The Role of Kynurenines in Cognitive Dysfunction in Bipolar Disorder

2021 ◽  
pp. 1-8
Author(s):  
Kaat Hebbrecht ◽  
Manuel Morrens ◽  
Erik J. Giltay ◽  
Alexander L.N. van Nuijs ◽  
Bernard Sabbe ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Cognitive Functioning ◽  
Processing Speed ◽  
Verbal Memory ◽  
Large Scale ◽  
Bipolar Depression ◽  
Low Grade ◽  
Therapeutic Implications ◽  
Depression Group

<b><i>Introduction:</i></b> Chronic low-grade inflammation is suggested to play a pathophysiological role in bipolar disorder (BD) and its related cognitive dysfunctions. Although kynurenine (KYN) pathway metabolites are key inflammatory mediators, studies investigating the association between KYN metabolism and cognition in BD are scarce. We aimed to explore the relationship between KYN metabolism and cognitive functioning across different mood states in BD. <b><i>Methods:</i></b> Sixty-seven patients with BD (35 depressed and 32 [hypo] manic) and 29 healthy controls were included. Cognitive functioning was assessed at 3 time intervals (baseline, 4, and 8 months) assessing processing speed, sustained attention, verbal memory, working memory, and response inhibition. Plasma samples for quantification of 3-hydroxykynurenine, quinolinic acid, and kynurenic acid (KYNA) were concurrently provided. Linear mixed models were used for statistical analysis. <b><i>Results:</i></b> The manic group showed deficits in all assessed cognitive domains with the exception of verbal memory at all test moments. The bipolar depression group showed deficits in the processing speed at all test moments. Throughout the whole follow-up period, KYNA was significantly lower in both patient groups than in controls. Only in the bipolar depression group, low KYNA was associated with worse global cognitive functioning (<i>B</i> = 0.114, <i>p</i> = 0.02) and slower processing speed in particular (<i>B</i> = 0.139, <i>p</i> = 0.03). <b><i>Conclusion:</i></b> Only in the bipolar depression group, lower KYNA was associated with worse cognitive functioning. Future large-scale longitudinal studies are warranted to confirm the role of KYN metabolites in cognitive impairment in patients with BD and the possible therapeutic implications of this relationship.

scholarly journals High BDNF serum levels are associated to good cognitive functioning in bipolar disorder

2019 ◽  
Vol 60 ◽  
pp. 97-107 ◽  
Author(s):  
Ester Mora ◽  
Maria J. Portella ◽  
Gerard Piñol-Ripoll ◽  
Ricard López ◽  
Daniel Cuadras ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bipolar Disorder ◽  
Cognitive Functioning ◽  
Verbal Memory ◽  
Cognitive Outcome ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Bipolar Patients ◽  
And Oxidative Stress

AbstractBackground: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) individuals. Conversely, inflammatory (interleukin 6 (IL-6)) (p = 0.019) and oxidative stress (p = 0.003) measures were increased in bipolar individuals compared to controls. BDNF levels were associated with executive functioning (β = 0.01, p = 0.02) and verbal memory (β = 0.013, p = 0.005), together with other demographic variables. In particular, verbal memory was also associated with obesity (β=-0.04, p = 0.005). Neither inflammatory markers, oxidative stress markers nor other relevant clinical variables showed any association with cognitive outcome.Conclusions:Of all the peripheral neurobiological factors analysed, BDNF was the only one significantly associated with cognitive dysfunction in bipolar disorder individuals. This study emphasizes the role of BDNF not only across mood phases but also in cognitive functioning.

Association between physical frailty and cognition in late-life depression

2016 ◽  
Vol 33 (S1) ◽  
pp. S84-S84
Author(s):  
M. Arts ◽  
R. Collard ◽  
H. Comijs ◽  
M. Zuidersma ◽  
S. de Rooij ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Functioning ◽  
Processing Speed ◽  
Verbal Memory ◽  
Late Life ◽  
Interference Control ◽  
Late Life Depression ◽  
Physical Frailty ◽  
Cognitive Frailty ◽  
Frailty Criteria

