Cytokines in Bipolar Disorder: Recent Findings, Deleterious Effects But Promise for Future Therapeutics

CNS Spectrums ◽  
2011 ◽  
Vol 16 (7) ◽  
pp. 157-168 ◽  
Author(s):  
Elisa Brietzke ◽  
Raquel Stabellini ◽  
Rodrigo Grassi-Oliveira ◽  
Beny Lafer
Keyword(s):  
Bipolar Disorder ◽  
Potential Role ◽  
Neuronal Survival ◽  
Cell Loss ◽  
Protein Levels ◽  
Functional Polymorphisms ◽  
Extracellular Stimuli ◽  
Peripheral Production ◽  
Bipolar Patients ◽  
Pituitary Adrenal Axis

AbstractAn emerging body of evidence points to impairments in neuroplasticity, cell resilience, and neuronal survival as major pathophysiological mechanisms in bipolar disorder. Neuronal survival is influenced by several factors including an orchestrated action of neurotransmitters, hormones, and neurotrophins. Patients with bipolar disorder exhibit increased peripheral level of inflammatory mediators such as cytokines, mainly during acute mood episodes. These mediators interact in several pathways involved in regulation of mood and energy including hypothalamic-pituitary-adrenal axis and monoamine metabolism. Importantly, inflammatory cytokines have a potential role in controlling neuronal and glial cell loss that occurs during mood episodes, especially during mania, as they are the most powerful extracellular stimuli to apoptosis. Bipolar patients have been reported to show imbalanced peripheral production of cytokines both at the mRNA and protein levels, associated signal transduction machinery, as well as to have specific functional polymorphisms in the genes that encode these cytokines. Interestingly, lithium, valproate, and several antidepressants have demonstrated to have immunomodulatory properties. Growing evidence supports the involvement of inflammatory mechanisms in bipolar disorder, opening new paths of investigation using immunomodulatory medications. These findings can offer not only an opportunity of treating mood symptoms but also understanding and reverting neurobiological changes associated with the disorder.

scholarly journals Patients’ adherence to smartphone apps in the management of bipolar disorder: a systematic review

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Marie-Camille Patoz ◽  
Diego Hidalgo-Mazzei ◽  
Bruno Pereira ◽  
Olivier Blanc ◽  
Ingrid de Chazeron ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bipolar Disorder ◽  
Mobile Health ◽  
Smartphone Apps ◽  
Exclusion Criteria ◽  
Future Studies ◽  
Health Apps ◽  
Definition Of ◽  
Bipolar Patients ◽  
Digital Or

Abstract Background Despite an increasing number of available mental health apps in the bipolar disorder field, these tools remain scarcely implemented in everyday practice and are quickly discontinued by patients after downloading. The aim of this study is to explore adherence characteristics of bipolar disorder patients to dedicated smartphone interventions in research studies. Methods A systematic review following PRISMA guidelines was conducted. Three databases (EMBASE, PsychInfo and MEDLINE) were searched using the following keywords: "bipolar disorder" or "mood disorder" or “bipolar” combined with “digital” or “mobile” or “phone” or “smartphone” or “mHealth” or “ehealth” or "mobile health" or “app” or “mobile-health”. Results Thirteen articles remained in the review after exclusion criteria were applied. Of the 118 eligible studies, 39 did not provide adherence characteristics. Among the selected papers, study length, sample size and definition of measures of adherence were strongly heterogeneous. Activity rates ranged from 58 to 91.6%. Conclusion The adherence of bipolar patients to apps is understudied. Standardised measures of adherence should be defined and systematically evaluated in future studies dedicated to these tools.

scholarly journals Response Processes to Looming Appetitive and Aversive Cues in Euthymic Bipolar Patients and Their First-Degree Relatives: An Exploratory Study

2020 ◽  
pp. 025371762097528
Author(s):  
Velprashanth Venkatesan ◽  
Christoday R J Khess ◽  
Umesh Shreekantiah ◽  
Nishant Goyal ◽  
K. K. Kshitiz
Keyword(s):  
Bipolar Disorder ◽  
Healthy Controls ◽  
Sensitivity To Reward ◽  
Bipolar Group ◽  
First Degree Relatives ◽  
Vulnerability Model ◽  
Increased Sensitivity ◽  
Appetitive Cues ◽  
Spectrum Disorders ◽  
Bipolar Patients

