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Journal of Affective Disorders Jun 2018Epigenetic mechanisms have been suggested to play a key role in the pathophysiology of bipolar disorder (BD), among which microRNAs (miRNAs) may be of particular... (Review)
Review
BACKGROUND
Epigenetic mechanisms have been suggested to play a key role in the pathophysiology of bipolar disorder (BD), among which microRNAs (miRNAs) may be of particular significance according to recent studies. We aimed to summarize miRNA studies in BD to identify consistent findings, limitations, and future directions of this emerging field.
METHODS
We performed a comprehensive search on PUBMED and Medline for studies investigating an association between BD and miRNAs. The included studies report miRNA alterations in postmortem brain tissues and in the periphery, cell culture and preclinical findings, genetic associations, and the effects of medications.
RESULTS
Several studies report changes in miRNA expression levels in postmortem brain and in the periphery of patients, although most of the results so far have not been replicated and are not concordant between different populations. Genetic studies also suggest that miRNA genes are located within susceptibility loci of BD, and also a putative role of miRNAs in modulating genes previously shown to confer risk of BD.
LIMITATIONS
We did not perform a systematic review of the literature, and miRNAs represent only one facet of the plethora of epigenetic mechanisms that might be involved in BD's pathophysiology.
CONCLUSIONS
miRNA findings in BD significantly vary between studies, but are consistent to suggest a key role for these molecules in BD's pathophysiology and treatment, particularly miR-34a and miR-137. Accordingly, miRNA might represent important biomarkers of illness to be used in the clinical settings, and potentially also for the development of novel therapeutics for BD in the near future.
Topics: Bipolar Disorder; Brain; Epigenomics; Genetic Markers; Humans; MicroRNAs; Transcriptome
PubMed: 28969861
DOI: 10.1016/j.jad.2017.09.025 -
Journal of Affective Disorders Aug 2023Bipolar disorder is a severe and chronic mental illness characterized by recurrent major depressive episodes and mania or hypomania. In addition to the burden of the... (Review)
Review
BACKGROUND
Bipolar disorder is a severe and chronic mental illness characterized by recurrent major depressive episodes and mania or hypomania. In addition to the burden of the disease and its consequences, self-stigma can impact people with bipolar disorder. This review investigates the current state of research in self-stigma in bipolar disorder.
METHODS
An electronic search was carried out until February 2022. Three academic databases were systematically searched, and best-evidence synthesis was made.
RESULTS
Sixty-six articles were related to self-stigma in bipolar disorder. Seven key themes were extracted from these studies: 1/ Comparison of self-stigma in bipolar disorder and other mental illnesses, 2/ Sociocultural context and self-stigma, 3/ Correlates and predictors of self-stigma, 4/ Consequences of self-stigma, 5/ Treatments and self-stigma, 6/ Management of self-stigma, and 7/ Self-stigma and recovery in bipolar disorder.
LIMITATIONS
Firstly, a meta-analysis could not be performed due to the heterogeneity of the studies. Secondly, limiting the search to self-stigma has excluded other forms of stigma that also have an impact. Thirdly, the under-reporting of negative or nonsignificant results due to publication bias and unpublished studies might have limited the accuracy of this reviews' synthesis.
CONCLUSION
Research on self-stigma in persons with bipolar disorder has been the focused on different aspects, and interventions to reduce self-stigmatization have been developed, but evidence of their effectiveness is still sparse. Clinicians need to be attentive to self-stigma, its assessment, and its empowerment in their daily clinical practice. Future work is required to establish valid strategies to fight self-stigma.
Topics: Humans; Bipolar Disorder; Depressive Disorder, Major; Social Stigma; Mania
PubMed: 37207946
DOI: 10.1016/j.jad.2023.05.041 -
Journal of Affective Disorders Jul 2023The possibility of atypical antipsychotics (AA) to induce manic symptoms has been raised by several articles. The objective of this study was to describe whether... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The possibility of atypical antipsychotics (AA) to induce manic symptoms has been raised by several articles. The objective of this study was to describe whether exposure to AA may induce mania in mood disorders.
METHODS
We performed a systematic review following the preferred reporting items for systematic reviews and meta-analysis guidelines. The systematic search encompassed all relevant studies published until April 4th, 2022. A meta-analysis testing whether treatment emergent mania (TEM) is more frequent with the use of AA compared with placebo was performed.
RESULTS
A total of 52 studies were included in the systematic review. We found 24 case reports or case series describing 40 manic/hypomanic episodes allegedly induced by AA. Twenty-one placebo-controlled trials were included in a meta-analysis including 4823 individuals treated with AA and 3252 individuals receiving placebo. Our meta-analysis showed that the use of AA protects against the development of TEM (OR: 0.68 [95 % CI: 0.52-0.89], p = 0.005).
