Manic Patients Research Articles

Insomnia and aggressiveness in affective disorders: Self-assessment versus clinical examination

IntroductionAlthough, disturbances of sleep, as well as aggressiveness, have been described in patients with mood disorders, these patients may not be aware of them.Objectives/aimsTo access the personal perception of sleep, disturbances and aggressiveness in patients with mood disorders, admitted to an acute psychiatric ward.MethodsDiagnostic data (ICD-10: F31–33), including mood evaluation, were prospectively collected for all patients admitted at the affective disorder ward at Centro Hospitalar Psiquiátrico de Lisboa (Portugal), during the third trimester of 2016. Then, 2 auto-questionnaires – Athens insomnia scale (AIS) and Buss and Perry aggression scale (both validated to the Portuguese population) – were applied to these patients. Statistical analysis was performed for possible correlations between patients’ mood and the questionnaires’ scores, using R software.ResultsThirty-eight patients admitted were enrolled in this study: 28 with bipolar disorder (19 manic, 4 depressive and 5 mixed episodes), and 10 with depressive disorder. Depressed patients presented statistically higher values in the AIS (average = 20), compared to manic (14) and mixed ones (17.2) (P = 0.031). However, there were no statistical differences found between depressed patients (bipolar versus non-bipolar). Even though manic patients presented an increased average score in the Buss and Perry questionnaire (both total–65; but also sub-scores), these values were not significantly different than depressed (60) or mixed patients’ scores (57.4).ConclusionsEven though some symptoms (like sleep or aggressiveness) seem to be relevant to the clinics, patients with affective disorders do not seem to be aware these disturbances, and therefore are not able to acknowledge their relevance.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Age at the onset of a first episode of psychotic mania: Does it have an impact on outcome?

PurposeStudies conducted in child psychiatry suggest that patients with earlier onset of psychosis have poorer outcome. Similar findings have been published regarding onset of bipolar disorder. However, few studies have been conducted in youth mental health program where these patients may actually receive treatment. Identification of subgroups with distinct need and outcome among first episode mania patients would facilitate the development of specific treatment strategies better suited to the actual needs of patients.MethodsSixty-seven patients with a first episode of psychotic mania were followed up over 12 months after recovery from this initial episode. Syndromic and symptomatic outcome were determined with the brief psychiatric rating scale, functional outcome with the quality of life scale and premorbid adjustment scale sub items.ResultsWhile 90% of patients achieved syndromic recovery (disappearance of manic syndrome) at 6 and 12 months, 40% had not recovered symptomatically, still presenting with depression and anxiety. Return to previous level of functioning was achieved only by 34% of patients at 6 months and 39% at 12 months. Age at the time of first manic episode with psychotic features was a significant predictor of recovery of functional level.ConclusionsWhile manic symptoms reduce quickly in most patients after a first episode of psychotic mania, an important number of patients still display symptoms of depression and anxiety after 12 months and 2/3 do not reach functional recovery. Younger age at first episode predicts risk of poorer functional outcome.Disclosure of interestThe authors have not supplied their declaration of competing interest.

A Magnetic Resonance Spectroscopy Study of Lovastatin for Treating Bipolar Mood Disorder: A 4-Week Randomized Double-Blind, Placebo- Controlled Clinical Trial.

No trial has examined the effect of lovastatin on the brain metabolites in patients with bipolar mood disorder. Current medications for treating bipolar disorders cause metabolic syndrome. It is supposed that lovastatin not only decreases the rate of metabolic syndrome but also impacts some brain metabolites and their ratio like common treatments that are measured by Magnetic Resonance Spectroscopy. 27 Manic phase patients were randomly allocated into two groups, lovastatin and placebo as their adjuant medication. Clinical symptoms were assessed at baseline, weeks 2, 4. The brain metabolites were measured at baseline and week 4. Regarding the change of clinical symptoms, no significant difference was found between two groups. However, lovastatin significantly increased the level of NAA in cingulate gyrus in comparison to the placebo group. Moreover, lovastatin more than placebo increased creatine in the left basal ganglia. Furthermore, choline/ creatine showed a significant decrease in the left basal ganglia in lovastatin group. Using MRS after treating with lovastatin showed lovastatin increases NAA in cingulate gyrus, indicating the possible effect of NAA for increasing the reduced viable neuron. Moreover, the increment of Cr by lovastatin in the left basal ganglia suggests the role of lovastatin for maintaining energy homeostasis, anti-apoptotic activity and ATP production in bipolar disorder. Some patents using lovastatin as an adjuant therapy for treating bipolar patients and depression in MDD patients are also outlined. This trial was registered in the Iranian Clinical Trials Registry (http://www.irct.ir/) (IRCT201302203930N18).

