Reduced Plasma Dopamine-β-Hydroxylase Activity Is Associated With the Severity of Bipolar Disorder: A Pilot Study

Dopamine-β-hydroxylase (DβH) is an enzyme converting dopamine to norepinephrine, a key neurotransmitter in mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD). Due to overlapping symptomology of unipolar and bipolar depression, the present study attempted to explorer if the plasma DβH activity could discriminate the depressive episodes of BD from MDD. The aim of this study was to compare the plasma DβH activity among MDD patients (n = 104), BD patients (n = 101), and healthy controls (n = 160). Clinical characteristics and cognitive function were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Patient Health Questionnaire-9 (PHQ-9), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Our data showed a lower plasma DβH activity in patients with BD, not MDD, than that in controls. For the BD patients, the plasma DβH activities were negatively correlated with HAM-D scores and HAM-A scores. However, there was no significant correlation between plasma DβH activity and severity of depressive symptoms in MDD patients. No significant correlation between DβH activities and cognitive assessments neither in BD nor in MDD patients. The present study provides evidence that BD is associated with decreased circulating DβH activity.

Download Full-text

Adaptation and validation of the Korean Version of the Bipolar Depression Rating Scale (K-BDRS)

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.592 ◽

2016 ◽

Vol 33 (S1) ◽

pp. s236-s237

Author(s):

W.M. Bahk ◽

M.D. Kim ◽

Y.E. Jung ◽

Y.S. Woo ◽

J. Lee ◽

...

Keyword(s):

Bipolar Disorder ◽

Depressive Symptoms ◽

Psychometric Properties ◽

Rating Scale ◽

Bipolar Depression ◽

Depression Scale ◽

Reliability And Validity ◽

Hamilton Depression Scale ◽

Young Mania ◽

Korean Version

ObjectivesThe Bipolar Depression Rating Scale (BDRS) is a scale for assessment of the clinical characteristics of bipolar depression. The primary aims of this study were to describe the development of the Korean version of the BDRS (K-BDRS) and to establish more firmly its psychometric properties in terms of reliability and validity.MethodsThe study included 141 patients (62 male and 79 female) who had been diagnosed with bipolar disorder, were currently experiencing symptoms of depression, and were interviewed using the K-BDRS. Other measures included the Montgomery and Asberg Depression Scale (MADRS), the 17-item Hamilton Depression Scale (HAMD), and the Young Mania Rating Scale (YMRS). Additionally, the internal consistency, concurrent validity, inter-rater reliability, and test-retest reliability of the K-BDRS were evaluated.ResultsThe Cronbach's α-coefficient for the K-BDRS was 0.866, the K-BDRS exhibited strong correlations with the HAMD (r = 0.788) and MADRS (r = 0.877), and the mixed symptoms score of the K-BDRS was significantly correlated with the YMRS (r = 0.611). An exploratory factor analysis revealed three factors that corresponded to psychological depressive symptoms, somatic depressive symptoms, and mixed symptoms.ConclusionsThe present findings suggest that the K-BDRS has good psychometric properties and is a valid and reliable tool for assessing depressive symptoms in patients with bipolar disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Download Full-text

The progression of 102 Brazilian patients with bipolar disorder: outcome of first 12 months of prospective follow-up

Trends in Psychiatry and Psychotherapy ◽

10.1590/2237-6089-2012-0048 ◽

2014 ◽

Vol 36 (1) ◽

pp. 16-22 ◽

Cited By ~ 2

Author(s):

Fernanda Novis ◽

Patricia Cirillo ◽

Rafael Assis da Silva ◽

Ana Letícia Santos ◽

Luciana Angélica Silva Silveira ◽

...