IntroductionCognitive frailty has recently been defined as the co-occurrence of physical frailty and cognitive impairment. Late-life depression is associated with both physical frailty and cognitive impairment, especially processing speed and executive functioning.Aim and objectivesIn this study, we investigated the association between physical frailty and cognitive functioning in depressed older persons.MethodsIn a total of 378 patients (> 60 years) with depression according to DSM-IV criteria and a MMSE score of 24 points or higher, the physical frailty phenotype as well as its individual criteria (weight loss, weakness, exhaustion, slowness, low activity) was studied. Cognitive functioning was examined in 4 domains: verbal memory, working memory, interference control, and processing speed.ResultsOf the 378 depressed patients (range 60–90 years; 66.1% women), 61 were classified as robust (no frailty criteria present), 214 as prefrail (1 or 2 frailty criteria present), and 103 as frail (> 3 criteria). Linear regression analyses, adjusted for confounders, showed that the severity of physical frailty was associated with poorer verbal memory, slower processing speed, and decreased working memory, but not with changes in interference control.ConclusionIn late-life depression, physical frailty is associated with poorer cognitive functioning, although not consistently for executive functioning. Future studies should examine whether cognitive impairment in the presence of physical frailty belongs to cognitive frailty and is indeed an important concept to identify a specific subgroup of depressed older patients, who need multimodal treatment strategies integrating physical, cognitive, and psychological functioning.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Tumoral Drug Metabolism: Overview and Its Implications for Cancer Therapy

2005 ◽  
Vol 23 (1) ◽  
pp. 205-229 ◽  
Author(s):  
M. Michael ◽  
M.M. Doherty
Keyword(s):  
Cancer Therapy ◽  
Drug Metabolism ◽  
Large Scale ◽  
New Technologies ◽  
Drug Efficacy ◽  
Metabolizing Enzymes ◽  
Therapeutic Implications ◽  
Firm Data ◽  
The Individual

Drug-metabolizing enzymes (DME) in tumors are capable of biotransforming a variety of xenobiotics, including antineoplastics, resulting in either their activation or detoxification. Many studies have reported the presence of DME in tumors; however, heterogenous detection methodology and patient cohorts have not generated consistent, firm data. Nevertheless, various gene therapy approaches and oral prodrugs have been devised, taking advantage of tumoral DME. With the need to target and individualize anticancer therapies, tumoral processes such as drug metabolism must be considered as both a potential mechanism of resistance to therapy and a potential means of achieving optimal therapy. This review discusses cytotoxic drug metabolism by tumors, through addressing the classes of the individual DME, their relevant substrates, and their distribution in specific malignancies. The limitations of preclinical models relative to the clinical setting and lack of data on the changes of DME with disease progression and host response will be discussed. The therapeutic implications of tumoral drug metabolism will be addressed—in particular, the role of DME in predicting therapeutic response, the activation of prodrugs, and the potential for modulation of their activity for gain are considered, with relevant clinical examples. The contribution of tumoral drug metabolism to cancer therapy can only be truly ascertained through large-scale prospective studies and supported by new technologies for tumor sampling and genetic analysis such as microarrays. Only then can efforts be concentrated in the design of better prodrugs or combination therapy to improve drug efficacy and individualize therapy.

scholarly journals B-52 Improvements in Cognitive Functioning in Inactive Professional Fighters

2019 ◽  
Vol 34 (6) ◽  
pp. 998-998
Author(s):  
L Bennett ◽  
C Bernick ◽  
W Ng
Keyword(s):  
Reaction Time ◽  
Cognitive Functioning ◽  
Sample Size ◽  
Cognitive Performance ◽  
Processing Speed ◽  
Verbal Memory ◽  
Vital Signs ◽  
Health Study ◽  
Time Points ◽  
Increased Risk

Abstract Objective Repetitive head injuries common in combat sports have been associated with increased risk for cognitive dysfunction. Interestingly, the Professional Fighter’s Brain Health Study (PFBHS) team has observed improvements in fighters’ cognitive performance following their transition to inactive fighting status. As this phenomenon was explored, it was hypothesized that fighters’ cognitive performance will initially improve following their discontinuation of fighting. Methods Longitudinal demographic, fighting history, and cognitive functioning data from 31 fighters who discontinued fighting during their participation in the PFBHS. Cognitive functioning was assessed via CNS Vital Signs and C3/iComet computerized batteries. Number of professional fights, as well as inactive fighting status, was determined using published professional online records. Fighters were considered inactive if they had gone two or more years without a professional match. Results Paired-samples t test was conducted to evaluate cognitive functioning in fighters at time 1 (actively fighting) and time 2 (inactive fighting status). When comparing cognitive function at across time points, performance on CNS Vital Signs measures of verbal memory, processing speed, psychomotor speed, and reaction time, as well as C3/iComet measures of set-shifting and complex reaction time, significantly improved at time 2 (all p’s < 0.05). Interestingly, performance did not improve across time points on a C3/iComet measure of processing speed (Trailmaking Test Part A). Conclusions Cognitive performance improved on most measures when fighters transitioned to inactive fighting status. Given the limited sample size, future analysis is necessary to evaluate the relationship between fighting status and cognitive performance in a larger sample size.