Increased affective empathy in bipolar patients during a manic episode.

Objective:To assess both cognitive and affective empathy in patients with bipolar disorder (BD) during an acute manic or depressive episode.Methods:The study included 25 patients with BD (aged 35±14 years) during an acute manic episode, 25 bipolar patients (aged 41±14 years) during a depressive episode, and 25 healthy control subjects (aged 36±11 years). Cognitive and affective empathy were assessed using the Multifaceted Empathy Test.Results:In both manic and depressive patients, a significant deficit in cognitive empathy was demonstrated. However, indices of affective empathy were significantly higher in the manic group than in depressed and control subjects. In the depressed patients, indices did not differ from those of healthy controls. For affective empathy, a significant positive correlation was found with intensity of manic symptoms and a negative correlation was found with intensity of depressive symptoms. No such correlations were observed with cognitive empathy.Conclusion:We found evidence of increased affective empathy (overempathizing) during a manic episode in bipolar patients. This phenomenon may be connected with disturbances in emotion inhibition related to anastrophic thinking and associated with increased activity of mirror neurons, all of which occur during a manic episode.

Treatment response in nonpsychotic vs psychotic manias - A follow up study from India.

Studies on treatment outcome in mania had been many. A few studies from the west address the issue of outcome in mood congruent and mood incongruent manias. None could be found from India. To compare the treatment response in three groups of patients with mania- Nonpsychotic, psychotic with mood congruent and psychotic with mood incongruent features. All consecutive manic patients admitted during 2013 to 2014, meeting inclusion and exclusion criteria were taken up. 28 patients with nonpsychotic Mania, 10 with mood congruent psychotic symptoms (MIC-) & 12 with mood incongruent psychotic features (MIC+). Diagnosis was confirmed using SCID. Mood stabilizers and Olanzapine or equivalent doses of antipsychotics were administered. Semi structured proforma was used for Socio Demographic & clinical details. YMRS, HDRS, Semi structured proforma to assess response (ISBD recommendations), CGI -BP & SAPS were used. Last 5 tools to assess the response to treatment at every 2 weeks, for 8 weeks. Statistical Package for Social Sciences, version 17.0 was used. These three groups did not show statistically significant difference in the socio-demographic variables. Severity of Mania was higher in Psychotic Mania. Psychotic Manias (group 2 and 3 combined) showed longer response time. However, mood incongruent psychotic manias when compared against the other 2 groups clubbed together did not differ significantly. All patients were from a tertiary referral centre and were hospitalized. Majority of them had a past history. The sample sizes were small. Treatment could not be fully matched. Our findings support the view that psychotic manias on the whole take significantly longer time than mania without psychotic symptoms to respond, and also scored higher on indices of severity. Mood Incongruent Psychotic Manias and Mood Congruent Psychotic Manias did not differ in severity & response time.

Behavioral and Electrophysiological Alterations for Reinforcement Learning in Manic and Euthymic Patients with Bipolar Disorder.

