The neurobiological hypothesis of neurotrophins in the pathophysiology of schizophrenia: A meta-analysis

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 funct...

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Published inJournal of psychiatric research Vol. 106; pp. 43 - 53
Main Authors Rodrigues-Amorim, Daniela, Rivera-Baltanás, Tania, Bessa, João, Sousa, Nuno, Vallejo-Curto, María de Carmen, Rodríguez-Jamardo, Cynthia, de las Heras, María Elena, Díaz, Roberto, Agís-Balboa, Roberto Carlos, Olivares, J.M., Spuch, Carlos
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.11.2018
Subjects
Adult
Female
Humans
Male
Middle Aged
Nerve Growth Factors - blood
Schizophrenia - blood
Young Adult
Online AccessGet full text

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Abstract 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. 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. 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. 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. •Neurotrophins are associated with the pathophysiology of schizophrenia.•Patients with schizophrenia have decreased levels of neurotrophins.•Peripheral levels of neurotrophins contribute to the neurobiological hypothesis of schizophrenia.
AbstractList 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. 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. 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. 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. •Neurotrophins are associated with the pathophysiology of schizophrenia.•Patients with schizophrenia have decreased levels of neurotrophins.•Peripheral levels of neurotrophins contribute to the neurobiological hypothesis of schizophrenia.
BACKGROUNDSchizophrenia 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. METHODSWe 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. RESULTSFifty-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. DISCUSSIONWe 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.
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. 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. 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. 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.
Author Vallejo-Curto, María de Carmen
Spuch, Carlos
Sousa, Nuno
Díaz, Roberto
Agís-Balboa, Roberto Carlos
Rodríguez-Jamardo, Cynthia
de las Heras, María Elena
Olivares, J.M.
Rodrigues-Amorim, Daniela
Rivera-Baltanás, Tania
Bessa, João
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Snippet Schizophrenia is associated with patterns of aberrant neurobiological circuitry. The disease complexity is mirrored by multiple biological interactions known...
BACKGROUNDSchizophrenia is associated with patterns of aberrant neurobiological circuitry. The disease complexity is mirrored by multiple biological...
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SubjectTerms Adult
Female
Humans
Male
Middle Aged
Nerve Growth Factors - blood
Schizophrenia - blood
Young Adult
Title The neurobiological hypothesis of neurotrophins in the pathophysiology of schizophrenia: A meta-analysis
URI https://dx.doi.org/10.1016/j.jpsychires.2018.09.007
https://www.ncbi.nlm.nih.gov/pubmed/30269004
https://search.proquest.com/docview/2115274811
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