Manic Phase Of Bipolar Disorder Research Articles

Career Aspirations for People With Serious Mental Disorders.

Career Aspirations for People With Serious Mental Disorders.

Sleep changes during a spontaneous manic episode: PSG assessment in a clinical context

Sleep plays a key role in the pathogenesis and clinical presentation of mood disorders. However, only a few studies have investigated sleep architecture during the manic episodes of Bipolar Disorder (BD) and changes in sleep parameters that follow clinical variations.Twenty-one patients (8 males, 13 females) affected by BD, manic phase, underwent polysomnographic recordings (PSG) at the beginning of the admission in our ward (T0) and after three weeks of hospital treatment (T1). All participants were clinically evaluated using Young Mania Rating Scale (YMRS), Pittsburgh Sleep Quality Index (PSQI) and Morningness-Eveningness Questionnaire (MEQ).During the admission, we observed an increase in both quantity (Total Sleep Time - TST) and quality (Sleep Efficiency - SE) of sleep. In addition, clinical improvement, evaluated with YMRS and PSQI scales, was accompanied by a significant increase in the percentage of REM sleep.According to our findings, the improvement of manic symptoms is accompanied by an increase in "REM pressure" (increase in REM% and REM density, reduction of REM latency).Overall, changes in sleep architecture appear to be markers sensitive to clinical variations during manic phases of Bipolar Disorder.

Carbamazepina no tratamento do transtorno bipolar: uma revisão sistemática

ABSTRACT Objective: Expand knowledge on the role and efficacy of carbamazepine (CBZ) in bipolar disorder (BD), based on original studies. Methods: The authors performed a systematic review of the scientific literature on the efficacy of CBZ in BD, using the PubMed/MEDLINE, Web of Science (ISI), and SciELO databases. The search terms were: (“carbamazepine”) AND (“bipolar” OR “mania” OR “manic”). There was no restriction on the year of publication. Results: A total of 27 articles were selected. Among the selected articles, 14 evaluated the use of CBZ in the manic phase of BD, two in the depressive phase of BD, and 11 in the maintenance phase of BD. In the studies on the manic phase of BD, CBZ proved superior to placebo (PLA). As for the depressive phase of BD, there were two studies, both with small samples. In the maintenance phase, CBZ was inferior to lithium, and no studies compared CBZ to PLA. Conclusion: The results of the clinical studies suggest that CBZ is effective for the treatment of the manic phase. Regarding the treatment of acute depression and maintenance of BD, the results of the studies indicate that there is not enough data demonstrating the effectiveness of CBZ.

Early synaptic deficits in GSK-3β overexpressing mice

Synaptic dysfunction is the prominent feature of many neuropsychiatric and neurological diseases, in which glycogen synthase kinase 3β (GSK-3β) has been shown to play a role. Overexpression of constitutively active form of GSK-3β (GSK-3β[S9A]) in mice recapitulates the cognitive and structural brain deficits characteristic for manic phase of bipolar disorder (BD). Yet, the mechanisms underlying GSK-3β-induced synaptic dysfunction have not been fully elucidated. The aim of the present study was to dissect the effect of GSK-3β overactivity on synaptic function in adolescent (3-week-old) mice. We found that overactivity of GSK-3β in adolescent transgenic mice leads to an alteration in dendritic spines morphology of granule cells in dentate gyrus (DG) without changes in overall spine density. There was an increase in the number of thin, presumably immature dendritic spines in GSK-3β[S9A] mice. Subsequent electrophysiological analysis showed changes in excitatory synaptic transmission manifested by an increase of inter-event intervals of miniature excitatory postsynaptic currents (mEPSCs) in DG granule cells and an increase in the number of silent (unfunctional) synapses at the perforant path-DG pathway in GSK-3β[S9A] mice. Altogether, our data indicate that GSK-3β overactivity leads to synaptic deficits in adolescent, GSK-3β[S9A] mice. These data might provide potential mechanisms underlying GSK-3β-induced synaptic dysfunction in psychiatric disorders.