Bipolar disorder is characterized by behavioral changes such as risk-taking and increasing goal-directed activities, which may result from altered reward processing. Patients with bipolar disorder show impaired reward learning in situations that require the integration of reinforced feedback over time. In this study, we examined the behavioral and electrophysiological characteristics of reward learning in manic and euthymic patients with bipolar disorder using a probabilistic reward task. Twenty-four manic and 20 euthymic patients with bipolar I disorder and 24 healthy control subjects performed the probabilistic reward task. We assessed response bias (RB) as a preference for the stimulus paired with the more frequent reward and feedback-related negativity (FRN) to correct identification of the rich stimulus. Both manic and euthymic patients showed significantly lower RB scores in the early learning stage (block 1) in comparison with the late learning stage (block 2 or block 3) of the task, as well as significantly lower RB scores in the early stage compared to healthy subjects. Relatively more negative FRN amplitude is elicited by no presentation of an expected reward, compared to that elicited by presentation of expected feedback. The FRN became significantly more negative from the early (block 1) to the later stages (blocks 2 and 3) in both manic and euthymic patients, but not in healthy subjects. Changes in RB scores and FRN amplitudes between blocks 2 and 3 and block 1 correlated positively in healthy controls, but correlated negatively in manic and euthymic patients. The severity of manic symptoms correlated positively with reward learning scores and negatively with the FRN. These findings suggest that patients with bipolar disorder during euthymic or manic states have behavioral and electrophysiological alterations in reward learning compared to healthy subjects. This dysfunctional reward processing may be related to the abnormal decision-making or altered goal-directed activities frequently seen in patients with bipolar disorder.

Efficacy of Sodium Valproate and Olanzapine in treating bipolar affective disorder 'mania' at a tertiary care hospital in Nepal: A comparative study

Background and Objectives: Bipolar affective disorder, mania is the mood of an abnormally elevated arousal energy level or a state of heightened overall activation with enhanced affective expression together with lability of affect. The objective of the study was to compare the efficacy of sodium valproate and olanzapine in bipolar affective disorder, mania patients at a tertiary care hospital in NepalMaterial and Methods: A randomized observational prospective open label study was conducted for one and half year at College of Medical Sciences-Teaching Hospital (CMS-TH), Bharatpur, Nepal in the Psychiatry Department. Sixty patients diagnosed with bipolar affective disorder, mania were enrolled. 30 patients received sodium valproate and 30 patients received olanzapine. Patients were monitored and evaluated on baseline (day 0), day 7 and day 30 and compared to the baseline for the severity of illness using the 11-item Young Mania Rating Scale (YMRS).Results: The mean baseline YMRS score for all cases on sodium valproate (n=30) on day 0 was 38.87 ± 3.73, while it was reduced to 13.90 ± 1.95 (p < 0.001) on day 30. Similarly, the mean baseline YMRS score for all cases on olanzapine (n=30) on day 0was 40.83 ± 6.50, while it was reduced to 14.47 ± 2.83 (p < 0.001) on day 30.The mean decrease in YMRS score by sodium valproate was 64.24% and by olanzapine was 64.56%.Conclusion: Treatment with sodium valproate and olanzapine significantly improves the mean mania ratings score and there is no statistically significant difference in efficacy of both the drugs in patients diagnosed with bipolar affective disorder, mania.Janaki Medical College Journal of Medical Sciences (2016) Vol. 4(1): 27-35

Decreased S100B serum levels after treatment in bipolar patients in a manic phase

BackgroundPrevious studies have suggested that patients with bipolar disorder might have brain damage. The aim of this study was to investigate the serum levels of brain injury biomarkers and S100A10 in bipolar patients in a manic phase, and evaluate the changes in S100B, neuron specific enolase (NSE), heat shock protein 70 (HSP70) and S100A10 after treatment. MethodWe consecutively enrolled 17 bipolar inpatients in a manic phase and 30 healthy subjects. Serum brain injury biomarkers and S100A10 were measured with assay kits. All patients were evaluated by examining the correlation between brain injury biomarkers and Young Mania Rating Scale (YMRS) scores. ResultWe found significantly decreased S100B levels only in bipolar manic patients after treatment (p=0.002), but S100B levels were not significantly different from those in healthy controls (p>0.05). ConclusionOur results indicate there were decreased S100B serum levels in bipolar patients in a manic phase after treatment and that increased serum S100B levels might be a possible indicator of transient disruption of the blood–brain barrier in bipolar patients in a manic phase.

