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BMC Psychiatry May 2022Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder.
METHODS
We conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5-17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children's Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression.
RESULTS
This study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint.
CONCLUSIONS
These pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02357290 . First Registration 06/02/2015.
Topics: Acetylcysteine; Adolescent; Antimanic Agents; Bipolar Disorder; Child; Child, Preschool; Humans; Mania; Pilot Projects
PubMed: 35505312
DOI: 10.1186/s12888-022-03943-x -
Nordic Journal of Psychiatry Feb 2021The number of studies investigating inflammatory biomarkers in bipolar disorder has increased significantly in recent years. The neutrophil to lymphocyte ratio (NLR),...
OBJECTIVES
The number of studies investigating inflammatory biomarkers in bipolar disorder has increased significantly in recent years. The neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) are inexpensive and easy to obtain values used to measure the level of inflammation. This study compared the NLR, PLR, and MLR values in the manic and euthymic phases of the same patients.
METHODS
Patients who met the inclusion criteria and were hospitalized due to bipolar affective disorder manic episodes at the Ondokuz Mayis University Faculty of Medicine inpatient psychiatry clinic between 01.01.2013 and 01.01.2019 were enrolled in the study. One hundred thirteen patients undergoing manic episodes were included. White blood cells, neutrophil, lymphocyte, platelet, and monocyte counts were retrospectively recorded from complete blood count data collected during the hospital stay, and NLR, PLR, and MLR values were calculated from these.
RESULTS
Neutrophil, platelet, and monocyte counts, as well as NLR, PLR, and MLR values were higher in the manic episodes of bipolar disorder compared to the control group. Decreased neutrophil and lymphocyte counts, and decreased NLR, PLR, and MLR were observed in the remission period after-treatment of the manic bipolar disorder episodes. In the euthymic phase of bipolar disorder, however, platelet and monocyte counts and MLR were higher than in the control group.
CONCLUSIONS
The study indicates that NLR and PLR may be used as state markers and that MLR may be used as a trait marker in bipolar disorder.
Topics: Biomarkers; Bipolar Disorder; Humans; Lymphocytes; Neutrophils; Retrospective Studies
PubMed: 32804583
DOI: 10.1080/08039488.2020.1807048 -
The Lancet. Psychiatry Sep 2019The recent conceptualisation of bipolar disorder as a neuroprogressive illness has highlighted the potential importance of prevention and early intervention in high-risk... (Review)
Review
The recent conceptualisation of bipolar disorder as a neuroprogressive illness has highlighted the potential importance of prevention and early intervention in high-risk populations. Undiagnosed bipolar disorder early in the disease course is associated with adverse clinical outcomes and impaired functioning for patients, which in turn has economic consequences. Despite the mounting evidence that childbirth is one of the most potent and specific triggers of manic symptoms, studies are not available on the effectiveness of targeted interventions in the prevention of bipolar disorder in women who have recently given birth. In this Personal View, we describe the clinical characteristics of women at risk of developing bipolar disorder after childbirth, before discussing opportunities for prevention and early intervention and outlining challenges in the assessment and management of women at risk of transitioning to bipolar disorder after childbirth. Existing evidence, although scarce, supports a clinical staging model by which at-risk women are managed with a variety of behavioural and pharmacological interventions aimed at preventing bipolar disorder. Close monitoring and early intervention might reduce the risk of hypomanic or manic symptoms in women at risk of developing bipolar disorder after childbirth; however, the potential benefits of early identification and intervention need to be carefully balanced against the additional risks for affected women.
