P01-171 Increased serum neurotrophin-4/5 levels in bipolar disorder (original) (raw)
Related papers
Increased serum neurotrophin-4/5 levels in bipolar disorder
Journal of Psychiatric Research, 2009
Neurotrophins are central to several aspects of central nervous system function, and emerging evidence links these growth factors to mood disorders. The purpose of this study was to investigate serum neurotrophin-4/5 (NT-4/5) levels in patients with bipolar disorder, both within mood episodes and in euthymia. Patients with bipolar I disorder (n = 154) and controls (n = 30) had their NT-4/5 serum levels assayed using an ELISA. Levels of NT-4/5 levels were significantly higher in bipolar disorder patients than in controls; NT-4/5 levels were increased in mania, depression and euthymia, but not significantly different between BD mood states. As far as are aware, this is the first study showing NT-4/5 immunocontent alterations in bipolar disorder. A tentative explanation would be that NT-4/5 increases is compensating for ongoing oxidative damage in dopaminergic neurons.
Decreased plasma neurotrophin-4/5 levels in bipolar disorder patients in mania
Revista Brasileira de Psiquiatria, 2014
Objective: To evaluate two poorly explored neurotrophins (NT), NT-3 and NT-4/5, in bipolar disorder (BD). Methods: Forty patients with type I BD (18 in remission and 22 in mania) and 25 healthy controls matched for age, gender, and educational attainment were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview; the Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to evaluate severity of symptoms in BD patients. Plasma levels of NT-3 and NT-4/5 were measured by enzyme-linked immunosorbent assay (ELISA). Results: BD patients in mania presented decreased NT-4/5 plasma levels in comparison with controls (p , 0.05). There were no significant differences in NT-3 plasma levels between BD patients and controls. Conclusion: These findings corroborate the view that neurotrophin dysfunction is associated with mood states in patients with BD.
Serum neurotrophin-3 is increased during manic and depressive episodes in bipolar disorder
Neuroscience Letters, 2007
Accumulating evidence suggest that neural changes and cognitive impairment may accompany the course of bipolar disorder. Such detrimental effects of cumulative mood episodes may be related to changes in neurotrophins that take place during mood episodes but not during euthymic phases. The present study investigated serum neurotrophin-3 (NT-3) levels in patients with bipolar disorder during manic, depressed, and euthymic states, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum NT-3 levels were increased in manic (p < 0.001) and depressed (p < 0.001) BD patients, as compared with euthymic patients and normal controls. These findings suggest that the NT-3 signaling system may play a role in the pathophysiology of BD.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2015
Elevated neurotrophin-3 and neurotrophin 4/5 levels in unmedicated bipolar depression and the effects of lithiumAbstract Background: Bipolar disorder (BD) has been associated with diverse abnormalities in neural plasticity and cellular resilience. Neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) support synaptic neuronal survival and differentiation. NT-3 and NT-4/5 levels were found to be altered in BD, potentially representing a physiological response against cellular stress. However, the use of psychopharmacological agents and heterogeneous mood states may constitute important biases in such studies. Thus, we aimed to assess NT-3 and NT-4/5 levels in medication-free BD type I or II individuals in a current depressive episode, before and after 6 weeks of lithium monotherapy and matched with healthy controls.
Journal of Psychiatric Research, 2010
Bipolar disorder (BD) has been increasingly associated with abnormalities in neuroplasticity. Previous studies demonstrated that neurotrophin-3 (NT-3) plays a role in the pathophysiology of mood disorders. The influence of medication in these studies has been considered a limitation. Thus, studies with drugfree vs. medicated patients are necessary to evaluate the role of medication in serum NT-3 levels. About 10 manic and 10 depressive drug-free, and 10 manic and 10 depressive medicated patients with BD type I were matched with 20 controls for sex and age. Patients were assessed using SCID-I, YMRS and HDRS. Serum NT-3 levels in drug-free and medicated patients is increased when compared with controls (2.51 ± 0.59, 2.56 ± 0.44 and 1.97 ± 0.33, respectively, p < 0.001 for drug-free/medicated vs. control). Serum NT-3 levels do not differ between medicated and drug-free patients. When analyzing patients according to mood states, serum NT-3 levels are increased in both manic and depressive episodes, as compared with controls (2.47 ± 0.43, 2.60 ± 0.59 and 1.97 ± 0.33, respectively, p < 0.001 for manic/depressive patients vs. controls). There is no difference in serum BDNF between manic and depressive patients. Results suggest that increased serum NT-3 levels in BD are likely to be associated with the pathophysiology of manic and depressive symptoms.