Pharmacotherapy Update: Quetiapine use in Bipolar Disorder—What does the evidence tell us?

2009 ◽  
Vol 1 ◽  
pp. CMT.S1136
Author(s):  
Mark Taylor ◽  
Kirsty Mackay ◽  
Polash Shajahan
Keyword(s):  
Bipolar Disorder ◽  
Weight Gain ◽  
Large Scale ◽  
Maintenance Treatment ◽  
Bipolar Depression ◽  
Mood Stabiliser ◽  
Serious Illness ◽  
Randomized Controlled ◽  
Second Generation Antipsychotic

Bipolar disorder is a common and serious illness usually requiring long term medication. We critically review the available evidence surrounding the increasing use of quetiapine, a second generation antipsychotic, in both the acute and maintenance phases of bipolar disorder. Large scale, randomized controlled data supports the use of quetiapine in both acute mania and acute bipolar depression, as a safe and effective treatment and probably best used in combination with a traditional ‘mood stabiliser’ such as lithium or divalproex. Also, quetiapine monotherapy has been shown to be effective in bipolar depression. Two recently published studies also confirm that quetiapine in combination with either lithium or divalproex ‘adds value’ to the maintenance treatment of bipolar disorder in terms of delaying relapse compared to either lithium or divalproex alone. Quetiapine is generally well tolerated, although further work on long term weight gain and emergent diabetes would be helpful.

Impaired recognition of happy facial expressions in bipolar disorder

2014 ◽  
Vol 26 (4) ◽  
pp. 253-259 ◽  
Author(s):  
Linette Lawlor-Savage ◽  
Scott R. Sponheim ◽  
Vina M. Goghari
Keyword(s):  
Bipolar Disorder ◽  
Emotion Recognition ◽  
Facial Expressions ◽  
Processing Speed ◽  
Facial Emotion Recognition ◽  
Facial Emotion ◽  
Recognition Ability ◽  
Recognition Condition ◽  
Bipolar Patients

BackgroundThe ability to accurately judge facial expressions is important in social interactions. Individuals with bipolar disorder have been found to be impaired in emotion recognition; however, the specifics of the impairment are unclear. This study investigated whether facial emotion recognition difficulties in bipolar disorder reflect general cognitive, or emotion-specific, impairments. Impairment in the recognition of particular emotions and the role of processing speed in facial emotion recognition were also investigated.MethodsClinically stable bipolar patients (n = 17) and healthy controls (n = 50) judged five facial expressions in two presentation types, time-limited and self-paced. An age recognition condition was used as an experimental control.ResultsBipolar patients’ overall facial recognition ability was unimpaired. However, patients’ specific ability to judge happy expressions under time constraints was impaired.ConclusionsFindings suggest a deficit in happy emotion recognition impacted by processing speed. Given the limited sample size, further investigation with a larger patient sample is warranted.

scholarly journals The Role of Electroconvulsive Therapy (ECT) in Bipolar Disorder: Effectiveness in 522 Patients with Bipolar Depression, Mixed-state, Mania and Catatonic Features

2017 ◽  
Vol 15 (3) ◽  
pp. 359-371 ◽  
Author(s):  
Giulio Perugi ◽  
Pierpaolo Medda ◽  
Cristina Toni ◽  
Michela Mariani ◽  
Chiara Socci ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Electroconvulsive Therapy ◽  
Mixed State ◽  
Bipolar Depression

scholarly journals Bipolar disorder and substance misuse: pathological and therapeutic implications of their comorbidity and cross-sensitisation