Keyword(s):

Bipolar Disorder ◽

Depressive Symptoms ◽

Rating Scale ◽

Depression Scale ◽

First Episode ◽

First Year ◽

International Studies ◽

Hamilton Depression Scale ◽

Adequate Treatment ◽

Depressive Episodes

INTRODUCTION: Prospective studies have shown that the course of bipolar disorder (BD) is characterized by the persistence of symptoms, predominantly depression, along most of the time. However, to our knowledge, no studies in Latin America have investigated it. OBJECTIVES: To replicate international studies using a Brazilian sample to prospectively analyze treatment outcomes in the first year and to determine potential chronicity factors. METHODS: We followed up 102 patients with BD for 12 months and evaluated the number of months with affective episodes and the intensity of manic and depressive symptoms using the Young Mania Rating Scale (YMRS) and the Hamilton Depression Scale (HAM-D17). Sociodemographic and retrospective clinical data were examined to determine possible predictors of outcome. RESULTS: Almost 50% of the patients had symptoms about half of the time, and there was a predominance of depressive episodes. Disease duration and number of depressive episodes were predictors of chronicity. Depressive polarity of the first episode and a higher number of depressive episodes predicted the occurrence of new depressive episodes. CONCLUSION: In general, BD outcome seems to be poor in the first year of monitoring, despite adequate treatment. There is a predominance of depressive symptoms, and previous depressive episodes are a predictor of new depressive episodes and worse outcome.

Download Full-text

Insight in bipolar disorder: a comparison between mania, depression and euthymia using the Insight Scale for Affective Disorders

Trends in Psychiatry and Psychotherapy ◽

10.1590/2237-6089-2015-0014 ◽

2015 ◽

Vol 37 (3) ◽

pp. 152-156 ◽

Cited By ~ 11

Author(s):

Rafael de Assis da Silva ◽

Daniel C. Mograbi ◽

Evelyn V. M. Camelo ◽

Jaqueline Bifano ◽

Mayra Wainstok ◽

...

Keyword(s):

Bipolar Disorder ◽

Clinical Management ◽

Affective Disorders ◽

Rating Scale ◽

Mood State ◽

Depression Scale ◽

Treatment Compliance ◽

Hamilton Depression Scale ◽

Young Mania ◽

Insight Into

Objective: To evaluate whether having general insight into bipolar disorder and its symptoms is affected by the mood state of the patient, using the Insight Scale for Affective Disorders, a hetero-application scale for people with mood disorders.Methods: Ninety-five patients with bipolar disorder were evaluated and divided into different groups according to the mood state presented during assessment (i.e., euthymia, mania and depression). Sociodemographic and clinical data (Hamilton Depression Scale, Young Mania Rating Scale, and Clinical Global Impressions Scale) were recorded. Insight was evaluated using the Insight Scale for Affective Disorders.Results: Patients with bipolar disorder in mania show less insight about their condition than patients in depression or euthymia, and less insight about their symptoms than patients with depression, with the exception of awareness of weight change.Conclusions: Loss of insight during mania may have important implications for treatment compliance and adherence and needs to be taken into account in the clinical management of people with bipolar disorder.

Download Full-text

Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms

International Journal of Bipolar Disorders ◽

10.1186/s40345-019-0155-y ◽

2019 ◽

Vol 7 (1) ◽

Author(s):

Maximilian Pilhatsch ◽

Thomas J Stamm ◽

Petra Stahl ◽

Ute Lewitzka ◽

Anne Berghöfer ◽

...

Keyword(s):

Bipolar Disorder ◽

Rating Scale ◽

Bipolar Depression ◽

Phenotypic Expression ◽

Anxiety Symptoms ◽

Controlled Study ◽

Double Blind ◽

Comorbid Anxiety ◽

Depressed Patients ◽

Depressive Episodes

Abstract Background Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression. Methods Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI). Results Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877). Conclusions This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients. Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012—Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839

Download Full-text

Differences in Kynurenine Metabolism During Depressive, Manic, and Euthymic Phases of Bipolar Affective Disorder

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190802145128 ◽

2020 ◽

Vol 20 (15) ◽

pp. 1344-1352 ◽

Cited By ~ 3

Author(s):

Alexander Maget ◽

Martina Platzer ◽

Susanne A. Bengesser ◽

Frederike T. Fellendorf ◽

Armin Birner ◽

...