Neurotrophins, inflammation and oxidative stress as illness activity biomarkers in bipolar disorder
Expert Review of Neurotherapeutics, 2013
Recent studies highlight the presence of systemic toxicity as an integral dimension of bipolar disorder pathophysiology, possibly linking this mood disorder with other medical conditions and comorbidities. This review summarizes recent findings on possible peripheral biomarkers of illness activity, with a focus on neurotrophins, inflammation and oxidative stress. The possible mechanisms underlying the systemic toxicity associated with acute episodes in bipolar disorder are also discussed. Finally, the authors outline novel therapies that emerge from this new research and the assessment of multiple biomarkers as a potential approach to improving management strategies in bipolar disorder.
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.
Neurotrophic and inflammatory markers in bipolar disorder: A prospective study
Psychoneuroendocrinology, 2017
Altered neurotrophic signaling is thought to impair neuroplasticity in bipolar disorder (BD). Brain-derived neurotrophic factor (BDNF) is proposed as a neurotrophic marker in BD. However, the current evidence for its use in monitoring disease activity and illness progression is conflicting and an exploration of additional neurotrophic markers is needed. This prospective case-control study investigated mood-specific changes in potential neurotrophic markers and their association to inflammatory activity. Patients with BD were included during an acute mood episode, either depressive (n = 35) or (hypo)manic (n = 32). Fifty-nine patients (88%) and 29 healthy controls (97%) completed the study. Peripheral blood levels of BDNF, vascular endothelial growth factor A (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and tumor necrosis factor alpha (TNF-α) were measured at baseline and after 2 months. Biomarker levels in patients were compared to controls and correlated to HDRS-17 and YMRS total scores and the PANSS positive subscale scores. Linear mixed model analysis revealed no significant differences in neurotrophic markers between patients and controls. We found significantly increased TNF-α levels in patients and a subsequent normalization during euthymia. None of the biomarkers strongly correlated to mood symptom severity. Despite standardized methodological practices, BDNF and VEGF levels had a wide distribution range. We need a better understanding of methodological aspects influencing the analysis of neurotrophic factors to improve future research on markers for mood state monitoring and illness progression in BD.
Biological hypotheses and biomarkers of bipolar disorder
Psychiatry and Clinical Neurosciences, 2016
The most common mood disorders are major depressive disorders and bipolar disorders (BD). The pathophysiology of BD is complex, multifactorial, and not fully understood. Creation of new hypotheses in the field gives impetus for studies and for finding new biomarkers for BD. Conversely, new biomarkers facilitate not only diagnosis of a disorder and monitoring of biological effects of treatment, but also formulation of new hypotheses about the causes and pathophysiology of the BD. BD is characterized by multiple associations between disturbed brain development, neuroplasticity, and chronobiology, caused by: genetic and environmental factors; defects in apoptotic, immune-inflammatory, neurotransmitter, neurotrophin, and calcium-signaling pathways; oxidative and nitrosative stress; cellular bioenergetics; and membrane or vesicular transport. Current biological hypotheses of BD are summarized, including related pathophysiological processes and key biomarkers, which have been associated with changes in genetics, systems of neurotransmitter and neurotrophic factors, neuroinflammation, autoimmunity, cytokines, stress axis activity, chronobiology, oxidative stress, and mitochondrial dysfunctions. Here we also discuss the therapeutic hypotheses and mechanisms of the switch between depressive and manic state.