Depressive Episodes In Bipolar Disorder Research Articles

Acupuncture at five Zang-shu and Ge-shu for bipolar depression: study protocol for a randomized controlled pilot trial

Background: Bipolar disorder is a very common, often misdiagnosed mental disorder strongly associated with comorbidity, disability, and premature mortality. Bipolar depression (i.e., depressive episode in bipolar disorder) is poorly responsive to available treatments. Acupuncture at five Zang-shu and Ge-shu, a prescription from Dr. Leting Wang, is a popular therapy for depression in China. Its effectiveness and safety for bipolar depression is yet to be verified by clinical study. Methods/design: The study is a single-center, prospective, randomized controlled trial involving 72 patients diagnosed with bipolar depression. Participants will be randomized either to the study group or the control group in a 1:1 ratio. All participants will receive mood stabilizer therapy. In addition, the study group will receive acupuncture therapy at five Zang-shu and Ge-shu, three times per week. The control group will orally take the antidepressant bupropion. Observation and intervention will last for 8 consecutive weeks. Outcome measurements include Hamilton Depression Rating Scale-17 (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), Clinical Global Impression Scale (CGI), Young Manic Rating Scale (YMRS), Treatment Emergent Symptom Scale (TESS), serum levels of anti-inflammatory cytokines (IL-4, IL-10, TGF-β), pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), brain-derived neurotrophic factor (BDNF) and C-Reactive Protein (CRP). Assessments will be conducted at baseline, 1st, 2nd, 4th and 8th week after randomization. Safety assessments will be performed throughout the study. Discussion: The results of this study are expected to verify the effectiveness and safety of acupuncture at five Zang-shu and Ge-shu for bipolar depression, and explore its therapeutic mechanisms from the point of anti- inflammation.

Olink proteomics analysis uncovers inflammatory proteins in patients with different states of bipolar disorder

Study Design: A prospective study. BackgroundThis study aims to investigate the relationship between different states of bipolar disorder (BD) and plasma inflammatory proteins, which may be used as their biomarkers. Materials and methodsWe totally collected admission plasma from 16 healthy subjects and 32 BD patients, including 16 patients with BD manic episodes (BD-M) and 16 patients with BD depressive episodes (BD-D). Ten samples in each group were analyzed by proximity extension assays of 92 inflammation-related proteins, and all samples were verified by ELISA. Receiver-operating characteristic (ROC) curve analysis was performed to identify the diagnostic ability and cut-off values of potential biomarkers. ResultsOur findings showed that BD patients had significantly higher levels of IL6, MCP-1, TGF-α, IL8, and IL10-RB in comparison with healthy subjects, and their cut-off values were 0.531 pg/ml, 0.531 pg/ml, 0.469 pg/ml, 0.406 pg/ml, and 0.406 pg/ml, respectively. The levels of IL6, MCP-1, TGF-α, and IL8 in BD-M patients were significantly greater than in healthy individuals, and their cut-off values were 0.813 pg/ml, 0.688 pg/ml, 0.438 pg/ml, and 0.625 pg/ml, respectively. Moreover, we found cut-off values of 0.500 pg/mL and 0.688 ng/mL for TGF-α and β-NGF, respectively, even though the levels in the BD-D group were much higher than in the control group. Furthermore, BD-M patients had significantly higher levels of IL6, FGF-19, IFN-γ, and IL-17C in comparison with BD-D patients. Likewise, 0.687 pg/ml, 0.500 pg/ml, 0.438 pg/ml, and 0.375 pg/ml were their cut-off values, respectively. Our findings also showed that the combination of these proteins had the highest diagnostic accuracy. ConclusionsOur findings showed that plasma inflammatory proteins were related to BD and its subtypes, which may be utilized as potential biomarkers of different stages of BD. Furthermore, we also found their cut-off values and their combinations to have the highest diagnostic accuracy, providing clinicians with a new method to rapidly differentiate BD and its subtypes and manage early targeted interventions.

Clinical decision support for bipolar depression using large language models.