Background: Patients with bipolar disorder demonstrate increased sensitivity to appetitive/rewarding stimuli even during euthymia. On presentation of arousing pictures, they show a peculiar response, suggesting heightened vigilance. While responding to looming arousing cues, studies show subjects with anxiety spectrum disorders exhibit increased reaction time (RT), explained by the “looming-vulnerability model.” This study aimed to investigate the responses to looming arousing cues in euthymic bipolar patients and their first-degree relatives, as compared to healthy controls. Method: A looming appetitive and aversive cue paradigm was designed for assessing the RT of patients to process appetitive and aversive cues. The behavioral inhibition/activation and sensitivity to reward/punishment amongst the groups were also assessed. Results: The bipolar group showed significantly longer RT to process appetitive cues irrespective of the looming condition. Aversive cues elicited significantly longer RT in both the bipolar group and in first-degree relatives, but only when presented with the looming condition. Significant looming bias was elicited in the bipolar group which suggested a particular cognitive style to looming cues. A composite measure of RT along with sensitivity to reward/punishment distinguishes the bipolar group and their first-degree relatives from the healthy controls. Conclusion: The looming vulnerability model may provide important insights for future exploration of cognitive endophenotypes in bipolar disorder.

Contribution of Growth Arrest-Specific 5/miR-674 to the Hypothalamus Pituitary Adrenal Axis Regulation Effect by Electroacupuncture following Trauma

2021 ◽  
pp. 1-13
Author(s):  
Jing Zhu ◽  
Chunxia Guo ◽  
Pingping Lu ◽  
Shuijin Shao ◽  
Bing Tu
Keyword(s):  
Hpa Axis ◽  
Interleukin 1 ◽  
Growth Arrest ◽  
Luciferase Assay ◽  
Function Evaluation ◽  
Protein Levels ◽  
Adrenal Axis ◽  
Post Surgery ◽  
Hypothalamus Pituitary Adrenal Axis ◽  
Pituitary Adrenal Axis

<b><i>Background:</i></b> Electroacupuncture (EA) can improve trauma-induced hypothalamus pituitary adrenal axis (HPA) hyperactivity. However, the mechanism underlying the EA effect has not been fully understood. <b><i>Methods and Study Design:</i></b> This study was undertaken to explore the role of hypothalamic growth arrest-specific 5 (Gas5) in the regulation of EA on HPA axis function post-surgery. Paraventricular nuclear Gas5 levels were upregulated in rats using an intracerebroventricular injection of pAAV-Gas5. Primary hypothalamic neurons and 293T cells were cultured for miRNA and siRNAs detection. Radioimmunoassay, PCR, Western blot, and immunohistochemistry were used for HPA axis function evaluation. <b><i>Results:</i></b> The overexpression of Gas5 abolished the effect of EA on the regulation of trauma-induced HPA axis hyperactivity. Using a bioinformatics analysis and dual luciferase assay, we determined that miRNA-674 was a target of Gas5. Additionally, miRNA-674 levels were found to have decreased in trauma rats, and this effect was reversed after EA intervention. TargetScan analysis showed that serum and glucocorticoid inducible kinase 1 (SGK1) were targets of miR-674. Moreover, we found that SGK1 protein levels increased in trauma rats and SGK1 expression inhibition alleviated HPA axis abnormality post-surgery. EA could improve the number of hypothalamus iba-1 positive cells and hypothalamic interleukin 1 beta protein expression. <b><i>Conclusions:</i></b> Our study demonstrated the involvement of the hypothalamic Gas5/miRNA-674/SGK1 signaling pathway in EA regulation of HPA axis function after trauma.

Blood Type and Bipolar Disorder

2002 ◽  
Vol 95 (3) ◽  
pp. 988-988
Author(s):  
Tamas Zonda ◽  
David Lester
Keyword(s):  
Bipolar Disorder ◽  
Blood Type ◽  
Type I ◽  
Type Ii ◽  
Bipolar Patients

Type I bipolar patients in Budapest were reported to have type O blood more often and types A and B blood less often than Type II bipolar patients.

