Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and bipolar disorder

doi:10.1016/j.neulet.2007.04.001

Neuroscience Letters

Volume 420, Issue 1, 8 June 2007, Pages 45-48

https://doi.org/10.1016/j.neulet.2007.04.001 Get rights and content

Abstract

There is evidence that major psychiatric discords such as schizophrenia (SZ) and bipolar disorder (BD) are associated with dysregulation of synaptic plasticity with downstream alterations of neurotrophins. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system (CNS), and performs many biological functions such as promoting the survival, differentiation, and plasticity of neurons. Variants in the BDNF gene increase the risk of SZ and bipolar disorder. Chronic administration of drugs used to treat SZ and BD, such as lithium, valproate, quetiapine, clozapine, and olanzapine, increases BDNF expression in rat brain. To examine serum BDNF, three groups of chronically medicated DSM-IV SZ patients, on treatment with clozapine (n = 27), typical (n = 14), and other atypical antipsychotics (n = 19), 30 euthymic BD patients, and 26 healthy control had 5 ml blood samples collected by venipuncture. Serum BDNF levels were significantly higher in SZ patients (p < 0.001) when compared to either controls or euthymic BD patients. Increased BDNF in SZ patients might be related to the course of illness or to treatment variables. Prospective studies are warranted.

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Acknowledgement

This study was supported by grants from FIPE-HCPA (#06344).