Reliability and Validity of the Korean Version of the Altman Self-Rating Mania Scale

Event Abstract Back to Event Reliability and Validity of the Korean Version of the Altman Self-Rating Mania Scale Sunhye Chung1 and Sungwon Choi1* 1 Duksung Women's University, Department of Psychology, Republic of Korea The Altman Self-Rating Mania Scale (ASRM) is a 5-item self-report instrument, designed to assess the presence and severity of manic symptoms; elevated/euphoric mood, increased self-esteem, decreased need for sleep, pressured speech, and psychomotor agitation. The primary purpose of the present study was to evaluate the reliability and validity of the Korean version of the ASRM (K-ASRM). The original ASRM scale was translated, and then this translated version was back-translated for the author of the original scale to confirm. The K-ASRM was administered to two groups, bipolar disorder (BD) group and healthy control group, whose ages ranged from 18 to 65 years. Participants in BD group were inpatients or outpatients, who were diagnosed with BD according to either the Structured Clinical Interview for DSM-IV or the DSM-5 criteria. The patients were divided into two sub-groups in accordance with different phases of the disorder: one group of patients with acute mania, who were currently experiencing manic with or without psychotic symptoms, hypomanic or mixed episode, and the other group constituted non-manic patients with a depressive episode or in remission. The Young Mania Rating Scale (YMRS) was concurrently assessed to measure validity for the BD group. Test-retest reliability was completed at intervals within 3 days for the mania sub-group and 7 days for the non-mania sub-group. As results, the score of K-ASRM had high concurrent validity and significant correlation with the scores of YMRS. The ROC curve analysis revealed that it could discriminate manic episode among BD patients and also between manic patients and healthy controls. The cut-off score and the results are similar to the results in the English version, indicating that the K-ASRM establishes a reliable and valid self-rating instrument to assess manic symptoms. The present study is notable in that it is the first translated self-rating mania scale, which validated from BD patients, available in Korea. Since the K-ASRM is a short scale to be conducted quickly and simply, it can be used as screening tool for research or clinical purpose. Moreover, it can be further applied as an intervention such as symptoms monitoring tool in a mobile application setting to help patients to increase awareness of own symptoms and track their symptoms change over time. Keywords: Altman Self-rating Mania Scale, ASRM, mania, Manic episode, Bipolar Disorder Conference: ISAD LONDON 2017: Perspectives on Mood and Anxiety Disorders: Looking to the future, London, United Kingdom, 6 Jul - 7 Jul, 2017. Presentation Type: Poster Topic: Diagnosis / Classification Citation: Chung S and Choi S (2019). Reliability and Validity of the Korean Version of the Altman Self-Rating Mania Scale. Front. Psychiatry. Conference Abstract: ISAD LONDON 2017: Perspectives on Mood and Anxiety Disorders: Looking to the future. doi: 10.3389/conf.fpsyt.2017.48.00037 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 May 2017; Published Online: 25 Jan 2019. * Correspondence: Prof. Sungwon Choi, Duksung Women's University, Department of Psychology, Seoul, Republic of Korea, sungwonchoi73@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sunhye Chung Sungwon Choi Google Sunhye Chung Sungwon Choi Google Scholar Sunhye Chung Sungwon Choi PubMed Sunhye Chung Sungwon Choi Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Neuroprotection after a first episode of mania: a randomized controlled maintenance trial comparing the effects of lithium and quetiapine on grey and white matter volume