Keyword(s):

Bipolar Disorder ◽

Kynurenic Acid ◽

Rating Scale ◽

Depression Scale ◽

Hamilton Depression Scale ◽

Monooxygenase Activity ◽

Kynurenine Aminotransferase ◽

Mood Symptoms ◽

Kynurenine Metabolism ◽

Current Mood

Background & Objectives: The kynurenine pathway is involved in inflammatory diseases. Alterations of this pathway were shown in psychiatric entities as well. The aim of this study was to determine whether specific changes in kynurenine metabolism are associated with current mood symptoms in bipolar disorder. Methods: Sum scores of the Hamilton Depression Scale, Beck Depression Inventory, and Young Mania Rating Scale were collected from 156 bipolar individuals to build groups of depressive, manic and euthymic subjects according to predefined cut-off scores. Severity of current mood symptoms was correlated with activities of the enzymes kynurenine 3-monooxygenase (ratio of 3-hydroxykynurenine/ kynurenine), kynurenine aminotransferase (ratio of kynurenic acid/ kynurenine) and kynureninase (ratio of 3-hydroxyanthranilic acid/ 3-hydroxykynurenine), proxied by ratios of serum concentrations. Results: Individuals with manic symptoms showed a shift towards higher kynurenine 3-monooxygenase activity (χ2 = 7.14, Df = 2, p = .028), compared to euthymic as well as depressed individuals. There were no differences between groups regarding activity of kynurenine aminotransferase and kynureninase. Within the group of depressed patients, Hamilton Depression Scale and kynurenine aminotransferase showed a significant negative correlation (r = -0.41, p = .036), displaying lower metabolism in the direction of kynurenic acid. Conclusion: Depression severity in bipolar disorder seems to be associated with a decreased synthesis of putative neuroprotective kynurenic acid. Furthermore, higher kynurenine 3-monooxygenase activity in currently manic individuals indicates an increased inflammatory state within bipolar disorder with more severe inflammation during manic episodes. The underlying pathophysiological mechanisms of the different affective episodes could represent parallel mechanisms rather than opposed processes.

Download Full-text

Case Report: Paliperidone Palmitate in the Management of Bipolar I Disorder With Non-compliance

Frontiers in Psychiatry ◽

10.3389/fpsyt.2020.529672 ◽

2021 ◽

Vol 11 ◽

Author(s):

Kanglai Li ◽

Yingtao Liao ◽

Zhihua Yang ◽

Caishuang Yang ◽

Minhua Chen ◽

...

Keyword(s):

Bipolar Disorder ◽

Rating Scale ◽

Safety Concern ◽

Paliperidone Palmitate ◽

Adjunctive Treatment ◽

Symptom Scale ◽

Young Mania ◽

Bipolar I Disorder ◽

Depressive Episodes

Background: Medication non-adherence is prevalent in patients with bipolar disorder (BD). Long-acting injectable antipsychotics (LAIAs) are widely used to improve compliance with treatment. This study aimed to illustrate the effectiveness, compliance, and safety profile of once-monthly paliperidone palmitate (PP1M), a novel therapeutic LAIA, in the management of bipolar I disorder (BDI).Method: A prospective follow-up was arranged to 11 BDI patients who were prescribed PP1M as monotherapy or adjunctive treatment. Severity of symptoms, disturbing behavior, status of employment, 17-item Hamilton Depression Rating Scale (HAMD-17), and Young Mania Rating Scale (YMRS) were evaluated at the baseline and the endpoint of follow-up. Clinical Global Impression—Bipolar Disorder—Severity of Illness Scale (CGI-BP) and Treatment Emergent Symptom Scale (TESS) were measured at each injection of PP1M. Compliance, relapse or switch, and new hospitalization were monitored through the period of follow-up.Results: The median duration of treatment was 14 months, ranging from 5 to 22 months. The scores (mean ± standard deviation) of HAMD-17, YMRS, and CGI-BP generally decreased from the baseline (16.1 ± 10.3, 30.9 ± 12.6, 5.3 ± 0.7) to the endpoint (7.4 ± 5.7, 3.7 ± 3.2, 2.3 ± 0.7). No disturbing behavior was detected at the endpoint. Neither new hospitalization nor manic/mixed episode occurred during treatment, whereas mild to moderate depressive episodes were reported in three cases. The status of employment of 10 participants (90.9%) was improved, and no new safety concern was detected.Conclusion: PP1M might offer a new valid treatment option in the long-term management of BDI, especially for those with poor compliance with oral medication. However, more studies are needed to further justify such role.