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2022, Asian Journal of Psychiatry
Brain-derived neurotrophic factor (BDNF) is involved in neuroplasticity underlying cognitive deficits, including working memory deficits (WMD), in schizophrenia. Methodological challenges and inconsistencies are reported with peripheral BDNF levels. Left dorsolateral prefrontal cortex (DLPFC) is proposed to underlie WMD, though inconsistently. We aimed to explore the correlations between brain activation during working memory task-based functional Magnetic Resonance Imaging (fMRI) and BDNF gene expression in schizophrenia patients with WMD.
26 patients with schizophrenia with established WMD were recruited for the study. Blood samples were collected to study lymphocyte BDNF gene expression. Patients underwent task-based fMRI to examine the working memory performance and related brain activation. Whole-brain analysis was performed with 2-back > 0-back and 2-back > rest contrast. The peak intensity values of the activation were used for correlation analysis.
Whole brain analysis with 2-back > rest contrast revealed maximum activation in left DLPFC, Brodmann area 9 (t = 10.54, FWE corrected p < 0.05). The baseline BDNF gene expression correlated positively with the peak intensity of brain activation in left DLPFC (r = 0.365, p = 0.033). Negative symptom score negatively correlated with BDNF gene expression (r = −0.499, p = 0.005) and left DLPFC fMRI activation (r = −0.393, p = 0.023) respectively.
We found a significant positive association between BDNF gene expression and the activation of the DLPFC during the working memory task. This novel observation needs further systematic evaluation to establish the potential role of peripheral BDNF expression in WMD in schizophrenia.
Diabetes mellitus, cognitive deficits and serum BDNF levels in chronic patients with schizophrenia: A case-control study
2021, Journal of Psychiatric Research
The relationship between serum BDNF levels and cognitive dysfunction in schizophrenia (SCZ) patients comorbid with type 2 diabetes mellitus (T2DM) has not been reported. Hence, this study aimed to explore whether and how the changes of serum BDNF levels were correlated with cognitive impairment in SCZ patients comorbid with T2DM. We recruited 472 inpatients with chronic SCZ (54 T2DM and 418 non-T2DM), and 225 healthy controls. Serum BDNF levels and routine biochemical parameters were measured. Psychopathological symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS) and cognitive function was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). SCZ patients with T2DM had significantly higher serum BDNF levels than SCZ patients without T2DM (F = 11.31, p = 0.001). SCZ patients with T2DM scored higher in delayed memory than SCZ patients without T2DM (77.17 ± 18.44 vs.66.24 ± 19.51, p = 0.000), and still showed significance after controlling for confounders. Further stepwise multiple regression analysis identified serum BDNF as an independent contributor to the RBANS attention of SCZ patients with T2DM (β = 0.30, t = 2.09, p = 0.042). The increase of BDNF levels and better cognitive performance, especially delayed memory, may be related to the pathophysiological process of T2DM in chronic SCZ patients.
Brain-derived neurotrophic factor (BDNF) levels in first-episode schizophrenia and healthy controls: A comparative study
2020, Asian Journal of Psychiatry
Abnormalities in brain development and plasticity have been associated with the pathophysiology of schizophrenia. The role of brain-derived neurotrophic factor (BDNF) in schizophrenia is the recent area of interest because it regulates neurogenesis. The current study aimed to assess and compare serum BDNF levels between first-episode schizophrenia patients and healthy controls, and evaluate its correlation with the socio-demographic and clinical variables.
It was a cross-sectional comparative study for the assessment of serum BDNF levels between patients with first-episode schizophrenia (N=50) and healthy controls (N-50) conducted in the Department of Psychiatry at a tertiary care public hospital attached to a medical school in North India. Participants were assessed for the socio-demographic parameters, nicotine dependence, and clinical details using structured scales. Serum BDNF level estimated using the sandwich ELISA technique. The comparison between the groups was done by using a Student t-test or chi-square test. Spearman correlation was performed between mean BDNF scores and demographic or illness variables in both first-episode schizophrenia and healthy control groups.
There was a significantly lower mean score of total serum BDNF levels in first-episode schizophrenia patients as compared to controls (8.44 ± 1.54 vs 10.44 ± 2.04; t = 5.52, p < 0.001; 95% CI = 1.28-2.71). The total FTND scores for smokeless tobacco use were negatively correlated to BDNF levels among healthy controls (r=-0.30, p=0.03) as well as in the first-episode schizophrenia group (r=-0.32, p= 0.04). None of the other illness-related variables were correlated to serum BDNF values in the first episode schizophrenia group.
Individuals with first-episode schizophrenia have lower serum BDNF levels than healthy controls. The illness-related factors such as duration of untreated psychosis or psychopathology were not correlated with BDNF levels. Thus abnormal signaling of BDNF can lead to abnormal brain functioning which can make an individual more susceptible to schizophrenia.
Peripheral blood BDNF-TrkB signaling in first-episode, drug-free patients with major depressive disorder and schizophrenia
2020, Neuroscience Letters
Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of psychiatric disorders, and studies have shown BDNF aberrations in major psychiatric diseases including schizophrenia (SCZ) and major depressive disorder (MDD). However, data from clinical studies were inconsistent. In this study, we recruited 34 patients with MDD, 77 patients with SCZ and 65 healthy control (HC) subjects to clarify the circulating BDNF levels in MDD and SCZ patients, and to assess whether serum BDNF levels were associated with the disease severity. Our results showed that serum BDNF levels were significantly decreased in the patients with SCZ (Mean difference = −4.517, 95%CI of difference = −7.854 to −1.180, p < 0.01) and MDD (Mean difference = −5.699, 95%CI of difference = −9.892 to −1.506, p < 0.01) when compared with HC subjects. Sub-group analyses suggested that BDNF levels were significantly reduced in the female SCZ (Mean difference = −5.700, 95%CI of difference = −10.21 to -1.189, p < 0.01) and MDD (Mean difference = −5.840, 95%CI of difference = −10.66 to −1.019, p < 0.05) patients, but not in male patients. Further analyses indicated that serum BDNF levels were not correlated with disease severity of MDD and SCZ. In addition, the transcriptional expression of TrkB was significantly down-regulated in the blood of MDD patients, but not in SCZ patients. However, there was no significant correlation between BDNF concentrations and TrkB mRNA levels. Taken together, our results revealed differential changes of BDNF-TrkB signaling in MDD and SCZ patients, therefore contributed to a better understanding of MDD and SCZ pathophysiology.
Adjunctive memantine for major mental disorders: A systematic review and meta-analysis of randomized double-blind controlled trials
2019, Schizophrenia Research
As a non-competitive N-methyl-d-aspartate receptor antagonist, memantine has been used to treat major mental disorders including schizophrenia, bipolar disorder, and major depressive disorder (MDD). This meta-analysis systematically investigated the effectiveness and tolerability of adjunctive memantine for patients with schizophrenia, bipolar disorder, and MDD.
Only randomized controlled trials (RCTs) were identified and included in the study. Data of the three disorders were separately synthesized using the RevMan 5.3 software.
Fifteen RCTs (n = 988) examining memantine (5–20 mg/day) as an adjunct treatment for schizophrenia (9 trials with 512 patients), bipolar disorder (3 trials with 319 patients), and MDD (3 trials with 157 patients) were analyzed. Memantine outperformed the comparator regarding total psychopathology with a standardized mean difference (SMD) of −0.56 [95% confidence interval (CI): −1.01, −0.11; I² = 76%, P = 0.01] and negative symptoms with an SMD of −0.71 (95% CI: −1.09, −0.33; I² = 74%, P = 0.0003) in schizophrenia, but no significant effects were found with regard to positive symptoms and general psychopathology in schizophrenia, or depressive and manic symptoms in bipolar disorder or depressive symptoms in MDD. Memantine outperformed the comparator in improving cognitive performance in schizophrenia with an SMD of 1.07 (95% CI: 0.53, 1.61; P < 0.0001, I² = 29%). No group differences were found in the rates of adverse drug reactions and discontinuation due to any reason in the three major mental disorders.
Memantine as an adjunct treatment appears to have significant efficacy in improving negative symptoms in schizophrenia. The efficacy and safety of adjunctive memantine for bipolar disorder or MDD needs to be further examined.
PROSPERO: 42018099045.
Brain-derived neurotrophic factor is associated with cognitive impairments in first-episode and chronic schizophrenia
2019, Psychiatry Research
Brain-derived neurotrophic factor (BDNF) may be related to the pathophysiology of schizophrenia. This study aims to examine the relation between plasma BDNF levels and the cognition of patients with schizophrenia. We recruited 31 patients with chronic schizophrenia, 34 first-episode patients, and 35 healthy control subjects. We examined the MATRICS Consensus Cognitive Battery (MCCB) and the plasma BDNF levels in all groups. The schizophrenic symptoms were assessed using the positive and negative syndrome scale. The BDNF levels of schizophrenic patients were remarkably lower than those of the controls. The cognitive MCCB global composite scores and part index scores of schizophrenic patients were remarkably lower than those of the controls. Moreover, remarkable correlations were observed between BDNF levels and partial cognitive dimensions, such as visual learning, memory, and processing speed. Therefore, BDNF may be involved in the pathophysiology and cognitive impairment of schizophrenia.

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Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and bipolar disorder

Abstract

Section snippets

Acknowledgement

Neurosci. Lett.

Neuron.

Neurosci. Lett.

Life Sci.

Prog. Neuropsychopharmacol. Biol. Psychiatry

Biol. Psychiatry

J. Psychiatr. Res.

Neurosci. Lett.

Prog. Neuropsychopharmacol. Biol. Psychiatry

Biol. Psychiatry

Am. J. Hum. Genet.

Neurosci. Lett.

Schizophr. Res.

Biochem. Biophys. Res. Commun.

J. Psychiatr. Res.

Neurosci. Lett.