Increased serum glial cell line-derived neurotrophic factor immunocontent during manic and depressive episodes in individuals with bipolar disorder (original) (raw)
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Neuroscience Letters, 2006
Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF) may be associated with the pathophysiology of bipolar disorder (BD). The present study investigated serum BDNF levels in manic, depressed, euthymic BD patients and in matched healthy controls, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum BDNF levels were decreased in manic (p = 0.019) and depressed (p = 0.027) BD patients, as compared with euthymic patients and controls. Serum BDNF levels were negatively correlated with the severity of manic (r = −0.37, p = 0.005) and depressive (r = −0.30, p = 0.033) symptoms. These findings further support the hypothesis that the BDNF signaling system may play a role in the pathophysiology of BD.
Neurotrophic factors in bipolar disorders patients with manic episode
TURKISH JOURNAL OF MEDICAL SCIENCES, 2020
Background/aim: Neurotrophins are one of the most important molecule groups affecting cerebral neuroplasticity. The amount of evidence about the role of changes in neuroplasticity in the pathophysiology of bipolar disease is growing. Materials and methods: We measured serum levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), glial cell-line derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor (FGF)-2, neuritin 1 (Nrn 1) in bipolar 1 manic episode patients (n = 45) and healthy control group. Results: When controlled for age, BMI and cortisol, it was found that the serum levels of BDNF, NGF, NT-3, VEGF and FGF-2 of bipolar manic episode patients were not statistically different compared to those of the control group. GDNF level and Nrn 1 levels were significantly lower (P = 0.003 and P = 0.025 respectively) while IGF-1 levels were significantly higher than the control group (P = 0.0001). ROC analysis was performed and the area under the the curve was calculated as 0.737, 0.766 for GDNF, IGF-1 respectively. Conclusion: The changes in the levels of GDNF, IGF-1 and Nrn 1 might be involved in pathopysiology of bipolar disorder, and GDNF, IGF-1 may be considered as state markers in bipolar manic episode.
Neuroscience Letters, 2010
Recent data indicate that neurotrophins may play a role in the physiopathology of bipolar disorder (BD) and may be useful as biomarkers of the disease. The aim of this study was to evaluate the plasma concentrations of brain-derived neurotrophic factor (BDNF) in BD patients, and to correlate their levels with clinical parameters. BDNF was measured in plasma from 53 BD type I subjects (34 during mania and 19 during euthymia) and 38 healthy controls by enzyme-linked immuno-sorbent assay (ELISA). Patients were assessed by a structured clinical interview (Mini-plus), Young mania and Hamilton depression rating scales. Plasma BDNF levels were significantly increased in patients with mania (P ≤ 0.001) and euthymia (P ≤ 0.001) when compared with controls, but did not correlate with any clinical parameters. BDNF concentration was higher in BD patients with 10 or more years of disease. BDNF plasma levels were increased in BD patients, mainly in those with a longer course of disease. In line with previous studies, it is conceivable that BDNF may play a role in the pathophysiology of BD.
Brain-derived neurotrophic factor and neuroplasticity in bipolar disorder
Expert Review of Neurotherapeutics, 2008
Initial descriptions of bipolar disorder (BD) emphasized that patients returned to a baseline condition after acute episodes. Such definitions were operational in teasing bipolar disorder apart from schizophrenia, where patients were described to be permanently impaired after the initial episodes. However, this view of BD as a disorder where cognition and overall functioning was spared has been changing after the scrutiny of new research. Currently, the cognitive impairment and neuroanatomical changes related to cumulative mood episodes, particularly manic episodes, are well described. In terms of neuropathological findings, recent data suggest that changes in neuronal plasticity, particularly in cell resilience and connectivity, are the main findings in BD. Data from differential lines of research converge to BDNF as an important contributor to the pathophysiology of BD. Serum BDNF levels have been shown to be decreased in depressive and manic episodes, returning to normal levels in euthymia. Moreover, factors that negatively influence the course of BD, such as life stress and trauma, have been shown to be associated with a decrease in serum BDNF levels among bipolar patients. These findings suggest that BDNF plays a central role in the transduction of psychosocial stress and recurrent episodes into the neurobiology of bipolar disorder. The present review discusses the role of BDNF as a mediator of the neuroplastic changes that occur in portion with mood episodes and the potential use of serum BDNF as a biomarker in BD.
Brain Sciences
Brain-derived neurotrophic factor (BDNF) plays a key role in brain development, contributing to neuronal survival and neuroplasticity. Previous works have found that BDNF is involved in several neurological or psychiatric diseases. In this review, we aimed to collect all available data on BDNF and bipolar disorder (BD) and assess if BDNF could be considered a biomarker for BD. We searched the most relevant medical databases and included studies reporting original data on BDNF circulating levels or Val66Met polymorphism. Only articles including a direct comparison with healthy controls (HC) and patients diagnosed with BD according to international classification systems were included. Of the 2430 identified articles, 29 were included in the present review. Results of the present review show a reduction in BDNF circulating levels during acute phases of BD compared to HC, which increase after effective therapy of the disorders. The Val66Met polymorphism was related to features usually ...