Download Full-text

Individual level prediction of emerging suicide events in the pharmacologic treatment of bipolar disorder

10.1101/2021.01.13.20246603 ◽

2021 ◽

Author(s):

Sean X. Luo ◽

Adam Ciarleglio ◽

Hanga Galfalvy ◽

Michael Grunebaum ◽

Leo Sher ◽

...

Keyword(s):

Bipolar Disorder ◽

Variable Selection ◽

Suicidal Behavior ◽

Predictive Models ◽

Suicide Attempts ◽

Bipolar Depression ◽

Depression Scale ◽

Hamilton Depression Scale ◽

Pharmacologic Treatment ◽

Survival Trees

AbstractBackgroundPatients with bipolar disorder have a high lifetime risk of suicide. Predicting, preventing and managing suicidal behavior are major goals in clinical practice. Changes in suicidal thoughts and behavior are common in the course of treatment of bipolar disorder.MethodsUsing a dataset from a randomized clinical trial of bipolar disorder treatment (N=98), we tested predictors of future suicidal behavior identified through a review of literature and applied marginal variable selection and machine learning methods. The performance of the models was assessed using the optimism-adjusted C statistic.ResultsNumber of prior hospitalizations, number of prior suicide attempts, current employment status and Hamilton Depression Scale were identified as predictors and a simple logistic regression model was constructed. This model was compared with a model incorporating interactions with treatment group assignment, and more complex variable selection methods (LASSO and Survival Trees). The best performing models had average optimism-adjusted C-statistics of 0.67 (main effects only) and 0.69 (Survival Trees). Incorporating medication group did not improve prediction performance of the models.ConclusionsThese results suggest that models with a few predictors may yield a clinically meaningful way to stratify risk of emerging suicide events in patients who are undergoing pharmacologic treatment for bipolar disorder.Significance StatementThis study aims to find out whether suicide events that occur during the pharmacological treatment of bipolar disorder, a severe psychiatric disorder that is highly associated with suicide behavior, can be predicted. Using existing methods, we developed and compared several predictive models. We showed that these models performed similarly to predictive models of other outcomes, such as treatment efficacy, in unipolar and bipolar depression. This suggests that suicide events during bipolar disorder may be a feasible target for individualized interventions in the future.

Download Full-text

Emotional Schemas: A New Cognitive Perspective for the Distinction Between Unipolar Depression and Bipolar Disorder

European Psychiatry ◽

10.1016/j.eurpsy.2017.02.016 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S243-S243 ◽

Cited By ~ 1

Author(s):

O. Onur

Keyword(s):

Bipolar Disorder ◽

Rating Scale ◽

Depression Scale ◽

Unipolar Depression ◽

Group Differences ◽

Young Mania ◽

Exploratory Investigation ◽

General Activation ◽

Dsm Iv ◽

Competing Interest

IntroductionClinicians need to make the differential diagnosis between unipolar depression and bipolar disorder to guide their treatment choices. Looking at the differences observed in the emotional schemas might help with this differentiation. This study is an exploratory investigation of schema theory's Leahy's emotional schemas among individuals diagnosed with bipolar disorder and unipolar depression.MethodsThree groups of subjects 56 unipolar depression in the remission period, 70 bipolar eutimic and 58 healthy controls were asked to fill out the Leahy Emotional Schema Scale (LESS). The clinicians diagnosed the participants according to the criteria of DSM-IV-TR with SCID-I, and rated the moods of the subjects with the Beck Depression Scale, and the Young Mania Rating Scale (YMRS). Statistical analyses were undertaken to identify the group differences on LESS.ResultsThe bipolar eutimic and unipolar depression patients’ scores on the LESS dimensions were significantly different from the healthy participants in the areas of control, consensus, acceptance of feelings, dissimilarity and simplistic view of emotions.ConclusionsThese results suggest that the metacognitive model of unipolar depression might be extrapolated for patients with bipolar disorder. Bipolar disorder may be associated with a general activation of the emotional schemas.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

Download Full-text

Obesity and quality of life in bipolar disorder

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.389 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S423-S424

Author(s):

R. Jouini ◽

H. Ben Ammar ◽

G. Hamdi ◽

N. Smari ◽

A. Aissa ◽

...