Lithium and quetiapine are effective treatments for bipolar disorder, but their potential neuroprotective effects in humans remain unclear. A single blinded equivalence randomized controlled maintenance trial was conducted in a prospective cohort of first-episode mania (FEM) patients (n=26) to longitudinally compare the putative protective effects of lithium and quetapine on grey and white matter volume. A healthy control sample was also collected (n=20). Using structural MRI scans, voxel-wise grey and white matter volumes at baseline and changes over time in response to treatment were investigated. Patients were assessed at three time points (baseline, 3 and 12-month follow-up), whereas healthy controls were assessed at two time points (baseline and 12-month follow-up). Patients were randomized to lithium (serum level 0.6 mmol l−1, n=20) or quetiapine (flexibly dosed up to 800 mg per day, n=19) monotherapy. At baseline, compared with healthy control subjects, patients with FEM showed reduced grey matter in the orbitofrontal cortex, anterior cingulate, inferior frontal gyrus and cerebellum. In addition, patients had reduced internal capsule white matter volume bilaterally (t1,66>3.20, P<0.01). Longitudinally, there was a significant treatment × time effect only in the white matter of the left internal capsule (F2,112=8.54, P<0.01). Post hoc testing showed that, compared with baseline, lithium was more effective than quetiapine in slowing the progression of white matter volume reduction after 12 months (t1,24=3.76, P<0.01). Our data support the role of lithium but not quetiapine therapy in limiting white matter reduction early in the illness course after FEM.

Effect of Increased Neutrophil-to-Lymphocyte Ratio (NLR) and Decreased Mean Platelet Volume (MPV) Values on Inflammation in Acute Mania.

The neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) are simple, low-cost, and useful inflammatory markers detected in routine complete blood count (CBC), and their use has recently become widespread. In this study, we aimed to investigate the presence of an inflammatory state in manic patients on the basis of NLR and MPV values. This retrospective study was performed on 76 patients with acute mania who were admitted to the Inpatients Psychiatry Clinic of Afyon Kocatepe University Hospital in Turkey. Diagnoses were based on Diagnostic and Statistical Manuel of Mental disorder (DSM-IV). The control group consisted of 74 healthy individuals recruited from the community. They were age- and sex-matched with the study group. NLR values of the manic patient group were 2.2±1.4 and those of the control group were 1.6±0.5. NLR values were significantly higher (p=0.004) and MPV values were significantly lower in the manic patient group than in the control group (10.0±1.2 vs. 10.9±2.3, p=0.027). Increased NLR and decreased MPV levels may reflect inflammation in manic patients, and inflammation may play a role in the complex pathophysiology of acute mania.

Antipsychotic adjunctive therapy to mood stabilizers and 1-year rehospitalization rates in bipolar disorder: A cohort study.

Antipsychotic adjunctive therapy to mood stabilizers (MSs) may improve relapse prevention; however, only a few naturalistic studies, reflecting more generalizable bipolar disorder (BD) samples, support this notion. We compared the 1-year rehospitalization rates of manic patients with bipolar I disorder (BD-I) who were discharged with MS (lithium or valproate) monotherapy or with adjunctive atypical or typical antipsychotic therapy. A total of 201 patients with BD-I who were hospitalized with manic episodes between 2005 and 2013 were retrospectively followed for 1-year rehospitalization rates according to treatment at discharge: MS monotherapy, MS with atypical antipsychotics, and MS with typical antipsychotics. Additionally, time to rehospitalization during the 1-year period after discharge was compared between treatment groups. Multivariable survival analyses adjusted for covariates known to influence rehospitalization were conducted. Rehospitalization rates within 1year were significantly lower in the MS with atypical antipsychotics group (6.3%) compared to the MS monotherapy group (24.3%, P=.008) and to the MS with typical antipsychotics group (20.6%, P=.02). Time to rehospitalization was significantly longer for the MS with atypical antipsychotics group (345.5days) compared to the MS monotherapy group (315.1days, P=.006) and to the MS with typical antipsychotics group (334.1days, P=.02). The MS with atypical antipsychotics group had a significantly reduced adjusted risk of rehospitalization (hazard ratio=0.17, 95% confidence interval: 0.05-0.61, P=.007) compared to the MS monotherapy group. Atypical antipsychotic adjunctive therapy to MSs may be more effective than MS monotherapy in preventing rehospitalization during the 1-year period after a BD manic episode.