Baseline and prodromal characteristics of first- versus multiple-episode mania in a French cohort of bipolar patients

2011 ◽  
Vol 27 (8) ◽  
pp. 557-562 ◽  
Author(s):  
J.-M. Azorin ◽  
A. Kaladjian ◽  
M. Adida ◽  
E. Fakra ◽  
E. Hantouche ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Suicide Attempts ◽  
Correct Diagnosis ◽  
Manic Episode ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Prodromal Phase ◽  
Multiple Episode ◽  
Patients At Risk ◽  
Bipolar Patients

AbstractObjective:To identify some of the main features of bipolar disorder for both first-episode (FE) mania and the preceding prodromal phase, in order to increase earlier recognition.Methods:One thousand and ninety manic patients (FE=81, multiple-episodes [ME]=1009) were assessed for clinical and temperamental characteristics.Results:Compared to ME, FE patients reported more psychotic and less depressive symptoms but were comparable with respect to temperamental measures and comorbid anxiety. The following independent variables were associated with FE mania: a shorter delay before correct diagnosis, greater substance use, being not divorced, greater stressors before current mania, a prior diagnosis of an anxiety disorder, lower levels of depression during index manic episode, and more suicide attempts in the past year.Conclusion:In FE patients, the diagnosis of mania may be overlooked, as they present with more psychotic symptoms than ME patients. The prodromal phase is characterised by high levels of stress, suicide attempts, anxiety disorders and alcohol or substance abuse. Data suggest to consider these prodromes as harmful consequences of temperamental predispositions to bipolar disorder that may concur to precipitate mania onset. Their occurrence should therefore incite clinicians to screen for the presence of such predispositions, in order to identify patients at risk of FE mania.

Risk and coaggregation of major psychiatric disorders among first-degree relatives of patients with bipolar disorder: a nationwide population-based study

2018 ◽  
Vol 49 (14) ◽  
pp. 2397-2404 ◽  
Author(s):  
Mu-Hong Chen ◽  
Ju-Wei Hsu ◽  
Kei-Lin Huang ◽  
Tung-Ping Su ◽  
Cheng-Ta Li ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Population Based ◽  
Autism Spectrum ◽  
The Public ◽  
First Degree Relatives ◽  
Relative Risks ◽  
Dependent Relationship ◽  
Increased Risk ◽  
Bipolar Patients

AbstractBackgroundBipolar disorder is a highly heritable mental illness that transmits intergeneratively. Previous studies supported that first-degree relatives (FDRs), such as parents, offspring, and siblings, of patients with bipolar disorder, had a higher risk of bipolar disorder. However, whether FDRs of bipolar patients have an increased risk of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) remains unclear.MethodsAmong the entire population in Taiwan, 87 639 patients with bipolar disorder and 188 290 FDRs of patients with bipolar disorder were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with bipolar disorder.ResultsFDRs of patients with bipolar disorder were more likely to have a higher risk of major psychiatric disorders, including bipolar disorder (RR 6.12, 95% confidence interval (CI) 5.95–6.30), MDD (RR 2.89, 95% CI 2.82–2.96), schizophrenia (RR 2.64, 95% CI 2.55–2.73), ADHD (RR 2.21, 95% CI 2.13–2.30), and ASD (RR 2.10, 95% CI 1.92–2.29), than the total population did. These increased risks for major psychiatric disorders were consistent across different familial kinships, such as parents, offspring, siblings, and twins. A dose-dependent relationship was also found between risk of each major psychiatric disorder and numbers of bipolar patients.ConclusionsOur study was the first study to support the familial coaggregation of bipolar disorder with other major psychiatric disorders, including schizophrenia, MDD, ADHD, and ASD, in a Taiwanese (non-Caucasian) population. Given the elevated risks of major psychiatric disorders, the public health government should pay more attention to the mental health of FDRs of patients with bipolar disorder.

scholarly journals Age at onset, course of illness and response to psychotherapy in bipolar disorder: results from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

2014 ◽  
Vol 44 (16) ◽  
pp. 3455-3467 ◽  
Author(s):  
A. Peters ◽  
L. G. Sylvia ◽  
P. V. da Silva Magalhães ◽  
D. J. Miklowitz ◽  
E. Frank ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Collaborative Care ◽  
Bipolar Depression ◽  
Age At Onset ◽  
Number Needed To Treat ◽  
Systematic Treatment ◽  
Illness Duration ◽  
Bipolar Patients ◽  
Depressive Episodes ◽  
Intensive Psychotherapy

Background.The course of bipolar disorder progressively worsens in some patients. Although responses to pharmacotherapy appear to diminish with greater chronicity, less is known about whether patients' prior courses of illness are related to responses to psychotherapy.Method.Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy with collaborative care (a three-session psycho-educational intervention). We assessed whether the number of previous mood episodes, age of illness onset, and illness duration predicted or moderated the likelihood of recovery and time until recovery from a depressive episode in patients in the two treatments.Results.Independently of treatment condition, participants with one to nine prior depressive episodes were more likely to recover and had faster time to recovery than those with 20 or more prior depressive episodes. Participants with fewer than 20 prior manic episodes had faster time to recovery than those with 20 or more episodes. Longer illness duration predicted a longer time to recovery. Participants were more likely to recover in intensive psychotherapy than collaborative care if they had 10–20 prior episodes of depression [number needed to treat (NNT) = 2.0], but equally likely to respond to psychotherapy and collaborative care if they had one to nine (NNT = 32.0) or >20 (NNT = 9.0) depressive episodes.Conclusions.Number of previous mood episodes and illness duration are associated with the likelihood and speed of recovery among bipolar patients receiving psychosocial treatments for depression.