2013 ◽  
Vol 202 (3) ◽  
pp. 172-176 ◽  
Author(s):  
Robert M. Post ◽  
Peter Kalivas
Keyword(s):  
Bipolar Disorder ◽  
Substance Use ◽  
Substance Misuse ◽  
Bipolar Illness ◽  
Cocaine Use ◽  
Therapeutic Implications ◽  
Positive Effects ◽  
The Common ◽  
Illness Progression

BackgroundBipolar disorder has a high co-occurrence with substance use disorders, but the pathophysiological mechanisms have not been adequately explored.AimsTo review the role of stress in the onset and recurrence of affective episodes and substance misuse.MethodWe review the mechanisms involved in sensitisation (increased responsivity) to recurrence of stressors, mood episodes and cocaine use.ResultsEvidence suggests that intermittent stressors, mood episodes and bouts of cocaine use not only show sensitisation to themselves, but cross-sensitisation to the others contributing to illness progression. Converseley, an understanding of the common mechanisms of sensitisation (such as regionally selective alterations in brain derived neurotrophic factor (BDNF) and hyperactivity of striatally based habit memories), could also result in single therapies (such as N-acetylcysteine) having positive effects in all three domains.ConclusionsThese interacting sensitisation processes suggest the importance of early intervention in attempting to prevent increasingly severe manifestations of bipolar illness and substance misuse progression.

scholarly journals Perform or wither: role of water users' associations in municipalities of Nepal

Water Policy ◽  
2019 ◽  
Vol 22 (S1) ◽  
pp. 90-106
Author(s):  
Sreoshi Singh ◽  
Krity Shrestha ◽  
Menaka Hamal ◽  
Anjal Prakash
Keyword(s):  
Large Scale ◽  
Water Systems ◽  
Low Grade ◽  
Water Shortages ◽  
Water Users ◽  
Two Cities ◽  
Long Time ◽  
User Groups ◽  
Supply Systems

Abstract In Nepal, water institutions have played a very significant role, and in Tansen and Damauli, the presence of user groups has indicated that proper management of water can help people avert critical water shortages. However, although in both Tansen and Damauli the user groups have been operating for a long time, their performances vary. In Tansen, infrastructural constraints tend to throw up challenges, although operational hazards associated with the supply systems are no less threatening. Moreover, there is large-scale corruption in the systems' upkeep and maintenance, allowing low grade vendors to operate in place of readily available efficient institutions. In Damauli, the systems have been rather perfectly managed, except for minor glitches from time to time. Funding has been good and community bonding has paid off. This paper delves into the community-managed water systems in the two cities and how the performance varies across them and the factors that play a role.

scholarly journals The role of multi-parametric magnetic resonance imaging (MRI) in early prediction of malignant transformation of low-grade Gliomas (A Systematic review)

2020 ◽  
Vol 5 (3) ◽  
pp. 014-029
Author(s):  
Mohammed Danfulani ◽  
Shamsuddeen Ahmad Aliyu
Keyword(s):  
Malignant Transformation ◽  
Large Scale ◽  
Reference List ◽  
Low Grade ◽  
Early Prediction ◽  
High Tendency ◽  
Hand Search ◽  
Low Grade Gliomas ◽  
Mri Studies

Introduction: Low-grade gliomas is the most common primary brain tumour, although the presentation may take up to two decades, there is high tendency of early malignant transformation which raise a growing concern. Multi-parametric MRI studies have the potential for predicting the early malignant transformation. Methods: A comprehensive electronic search of various databases was conducted together with forward tracking of the reference list to retrieve relevant qualitative primary studies. Moreover, hand search for journal that was not available electronically was also conducted. Through assessment of the relevant studies was ensured and the included studies were carefully selected. The relevant data was extracted by data extraction form recommended by Cochrane collaborations. Results: The search yielded 1158 which was narrowed down to eight (8) studies that satisfied the inclusion criteria. These studies are assessing the role of different MRI parameters in predicting the early malignant transformation of Low-grade gliomas. The risk of bias and the applicability concern of the included studies are low. Conclusion: Based on the findings of this review; Multi-parametric MRI studies have the potential of predicting the early malignant transformation of low-grade gliomas. There is need for high quality large scale, prospective studies on the role of multi-parametric MRI studies in early prediction of malignant transformation of LGGs and meta-analysis of these studies is highly recommended.

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