LIMITATIONS
AA-induced mania/hypomania was not the primary outcome in any of the observational or interventional studies. TEM was not homogeneously defined across studies. In most case reports it was not possible to establish causality between the use of AA and the development of manic symptoms.
CONCLUSIONS
TEM is more frequent with placebo than with AA, which suggests that AA exposure does not represent a relevant risk for TEM. Mania/hypomania induced by an AA seems to be rare events, since anecdotal evidence from case reports and case series were not observed in observational prospective and interventional studies.
Topics: Humans; Antipsychotic Agents; Bipolar Disorder; Mania; Prospective Studies; Mood Disorders
PubMed: 37084970
DOI: 10.1016/j.jad.2023.04.037 -
Pharmaceuticals (Basel, Switzerland) Dec 2022The effects of acetylsalicylic acid (ASA) on mood disorders (MD) and on inflammatory parameters in preclinical and clinical studies have not yet been comprehensively... (Review)
Review
The effects of acetylsalicylic acid (ASA) on mood disorders (MD) and on inflammatory parameters in preclinical and clinical studies have not yet been comprehensively evaluated. The aim of this study was to systematically summarize the available knowledge on this topic according to PRISMA guidelines. Data from preclinical and clinical studies were analyzed, considering the safety and efficacy of ASA in the treatment of MD and the correlation of inflammatory parameters with the effect of ASA treatment. Twenty-one studies were included. Both preclinical and clinical studies found evidence indicating the safety and efficacy of low-dose ASA in the treatment of all types of affective episodes in MD. Observational studies have indicated a reduced risk of all types of affective episodes in chronic low-dose ASA users (HR 0.92, 95% CI: 0.88, 0.95, p < 0.0001). An association between ASA response and inflammatory parameters was found in preclinical studies, but this was not confirmed in clinical trials. Further long-term clinical trials evaluating the safety and efficacy of ASA in recurrent MD, as well as assessing the linkage of ASA treatment with inflammatory phenotype and cytokines, are required. There is also a need for preclinical studies to understand the exact mechanism of action of ASA in MD.
PubMed: 36678565
DOI: 10.3390/ph16010067 -
Psychiatry Research Aug 2022Sars-CoV-2 is a respiratory virus that can access the central nervous system, as indicated by the presence of the virus in patients' cerebrospinal fluid and the... (Review)
Review
Sars-CoV-2 is a respiratory virus that can access the central nervous system, as indicated by the presence of the virus in patients' cerebrospinal fluid and the occurrence of several neurological syndromes during and after COVID-19. Growing evidence indicates that Sars-CoV-2 can also trigger the acute onset of mood disorders or psychotic symptoms. COVID-19-related first episodes of mania, in subjects with no known history of bipolar disorder, have never been systematically analyzed. Thus, the present study assesses a potential link between the two conditions. This systematic review analyzes cases of first appearance of manic episodes associated with COVID-19. Clinical features, pharmacological therapies, and relationships with pre-existing medical conditions are also appraised. Medical records of twenty-three patients fulfilling the current DSM-5 criteria for manic episode were included. Manic episodes started, on average, after 12.71±6.65 days from the infection onset. Psychotic symptoms were frequently reported. 82.61% of patients exhibited delusions, whereas 39.13% of patients presented hallucinations. A large discrepancy in the diagnostic workups was observed. Mania represents an underestimated clinical presentation of COVID-19. Further studies should focus on the pathophysiological substrates of COVID-19-related mania and pursue appropriate and specific diagnostic and therapeutic workups.
Topics: Bipolar Disorder; COVID-19; Diagnostic and Statistical Manual of Mental Disorders; Humans; Mania; SARS-CoV-2
PubMed: 35716481
DOI: 10.1016/j.psychres.2022.114677 -
CNS Drugs Apr 2022Bipolar disorder (BD) is a chronic relapsing-remitting psychiatric disorder. Sleep and circadian rhythm disturbances persist during acute mood episodes of the disorder... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bipolar disorder (BD) is a chronic relapsing-remitting psychiatric disorder. Sleep and circadian rhythm disturbances persist during acute mood episodes of the disorder and during euthymia. However, the treatment potential of hypnotic agents that might be used to manage sleep disturbance in BD is not well understood. Similarly, melatonin and medications with a melatonin-receptor agonist mechanism of action may have chronotherapeutic potential for treating people with the disorder, but the impact of these substances on sleep and circadian rhythms and core symptoms in BD is unclear.
OBJECTIVE
Our aim was to conduct a systematic review and meta-analysis evaluating the current evidence for hypnotic and melatonin/melatonin-receptor agonist pharmacotherapy for symptoms of sleep disturbance, mania, and depression in patients with BD.
