Medicine, Zagreb, Croatia
| | - N Pivac
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia; University of Applied Sciences Hrvatsko Zagorje Krapina, Krapina, Croatia.
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Peng P, Wang D, Wang Q, Zhou Y, Hao Y, Chen S, Wu Q, Liu T, Zhang X. Positive association between increased homocysteine and deficit syndrome in Chinese patients with chronic schizophrenia: a large-scale cross-sectional study. Eur Arch Psychiatry Clin Neurosci 2024; 274:1105-1113. [PMID: 37943336 DOI: 10.1007/s00406-023-01706-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 10/15/2023] [Indexed: 11/10/2023]
Abstract
Emerging studies indicate that oxidative stress may contribute to deficit syndrome (DS) in patients with schizophrenia. Homocysteine (Hcy) is a well-known marker and mediator of oxidative stress that exhibits tight associations with schizophrenia. However, no previous studies have assessed the relationship of DS with Hcy. This study evaluated the prevalence, clinical characteristics, and association of DS with Hcy in 491 patients with schizophrenia. Plasma levels of Hcy and other metabolic parameters were measured. Positive and Negative Syndrome Scale and the proxy scale for deficit syndrome were employed to assess psychiatric symptoms and DS. The logistic regression model was conducted to assess independent factors associated with DS, and the Area Under the Curve (AUC) was used to assess the performance of our model. There was a high incidence of hyperhomocysteinemia (58.8%) and DS (24.4%). Plasma Hcy levels were significantly higher in patients with DS. Age, Hcy levels, and psychiatric symptoms were independently associated with DS. The combination of these variables perfectly differentiated DS and non-DS patients with an AUC value of 0.89. Our study suggests that elevated Hcy levels may be related to DS. Routine monitoring of Hcy is essential and may facilitate early detection of DS in patients with schizophrenia.
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Affiliation(s)
- Pu Peng
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Dongmei Wang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
| | - Qianjin Wang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Yanan Zhou
- Department of Psychiatry, Hunan Brain Hospital (Hunan Second People's Hospital), Changsha, China
| | - Yuzhu Hao
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Shubao Chen
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Qiuxia Wu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Tieqiao Liu
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
| | - Xiangyang Zhang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
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Al-Musawi AF, Al-Hakeim HK, Al-Khfaji ZA, Al-Haboby IH, Almulla AF, Stoyanov DS, Maes M. In Schizophrenia, the Effects of the IL-6/IL-23/Th17 Axis on Health-Related Quality of Life and Disabilities Are Partly Mediated by Generalized Cognitive Decline and the Symptomatome. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:15281. [PMID: 36429996 PMCID: PMC9690590 DOI: 10.3390/ijerph192215281] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 10/31/2022] [Accepted: 11/15/2022] [Indexed: 05/08/2023]
Abstract
Schizophrenia patients show increased disabilities and lower quality of life (DisQoL). Nevertheless, there are no data on whether the activation of the interleukin (IL)-6, IL-23, T helper (Th)-17 axis, and lower magnesium and calcium levels impact DisQoL scores. This study recruited 90 patients with schizophrenia (including 40 with deficit schizophrenia) and 40 healthy controls and assessed the World Health Association QoL instrument-Abbreviated version and Sheehan Disability scale, Brief Assessment of Cognition in Schizophrenia (BACS), IL-6, IL-23, IL-17, IL-21, IL-22, tumor necrosis factor (TNF)-α, magnesium and calcium. Regression analyses showed that a large part of the first factor extracted from the physical, psychological, social and environmental HR-QoL and interference with school/work, social life, and home responsibilities was predicted by a generalized cognitive deterioration (G-CoDe) index (a latent vector extracted from BACs scores), and the first vector extracted from various symptom domains ("symptomatome"), whereas the biomarkers had no effects. Partial Least Squares analysis showed that the IL6IL23Th17 axis and magnesium/calcium had highly significant total (indirect + direct) effects on HR-QoL/disabilities, which were mediated by G-CoDe and the symptomatome (a first factor extracted from negative and positive symptoms). The IL6IL23Th17 axis explained 63.1% of the variance in the behavioral-cognitive-psycho-social (BCPS) worsening index a single latent trait extracted from G-CoDe, symptomatome, HR-QoL and disability data. In summary, the BCPS worsening index is partly caused by the neuroimmunotoxic effects of the IL6IL23Th17 axis in subjects with lowered antioxidant defenses (magnesium and calcium), thereby probably damaging the neuronal circuits that may underpin deficit schizophrenia.