Management of depressive episodes in bipolar disorder remains challenging for clinicians despite the availability of treatment guidelines. In other contexts, large language models have yielded promising results for supporting clinical decisionmaking. We developed 50 sets of clinical vignettes reflecting bipolar depression and presented them to experts in bipolar disorder, who were asked to identify 5 optimal next-step pharmacotherapies and 5 poor or contraindicated choices. The same vignettes were then presented to a large language model (GPT4-turbo; gpt-4-1106-preview), with or without augmentation by prompting with recent bipolar treatment guidelines, and asked to identify the optimal next-step pharmacotherapy. Overlap between model output and gold standard was estimated. The augmented model prioritized the expert-designated optimal choice for 508/1000 vignettes (50.8%, 95% CI 47.7-53.9%; Cohen's kappa = 0.31, 95% CI 0.28-0.35). For 120 vignettes (12.0%), at least one model choice was among the poor or contraindicated treatments. Results were not meaningfully different when gender or race of the vignette was permuted to examine risk for bias. By comparison, an un-augmented model identified the optimal treatment for 234 (23.0%, 95% CI 20.8-26.0%; McNemar's p < 0.001 versus augmented model) of the vignettes. A sample of community clinicians scoring the same vignettes identified the optimal choice for 23.1% (95% CI 15.7-30.5%) of vignettes, on average; McNemar's p < 0.001 versus augmented model. Large language models prompted with evidence-based guidelines represent a promising, scalable strategy for clinical decision support. In addition to prospective studies of efficacy, strategies to avoid clinician overreliance on such models, and address the possibility of bias, will be needed.

Exploring hub genes and crucial pathways linked to oxidative stress in bipolar disorder depressive episodes through bioinformatics analysis.

Bipolar disorder (BD) is a complex and serious psychiatric condition primarily characterized by bipolar depression, with the underlying genetic determinants yet to be elucidated. There is a substantial body of literature linking psychiatric disorders, including BD, to oxidative stress (OS). Consequently, this study aims to assess the relationship between BD and OS by identifying key hub genes implicated in OS pathways. We acquired gene microarray data from GSE5392 through the Gene Expression Omnibus (GEO). Our approach encompassed differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Protein-Protein Interaction (PPI) Network analysis to pinpoint hub genes associated with BD. Subsequently, we utilized Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to identify hub genes relevant to OS. To evaluate the diagnostic accuracy of these hub genes, we performed receiver operating characteristic curve (ROC) analysis on both GSE5388 and GSE5389 datasets. Furthermore, we conducted a study involving ten BD patients and ten healthy controls (HCs) who met the special criteria, assessing the expression levels of these hub genes in their peripheral blood mononuclear cells (PBMCs). We identified 411 down-regulated genes and 69 up-regulated genes for further scrutiny. Through WGCNA, we obtained 22 co-expression modules, with the sienna3 module displaying the strongest association with BD. By integrating differential analysis with genes linked to OS, we identified 44 common genes. Subsequent PPI Network and WGCNA analyses confirmed three hub genes as potential biomarkers for BD. Functional enrichment pathway analysis revealed their involvement in neuronal signal transduction, oxidative phosphorylation, and metabolic obstacle pathways. Using the Cytoscape plugin "ClueGo assay," we determined that a majority of these targets regulate neuronal synaptic plasticity. ROC curve analysis underscored the excellent diagnostic value of these three hub genes. Quantitative reverse transcription-PCR (RT-qPCR) results indicated significant changes in the expression of these hub genes in the PBMCs of BD patients compared to HCs. We identified three hub genes (TAC1, MAP2K1, and MAP2K4) in BD associated with OS, potentially influencing the diagnosis and treatment of BD. Based on the GEO database, our study provides novel insights into the relationship between BD and OS, offering promising therapeutic targets.

An Update on the Efficacy of Single and Serial Intravenous Ketamine Infusions and Esketamine for Bipolar Depression: A Systematic Review and Meta-Analysis.