Topics: Adolescent; Bipolar Disorder; Cyclothymic Disorder; Early Diagnosis; Female; Health Status Indicators; Humans; Infant, Newborn; Infanticide; Monitoring, Physiologic; Parturition; Postpartum Period; Pregnancy; Prospective Studies; Puerperal Disorders; Suicide, Attempted; Young Adult
PubMed: 30981755
DOI: 10.1016/S2215-0366(19)30092-6 -
Psychiatric Genetics Feb 2021Bipolar disorder (BD) is a chronic, disabling disease characterised by alternate mood episodes, switching through depressive and manic/hypomanic phases. Mood... (Review)
Review
INTRODUCTION
Bipolar disorder (BD) is a chronic, disabling disease characterised by alternate mood episodes, switching through depressive and manic/hypomanic phases. Mood stabilizers, in particular lithium salts, constitute the cornerstone of the treatment in the acute phase as well as for the prevention of recurrences. The pathophysiology of BD and the mechanisms of action of mood stabilizers remain largely unknown but several pieces of evidence point to gene x environment interactions. Epigenetics, defined as the regulation of gene expression without genetic changes, could be the molecular substrate of these interactions. In this literature review, we summarize the main epigenetic findings associated with BD and response to mood stabilizers.
METHODS
We searched PubMed, and Embase databases and classified the articles depending on the epigenetic mechanisms (DNA methylation, histone modifications and non-coding RNAs).
RESULTS
We present the different epigenetic modifications associated with BD or with mood-stabilizers. The major reported mechanisms were DNA methylation, histone methylation and acetylation, and non-coding RNAs. Overall, the assessments are poorly harmonized and the results are more limited than in other psychiatric disorders (e.g. schizophrenia). However, the nature of BD and its treatment offer excellent opportunities for epigenetic research: clear impact of environmental factors, clinical variation between manic or depressive episodes resulting in possible identification of state and traits biomarkers, documented impact of mood-stabilizers on the epigenome.
CONCLUSION
Epigenetic is a growing and promising field in BD that may shed light on its pathophysiology or be useful as biomarkers of response to mood-stabilizer.
Topics: Adult Survivors of Child Adverse Events; Affect; Bipolar Disorder; DNA Methylation; Epidemiologic Research Design; Epigenesis, Genetic; Female; Gene-Environment Interaction; Genetic Association Studies; Histone Code; Humans; Male; Organ Specificity; Psychotropic Drugs; RNA, Untranslated
PubMed: 33290382
DOI: 10.1097/YPG.0000000000000267 -
Journal of the American Association of... Oct 2020This review is intended to guide primary care providers in differentiating patients with bipolar depression from those with unipolar depression and inform patient...
This review is intended to guide primary care providers in differentiating patients with bipolar depression from those with unipolar depression and inform patient management. Up to 64% of clinical encounters for depression occur in primary care, with misdiagnosis of bipolar depression common in both primary care and psychiatry. Although bipolar disorder is characterized by manic, hypomanic, and depressive episodes, the most common and debilitating symptomatic presentation is depression. Misdiagnosis as unipolar depression is common, often resulting in mistreatment with an unopposed monoamine antidepressant. Antidepressants are often ineffective for treating bipolar depression and may cause detrimental consequences such as treatment-emergent hypomania/mania, rapid cycling, or increased suicidality. Factors that are suggestive of bipolar disorder versus unipolar depression include early-onset depression, frequent depressive episodes, family history of serious mental illness, hypomania/mania symptoms within the depressive episode, and nonresponse to antidepressants. Comorbid medical (e.g., cardiovascular disease, hypertension, obesity) and psychiatric (e.g., attention-deficit/hyperactivity disorder, anxiety disorder, personality disorders, and substance use disorder) conditions are common and contribute to premature mortality for patients with bipolar disorder compared with the general public. Cariprazine, fluoxetine/olanzapine, lurasidone, and quetiapine are approved to treat bipolar depression; only cariprazine and quetiapine are approved to treat both bipolar mania and depression. Primary care providers who can differentiate presenting symptoms of bipolar depression from unipolar depression and offer appropriate treatment options will optimize patient care in clinical practice. Relevant information for this review was identified through a multistep literature search of PubMed using the terms bipolar depression/bipolar disorder plus other relevant terms.
Topics: Bipolar Disorder; Cost of Illness; Depression; Diagnosis, Differential; Diagnostic Techniques and Procedures; General Practice; Humans
PubMed: 33017361
DOI: 10.1097/JXX.0000000000000499 -
Journal of Affective Disorders Mar 2021Neural abnormalities in emotional response inhibition still exist in the euthymic phase of bipolar disorder (BD). Few studies on comparisons of functional magnetic...