METHODS
AMED, Embase, MEDLINE and PsychINFO databases were searched for studies published in English from the date of inception to 31 October 2021. Studies included in this review were randomised controlled trials (RCTs) and non-controlled/non-randomised studies for BD that examined hypnotic medications selected based on a common pattern of usage for treating insomnia (i.e. chloral, clomethiazole, diphenhydramine, doxepin, doxylamine, promethazine, suvorexant, zaleplon, zolpidem, zopiclone, and eszopiclone) and melatonin and the melatonin-receptor agonist drugs ramelteon and agomelatine. Risk of bias was assessed using the RoB2 and AXIS tools. Pooled effect sizes for RCT outcomes were estimated using random-effects models.
RESULTS
A total of eleven studies (six RCTs and five experimental feasibility studies) involving 1279 participants were included. Each study examined melatonin or melatonin-receptor agonists. No studies of hypnotics were found that fulfilled the review inclusion criteria. Pilot feasibility studies suggested beneficial treatment effects for symptoms of sleep disturbance, depression, and mania. However, the pooled effect of the two available RCT studies assessing sleep quality via Pittsburgh Sleep Quality Index scores was not statistically significant (g = - 0.04 [95% CI - 0.81 to 0.73]) and neither was the pooled effect for depressive symptoms (four studies; g = - 0.10 [95% CI - 0.27 to 0.08]). Some RCT evidence suggests ramelteon might prevent relapse into depression in BD. The largest efficacy signal detected was for manic symptoms (four studies; g = - 0.44 [95% CI - 1.03 to 0.14]) but there was substantial heterogeneity between studies and patient characteristics. In the two RCTs assessing manic symptoms during acute mania, adjunctive melatonin demonstrated superior treatment effects versus placebo.
CONCLUSIONS
There is a paucity of studies examining pharmacological interventions for sleep and circadian rhythm disturbance in BD. Few studies assessed sleep-related symptoms, and none quantitatively examined endogenous melatonin patterns or other circadian rhythms. Melatonin may be a promising candidate for the adjunctive treatment of bipolar mania. However, dose-finding studies and studies with larger sample sizes are needed to confirm its efficacy. We recommend parallel monitoring of sleep and circadian rhythms in future trials. Chronobiology-informed trial designs are needed to improve the quality of future studies.
PROTOCOL REGISTRATION
PROSPERO (CRD42020167528).
Topics: Bipolar Disorder; Humans; Hypnotics and Sedatives; Mania; Melatonin; Sleep; Sleep Wake Disorders
PubMed: 35305257
DOI: 10.1007/s40263-022-00911-7 -
Acta Psychiatrica Scandinavica Dec 2023Emotion dysregulation (ED) is a transdiagnostic construct characterized by difficulties regulating intense emotions. People with bipolar disorder (BD) are more likely to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Emotion dysregulation (ED) is a transdiagnostic construct characterized by difficulties regulating intense emotions. People with bipolar disorder (BD) are more likely to show ED and use maladaptive emotion regulation strategies than adaptive ones. However, little is known about whether ED in BD is a trait or it is rather an epiphenomenon of mood symptoms.
METHODS
We conducted a systematic review and meta-analysis of the evidence across major literature databases reporting correlations between measures of emotion regulation (overall ED and different emotion regulation strategies) and measures of depressive and (hypo)manic symptoms in BD from inception until April 12th, 2022.
RESULTS
Fourteen studies involving 1371 individuals with BD were included in the qualitative synthesis, of which 11 reported quantitative information and were included in the meta-analysis. ED and maladaptive strategies were significantly higher during periods with more severe mood symptoms, especially depressive ones, while adaptive strategies were lower.
CONCLUSION
ED significantly correlates with BD symptomatology, and it mainly occurs during mood alterations. ED may be a target for specific psychotherapeutic and pharmacological treatments, according to precision psychiatry. However, further studies are needed, including patients with mood episodes and longitudinal design, to provide more robust evidence and explore the causal direction of the associations.