Ketamine has shown rapid antidepressant and anti-suicidal effects in treatment-resistant depression (TRD) with single and serial intravenous (IV) infusions, but the effectiveness for depressive episodes of bipolar disorder is less clear. We conducted an updated systematic review and meta-analysis to appraise the current evidence on the efficacy and tolerability of ketamine/esketamine in bipolar depression. A search was conducted to identify randomized controlled trials (RCTs) and non-randomized studies examining single or multiple infusions of ketamine or esketamine treatments. A total of 2657 articles were screened; 11 studies were included in the systematic review of which 7 studies were included in the meta-analysis (five non-randomized, N = 159; two RCTs, N = 33) with a mean age of 42.58 ± 13.1 years and 54.5% females. Pooled analysis from two RCTs showed a significant improvement in depression symptoms measured with MADRS after receiving a single infusion of ketamine (1-day WMD = -11.07; and 2 days WMD = -12.03). Non-randomized studies showed significant response (53%, p < 0.001) and remission rates (38%, p < 0.001) at the study endpoint. The response (54% vs. 55%) and remission (30% vs. 40%) rates for single versus serial ketamine infusion studies were similar. The affective switch rate in the included studies approximated 2.4%. Esketamine data for bipolar depression are limited, based on non-randomized, small sample-sized studies. Further studies with larger sample sizes are required to strengthen the evidence.

Bipolar Disorder and Antidepressant Associated Hypomania

The impact of antidepressant associated hypomania on monomanic depression and its relationship to bipolar disorder. This review attempts to investigate and review current research on bipolar disorder diagnosis, the neurobiological mechanisms of antidepressant-associated hypomania, risk factors, and how to manage the occurrence of this condition. Bipolar disorder is a widespread, debilitating, recurrent, variable-severity mental health condition in which the patient exhibits two different states and unpredictable mood switching. Mania, hypomania, mixed states, depression, and depression interspersed with moments of relative health are the stages of the disorder. Early identification of bipolar disorder can improve prognosis. Patients with monophasic episodes are uncommon, as the clinical manifestation of bipolar illness is unpredictable. Throughout their lives, individuals with bipolar disorder alternate between episodes of mania or hypomania and depression. Depressive episodes in bipolar disorder are referred to as bipolar depression, and the underlying core symptom is depressed mood, which are essentially identical to the diagnostic criteria and clinical symptoms of uniphasic depression, so there is a high risk of misdiagnosis during the initial visit. Patients often choose to seek specialist help during depressive episodes, and this can lead to a tendency to overlook whether a patient has bipolar disorder. Antidepressant monotherapy is contraindicated for hypomanic episodes. Antidepressants tend to induce hypomanic and manic episodes, a phenomenon known as antidepressant-associated hypomania (AAH). All antidepressant drugs may cause mania. One is drug induced mania; The other is considered a potential bipolar disorder. There is a high co-occurrence of psychiatric disorders, but only bipolar disorder, monophasic depression, and antidepressant-induced hypomanic episodes are discussed here.

Explainable machine-learning algorithms to differentiate bipolar disorder from major depressive disorder using self-reported symptoms, vital signs, and blood-based markers