Journal of Affective Disorders, 2014
Background: Early detection and diagnosis of bipolar disorder can be difficult. Tools are needed to help clinicians detect bipolar disorder earlier, which would ameliorate the prognosis. Methods: ELISA kits that distinguish between mature brain derived neurotrophic factor (BDNF) and proBDNF, we compared serum levels of mature BDNF, proBDNF, and matrix metalloproteinase-9 (MMP-9) in two independent cohorts (Sahlgrenska cohort and Karolinska cohort) of mood-stabilized bipolar patients and healthy controls. The total sample size in both cohorts consisted of 263 (48þ215) bipolar patients and 155 (43þ112) healthy controls. Results: Levels of mature BDNF and the ratio mature BDNF/proBDNF were significantly higher in patients than in controls. Serum levels of proBDNF were significantly lower in patients compared to controls. Serum levels of MMP-9 did not differ between the groups but MMP-9 correlated positively and significantly with mature BDNF.
Circulating levels of GDNF in bipolar disorder
Neuroscience Letters, 2011
Neurotrophic factors regulate the survival and growth of neurons, and influence synaptic efficiency and plasticity. Several studies suggest the existence of a relationship between changes in neurotrophic levels and bipolar disorder (BD). The glial cell-line derived neurotrophic factor (GDNF) influences monoaminergic neurons and glial cells, but its role in BD patients is controversial. In order to elucidate it we evaluated plasma levels of GDNF in a sample of 70 BD patients (35 in mania and 35 in euthymia) and compared with 50 healthy controls matched for age, gender and educational levels. GDNF plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients were assessed by a Mini-International Neuropsychiatric Interview (MINI-plus), Young Mania and Hamilton Depression Rating Scales. Plasma GDNF levels were significantly increased in BD patients in euthymia compared with BD patients in mania and healthy controls (p < 0.05). GDNF plasma levels were correlated with age ( = 0.30, p < 0.05) and negatively correlated with manic symptoms in BD patients ( = −0.54, p < 0.05). Our results provide evidence that peripheral levels of GDNF are related with different mood states in BD, reinforcing the involvement of neurotrophic factors in its physiopathology.
Journal of Affective Disorders, 2014
Introduction: Glial Derived Neurotrophic Factor (GDNF) plays an important role in the survival and differentiation of neurons. We examined 5 0 upstream and 3 0 untranslated region of the GDNF gene by PCR amplification and direct sequencing to explore the effect of alteration in the potentially regulated part of GDNF in bipolar disorder. Materials and methods: Sixty-six patients with bipolar disorder, 27 first degree relatives of these patients and 56 healthy volunteers were screened for mutations and polymorphisms in GDNF gene. Results: Seven previously reported polymorphisms and additional three novel allele variants of GDNF were detected. Association test of rs2075680 C4 A SNP showed significant difference between patients and healthy subjects with higher allele frequency in healthy subjects performing Chi-square test. However, there was no significant difference after multiple test corrections between groups. There were no significant differences in association test of rs2075680 C 4A SNP between first degree relatives and healthy volunteers/patients. rs142426358 T 4C SNP was seen only in one patient with an early age of illness onset. New T4A alterations were found in chromosome locations 5:37812784 and 5:37812782 in two male bipolar disorder patients with age of illness onset 12 and 24 years. Limitations: The sample size was relatively small. Discussion: Our study proposes the suggestive association between polymorphisms in the potential regulatory sites of GDNF and bipolar disorder.
Plasma brain-derived neurotrophic factor in bipolar and unipolar depression
2010
Objective There is increasing evidence that Brain-Derived Neurotrophic Factor may be involved in the pathophysiology of depression and the actions of antidepressants. At the same time, the differential diagnosis between unipolar and bipolar depression is often a challenge with important treatment implications. The aim of the present study was to analyze the relationship between Brain-Derived Neurotrophic Factor levels and clinical variables in subjects with unipolar versus bipolar depression. Method Thirty-three outpatients (17 with unipolar and 16 with bipolar depression) and 15 healthy controls were consecutively enrolled at the Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies of the University of Pisa. Brain-Derived Neurotrophic Factor concentrations were measured with an enzyme-linked immunosorbent assay method. Severity of depression was assessed by means of the 21-item Hamilton Rating Scale for Depression and the Clinical Global Impressions-Severity of Illness scale. Fifteen healthy subjects, with no history of past or current chronic physical or mental disorders and not taking regular medications, were recruited as the control group. Results Compared to healthy controls, plasma Brain-Derived Neurotrophic Factor concentrations were significantly reduced in patients with unipolar or bipolar depression, with no significant difference between the two groups. Statistical analyses showed significant intergroup differences in the age of onset, presence of psychotic symptoms and cognitive disturbances (Table I). Significant and negative correlations were found in the total sample between Brain-Derived Neurotrophic Factor levels and the Hamilton Rating Scale for Depression total scores (r =-0.511, p = 0.002), the retardation factor scores (r =-0.416, p = 0.016) and Clinical Global Impressions "severity of illness" scores (r =-0.385, p = 0.027). When the same analyses were repeated in each group separately, these findings were confirmed only in patients with bipolar depression (Figs. 1, 2). Conclusion Our results show that lower Brain-Derived Neurotrophic Factor levels may be related to both severity of depression and retardation symptoms in bipolar depression. Further studies need to ascertain whether and how the Brain-Derived Neurotrophic Factor levels may be associated with any psychopathological dimensions of the depressive state and be used as a biological marker to differentiate bipolar from unipolar depression.