C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis

Inflammatory processes and neural-immune interactions have been implicated in the pathogenesis of psychiatric conditions, but studies in bipolar disorder are inconclusive so far. We aimed to investigate whether peripheral concentrations of C-reactive protein (CRP), an acute-phase response protein of inflammatory activity, are increased in bipolar disorder across the mood spectrum. In this systematic review and meta-analysis, we searched MEDLINE, the Cochrane Library, Scopus, and Web of Knowledge from database inception to Aug 14, 2016, for studies that measured serum and plasma CRP concentrations in adult patients with bipolar disorder (as defined by DSM-IV-TR) and healthy controls. We extracted data from published reports. We did three between-group meta-analyses comparing CRP concentrations in patients in mania, depression, or euthymia, with those in healthy controls (cross-sectional studies), and two within-group meta-analyses comparing changes in CRP concentrations before and after treatment of an index manic or depressive episode (longitudinal studies). We used Hedges' adjusted g to calculate effect sizes and pooled results using random-effect models. We also did meta-regression analyses by mood state to investigate possible moderators of CRP concentrations. We identified 27 studies representing 2161 patients with bipolar disorder and 81 932 healthy controls. Compared with healthy individuals, CRP concentrations were moderately increased in people with bipolar disorder during depression (g 0·67, 95% CI 0·23 to 1·11; p=0·003) and euthymia (0·65, 0·40 to 0·90; p<0·0001) and more substantially increased during mania (0·87, 0·58 to 1·15; p<0·0001). The extent of the increases in CRP concentrations in mania and depression was not related to symptom severity (p=0·256 for mania and p=0·626 for depression). CRP concentrations were moderately decreased after resolution of an index manic episode (-0·36, -0·66 to -0·05; p=0·022) and slightly decreased after resolution of an index depressive episode (-0·18, -0·30 to -0·07; p=0·002). CRP concentrations are increased in bipolar disorder regardless of mood state, but are higher during mania than in depression and euthymia, suggesting an increased inflammatory burden in mania. None.

The effects of reduced dopamine transporter function and chronic lithium on motivation, probabilistic learning, and neurochemistry in mice: Modeling bipolar mania

BackgroundBipolar disorder (BD) mania patients exhibit poor cognition and reward-seeking/hypermotivation, negatively impacting a patient's quality of life. Current treatments (e.g., lithium), do not treat such deficits. Treatment development has been limited due to a poor understanding of the neural mechanisms underlying these behaviors. Here, we investigated putative mechanisms underlying cognition and reward-seeking/motivational changes relevant to BD mania patients using two validated mouse models and neurochemical analyses. MethodsThe effects of reducing dopamine transporter (DAT) functioning via genetic (knockdown vs. wild-type littermates), or pharmacological (GBR12909- vs. vehicle-treated C57BL/6J mice) means were assessed in the probabilistic reversal learning task (PRLT), and progressive ratio breakpoint (PRB) test, during either water or chronic lithium treatment. These tasks quantify reward learning and effortful motivation, respectively. Neurochemistry was performed on brain samples of DAT mutants ± chronic lithium using high performance liquid chromatography. ResultsReduced DAT functioning increased reversals in the PRLT, an effect partially attenuated by chronic lithium. Chronic lithium alone slowed PRLT acquisition. Reduced DAT functioning increased motivation (PRB), an effect attenuated by lithium in GBR12909-treated mice. Neurochemical analyses revealed that DAT knockdown mice exhibited elevated homovanillic acid levels, but that lithium had no effect on these elevated levels. ConclusionsReducing DAT functioning recreates many aspects of BD mania including hypermotivation and improved reversal learning (switching), as well as elevated homovanillic acid levels. Chronic lithium only exerted main effects, impairing learning and elevating norepinephrine and serotonin levels of mice, not specifically treating the underlying mechanisms identified in these models.