Background and objectiveCaused by shared genetic risk factors and similar neuropsychological symptoms, bipolar disorder (BD) and major depressive disorder (MDD) are at high risk of misdiagnosis, which is associated with ineffective treatment and worsening of outcomes. We aimed to develop a machine learning (ML)-based diagnostic system, based on electronic medical records (EMR) data, to mimic the clinical reasoning of human physicians to differentiate MDD and BD (especially BD depressive episodes) patients about to be admitted to a hospital and, hence, reduce the misdiagnosis of BD as MDD on admission. In addition, we examined to what extent our ML model could be made interpretable by quantifying and visualizing the features that drive the predictions. MethodsBy identifying 16,311 patients admitted to a hospital located in western China between 2009 and 2018 with a recorded main diagnosis of MDD or BD, we established three sub-cohorts with different combinations of features for both the MDD-BD cohort and the MDD-BD depressive episodes cohort, respectively. Four different ML algorithms (logistic regression, extreme gradient boosting (XGBoost), random forest, and support vector machine) and four train-test splits were used to train and validate diagnostic models, and explainable methods (SHAP and Break Down) were utilized to analyze the contribution of each of the features at both population-level and individual-level, including feature importance, feature interaction, and feature effect on prediction decision for a specific subject. ResultsThe XGBoost algorithm provided the best test performance (AUC: 0.838 (0.810–0.867), PPV: 0.810 and NPV: 0.834) for separating patients with BD from those with MDD. Core predictors included symptoms (mood-up, exciting, bad sleep, loss of interest, talking, mood-down, provoke), along with age, job, myocardial enzyme markers (creatine kinase, hydroxybutyrate dehydrogenase), diabetes-associated marker (glucose), bone function marker (alkaline phosphatase), non-enzymatic antioxidant (uric acid), markers of immune/inflammation (white blood cell count, lymphocyte count, basophil percentage, monocyte count), cardiovascular function marker (low density lipoprotein), renal marker (total protein), liver biochemistry marker (indirect bilirubin), and vital signs like pulse. For separating patients with BD depressive episodes from those with MDD, the test AUC was 0.777 (0.732–0.822), with PPV 0.576 and NPV 0.899. Additional validation in models built with self-reported symptoms removed from the feature set, showed test AUC of 0.701 (0.666–0.736) for differentiating BD and MDD, and AUC of 0.564 (0.515–0.614) for detecting patients in BD depressive episodes from MDD patients. Validation in the datasets without removing the patients with comorbidity showed an AUC of 0.826 (0.806–0.846). ConclusionThe diagnostic system accurately identified patients with BD in various clinical scenarios, and differences in patterns of peripheral markers between BD and MDD could enrich our understanding of potential underlying pathophysiological mechanisms of them.

Ketamine infusions for treatment-resistant bipolar depression: Commentary.

Ketamine infusions for treatment-resistant bipolar depression: Commentary.

Focus on olanzapine

No AccessFocus on olanzapine S Davis S Davis1 Search for more papers by this author Affiliations 1Amayeza Info Services, South Africa Published Online:1 Mar 2023https://doi.org/10.36303/SAGP.0172https://hdl.handle.net/10520/ejc-mp_sagp_v4_n2_a8SectionsPDFView Full Text ToolsAdd to favouritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditGMailOutlookCopy LinkMendeley AboutAbstractOlanzapine is indicated for the management of manifestations of psychotic disorders, acute episodes of moderate to severe mania, and prevention of recurrence of manic or depressive episodes of bipolar disorder.1,21. Rossiter DSouth African Medicines Formulary14thCape TownSouth African Medical Association2022 Google Scholar2. Zyprexa (olanzapine tablets, VELOTAB and Powder for IM injection)Package Insert Eli Lilly (S.A.) (Pty) LimitedBryanston1Dec2006 Google Scholar3. "Olanzapine" MerativeTM Micromedex® DRUGDEX® (electronic version)MerativeAnn Arbor, Michigan, USAAvailable from: https://www.micromedexsolutions.com/Accessed 10 Feb 2023 Google Scholar4. Thomas KSaadabadi A "Olanzapine. Updated 8 Sept 2022" StatPearls [Internet]Treasure Island (FL)StatPearls Publishing2022JanAvailable from: https://www.ncbi.nlm.nih.gov/books/NBK532903/Accessed 10 Feb 2023 Google Scholar5. Bobo WVShelton RC "Bipolar major depression in adults: Efficacy and adverse effects of second-generation antipsychotics. Updated 1 Aug 2022" UpToDateAvailable from: https://www.uptodate.com/contents/bipolar-major-depression-in-adults-efficacy-and-adverse-effects-of-second-generation-antipsychoticsAccessed 10 Feb 2023 Google Scholar6. Zhang JPGallego JARobinson DGet al. "Efficacy and safety of individual second-generation vs first-generation antipsychotics in first episode psychosis: A systematic review and meta-analysis" Int J Neuropsychopharmacol2013 166120518 DOI: https://doi.org/10.1017/S1461145712001277 Google Scholar Previous article Next article FiguresReferencesRelatedDetails None Volume 4, Issue 2 | Mar 2023 Downloaded 6 times LanguagesEnglish InformationCopyright © 2023, Medpharm Publications:All rights reservedPDF download Disclosure The authors confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. The authors confirm that they have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. Ethical conduct of research The authors state that they have obtained appropriate institutional review board outlined in the Declaration of Helsinki for all human or animal experimental investigations. A signed informed consent document has been obtained from all participants included in the study.