Manic patients and sleep management: the role of polysomnography in clinical practice

IntroductionSleep plays a key role in the pathogenesis and clinic of mood disorders. However, few studies have investigated electroencephalographic sleep parameters during the manic phases of Bipolar Disorder (BD).ObjectivesSleep management is a priority objective in the treatment of the manic phases of BD and the polysomnographic investigation can be a valid tool both in the diagnostic phase and in monitoring clinical progress.MethodsTwenty-one patients affected by BD, manic phase, were subjected to sleep monitoring via PSG in the acute phase (at the entrance to the ward) and in the resolution phase (near discharge). All participants were also clinically evaluated using Young Manic Rating Scale (YMRS) Pittsburgh Sleep Quality Index (PSQI), Morningness-eveningness Questionnaire (MEQ) at different timepoints.ResultsOver the hospitalization time frame there was an increase in quantity (Total Sleep Time) and an improvement in the quality and effectiveness of sleep (Sleep Efficiency). In addition, from the point of view of the EEG structure, clinical improvement was accompanied by an increase in the percentage of REM sleep.ConclusionsSleep monitoring by PSG can be a valuable tool in the clinical setting both in the diagnostic phase, “objectively” ascertaining the amount of sleep, and in the prognostic phase, identifying electroencephalographic characteristics that can predict the patient’s progress and response to drug therapy. The improvement in effectiveness and continuity of sleep and the change in its structure that accompanies the resolution of manic symptoms also testifies how the regularization of the sleep-wake rhythm is to be considered a priority in treating manic phases.DisclosureNo significant relationships.

Serum uric acid as biomarker for mania: An exploratory prospective study

Bipolar Disorder is a major mental illness characterized by episodic occurrence of mood symptoms which can be of mania, depression or a mixed episode. The role of Uric Acid in the etiopathogenesis of episodic mental illnesses might be considered recognized long back in 19th century. Lithium was used as treatment for gouty arthritis and that in some cases helped to control mental illnesses. Multiple role of uric acid in the Central Nervous System have been recognized now. In the present study 30 patients in manic episodes were included and their serum Uric Acid level was compared to age and sex matched healthy controls twice at the interval of three weeks. It was found that Uric Acid level of cases was significantly higher than in controls before the initiation of treatment. Uric Acid level of manic group showed a significant decline after three weeks of treatment initiation. There was no significant change in Uric Acid level of control group after three weeks Serum Uric Acid levels are elevated during manic phase of Bipolar Disorder and decreases after initiation of treatment. There may be more research to find whether uric acid can be considered a biomarker for Bipolar illnesses and also an indicator for treatment response.

Levetiracetam adjunct to quetiapine for the acute manic phase of bipolar disorder: a randomized, double-blind and placebo-controlled clinical trial of efficacy, safety and tolerability.

Unsatisfactory responses to bipolar disorder treatments have necessitated novel therapeutic approaches. Evidence of levetiracetam's effectiveness in mania was reported in previous studies. This study evaluated its efficacy, safety and tolerability as an adjunct to quetiapine in mania. Forty-four patients with Young Mania Rating Scale (YMRS) score ≥20 entered and were randomized to receive levetiracetam plus quetiapine or placebo plus quetiapine for 6 weeks. Patients were assessed using the YMRS and Beck Scale for Suicidal Ideations (BSSI) at baseline and weeks 2, 4 and 6. Changes in the scores, remission rates and response to treatment were compared between the groups. Forty patients completed the trial. The general linear model (GLM) repeated measures demonstrated a significant effect for time × treatment interaction on the YMRS score during the trial (P = 0.04). A greater reduction in YMRS scores was seen in the levetiracetam group compared with the placebo group from baseline to week 4 (P = 0.045). Response to treatment was significantly better in the levetiracetam group (P = 0.046). No significant effect for time × treatment interaction on BSSI score was seen in GLM repeated measures. Finally, there was no significant difference in the frequency of adverse events. Adjunctive levetiracetam is effective, safe and well-tolerated in patients with mania. Further high-quality, large-scale trials are recommended.

