Daniela Rodrigues-Amorim1, Tania Rivera-Baltanás1, João Bessa2, Nuno Sousa2, María de Carmen Vallejo-Curto1, Cynthia Rodríguez-Jamardo1, María Elena de Las Heras1, Roberto Díaz3, Roberto Carlos Agís-Balboa1, J M Olivares4, Carlos Spuch5. 1. Neuroscience Translational Group, Galicia Sur Health Research Institute, SERGAS-UVIGO, CIBERSAM, Spain. 2. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal. 3. Hospital Universitari Institut Pere Mata, IISPV, URV, CIBERSAM, Reus, Spain; Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile. 4. Neuroscience Translational Group, Galicia Sur Health Research Institute, SERGAS-UVIGO, CIBERSAM, Spain. Electronic address: jose.manuel.olivares.diez@sergas.es. 5. Neuroscience Translational Group, Galicia Sur Health Research Institute, SERGAS-UVIGO, CIBERSAM, Spain. Electronic address: carlos.spuch.calvar@sergas.es.
Abstract
BACKGROUND: Schizophrenia is associated with patterns of aberrant neurobiological circuitry. The disease complexity is mirrored by multiple biological interactions known to contribute to the disease pathology. One potential contributor is the family of neurotrophins which are proteins involved in multiple functional processes in the nervous system, with crucial roles in neurodevelopment, synaptogenesis and neuroplasticity. With these roles in mind, abnormal neurotrophin profiles have been hypothesized to contribute to the pathology of schizophrenia. METHODS: We performed a systematic review and a meta-analysis to scrutinize the neurobiological hypothesis of neurotrophins in schizophrenia, examining the correlation between peripheral levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3) and neurotrophin 4/5 (NT-4/5) associated with schizophrenia. RESULTS: Fifty-two studies were reviewed and twenty-two studies were included in this meta-analysis. Using a random effects model, we confirmed that decreased levels of neurotrophins (BDNF, NGF and NT-4/5) were associated with schizophrenia (Hedges's g = -0.846; SE = 0.058; 95% confidence interval: -0.960 to -0.733; Z-value = -14.632; p-value = 0.000). Subgroup analysis indicated that neurotrophin levels are significantly decreased in both medicated and drug-näive patients. Meta-regression of continuous variables such as mean age, duration of illness and PANSS total score did not show significant effects (p > 0.05) in relation to neurotrophins levels. DISCUSSION: We confirm that decreased peripheral neurotrophin levels are significantly associated with schizophrenia, thereby confirming the neurobiological hypothesis of neurotrophins in schizophrenia. Low levels of neurotrophins in peripheral blood of patients with schizophrenia may explain, in part, the pathophysiology of schizophrenia.
BACKGROUND:Schizophrenia is associated with patterns of aberrant neurobiological circuitry. The disease complexity is mirrored by multiple biological interactions known to contribute to the disease pathology. One potential contributor is the family of neurotrophins which are proteins involved in multiple functional processes in the nervous system, with crucial roles in neurodevelopment, synaptogenesis and neuroplasticity. With these roles in mind, abnormal neurotrophin profiles have been hypothesized to contribute to the pathology of schizophrenia. METHODS: We performed a systematic review and a meta-analysis to scrutinize the neurobiological hypothesis of neurotrophins in schizophrenia, examining the correlation between peripheral levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3) and neurotrophin 4/5 (NT-4/5) associated with schizophrenia. RESULTS: Fifty-two studies were reviewed and twenty-two studies were included in this meta-analysis. Using a random effects model, we confirmed that decreased levels of neurotrophins (BDNF, NGF and NT-4/5) were associated with schizophrenia (Hedges's g = -0.846; SE = 0.058; 95% confidence interval: -0.960 to -0.733; Z-value = -14.632; p-value = 0.000). Subgroup analysis indicated that neurotrophin levels are significantly decreased in both medicated and drug-näive patients. Meta-regression of continuous variables such as mean age, duration of illness and PANSS total score did not show significant effects (p > 0.05) in relation to neurotrophins levels. DISCUSSION: We confirm that decreased peripheral neurotrophin levels are significantly associated with schizophrenia, thereby confirming the neurobiological hypothesis of neurotrophins in schizophrenia. Low levels of neurotrophins in peripheral blood of patients with schizophrenia may explain, in part, the pathophysiology of schizophrenia.
Authors: Natalia Rodríguez; Patricia Gassó; Albert Martínez-Pinteño; Àlex-González Segura; Gisela Mezquida; Lucia Moreno-Izco; Javier González-Peñas; Iñaki Zorrilla; Marta Martin; Roberto Rodriguez-Jimenez; Iluminada Corripio; Salvador Sarró; Angela Ibáñez; Anna Butjosa; Fernando Contreras; Miquel Bioque; Manuel-Jesús Cuesta; Mara Parellada; Ana González-Pinto; Esther Berrocoso; Miquel Bernardo; Sergi Mas Journal: Schizophrenia (Heidelb) Date: 2022-04-27
Authors: Benjamin I Perry; Rachel Upthegrove; Nils Kappelmann; Peter B Jones; Stephen Burgess; Golam M Khandaker Journal: Brain Behav Immun Date: 2021-07-16 Impact factor: 19.227
Authors: Daniela Rodrigues-Amorim; Tania Rivera-Baltanás; María Del Carmen Vallejo-Curto; Cynthia Rodriguez-Jamardo; Elena de Las Heras; Carolina Barreiro-Villar; María Blanco-Formoso; Patricia Fernández-Palleiro; María Álvarez-Ariza; Marta López; Alejandro García-Caballero; José Manuel Olivares; Carlos Spuch Journal: Sci Rep Date: 2020-08-31 Impact factor: 4.379