Serum neurotrophin-3 is increased during manic and depressive episodes in bipolar disorder (original) (raw)

Increased neurotrophin-3 in drug-free subjects with bipolar disorder during manic and depressive episodes

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.

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.

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.

Elevated neurotrophin-3 and neurotrophin 4/5 levels in unmedicated bipolar depression and the effects of lithium

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.

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.

Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: A systematic review and meta-regression analysis

Journal of Psychiatric Research, 2011

Brain-derived neurotrophic factor (BDNF) plays a central role in synaptic plasticity and neurogenesis. Bipolar disorder (BD) is among the most disabling of all psychiatric disorders and is associated with poor outcomes. Some studies suggest that BDNF levels decrease during mood states and remain normal during euthymia, but other studies have contradicted this paradigm. Therefore, the aim of this study was to perform a meta-analysis of all studies that measured peripheral BDNF levels in adults with BD. We conducted a systematic review using electronic databases. Inclusion criteria were studies that measured BDNF in plasma or serum in vivo in adult patients with BD. The resulting studies were compiled to measure the effect sizes (ESs) of the differences in BDNF levels between BD patients in different mood states and controls. Thirteen studies were included with a total of 1113 subjects. The BDNF levels were decreased in both mania and depression when compared to controls (ES À0.81, 95% CI À1.11 to À0.52, p < 0.0001 and ES À0.97, 95% CI À1.79 to À0.51, p ¼ 0.02, respectively). The BDNF levels were not different in euthymia when compared to controls (ES À0.20, 95% CI À0.61 to 0.21, p ¼ 0.33). Metaregression analyses in euthymia showed that age (p < 0.0001) and length of illness (p ¼ 0.04) influenced the variation in ES. There was also an increase in BDNF levels following the treatment for acute mania (ES À0.63, 95% CI À1.11 to À0.15, p ¼ 0.01). In conclusion, BDNF levels are consistently reduced during manic and depressive episodes and recover after treatment for acute mania. In euthymia, BDNF decreases with age and length of illness. These data suggest that peripheral BDNF could be used as a biomarker of mood states and disease progression for BD.

Biological aspects and candidate biomarkers for psychotic bipolar disorder: A systematic review

Psychiatry and Clinical Neurosciences, 2016

Aim: We carried out a systematic review of the available literature about potential biomarkers of psychotic bipolar disorder (BD-P), a specific subset presenting worse outcome and greater risk of relapse than non-psychotic bipolar disorder (BD-NP). Methods: We searched the main psychiatric databases (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles with the main topic of BD-P compared to schizophrenia/BD-NP/healthy controls (HC) written in English from 1994 to 2015 were included. Results: BD-P patients presented higher kynurenic acid levels in the cerebrospinal fluid, elevated anti-Saccharomyces cerevisiae antibodies levels, and lower serum levels of dehydroepiandrosterone sulfate and progesterone than BD-NP/HC. Event-related potentials abnormalities have been identified in BD-P with respect to BD-NP. BD-P patients also presented bigger ventricles but similar hippocampal volumes compared to BD-NP/HC. Although the results are contrasting, some cognitive deficits seemed to be related to the psychotic dimension of bipolar affective disorder, such as impairment in verbal/logical memory, working memory, verbal and semantic fluency and executive functioning. Finally, polymorphisms of genes, such as NRG1, 5HTTLPR (s), COMT, DAOA and some chromosome regions (16p12 and 13q), were positively associated with BD-P. Conclusion: Data about the identification of specific biomarkers for BD-P are promising, but most of them have not yet been replicated. They could lead the clinicians to an early diagnosis and proper treatment, thus ameliorating outcome of BD-P and reducing the biological changes associated with a long duration of illness. Further studies with bigger samples are needed to detect more specific biological markers of the psychotic dimension of bipolar affective disorder.

Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes

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.

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.