Biological determinants of functioning in euthymic patients with Bipolar Disorder: A multicentric 3-year cohort study (original) (raw)
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High BDNF serum levels are associated to good cognitive functioning in bipolar disorder
European Psychiatry, 2019
Background:Neurotrophins such as brain-derived neurotrophic factor (BDNF), inflammation and oxidative damage may contribute to the pathophysiology of bipolar disorder (BD) in terms of illness activity. To date, there is a lack of studies linking the cognitive impairment observed in BD with these neurobiological mechanisms. This study aimed to investigate the role of these neurobiological factors in clinical and cognitive outcomes in a sample of bipolar individuals.Methods:We measured serum BDNF, cytokines and oxidative stress markers in a sample of 133 individuals: 52 euthymic bipolar patients, 32 manic patients and 49 healthy controls. They were all assessed with a comprehensive cognitive battery. Sociodemographic and clinical data were collected. Multiple linear regression models were built to study associations of neurotrophins and inflammatory and oxidative measures with cognitive functioning.Results:BDNF levels were decreased in euthymic (p = 0.039) and manic (p < 0.001) ind...
Background: Despite the old Kraepelinean concept that bipolar disorder (BD) does not evolve with cognitive decline, the presence of cognitive impairment, especially executive dysfunction has been recognized in BD patients. Brain-derived neurotrophic factor (BDNF) and proinflammatory molecules are important contributors to the pathophysiology of BD, and imbalance in peripheral levels of these molecules may be implicated in the cognitive decline observed in BD patients. We aimed to investigate the executive performance of BD type I euthymic patients and its relation with the plasma levels of BDNF, TNF-α and its related soluble receptors (sTNFR1 and sTNFR2). Methods: We evaluated executive functioning through the Frontal Assessment Battery (FAB). Plasma levels of BDNF, TNF-α, sTNFR1 and sTNFR2 were measured using enzyme-linked immunosorbent assay (ELISA) in 25 euthymic type I BD patients and 25 age and gender matched healthy controls. Results: BD patients had an impairment in executive functioning (p b 0.006), particularly sensitivity of interference (p = 0.02), inhibitory control (p = 0.02), and increased BDNF plasma levels (p = 0.001) in comparison with controls. Plasma levels of TNF-α were correlated with inhibitory control in BD patients (ρ = 0.50, p = 0.02) while motor programming was negatively correlated with sTNFR2 plasma levels (ρ = − 0.47, p = 0.02) in controls. Executive function correlated with age and MMSE, but not with BDNF, neither was influenced by psychiatric and clinical comorbidities nor medications in use. Conclusion: BDNF is altered in BD but do not correlate with executive functioning.
Brain Behavior and Immunity, 2020
Background: Bipolar disorder (BD) is one of the most disabling mental health conditions in the world. Symptoms of cognitive impairment in BD contribute directly to occupational and social deficiencies and are very difficult to treat. Converging evidence suggests that BD patients have increased peripheral markers of inflammation. The hypothesis of neuroprogression in BD postulates that cognitive deficits develop over the course of the illness and are influenced by prior severe mood episodes, leading to wear-and-tear on the brain-however, there exists a paucity of data statistically testing a mediating role of immune molecules in cognitive dysfunction in BD. Methods: This is a cross-sectional study. We measured serum levels of tumor necrosis factor alpha (TNF-α), and soluble (s) TNF receptors one and two (sTNF-R1 and sTNF-R2) in 219 euthymic BD patients and 52 Healthy Controls (HCs). Structural equation modeling (SEM) was used for the primary purpose of assessing whether TNF markers (measured by the multiple
Objective: In this article, we focus on assessing two key predictors of outcomes in Bipolar Disorder (BD): cognition and functionality performance, and researching for a correlation between them. Methods: Subjects were patients with BD in the euthymic phase (n=50), and healthy controls (n=25). Psychosocial functioning was evaluated using the Functioning Assessment Short Test (FAST), and the same group underwent the Frontal Assessment Battery (FAB) to assess the Executive Functions (EF). Clinical and sociodemographic characteristics were analyzed using one-way analysis of variance or the chisquare test. To verify a correlation between FAB and FAST tests, we used the Spearman Correlation Coefficient. Results: Patients with BD showed higher FAST total scores (24.60±11.09) than healthy controls (9.80±5.94) (p< 0.001), and patients with BD showed lower FAB total scores (13.56±2.81) than healthy control (15.72±1.64) (p<0.001). Associated with these results, bipolar patients showed higher FAST scores in all domains predominantly with moderate impairment (score 21-40), and also lower scores in the following three domains: conceptualization, sensitivity to interference, and inhibitory control in the FAST test (p<0.05). The correlation between the variables FAB and FAST presented a moderate intensity (r 2 =-0.539). Conclusion: This study reinforced the impact of BD in functionality and the EF, demonstrating alterations in several domains: social, occupational, and cognitive functions impairment. Understanding them is crucial for these patients, which increases the possibility of rehabilitation and the response to treatment. I. INTRODUCTION Bipolar Disorder (BD) is a chronic and severe disease that affects approximately 1.1% of the world population and is associated with a high rate of morbidity, mortality, suicide, and clinical comorbidities [1]. Its pathophysiology is complex, multifactorial, and is not yet fully understood, being influenced by genetic and environmental factors [2]. Multiple changes occur in the brain, such as neuroplasticity, neurotransmission failures, apoptosis, activation in the immune-inflammatory process, and more recently, oxidative stress [3]. These events involve a pathological reorganization in the brain and therefore are associated with morphological modifications, such as the reduced volume of the Luiz Arthur Rangel Cyrino et. al.