Characteristics and Correlates of Metabolic Syndrome in Adolescents with Unipolar and Bipolar Depression: Results from a Cross-National Inpatient Case-Control Study.

<b>Abstract</b> <b><i>Objectives:</i></b> To assess characteristics and correlates of metabolic syndrome (MetS) in adolescents with major depressive disorder (MDD) or bipolar disorder-depressive episode (BP-d). <b><i>Methods:</i></b> Case-control study, using national inpatient sample data, including adolescents (age, 12-18 years) with a primary diagnosis of MDD or BP-d. Using propensity score matching (based on age, sex, and race/ethnicity), we extracted cases with MetS (≥3 of the following conditions: obesity, diabetes, hypercholesterolemia, and hypertension) and controls without MetS. We used a multivariable logistic regression model calculating adjusted odds ratios (aORs) for potential correlates of MetS, focusing on primary mood disorders and psychiatric comorbidities. <b><i>Results:</i></b> In 607 age-/sex-/race/ethnicity-matched adolescents (MDD = 83.5%, BP-d = 16.5%), comparing those with (<i>N</i> = 332) versus without MetS (<i>N</i> = 275), MetS was most prevalent in later-age adolescents (mean age 16.3 years), females (58.1%), Whites (40.3%), and Blacks (31.5%). MetS was characterized by obesity (84.9% vs. 3.6%), hypertension (81% vs. 1.8%), diabetes (72.8% vs. 9.1%), and hypercholesterolemia (67.2% vs. 3.6%) (all <i>p</i> &lt; 0.001). MetS was associated with a primary diagnosis of BP-d versus MDD (aOR 2.42, 95% confidence interval [CI] 1.47-3.97) and comorbid disruptive behavior disorders (DBD) (aOR 4.45, 95% CI 1.55-12.78), while comorbid substance use disorder reduced MetS risk (aOR 0.31, 95% CI 0.19-0.50). <b><i>Conclusion:</i></b> In adolescents with MDD or BP-d, MetS was associated with a primary BP-d diagnosis, and comorbid DBD. MetS-related parameters should be screened for early in adolescents with depression-spectrum disorders aiming to prevent the development or effects of MetS.

STEVEN JOHNSONS SYNDROM ON LAMOTRIGINE

Introduction: Lamotrigine is an anti-epileptic drug indicated for the treatment of bipolar disorder and recurrent depressive disorders. Its efficacy has been demonstrated. However, its use may be limited by the risk of severe, life-threatening allergic reactions. Objectives And Methods: We report hereafter the clinical case of a patient suffering from bipolar depression treated with lamotrigine which induced skin allergies in her. Our objective will be to detail the rules of prescribing the treatment, to describe Steven Johnson syndrome, a serious adverse effect to lamotrigine, to discuss the urgent course of action in the event of severe allergic reactions to lamotrigine as well as the therapeutic options after a hypersensitivity reaction to lamotrigine. Clinical Vignette:This is a patient followed in psychiatry for bipolar disorder, put on esitalopram clomipramine, aripiprazole and Lamotrigine, who was admitted to dermatology for minimal erythematous maculo-papular rash on the face and limbs with involvement of the oral and genital mucosa appeared 4 weeks after introduction of lamotrigine. Conclusion: Despite the efficacy of lamotrigine as an effective mood regulator in the treatment of recurrent depressive episodes and depressive episodes in bipolar disorder, this antiepileptic drug must be used with caution to avoid serious life-threatening reactions.