BACKGROUND
Neural abnormalities in emotional response inhibition still exist in the euthymic phase of bipolar disorder (BD). Few studies on comparisons of functional magnetic resonance imaging (fMRI) manifestations between different mood phases of pediatric bipolar disorder (PBD) have ever been published. The goal of this study was to explore the differences in neural activities between manic and euthymic PBD during emotional response inhibition.
METHODS
Simultaneous imaging of neural activity was recorded during an emotional Go/Nogo paradigm and the effect of emotional response inhibition was analyzed. Neural activities were compared between the three groups.
RESULTS
In the presence of emotional versus neutral distractors, both manic and euthymic PBD subjects similarly showed widespreadly increased activities in the cognitive and emotional regulation circuits compared with healthy individuals. Compared with euthymic PBD patients, those with manic PBD exhibited increased activities in the left superior frontal gyrus. Hyperactivity in the left superior frontal, left middle frontal and right inferior frontal gyrus in manic PBD was positively associated with false response errors.
CONCLUSION
Increased activity in the left superior frontal gyrus may be characteristic of manic episodes in PBD patients, and such a disparity between manic and euthymic phrases may attribute to more severe emotional dysregulation.
Topics: Bipolar Disorder; Brain Mapping; Child; Cyclothymic Disorder; Emotions; Humans; Inhibition, Psychological; Magnetic Resonance Imaging
PubMed: 33401127
DOI: 10.1016/j.jad.2020.12.105 -
Translational Psychiatry Apr 2022Manic episodes are a defining, frequent and dramatically disabling occurrence in the course of Bipolar Disorder type I. Current pharmacotherapy of mania lists a good... (Review)
Review
Manic episodes are a defining, frequent and dramatically disabling occurrence in the course of Bipolar Disorder type I. Current pharmacotherapy of mania lists a good number of agents, but differences in efficacy and safety profiles among these agents must be considered in order to tailor personalized therapies, especially when the long-term course of the illness is considered. There is wide room and need to ameliorate current pharmacological approaches to mania, but ongoing pharmacological research on the topic is scant. In this work we try to critically assess clinical factors and patients' characteristics that may influence the treatment choice for manic episodes. In addition, we conduct a narrative review on experimental pharmacology of bipolar mania and psychotic disorders, presenting a critical overview on agents which could represent treatment alternatives for a manic episode in the next future. Results show limited novel or ongoing research on agents acting as mood stabilizers (Ebselen, Valnoctamide and Eslicarbazepine did not reach statistical significance in demonstrating antimanic efficacy). As for the emerging experimental antipsychotic, some of them (including KarXT, SEP-363856, RO6889450, ALKS3831) have demonstrated good antipsychotic efficacy and a favorable safety profile, but little is known about their use in patients with bipolar disorder and specifically designed trials are needed. Lastly, some benefits for the treatment of mania could be expected to come in the next future from non-mood stabilizers/non-antipsychotic agents (especially PKC inhibitors like Endoxifen): long-term trials are needed to confirm positive results in terms of long-term efficacy and safety.
Topics: Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Mania; Psychotic Disorders
PubMed: 35461339
DOI: 10.1038/s41398-022-01928-8 -
The Journal of Neuropsychiatry and... 2022The aim of this study was to assess the perception of speech in adverse acoustic conditions during manic and depressive episodes of mood disorders.
OBJECTIVE
The aim of this study was to assess the perception of speech in adverse acoustic conditions during manic and depressive episodes of mood disorders.
METHODS
Forty-three patients with bipolar disorder (mania, N=20; depression, N=23) and 32 patients with unipolar depression were included for analyses. Thirty-five participants served as the control group. The study of speech understanding was carried out using the Polish Sentence Matrix Test, allowing for the determination of the speech reception threshold (SRT). The test was performed in the clinical groups both during an acute episode and remission; during remission, patients underwent audiometric evaluation.