P.2.d.005 - One-year rehospitalization rates in bipolar disorder manic patients discharged on mood stabilizers versus mood stabilizer combined with antipsychotics

P.2.d.005 - One-year rehospitalization rates in bipolar disorder manic patients discharged on mood stabilizers versus mood stabilizer combined with antipsychotics

Associations of Serum Cytokine Receptor Levels with Melancholia, Staging of Illness, Depressive and Manic Phases, and Severity of Depression in Bipolar Disorder.

To examine cytokine receptor biomarkers in bipolar disorder (BD), we recruited 133 well-phenotyped BD patients and 50 normal controls and measured serum levels of soluble interleukin 1 receptor antagonist (sIL-1RA), soluble interleukin-2 receptor (sIL-2R), sIL-6R, and tumor necrosis factor receptor 60 and 80kDa (sTNFR60/80). sIL-1RA and sTNFR80 are significantly higher in BD than in controls and sTNFR80 and higher in melancholic than in non-melancholic patients and controls. Kapczinski's stages 3 + 4 are characterized by lowered sIL-2R and increased sTNFR80 levels. Acute phase depression is characterized by increased sTNFR80 levels as compared with controls, manic, and euthymic patients. Both sTNFR60 and sTNFR80 levels are significantly and positively related with severity of depression but not mania. Logistic regression analysis showed that the significant predictors for BD are increased sIL-1RA levels, nicotine dependence and a family history of depression and alcoholism. The risk factors for stages 3 + 4 are lowered sIL-2R levels and nicotine dependence. Melancholia is predicted by higher sTNFR80 levels and female sex. Severity of depression is predicted by female sex, nicotine dependence, and increased sTNFR60 and sTNFR80 levels. Cell-mediated immunity is activated during a current episode of depression but not (hypo)mania or the euthymic state. There are no associations between the biomarkers and age at onset, duration of illness, severity of mania, bipolar (BP)2 or BP1 subtypes, rapid cycling, atypical depression, psychotic or suicidal symptoms, and a family history of psychiatric disease. The results show that increased sIL-1RA may be a trait marker of BD, increased sTNFR80 a state marker of the depressive phase, especially melancholia, while lower sIL-2R but higher sTNFR80 may be staging biomarkers.

Early report on brain arousal regulation in manic vs depressive episodes in bipolar disorder

The arousal regulation model of affective disorders attributes an important role in the pathophysiology of affective disorders to dysregulation of brain arousal regulation. According to this model, sensation avoidance and withdrawal in depression and sensation seeking and hyperactivity in mania can be explained as auto-regulatory attempts to counteract a tonically high (depression) or unstable (mania) arousal. The aim of this study was to compare brain arousal regulation between manic and depressive bipolar patients and healthy controls. We hypothesized that currently depressed patients with bipolar disorder show hyperstable arousal regulation, while currently manic patients show unstable arousal regulation. Twenty-eight patients with bipolar disorder received a 15-min resting electroencephalogram (EEG) during a depressive episode and 19 patients received the same during a manic/hypomanic episode. Twenty-eight healthy control subjects were matched for age and sex. The Vigilance Algorithm Leipzig (VIGALL), which classifies 1-s EEG segments as one of seven EEG-vigilance substages, was used to measure brain arousal regulation. Manic patients showed more unstable EEG-vigilance regulation as compared to the control sample (P=.004) and to patients with a depressive episode (P≤.001). Depressive patients had significantly higher mean vigilance levels (P=.045) than controls. A clear difference was found in the regulation of brain arousal of manic patients vs depressive patients and controls. These data suggest that brain arousal might depend on the current mood state, which would support the arousal regulation model of affective disorders.

