Reduced serum BDNF levels in patients with chronic schizophrenic disorder in relapse, who were treated with typical or atypical antipsychotics

Rizos, Emmanouil; Papadopoulou, Aikaterini; Laskos, E.; Michalopoulou, Panayiota G.; Kastania, Anastasia N.; Vasilopoulos, Dimitrios; Katsafouros, Konstantinos; Lykouras, Lefteris

doi:10.3109/15622970802182733

Cited by 91 publications

(49 citation statements)

References 36 publications

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“…Reversal of an increased yawning response indicates that olanzapine alleviated increases in D 2 receptor sensitivity, and that increases in D 2 receptor sensitivity are likely responsible for behavioral effects reported. In vitro analyses showed that decreases in hippocampal brain-derived neurotrophic factor and nerve growth factor protein produced by neonatal quinpirole were alleviated by olanzapine to control levels after an 8-day washout, also consistent with findings of this drug treatment in humans [84]. Interestingly, olanzapine treatment failed to alleviate significant decreases of genetic expression of nerve growth factor or brain-derived neurotrophic factor in the hippocampus or frontal cortex [64], suggesting that the effects of olanzapine in this model may be focused on changes in protein.…”

Section: Model Validationsupporting

confidence: 66%

Schizophrenia and Substance Abuse Comorbidity: Nicotine Addiction and the Neonatal Quinpirole Model

Brown¹,

Maple²,

Perna³

et al. 2012

Dev Neurosci

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This review focuses on nicotine comorbidity in schizophrenia, and the insight into this problem provided by rodent models of schizophrenia. A particular focus is on age differences in the response to nicotine, and how this relates to the development of the disease and difficulties in treatment. Schizophrenia is a particularly difficult disease to model in rodents due to the fact that it has a plethora of symptoms ranging from paranoia and delusions of grandeur to anhedonia and negative affect. The basis of these symptoms is believed to be due to neurochemical abnormalities and neuropathology in the brain, which most models have attempted to emulate. A brief review of findings regarding nicotine use and abuse in schizophrenics is presented, with findings using rodent models that have been able to provide insight into the mechanisms of addiction. A common clinical approach to the treatment of nicotine addiction in the schizophrenic population has been that these drugs are used for self-medication purposes, and it is clear that self-medication may actually be directed at several symptoms, including cognitive impairment and anhedonia. Finally, our laboratory has reported across a series of studies that neonatal treatment with the dopamine D₂/D₃ receptor agonist quinpirole results in long-term increases in dopamine-like receptor sensitivity, consistent with data reporting increases in dopamine D₂ receptor function in schizophrenia. Across these studies, we have reported several behavioral, neurochemical, and genetic consistencies with the disease, and present a hypothesis for what we believe to be the basis of psychostimulant addiction in schizophrenia.

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Section: Model Validationsupporting

confidence: 66%

Schizophrenia and Substance Abuse Comorbidity: Nicotine Addiction and the Neonatal Quinpirole Model

Brown¹,

Maple²,

Perna³

et al. 2012

Dev Neurosci

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“…Despite a host of existing trials addressing the effects of pharmacological interventions (PIs) on peripheral BDNF levels in schizophrenia, while discrepant findings have been observed both in serum and plasma levels of BDNF [41,42,43,44,45,46,47,48], few studies have examined the association between NPIs and peripheral BDNF levels in patients with schizophrenia, and the results of studies have been discordant. This meta-analysis included six RCTs with 289 participants in total.…”

Section: Discussionmentioning

confidence: 99%

“…For example, a reduction in BDNF concentrations has been reported in the prefrontal cortex (PFC) and hippocampus in schizophrenia compared with controls [51,52,53,54]. A reduction in peripheral BDNF levels has been reported in patients with schizophrenia compared to healthy controls [31,41,44,55,56], including medication naïve and first-episode schizophrenia patients [12,43,57,58,59,60]. However, a few studies reported increased serum BDNF levels [61,62] or no significant differences in serum BDNF levels [63,64].…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of Non-Pharmacological Interventions on Brain-Derived Neurotrophic Factor in Schizophrenia: A Systematic Review and Meta-Analysis