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Affiliation(s)
- Ali Fattah Al-Musawi
- Department of Clinical Pharmacy and Laboratory Sciences, College of Pharmacy, University of Al-Kafeel, Kufa 54001, Iraq
| | | | - Zahraa Abdulrazaq Al-Khfaji
- Department of Pharmacology, Toxicology and Clinical Pharmacy, Al-Zahraa University for Women, Karbala 56001, Iraq
| | | | - Abbas F. Almulla
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf 54001, Iraq
- Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, PathumWan, Bangkok 10330, Thailand
| | - Drozdstoj St. Stoyanov
- Department of Psychiatry, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria
- Research Institute, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria
| | - Michael Maes
- Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, PathumWan, Bangkok 10330, Thailand
- Department of Psychiatry, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria
- Research Institute, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria
- IMPACT, School of Medicine, Barwon Health, The Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong 3217, Australia
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Liang XH, Ren YL, Liang XY, Chen JY, Qu P, Tang X. Relationship between quality of life and adolescent glycolipid metabolism disorder: A cohort study. World J Diabetes 2022; 13:566-580. [PMID: 36051423 PMCID: PMC9329843 DOI: 10.4239/wjd.v13.i7.566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 04/29/2022] [Accepted: 06/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The prevalence of glucolipid metabolic disorders (GLMDs) in children and adolescents has a recognized association with cardiovascular diseases and type 2 diabetes mellitus in adulthood. Therefore, it is important to enhance our under-standing of the risk factors for GLMD in childhood and adolescence. AIM To explore the relationship between quality of life (QoL) and adolescent GLMD. METHODS This study included 1956 samples in 2019 from a cohort study established in 2014. The QoL scale and glycolipid indexes were collected during follow-up; other covariates of perinatal factors, physical measures, and socioeconomic indicators were collected and adjusted. A generalized linear regression model and logistic regression model were used to analyse the correlation between QoL and GLMD. RESULTS Higher scores of QoL activity opportunity, learning ability and attitude, attitude towards doing homework, and living convenience domains correlated negatively with insulin and homeostasis model assessment insulin resistance (IR) levels. Psychosocial factors, QoL satisfaction factors, and total QoL scores had significant protective effects on insulin and IR levels. Activity opportunity, learning ability and attitude, attitude towards doing homework domains of QoL, psychosocial factor, and total score of QoL correlated positively with high density lipoprotein. In addition, the attitude towards doing homework domain was a protective factor for dyslipidaemia, IR > 3, and increased fasting blood glucose; four factors, QoL and total QoL score correlated significantly negatively with IR > 3. In subgroup analyses of sex, more domains of QoL correlated with insulin and triglyceride levels, dyslipidaemia, and IR > 3 in females. Poor QoL was associated with an increased prevalence of GLMD, and the effect was more pronounced in males than in females. Measures to improve the QoL of adolescents are essential to reduce rates of GLMD. CONCLUSION Our study revealed that QoL scores mainly correlate negatively with the prevalence of GLMD in adolescents of the healthy population. The independent relationship between QoL and GLMD can be illustrated by adjusting for multiple covariates that may be associated with glycaemic index. In addition, among females, more QoL domains are associated with glycaemic index.
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Affiliation(s)
- Xiao-Hua Liang
- Department of Clinical Epidemiology and Biostatistics, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Health and Nutrition, Chongqing 400016, China
| | - Yang-Ling Ren
- Department of Clinical Epidemiology and Biostatistics, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Health and Nutrition, Chongqing 400016, China
| | - Xiao-Yue Liang
- Department of Clinical Epidemiology and Biostatistics, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Health and Nutrition, Chongqing 400016, China
| | - Jing-Yu Chen
- Ultrasound Department of Children’s Hospital of Chongqing Medical University, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
| | - Ping Qu
- Department of Clinical Epidemiology and Biostatistics, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Health and Nutrition, Chongqing 400016, China
| | - Xian Tang
- Department of Clinical Epidemiology and Biostatistics, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Health and Nutrition, Chongqing 400016, China
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