Effects of Treatment of Acute Major Depressive Episodes in Bipolar I Versus Bipolar II Disorders With Quetiapine.

Several second-generation antipsychotic drugs (SGAs) have evidence of benefit for acute major depressive episodes in bipolar disorder (BD) patients. However, their comparative efficacy in types I vs II BD (BD1 vs BD2) remains uncertain. We carried out a systematic literature search for randomized, double-blinded, controlled treatment trials for acute major depressive episodes involving head-to-head comparisons of BD1 versus BD2 subjects, followed by meta-analyses and meta-regression modeling. Seven reports met out inclusion criteria, yielding 22 comparisons of SGA versus placebo averaging 8.3 weeks in duration. All trials involved quetiapine, which was much more effective than placebo (pooled standardized mean difference [SMD] = 1.76 [95% confidence interval, 1.40-2.12], P < 0.0001). Estimated % improvement averaged 53.5% [46.5-60.5] with quetiapine vs 39.8% [34.2-45.4] with placebo ( P < 0.0001); their ratio was somewhat larger with BD1 (1.56 [1.26-1.86]) versus BD2 subjects (1.22 [1.07-1.37], P = 0.04; as was SMD (BD1: 2.35 [1.83-2.86]; BD2: SMD = 1.44 [1.05-1.82]). Meta-regression found diagnosis (BD1 > BD2) to be the only factor significantly associated with the meta-analytic outcome. Although data are limited, depressed BD1 patients may respond somewhat better to quetiapine than BD2. Additional head-to-head diagnostic comparisons are needed with other SGAs, as well as evaluation of monotherapy versus various combinations that include SGAs in both short- and long-term use.

Investigation of systemic immune-inflammation index, neutrophil/high-density lipoprotein ratio, lymphocyte/high-density lipoprotein ratio, and monocyte/high-density lipoprotein ratio as indicators of inflammation in patients with schizophrenia and bipolar disorder.

BackgroundThe systemic immune-inflammation index (SII), system inflammation response index (SIRI), neutrophil/high-density lipoprotein (HDL) ratio (NHR), lymphocyte/HDL ratio (LHR), monocyte/HDL ratio (MHR), and platelet/HDL ratio (PHR) have been recently investigated as new markers for inflammation. The purpose of this research is to use large-scale clinical data to discuss and compare the predictive ability of the SII, SIRI, NHR, LHR, MHR, and PHR in patients with schizophrenia (SCZ) and bipolar disorder (BD), to investigate potential biomarkers.Materials and methodsIn this retrospective, naturalistic, cross-sectional study, we collected the hematological parameter data of 13,329 patients with SCZ, 4,061 patients with BD manic episodes (BD-M), and 1,944 patients with BD depressive episodes (BD-D), and 5,810 healthy subjects served as the healthy control (HC) group. The differences in the SII, SIRI, NHR, LHR, MHR, and PHR were analyzed, and a receiver operating characteristic (ROC) curve was used to analyze the diagnostic potential of these parameters.ResultsCompared with the HC group, the values of the SII, SIRI, NHR, LHR, MHR, and PHR and the levels of neutrophils, monocytes, and triglycerides (TG) were higher in SCZ and BD groups, and levels of platelets, cholesterol (CHO), HDL, low-density lipoprotein (LDL), and apoprotein B (Apo B) were lower in SCZ and BD groups. Compared to the BD group, the values of the SIRI, lymphocytes, monocytes, and HDL were lower and the values of the SII, NHR, PHR, and platelet were higher in the SCZ group. In contrast to the BD-D group, the values of the SII; SIRI; NHR; and MHR; and levels of neutrophils, monocytes, and platelets were higher in the BD-M group, and the levels of CHO, TG, LDL, and Apo B were lower in the BD-M group. The MHR and NHR were predictors for differentiating the SCZ group from the HC group; the SIRI, NHR, and MHR were predictors for differentiating the BD-M group from the HC group; and the MHR was a predictor for differentiating the BD-D group from the HC group. The combination model of the indicators improved diagnostic effectiveness.ConclusionOur study highlights the role of systemic inflammation in the pathophysiology of SCZ, BD-M, and BD-D, the association between inflammation and lipid metabolism, and these inflammation and lipid metabolism indicators showed different variation patterns in SCZ, BD-D, and BD-M.