Застосування солей літію в медицині та ознаки отруєння ними

Препарати літію — психотропні лікарські засоби з групи нормотиміків. Їх найважливіше значення полягає в лікуванні афективних розладів, перш за все маніакальних фаз біполярного розладу, а також у профілактиці їх загострень і лікуванні тяжких і резистентних депресій, вони здатні запобігати самогубствам. В основі лікування біполярних розладів препаратами літію лежить їх властивість селективно інгібувати кіназу-3-глікогенсинтетазу шляхом конкуренції з іонами магнію. Літій — лужний метал, тому в медицині він застосовується у вигляді солей, в основному у вигляді карбонату, а також цитрату, сукцинату, оротату, хлориду й сульфату літію. Окрім галузі психіатрії, літій та його сполуки застосовуються при виробництві пластмас, органічному синтезі, у склодувній промисловості, фармацевтичній хімії. Отруєння літієм у психіатричній практиці часто має ятрогенну природу. Літій впливає на вивільнення серотоніну й чутливість рецепторів, а також модулює дію норадреналіну. На сьогодні вважається, що механізм дії літію пов’язаний з виснаженням запасів інозитолу в центральній нервовій системі (ЦНС). Неврологічний симптомокомплекс отруєння літієм складається з атаксії, погіршення зору, втрати пам’яті, запаморочення, втрати орієнтації, судом, ступору й коми. Чим довше зберігається токсичний рівень літію в крові, тим більша ймовірність необоротних змін ЦНС. При інтоксикації літієм хворий повинен бути госпіталізований. Перша допомога: всередину натрію хлорид і розчин калію хлориду. Необхідно кілька разів на день вимірювати концентрацію літію в плазмі крові. Для швидкого зниження концентрації літію часто ефективне введення фізіологічного розчину внутрішньовенно зі швидкістю 150–200 мл на годину. Перш за все проводять промивання шлунка й кишечника (особливо при отруєнні препаратами тривалої дії). Оскільки в шлунковому соку часто виявляється висока концентрація літію, показана тривала аспірація шлунка. При епілептичних нападах, пригніченні ЦНС, артеріальній гіпотонії й аритміях лікування патогенетичне. Найбільш ефективним методом є гемодіаліз. Проте потрібно відзначити, що об’єктивно позитивні зміни при літієвій терапії (якщо вона успішна) набагато перевершують негативний вплив можливих побічних ефектів.

Abstracts

Abstracts

Chronic lithium treatment alters the excitatory/ inhibitory balance of synaptic networks and reduces mGluR5-PKC signalling in mouse cortical neurons.

Background:Bipolar disorder is characterized by cyclical alternation between mania and depression, often comorbid with psychosis and suicide. Compared with other medications, the mood stabilizer lithium is the most effective treatment for the prevention of manic and depressive episodes. However, the pathophysiology of bipolar disorder and lithium’s mode of action are yet to be fully understood. Evidence suggests a change in the balance of excitatory and inhibitory activity, favouring excitation in bipolar disorder. In the present study, we sought to establish a holistic understanding of the neuronal consequences of lithium exposure in mouse cortical neurons, and to identify underlying mechanisms of action.Methods:We used a range of technical approaches to determine the effects of acute and chronic lithium treatment on mature mouse cortical neurons. We combined RNA screening and biochemical and electrophysiological approaches with confocal immunofluorescence and live-cell calcium imaging.Results:We found that only chronic lithium treatment significantly reduced intracellular calcium flux, specifically by activating metabotropic glutamatergic receptor 5. This was associated with altered phosphorylation of protein kinase C and glycogen synthase kinase 3, reduced neuronal excitability and several alterations to synapse function. Consequently, lithium treatment shifts the excitatory–inhibitory balance toward inhibition.Limitations:The mechanisms we identified should be validated in future by similar experiments in whole animals and human neurons.Conclusion:Together, the results revealed how lithium dampens neuronal excitability and the activity of the glutamatergic network, both of which are predicted to be overactive in the manic phase of bipolar disorder. Our working model of lithium action enables the development of targeted strategies to restore the balance of overactive networks, mimicking the therapeutic benefits of lithium but with reduced toxicity.

Lithium intoxication\u2013induced dysgeusia accompanied by glossalgia in a patient receiving lithium carbonate: a case report

BackgroundLithium carbonate is widely used as a first-line therapeutic agent for the depressive and manic phases of bipolar disorder. Although limb tremors and hypothyroidism are well-known side effects of lithium carbonate, other rare adverse reactions can also occur.Case presentationA 53-year-old Japanese woman diagnosed with lithium intoxication developed dysgeusia and glossalgia during treatment with lithium carbonate. She also showed symptoms of a swaying gait, finger tremors, and dysarthria. All of these symptoms subsided when her blood lithium concentration was reduced to a level below that which induces intoxication.ConclusionsWe present a rare case of lithium carbonate–induced dysgeusia accompanied by glossalgia. Early detection of these symptoms is important in clinical settings because they can be overlooked until patients lose their appetite, which severely impairs their quality of life.

Development of Sensitive and High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Method for Quantification of Haloperidol in Human Plasma with Phospholipid Removal Pretreatment.