Quality of life in bipolar disorders compared to schizophrenia

2011 ◽  
Vol 26 (S2) ◽  
pp. 231-231
Author(s):  
L. Zouari ◽  
I. Abida ◽  
M. Walha ◽  
J. Masmoudi ◽  
J. Ben Thabet ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Bipolar Disorder ◽  
Short Form ◽  
Age At Onset ◽  
Bipolar Disorders ◽  
Subscale Score ◽  
Sf 36 ◽  
Schizophrenic Patients ◽  
Bipolar Patients

IntroductionThe classic opinion of a favorable prognosis of bipolar disorders, compared to schizophrenia, is refuted by modern conceptions.ObjectivesThe aim of this study was to assess the quality of life (QOL) in bipolar patients compared to schizophrenic patients’, and to identify clinical and sociodemographic variables statistically associated to a poor QOL in bipolar disorder patients.MethodsOne hundred and twenty outpatients, 50 with bipolar disorder and 70 with schizophrenia, according to DSM-IV-TR criteria, were included in the study. The QOL has been assessed, in all patients, using the «36 item Short-Form Health Survey» (SF-36).ResultsThirty-six percent of the bipolar patients had a poor QOL, versus 37% among the schizophrenic patients. The bipolar patients had the score of the standardized vitality subscale significantly lower than schizophrenic patients’ (p = 0.036); the latter had the standardized general health subscale score significantly lower (p = 0.03). There were no other statistically significant differences. The multivariate analyses showed three variables significantly correlated to a poor QOL in bipolar patients: age at the time of the study ≥ 40 years (p = 0.01), professional irregularity or inactivity (p = 0.005), age at onset ≥ 25 years (p = 0.004).ConclusionOur survey of the QOL in bipolar patients showed that it did not differ globally from the schizophrenic patients’, with the SF-36 scale. Results reported in the literature are not in agreement. Further longitudinal studies on several months, with other assessments, would permit to verify the validity of our results.

Thought overactivation as a marker of bipolar disorder

2016 ◽  
Vol 33 (S1) ◽  
pp. s222-s223 ◽  
Author(s):  
M. Ferrari ◽  
P. Ossola ◽  
V. Lucarini ◽  
V. Accardi ◽  
C. De Panfilis ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Mood Disorders ◽  
Subjective Experience ◽  
Small Sample Size ◽  
Mental States ◽  
Small Sample ◽  
Bipolar Spectrum ◽  
Global Functioning ◽  
Competing Interest ◽  
Bipolar Patients

IntroductionRecent studies have underlined the importance of considering the form of thoughts, beyond their content, in order to achieve a better phenomenological comprehension of mental states in mood disorders. The subjective experience of thought overactivation is an important feature of mood disorders that could help in identifying, among patients with a depressive episode, those who belong to the bipolar spectrum.ObjectivesPatients with a diagnosis of bipolar disorder (BD) were compared with matched healthy controls (HC) on a scale that evaluates thought overactivation.AimsValidate the Italian version of a scale for thought overactivation (i.e. STOQ) in a sample of bipolar patients.MethodsThirty euthymic BD and 30 HC completed the Subjective Thought Overactivation Questionnaire (STOQ), the Ruminative Responses Scale (RRS), the Beck Depression Inventory-II (BDI-II) and global functioning (VGF).ResultsThe 9-items version of the STOQ has been back translated and its internal consistency in this sample was satisfactory (alpha = .91). Both the brooding subscore of RRS (b-RRS) (r = .706; P < .001) and STOQ (r = .664; P < .001) correlate significantly with depressive symptoms whereas only the first correlate with VGF (r = –.801; P < .001). The two groups did not differed in the b-RRS (HC = 8.41 vs BD = 9.72; P = .21), whereas BD where significantly higher in the STOQ total score (HC = 6.62 vs. BD = 14.9; P = .007).ConclusionOur results, although limited by the small sample size, confirm the validity of the STOQ and suggest that this scale could grasp a feature characteristic of BD, independently from their tendency to ruminate. The latter seems to impact more on global functioning.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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