The Efficacy and Safety of Transcranial Magnetic Stimulation in Treatment-Resistant Bipolar Depression.

The aim of the current study is to investigate the efficacy and safety of Transcranial magnetic stimulation (TMS) treatment, a non-invasive brain stimulation technique, on depressive symptoms in treatment-resistant bipolar depression (TRBD). The study included 29 patients between the ages of 18-65, with bipolar disorder depressive episode according to DSM-5 and with the decision of non-response to treatment according to the Canadian Mood and Anxiety Treatment Network (CANMAT). Patients were divided into two groups double-blind-randomly, 20 sessions of TMS and 20 sessions of sham TMS were applied crossover. Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory (BDI), Young Mania Rating Scale (YMRS) and TMS Side Effect Questionnaire were applied to the patients before the treatment, at the 2nd week which is the crossover phase, and at the end of the treatment at 4th week. In both groups, the severity of depression was decreased significantly according to HAM-D and BDI scores after the procedure. As well as active stimulation, some positive placebo effects were observed with sham stimulation. But the decreases seen in HAM-D and BDI scores and response to the treatment were higher during the weeks when the groups received active stimulation (respectively p=0.000, p=0.001, p=0.005). At the end of the study, according to HAM-D, 55.7% of the patients showed response to the treatment, 24.13% partial response. According to BDI, 41.37% of the patients showed response to the treatment, and 31.03% partial response. No associations were found between TMS response and sociodemographic - clinical features, or type of the disease (p>0.05). During the study, no serious adverse effects such as seizures or manic / hypomanic switches were observed. The results of our study showed that TMS treatment is an effective and safe treatment for patients with treatment-resistant bipolar depression.

Electroconvulsive therapy (ECT) in the management of a bipolar disorder with comorbid OCD: a case report and review of the literature

IntroductionNumerous clinical and epidemiological studies show an increased prevalence of anxiety disorders, including obsessive-compulsive disorder, in subjects followed for bipolar disorder. This comorbidity is not without consequence on the evolutionary course of the mood disorder, with frequent relapse, a lower pharmacological sensitivity and an increased risk of suicide.ObjectivesWe aim to analyze through a clinical observation and according to the data of the literature the place of ECT in the management of a bipolar disorder with comorbid OCD.MethodsIn this work, we reported a case of a patient in which depressive episodes of bipolar disorder and OCD comorbidity were present and the symptoms were resolved using ECT.ResultsMrs. TN with family history of suicide had experienced her first depressive episode in 2005 in post-partum, when she had 31 years old. The diagnosis of bipolar disorder II with comorbid OCD was retained after she has had several depressive relapses with few hypomanic ones and reported obsessive suicidal ideation with many religious compulsions. Despite several pharmacotherapeutic combinations (Teralithe, Olanzapine and Venlafaxine) a remission of the symptoms could only be obtained after 15 sessions of ECT that she has had in 2017.ConclusionsECT can be a very good substitute for the treatment of mood disorders with comorbid OCD resistant to pharmacotherapy.DisclosureNo significant relationships.