Haloperidol, butyrophenone derivative, is a typical antipsychotic drug used in the treatment of schizophrenia, manic phase of bipolar disorder, and acute psychomotor agitations. According to the recent guidelines for therapeutic drug monitoring, it is strongly recommended to measure plasma level during the therapy with haloperidol. The objective of this study was to develop and validate a simple liquid chromatography-tandem mass spectrometry-based method to quantitate haloperidol in human plasma. After one-step extraction procedure using OSTROTM plate, gradient elution on Acquity UPLC BEH C18 (50 ×2.1mm, 1.7μm) column over 3.2 min was performed. The detection was conducted on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode in positive ionization mode with transitions at m/z 376.29 → 165.14 and m/z 380.28 → 169.17 for haloperidol and haloperidol-d4 (used as an internal standard), respectively. The method was fully validated to cover wide concentration range of 0.05-80 ng/mL in human plasma and meets the criteria for the selectivity, linearity and lower limit of detection, precision and accuracy, matrix effect, extraction recovery, carryover, dilution integrity and stability. The extraction recovery was nearly 100%, and no significant matrix effects were observed. Therefore, the method is applicable to routine therapeutic drug monitoring in patients' plasma.

QT and P-wave dispersion during the manic phase of bipolar disorder.

Background and aimPatients with bipolar disorder (BD) are at increased risk for cardiovascular diseases and complications. This increased risk is considered to be associated with the autonomic nervous system (ANS) abnormalities. However, there is little or no documentation of the relationship between this increased risk and the phases of BD. In this study, we aimed to compare the changes in the QT dispersion (QTd) and P-wave dispersion (Pd), which are predictors of sudden cardiac death and atrial fibrillation, between the patients with manic BD and healthy controls.Participants and methodsThe study included a patient group of 44 patients (26 female and 18 male) that were hospitalized due to a diagnosis of manic BD and met the inclusion criteria, and a control group of 34 age- and gender-matched healthy individuals (21 female and 13 male) with no history of psychiatric and neurological disorders. The QTd and Pd values were determined in each participant by performing the standard 12-lead body surface electrocardiography (ECG).ResultsThe principal electrocardiographic indicators including corrected maximum QT interval, corrected QT dispersion, and minimum P-wave duration significantly increased in the patient group compared to the control group (t=2.815, p<0.01; t=4.935, p<0.001; t=3.337, p<0.001, respectively).ConclusionThe results indicated that patients with manic BD are at increased risk for cardiovascular autonomic dysfunction. Therefore, clinicians should be more careful about ECG changes and related possible cardiac conduction problems such as cardiac arrthythmias in patients with manic BD. Further longitudinal studies are needed to investigate BD and its phases (depression, mania, and hypomania) with regard to ANS and cardiac abnormalities.

Auditory–Visual Speech Integration in Bipolar Disorder: A Preliminary Study

This study aimed to investigate how individuals with bipolar disorder integrate auditory and visual speech information compared to healthy individuals. Furthermore, we wanted to see whether there were any differences between manic and depressive episode bipolar disorder patients with respect to auditory and visual speech integration. It was hypothesized that the bipolar group’s auditory–visual speech integration would be weaker than that of the control group. Further, it was predicted that those in the manic phase of bipolar disorder would integrate visual speech information more robustly than their depressive phase counterparts. To examine these predictions, a McGurk effect paradigm with an identification task was used with typical auditory–visual (AV) speech stimuli. Additionally, auditory-only (AO) and visual-only (VO, lip-reading) speech perceptions were also tested. The dependent variable for the AV stimuli was the amount of visual speech influence. The dependent variables for AO and VO stimuli were accurate modality-based responses. Results showed that the disordered and control groups did not differ in AV speech integration and AO speech perception. However, there was a striking difference in favour of the healthy group with respect to the VO stimuli. The results suggest the need for further research whereby both behavioural and physiological data are collected simultaneously. This will help us understand the full dynamics of how auditory and visual speech information are integrated in people with bipolar disorder.

Scope and Characteristics of Suicide Attempts Among Manic Patients With Bipolar Disorder.