Neuroprogression and episode recurrence in bipolar I disorder: A study of gray matter volume changes in first‐episode mania and association with clinical outcome

Bipolar I disorder (BD-I) is associated with gray matter volume (GMV) alterations in neural regions important for emotional regulation. Reductions found in patients with multiple episodes are not seen at illness onset, suggesting that changes occur with illness progression, although no prospective studies to date have examined this. In the present study, we assessed GMV at baseline and one year following a first manic episode, examining the impact of episode recurrence on the trajectory of change. A total of 41 recently remitted first manic episode patients with BD-I and 25 healthy subjects (HS) underwent 3T magnetic resonance imaging at baseline and one year later. Using voxel-based morphometry, we compared GMV change between HS, patients who experienced a recurrence of a mood episode (BDrecurr ), and patients in sustained remission (BDwell ). The GMV change from baseline to one year did not differ significantly between HS and the full BD-I group or BDwell and HS. However, the BDrecurr group had greater GMV loss than HS in left frontal and bilateral temporal regions, and BDwell patients involving bilateral frontal, temporal and left parietal regions. GMV change early in the course of BD-I is associated with clinical outcome, such that neuroprogression found in patients who experience a recurrence of a mood episode is not seen in those with sustained remission. These findings have important implications for the treatment of BD-I as they suggest that prevention of recurrence might minimize neuroprogression of the disease, possibly requiring a multipronged early intervention approach to achieve this goal.

Early ERP modulation during mood adjectives processing in patients with affective disorders

Attentional bias is considered a key feature in mood disorders, and yet little is known of its neural correlates within the early stream of information processing in manic and depressed patients. The study aimed to capture and detail attentional bias during emotional word processing in patients within the first 500ms of stimulus exposition. 28 mood adjectives (14 positive and 14 negative) were used as stimuli. We expected differences in adjective encoding between groups during lexico-semantic analysis based on varying attentional resource allocation. Differences were evidenced within the first 100ms after stimulus onset with higher amplitudes for both patient groups than controls, possibly indicating more automatic attention allocation to stimuli during sensory analysis stages. Between 200–290ms after the words' onset, a specific valence mood-word mismatch was registered which approached significance, with higher responses evoked to negative than positive words in manic patients, and the opposite pattern of activity observed in depressed patients, suggesting cognitive bias based on mood incongruence during the lexico-semantic analysis stage. There was also a lateralized pattern of activity, with higher amplitudes over the right hemisphere posteriorly, and higher over the left frontally in the patient groups, especially in the manic individuals. The study points to attentional bias based on mood incongruence processing during crucial stages of meaning encoding within the early stream of information processing.

Suicidality and symptoms of anxiety, irritability, and agitation in patients experiencing manic episodes with depressive symptoms: a naturalistic study.

PurposePatients with a bipolar I disorder (BD-I) manic episode meeting the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), criteria for “with mixed features” have a high incidence of suicide attempts and of anxiety, irritability, and agitation (AIA) symptoms. The aim of this analysis was to explore the relationship between suicidality and AIA symptoms in patients with BD-I experiencing mania with depressive symptoms, using data from a previous naturalistic study.Patients and methodsPsychiatrists completed an online questionnaire about their adult patients who had a current BD-I manic episode. Questions covered the DSM-5 “with mixed features” specifier, the severity of AIA symptoms, the frequency and controllability of suicidal ideation, and the number of suicide attempts.ResultsOf 1,035 patients with BD-I mania who were included in the analyses, 348 (33.6%) met the criteria for the DSM-5 “with mixed features” specifier (three or more depressive symptoms). These patients were further stratified according to the severity of their AIA symptoms: “mild AIA” (zero or one AIA symptom above a severity threshold; 105 patients) or “severe AIA” (all three AIA symptoms above a severity threshold; 167 patients). A greater incidence of suicidal ideation was observed in the severe AIA group (71.9%) than in the mild AIA group (47.6%). Twice as many patients had easily controlled suicidal ideation than difficult-to-control suicidal ideation in both subgroups. The mean number of suicide attempts was higher in the severe AIA group than in the mild AIA group, during the current episode (0.84 vs 0.34 attempts, respectively; P<0.05) and over the patient’s lifetime (1.56 vs 1.04 attempts, respectively).ConclusionThe high risk of suicide among BD-I mania patients with depressive symptoms is further increased when they experience severe AIA symptoms. Recognizing AIA symptoms in BD-I mania could provide a means of identifying patients with depressive symptoms, as well as those who may be suicidal, thereby allowing for appropriate, tailored treatment.