Keyword(s):

Quality Of Life ◽

Bipolar Disorder ◽

Scale Score ◽

Rating Scale ◽

Short Form ◽

Depression Scale ◽

Overweight And Obesity ◽

Hamilton Depression Scale ◽

Bipolar Patients

IntroductionOverweight and obesity, despite their comorbidities and mortality, could deteriorate the quality of life of people with bipolar disorder.ObjectivesThe objective of this study is to evaluate the quality of life among patients with bipolar disorder and investigate a possible interaction between obesity and deterioration of the quality of life.AimsThis study aims to highlight the importance of preventing overweight and obesity in people with bipolar disorder to obtain an adequate quality of life subsequently an acceptable control of the illness.MethodsFifty euthymic bipolar patients (Hamilton Depression Scale score ≤ 8, and Young Mania Rating Scale score ≤ 6) received the Medical Outcomes Study 36-Item Short-Form Health Survey in Arabic validated version in order to investigate the quality of life.ResultsWe examined 50 euthymic bipolar patients (60% men, 40% women). The average age was 46, 5 years (23–70). Most patients (69%) were over weighted (BMI ≥ 25.0 kg/m2) (body mass index), of whom 40% were obese (BMI ≥ 30.0 kg/m2). Seventy-two percent of the investigated patients had an affected quality of life (score < 66.7). The mental items were deteriorated in 80% of the cases. An affected quality of life was correlated with obesity. The BMI was significantly and negatively correlated with the scores of dimensions D4 (mental health) and D8 (perceived health) (P < 0.01).ConclusionThe investigation of quality of life in people with mental disorder enables to reveal the social handicap caused by these illnesses consequently emphasizes health care in mental affections.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Download Full-text

Mitochondrial modulators in the treatment of bipolar depression: a systematic review and meta-analysis

Translational Psychiatry ◽

10.1038/s41398-021-01727-7 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Liang Liang ◽

Junyu Chen ◽

Ling Xiao ◽

Qing Wang ◽

Gaohua Wang

Keyword(s):

Depressive Symptoms ◽

Subgroup Analysis ◽

Rating Scale ◽

Bipolar Depression ◽

Meta Analysis ◽

Depression Scale ◽

Small Sample ◽

Antidepressant Effect ◽

Young Mania ◽

Scale Scores

AbstractMitochondrial dysfunction has been implicated in the risk, pathophysiology, and progression of mood disorders, especially bipolar disorder (BD). Thus, the objective of this meta-analysis was to determine the overall antidepressant effect of mitochondrial modulators in the treatment of bipolar depression. Outcomes included improvement in depression scale scores, Young Mania Rating Scale (YMRS) and Clinical Global Impression-Severity Scale (CGI-S) score. Data from randomized controlled trials (RCTs) assessing the antidepressant effect of diverse mitochondrial modulators were pooled to determine standard mean differences (SMDs) compared with placebo.13 RCTs were identified for qualitative review. The overall effect size of mitochondrial modulators on depressive symptoms was −0.48 (95% CI: −0.83 to −0.14, p = 0.007, I2 = 75%), indicative of a statistically significant moderate antidepressant effect. In the subgroup analysis, NAC improved depressive symptoms compared with placebo (−0.88, 95% CI: −1.48 to −0.27, I2 = 81%). In addition, there was no statistical difference between mitochondrial modulators and placebo in YMRS. Although mitochondrial modulators were superior to placebo in CGI-S score (−0.44, 95% CI: −0.83 to −0.06, I2 = 71%), only EPA was superior to placebo in subgroup analysis. Overall, a moderate antidepressant effect was observed for mitochondrial modulators compared with placebo in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis.

Download Full-text