Sanada

Zorrilla

Iwata

et al. 2016

IJMS

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Several studies have investigated the relationship between non-pharmacological interventions (NPIs) and peripheral brain-derived neurotrophic factor (BDNF) in schizophrenia patients. We conducted a systematic review and meta-analysis to review the efficacy of NPIs on peripheral serum and plasma BDNF in subjects with schizophrenia (including schizoaffective disorder). Meta-analyses were conducted to examine the effects of NPIs on blood BDNF levels by using the standardized mean differences (SMDs) between the intervention groups and controls. In total, six randomized controlled trials with 289 participants were included. Of them, five studies used exercise, physical training or diet products. One study used cognitive training. Overall, the BDNF levels in the NPI group increased significantly compared with the control groups (SMD = 0.95, 95% confidence interval (CI) = 0.07 to 1.83, p = 0.03). Subgroup analyses indicated beneficial effects of a non-exercise intervention on peripheral BDNF levels (SMD = 0.41, 95% CI = 0.08 to 0.74, p = 0.01). Meta-regression analyses showed that the completion rate influenced the variation in SMD (p = 0.01). Despite insufficient evidence to draw a conclusion, our results suggest that use of NPIs as adjunctive treatments, specifically non-exercise interventions, may affect positively serum or plasma BDNF in patients with schizophrenia.

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“…Furthermore, BDNF was found to positively associate with the clozapine daily dose in schizophrenics (62). Rizos et al (63) showed that a period of 6 weeks on antipsychotic medication did not affect serum BDNF levels in schizophrenics compared to their own BDNF levels at the study entry. However, they noted that the subgroup of patients on olanzapine manifested increased serum BDNF levels compared to the haloperidol, risperidone and amisulpride subgroups.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Accuracy of Brain-derived Neurotrophic Factor and Nitric oxide in Patients with Schizophrenia. A pilot study/ Dijagnostička tačnost moždanog neurotrofičkog faktora i azot-monoksida kod obolelih od shizofrenije.Pilot studija

Djordjević¹,

Lazarević

Ćosić³

et al. 2016

Journal of Medical Biochemistry

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SummaryBackgroundBrain-derived neurotrophic factor (BDNF) and nitric oxide (NO) play multiple roles in the developing and adult CNS. Since BDNF and NO metabolisms are dysregulated in schizophrenia, we measured these markers simultaneously in the blood of schizophrenics and assessed their diagnostic accuracy.MethodsThirty-eight patients with schizophrenia classified according to demographic characteristics, symptomatologyand therapy and 39 age- and gender-matched healthy controls were enrolled. BDNF was determined by the ELISA technique while the concentration of nitrite/nitrate (MJX-TeXAtom-ORDNO2−MJX-TeXAtom-ORD/MJX-TeXAtom-ORDNO3−) was measured by the colorimetric method.ResultsSerum BDNF levels were significantly lower (20.38±3.73 ng/mL, P = 1.339E-05), whilst plasma MJX-TeXAtom-ORDNO2−MJX-TeXAtom-ORD/MJX-TeXAtom-ORDNO3− concentrations were significantly higher (84.3 (72–121) μmol/L, P=4.357E-08) in patients with schizophrenia than in healthy controls (25.65±4.32 ng/mL; 60.9 (50–76) μmol/L, respectively). The lowest value of BDNF (18.14±3.26 ng/mL) and the highest MJX-TeXAtom-ORDNO2−MJX-TeXAtom-ORD/MJX-TeXAtom-ORDNO3− concentration (115.3 (80–138) μmol/L) were found in patients treated with second-generation antipsychotics (SGA). The patients diseased before the age of 24 and the patients suffering for up to one year had significantly lower serum BDNF levels than those diseased after the age of 24 and the patients who were ill longer than one year. Both BDNF and MJX-TeXAtom-ORDNO2−MJX-TeXAtom-ORD/MJX-TeXAtom-ORDNO3− showed good diagnostic accuracy, but BDNF had better ROC curve characteristics, especially in patients with negative symptomatology.ConclusionsBDNF and nitrite/nitrate showed inverse changes in schizophrenic patients. The most pronounced changes were found in patients treated with second-generation antipsychotics. Although BDNF is not specific of schizophrenia, it may be a clinically useful biomarker for the diagnosis of patients expressing predominantly negative symptoms.

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Reduced serum BDNF levels in patients with chronic schizophrenic disorder in relapse, who were treated with typical or atypical antipsychotics

Cited by 91 publications

References 36 publications

Schizophrenia and Substance Abuse Comorbidity: Nicotine Addiction and the Neonatal Quinpirole Model

Schizophrenia and Substance Abuse Comorbidity: Nicotine Addiction and the Neonatal Quinpirole Model

The Efficacy of Non-Pharmacological Interventions on Brain-Derived Neurotrophic Factor in Schizophrenia: A Systematic Review and Meta-Analysis

Diagnostic Accuracy of Brain-derived Neurotrophic Factor and Nitric oxide in Patients with Schizophrenia. A pilot study/ Dijagnostička tačnost moždanog neurotrofičkog faktora i azot-monoksida kod obolelih od shizofrenije.Pilot studija

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