Suicide is often associated with depression in patients suffering from bipolar disorder (BD) and less is known about its relation to mania. Available data suggest that patients in the manic phase of BD may be at risk of suicide. We characterized suicide attempts in a cohort of patients with BD in manic and mixed phases. We focused on the scope, rate, and characteristics of suicide attempts among BD patients during manic or mixed states. Associations between suicide as well as clinical and sociodemographic variables were analyzed using computerized medical chart data from 209 adult inpatients diagnosed (DSM-IV) as experiencing manic and mixed BD episodes. The rate of recent suicide attempts among BD inpatients with manic and mixed episodes was 10.5%. Married patients had a decreased rate of suicide attempts. Comorbid alcohol or substance abuse were correlated with an increased risk of suicide attempts. Presence of suicidal ideation increased suicide risk while older age was linked to a decrease in the rate of suicide attempts. The retrospective design of the study and overrepresentation of the clinical severity of BD were limitations. The rate of suicide attempts in the manic and mixed phases of BD is substantial and calls for raising awareness among psychiatrists.

Aripiprazole as an adjuvant treatment for obsessive and compulsive symptoms in manic phase of bipolar disorder: A randomized, double-blind, placebo-controlled clinical trial

Background and objectiveOur Objective is to study the effects of aripiprazole as an adjuvant treatment for obsessive and compulsive (OC) symptoms in patients with bipolar disorder (BD) type I, manic phase. Patients and methodsIn this 8-week, double-blind, placebo-controlled randomized clinical trial, 56 patients with BD who had OC symptoms were randomly allocated to receive aripiprazole or placebo plus their routine medication regimen (lithium + clonazepam). Yale Brown obsessive compulsive behavior scale (YBOCS) was administered to evaluate the outcomes. Adverse effects were also registered. ResultsOf 56 BD patients with OC symptoms which were randomly allocated in two groups of aripiprazole (n = 29) and placebo group (n = 27), 46 patients (23 in aripiprazole group and 23 in placebo group) completed the trial. Throughout the trial, the mean score of YBOCS in the aripiprazole group decreased from 21 ± 4.81 to 9.6 ± 2.2 (P < 0.001) and in the placebo group dropped from 20.46 ± 4.8 to 17.32 ± 3.7 (P < 0.001). At the end of the study, 21 (91.30%) patients in the aripiprazole group and 1 (4.34%) patient in the placebo group had >34% decline in YBOCS score (P < 0.01). No serious adverse effects were reported in any groups. ConclusionsThe results of our study revealed that aripiprazole can be used as an effective adjuvant agent for treatment of obsessive and compulsive symptoms in manic patients.

Memantine as an Adjuvant Treatment for Obsessive Compulsive Symptoms in Manic Phase of Bipolar Disorder. A Randomized, Double-Blind, Placebo-Controlled Clinical Trial: Erratum

Memantine as an Adjuvant Treatment for Obsessive Compulsive Symptoms in Manic Phase of Bipolar Disorder. A Randomized, Double-Blind, Placebo-Controlled Clinical Trial: Erratum

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10−7) and PKP4 (P=8.67 × 10−7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10−3]), SCZ (rg=0.34 [P=4.37 × 10−5]) and MDD (rg=0.57 [P=1.04 × 10−3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.

Memantine as an Adjuvant Treatment for Obsessive Compulsive Symptoms in Manic Phase of Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

The aim of this study is to examine the effects of memantine as an adjuvant treatment for obsessive compulsive (OC) symptoms in patients with bipolar disorder (BD) type I, manic phase. In this 16-week double-blind placebo-controlled randomized clinical trial, 58 patients in the manic phase of BD who had OC symptoms were randomly allocated to receive memantine or placebo plus their routine medications (lithium + olanzapine + clonazepam). The Yale Brown Obsessive Compulsive Behavior Scale was used to assess the outcomes. Adverse effects were also recorded. Thirty-eight patients (19 in the memantine group and 19 in the placebo group) completed the trial. Throughout the trial, the mean score decreased from 20.26 ± 5.91 to 9.73 ± 5.44 in the memantine group (P < 0.000) and from 22.89 ± 5.70 to 16.63 ± 4.00 in the placebo group (P < 0.000). At the end of the study, 15 (78.94%) patients in the memantine group and 7 (36.84%) patients in the placebo group demonstrated more than 34% decline in the Yale Brown Obsessive Compulsive Behavior Scale score (P < 0.01). No serious adverse effects were reported. Our double-blind controlled clinical trial showed that memantine is an effective adjuvant agent for reducing OC symptoms in patients with BD. However, it needs to be noted that our study is preliminary, and larger double-blind controlled studies are needed to confirm the results.

Droperidol for psychosis-induced aggression or agitation.

Droperidol for psychosis-induced aggression or agitation.