Topics: Humans; Bipolar Disorder; Emotions; Affect; Affective Symptoms; Emotional Regulation
PubMed: 37740499
DOI: 10.1111/acps.13618 -
European Child & Adolescent Psychiatry Sep 2023Electroconvulsive therapy (ECT) is a well-established treatment for adults with mood disorders. However, its use in child and adolescent populations is less common. At... (Review)
Review
Electroconvulsive therapy (ECT) is a well-established treatment for adults with mood disorders. However, its use in child and adolescent populations is less common. At the same time, approximately 60% of child and adolescent patients do not respond satisfactorily to first-line treatments for mood disorders. Given the need for effective treatments for severe mood disorders in adolescents and the low use rate of ECT, this systematic review examines the existing literature on the effectiveness and adverse effect profile of ECT when used for treatment-resistant mood disorders in children and adolescents. Searches were conducted in Medline, Embase, and PsycInfo using search terms related to (1) children and adolescents, (2) mood disorders, and (3) ECT. Searches identified 1715 unique articles. The full text of 71 selected articles were reviewed, leading to 41 studies included in the study. A standardized data extraction tool was used to collect key information from each study (i.e. author and publication year, objectives, participants and setting, design, measures, clinical outcomes, and side effects). As most of the studies found were case series, the Joanna Briggs Institute Case Series Critical Appraisal tool was used to assess quality. Studies were summarized qualitatively by comparing findings across key study parameters. Our review identified 41 studies for inclusion. Twenty were case series, two were case-control studies, and nineteen were case reports. Overall treatment response rates ranged from 51 to 92%, with patients receiving an average of 12 treatments. Among studies with n > 30, response rates were largely 70-82% for depression and 87-90% for mania. Seven studies used the Mini-Mental State Exam and found no evidence of significant post-treatment cognitive impairment. The majority of side effects were minor and transient. Tardive seizure was reported in 4 (0.6%) patients. ECT was discontinued early due to side effects in 11 (1.5%) cases. No fatalities were reported. Our data suggest that ECT is safe and effective for the treatment of mood disorders in child and adolescent populations, and should be considered in severe and treatment-refractory cases. Controlled studies with objective measures and long-term follow-up are needed to advance the evidence base.
Topics: Adult; Humans; Adolescent; Child; Mood Disorders; Electroconvulsive Therapy; Treatment Outcome; Case-Control Studies
PubMed: 34999973
DOI: 10.1007/s00787-022-01942-7 -
Sleep Medicine Reviews Oct 2017A sizeable literature has implicated sleep in the phenomenological experience of various mood disorders, vulnerability to psychopathology, and overall poor psychological... (Review)
Review
A sizeable literature has implicated sleep in the phenomenological experience of various mood disorders, vulnerability to psychopathology, and overall poor psychological functioning. By contrast, positive affective states (e.g., joy, happiness, vigor, positive mood) that may contribute to sleep have been understudied. This systematic review integrates findings from cross-sectional, longitudinal, ambulatory, and experimental studies that investigate the association between positive affect and sleep. A comprehensive search for all available research on the topic was performed in three electronic bibliographic databases (PubMed, PsycINFO, CINAHL). Two independent reviewers extracted data on study characteristics and quality. From 10,853 retrieved articles, 44 fulfilled inclusion criteria and formed the base of the review. The majority of studies (68.2%, n = 30) were classified as weak or having high risk of bias. In general, the pattern of findings suggests that aggregate or trait measures provide the most consistent evidence of an association between positive affect and sleep in healthy populations. More limited empirical data exist on the association between positive affect and sleep in clinical populations. We conclude that more rigorous and theoretically informed research is needed before firm conclusions can be drawn about the possible beneficial impact of positive affect on sleep outcomes.
Topics: Emotions; Health Status; Humans; Mental Disorders; Sleep
PubMed: 27553441
DOI: 10.1016/j.smrv.2016.07.006 -
Expert Opinion on Pharmacotherapy 2023The data suggests that in children and adolescents, bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) may be strongly correlated. Even though... (Review)
Review
INTRODUCTION
The data suggests that in children and adolescents, bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) may be strongly correlated. Even though drugs for ADHD and BD are largely accepted, there is relatively little research on the management of comorbidity in children and adolescents, particularly in terms of safety. We provide a synthesis of these findings because one hasn't been made yet.
AREAS COVERED
As a primary outcome, we wanted to determine whether stimulant or non-stimulant treatment of children and adolescents with ADHD and comorbid BD was effective. As a secondary outcome, we wanted to determine tolerability, especially the risk of mood switch.
EXPERT OPINION
The findings of this systematic review suggest that methylphenidate, when used with a mood stabilizer, may be safe and not significantly increase the risk of a manic switch or psychotic symptoms when used to treat ADHD that co-occurs with a BD. In situations where stimulants are ineffective or have low tolerance, atomoxetine also seems to be a good alternative, and also in cases of co-morbid anxiety, oppositional defiant disorder, conduct disorders, ICT disorders, and substance use disorders. Additional research with a higher level of evidence is necessary to corroborate these preliminary findings.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Atomoxetine Hydrochloride; Methylphenidate; Central Nervous System Stimulants
PubMed: 37300473
DOI: 10.1080/14656566.2023.2224920