RESULTS
Compared with control subjects, patients with mood disorders had worse speech understanding (higher SRT), regardless of the episode or remission. A manic episode in the course of bipolar disorder was not associated with worse speech understanding compared with remission of mania. However, an episode of depression in the course of both bipolar disorder and unipolar depression was associated with worse speech understanding compared with remission of depression. In bipolar depression, this correlated with age, duration of the disorder, number of episodes, and number of hospitalizations, as well as in remission with age and duration of illness. In unipolar depression, poor speech understanding was more severe in individuals with hearing impairment.
CONCLUSIONS
These findings revealed that patients with mood disorders had impaired speech understanding, even while in remission, and manic episodes in the course of bipolar disorder were not associated with impaired speech understanding compared with mania remission.
Topics: Bipolar Disorder; Depressive Disorder; Humans; Mania; Mood Disorders; Speech
PubMed: 35414193
DOI: 10.1176/appi.neuropsych.21050125 -
Current Psychiatry Reports Feb 2022The perinatal period is a time of increased vulnerability for people with bipolar disorder (BD). The purpose of this review is to provide an update of the literature... (Review)
Review
PURPOSE OF REVIEW
The perinatal period is a time of increased vulnerability for people with bipolar disorder (BD). The purpose of this review is to provide an update of the literature from the last 3 years regarding course of illness and treatments for BD in the perinatal period to guide clinical care.
RECENT FINDINGS
Postpartum manic and depressive episodes are emerging as having a unique presentation that may differentiate them from non-perinatal mood episodes. Many important updates regarding medication treatment in the perinatal period have been published recently that have considered the risks of untreated illness versus treatment risks in this population.' Despite significant research, there are still gaps in knowledge regarding safety and efficacy of medications for the mother and child. Crucial future areas of study include improved screening guidelines, randomized controlled trials examining medication safety in pregnancy and lactation, and efficacy of nonpharmacologic treatments.
Topics: Bipolar Disorder; Female; Humans; Infant, Newborn; Postpartum Period; Pregnancy; Risk Factors
PubMed: 35166993
DOI: 10.1007/s11920-022-01323-6 -
Bipolar Disorders Mar 2021Individuals with bipolar disorder are at increased risk of dying by suicide compared to healthy controls and those with unipolar depression. Previous studies show that...
UNLABELLED
Individuals with bipolar disorder are at increased risk of dying by suicide compared to healthy controls and those with unipolar depression. Previous studies show that depressive symptoms and mixed episodes of mania and depression are related to suicide. However, most of these studies adopt a variable-centered approach to understanding how specific symptoms relate to suicidal ideation, without addressing how these symptoms and symptom profiles relate to suicidal behaviors.
OBJECTIVES
Using latent class analysis, this study adopts a person-centered approach to examine whether subtypes of patients with bipolar disorder differ in their levels of suicidal ideation and behaviors.
METHODS
A total of 150 patients from a behavioral health outpatient clinic were recruited. Latent classes were generated based on self reports of their depressive and manic symptoms.
RESULTS
Five classes of patients with bipolar disorder were identified, namely, a minimal symptom, mania, moderately depressed, severely depressed, and mixed depression-mania subtypes. Those in the severely depressed and mixed depression-mania groups reported significantly higher levels of suicidal ideation and behaviors compared to the other groups.
CONCLUSIONS
Our findings provide further support for the strong relationship between depressive symptoms and suicidality. These findings are significant as they shed light on the different suicide risk profiles among a heterogenous group of patients with bipolar disorder. Name of clinical trial: Suicidal Behavior in Patients Diagnosed with Bipolar Disorder: The Roles of Biological and Childhood and Adult Environmental Risk Factors. ClinicalTrials.gov Identifier: NCT02604277.
Topics: Adult; Bipolar Disorder; Child; Depressive Disorder; Humans; Latent Class Analysis; Suicidal Ideation; Suicide
PubMed: 32579284
DOI: 10.1111/bdi.12967