BJPsych Open, 2021
Background Neurobiological research frequently implicates inflammatory and neurogenic components with core aspects of bipolar disorder. Even in periods of symptom remission (euthymia), individuals with bipolar disorder experience cognitive impairments, which are increasingly being proposed as an outcome for interventions; identifying biomarkers associated with cognitive impairment in people with bipolar disorder could advance progress in this therapeutic field through identifying biological treatment targets. Aims We aimed to identify proteomic biomarker correlates of cognitive impairment in individuals with euthymic bipolar disorder. Method Forty-four adults with a bipolar disorder diagnosis in euthymia underwent a battery of cognitive assessments and provided blood for biomarkers. We examined a comprehensive panel of inflammatory and trophic proteins as putative cross-sectional predictors of cognition, conceptualised according to recommended definitions of clinically significant c...
Levels of TNF-α, soluble TNF receptors (sTNFR1, sTNFR2), and cognition in bipolar disorder
Human Psychopharmacology: Clinical and Experimental, 2013
Objective Tumor necrosis factor-alpha (TNF-a) may play an important role in bipolar disorder (BD) pathogenesis. There is only one study about a relationship between TNF-a levels and cognitive impairments in BD. The aim of the present study was to see whether TNF-a, soluble P55 TNF receptor (sTNFR1), and soluble P75 TNF receptor (sTNFR2) levels in BD patients are different from controls and to investigate the relationships between the levels of TNF-a, sTNFR1, and sTNFR2 and the cognitive functions in euthymic BD patients and controls. Methods We assessed 54 BD type I patients and 18 controls by using a battery of neuropsychological tests. Serum TNF-a levels were measured using a commercially available enzyme-linked immunosorbent assay, whereas serum sTNFR1 and sTNFR2 levels were measured using a commercially enzyme-amplified sensitivity immunoassay kit. Results We found that levels of sTNFR1 and sTNFR2 in BD patients were different from controls. No difference was detected between the BD group and the control group for levels of TNF-a. TNF-a level was found to have a negative correlation with the delayed recall in RAVLT. Conclusions High levels of sTNFR1 and sTNFR2 in euthymic patients showed that it may support that proinflammatory process continues in euthymic period. This is the first study which showed increased sTNFR2 levels in euthymic period, which could be interpreted as a compensatory mechanism and again the first which deals with verbal memory.
In this study, we focus on assessing two key predictors and outcomes in Bipolar Disorder (BD), which are: cognition and functionality performance, dividing them into two subgroups, and then researching for a correlation between them. Methods; Fifty patients with BD in a euthymic phase were divided into two subgroups (≤ 3 years (n=25) and ≥ 10 years (n=25) of the disease) and were then compared with healthy controls (n=25). Psychosocial functioning was assessed using the Short Functionality Assessment Test (FAST), and the Frontal Assessment Battery (FAB) test to assess frontal cognitive functions. Clinical and sociodemographic characteristics were analyzed using unilateral variance analysis, or the chi-square test. In order to verify the correlation between the FAB and FAST tests, Spearman's correlation coefficient test was used Results: Both subgroups of euthymic patients had higher FAST total scores than the healthy control group (9.80 ± 5.94). The groups with ≤ 3 years (20.63 ± 8.21), and ≥ 10 years (27.80 ± 12.50) of the disease presented(p<0.001). Associated with these results, bipolar patients had higher FAST scores in all domains, predominantly with moderate impairment (score 21-40), and lower scores in the following four FAB test domains: conceptualization, sensitivity to interference, inhibitory control, and motor series (p<0.05). The correlation between the FAB and FAST tests showed moderate intensity (r 2 =-0.539). Conclusion: This study reinforced the impact of BD on functionality and frontal cognitive functions, demonstrating changes in several domains, and impairment in social, occupational, and cognitive functions in patients with different times of disease onset. Understanding all factors is essential for these patients, which increases the possibility of rehabilitation and response to treatment.
Cognitive profiles in euthymic patients with bipolar disorders: results from the FACE-BD cohort
Bipolar disorders, 2017
Although cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, little is known about cognitive phenotype heterogeneity among patients with BD. We investigated neuropsychological performance in 258 euthymic patients with BD recruited via the French network of expert centers for BD. We used a test battery assessing six domains of cognition. Hierarchical cluster analysis of the cross-sectional data was used to determine the optimal number of subgroups and to assign each patient to a specific cognitive cluster. Subsequently, subjects from each cluster were compared on demographic, clinical functioning, and pharmacological variables. A four-cluster solution was identified. The global cognitive performance was above normal in one cluster and below normal in another. The other two clusters had a near-normal cognitive performance, with above and below average verbal memory, respectively. Among the four clusters, significant differences...
Clinical practice and epidemiology in mental health : CP & EMH, 2017
Cognitive impairment may affect patients with Bipolar Disorder (BD) beyond the acute episodes, qualifying as a potential endophenotype. However, which cognitive domains are specifically affected in euthymic patients with BD and the potential influence of confounding factors (e.g., age and concomitant pharmacological treatment) are still a matter of debate. The present study was, therefore, conducted to assess cognitive performance across specific domains in euthymic bipolar patients, not older than 50 years (to avoid potential age-related bias) versus healthy controls (HCs). A cognitive task battery, including the Wisconsin Card Test, Span Attention Test, Tower of London, Trail Making Test, Verbal Fluency Test, Matrices Scores and N-Back, was administered to 62 subjects (30 bipolar patients and 32 matched HCs) and differences between the groups analyzed. Bipolar patients performed significantly worse than HCs in the Span Forward task, in the expression of Verbal Fluency Test (Catego...