Efficacy and safety of scopolamine compared to placebo in individuals with bipolar disorder who are experiencing a depressive episode (SCOPE-BD): study protocol for a randomised double-blind placebo-controlled trial

BackgroundCurrent treatment options for the management of depressive episodes in bipolar disorder are often sub-optimal, with some treatments either noted to be only partially effective or to require long durations of treatment prior to a therapeutic response. Therefore, pharmaco-therapeutic options that reduce depressive symptoms in a more rapid manner might provide a viable therapeutic option for some people. Intravenous (IV) scopolamine, a pan muscarinic antagonist, has been demonstrated in a number of studies to confer a rapid antidepressant effect, albeit no study to date has exclusively evaluated its potential therapeutic effect in a cohort consisting solely of individuals with bipolar disorder.MethodsIndividuals with bipolar disorder who are currently experiencing a depressive episode of at least moderate severity will be included in this study. Eligible participants will undergo a screening and placebo-run in visit and will be randomised at visit 3 to the treatment or placebo group. Participants will receive the three blinded infusions over the course of 2 weeks, with two subsequent follow-up visits, 1 and 3 weeks after the last infusion visit. The total duration of the study will be approximately 6 weeks. Patients will continue their regular treatment regime in addition to study medication. Objective and subjective mood questionnaires, cognitive assessments and other psychometric instruments will be administered and recorded.DiscussionTo our knowledge, this is the first study to investigate the antidepressant effects of IV scopolamine in an exclusively bipolar disorder cohort. Trial findings will contribute to the evidence base regarding the cholinergic hypothesis of mood disorders and specifically might result in an additional safe therapeutic option for the management of depressive episodes in bipolar disorder.Trial registrationClinicalTrials.gov NCT04211961. December 26, 2019. EudraCT Number 2017-003112-39

Listening to the Shenzhen Primary Healthcare Context to Adapt the mhGAP-IG.v2 for the Assessment of Depression: Qualitative Workshops with Primary Healthcare Leaders

In Shenzhen, despite recent primary and mental healthcare reform, Primary healthcare doctors (PHC) have limited access to diagnostic tools and a significant mental health treatment gap presides. The World Health Organization’s (WHO) mental health gap intervention guide (mhGAP-IG.v2) offers a non-specialist and evidence-based guide for the assessment of depression however requires adaptation to the context of use. Bilingual (Mandarin and English) qualitative research was undertaken with 30 PHC leaders from Shenzhen to compare their assessment approach for depression against the mhGAP-IG.v2 in order to identify context-specific modifications for a local guide. Local assessment differentiators included: a need for culturally sensitive translation of depression symptoms; a preference for a broad, non-hierarchical symptom presentation (including somatic, behavioural and anxiety items); national prioritisation of suicide patients; the integration of family into the cycle of care; limited primary care awareness of a depressive episode in Bipolar Disorder; and China’s specialist-led diagnostic approach. Contextual modification of mhGAP-IG.v2 is recommended to take account of China’s unique cultural and primary health system response to depression. Ongoing mental health training is required to develop professional confidence in the recognition of mental disorders.

Comparison of the intensity of peripheral inflammation between major depressive disorder and bipolar depression by means of neutrophil-lymphocyte and plateletlymphocyte ratios: The possible role of clinical severity and psychotic features

Objective: The present study aimed to compare the intensity of inflammation between major depressive disorder (MDD) and bipolar disorder-depressive episode (BD-D) by using neutrophil to lymphocyte (NLR) and platelet to lymphocyte ratios (PLR) as nonspecific markers for peripheral immune response, and to investigate whether and how these parameters correlate with the clinical characteristics of the depressive episodes within and between the diagnoses. Patients and Methods: The medical records of 209 psychiatric inpatients (126 diagnosed with MDD, 83 with BD-D) and 150 healthy controls (HC) were retrospectively screened to obtain NLR and PLR values. Results: Both MDD and BD-D presented with significantly elevated NLR and PLR compared to HC, with the increase being associated with the severity of depression but not with the presence of psychotic features. The severity of inflammation was found to be of a comparable magnitude between the two conditions, or at least indistinguishable by means of the NLR and PLR. Conclusion: Our results suggest that both MDD and BD-D involve a presumably complex inflammatory process resulting in an observable, albeit nonspecific alteration in the distribution of peripheric blood cells. Moreover, the magnitude of the observed immune response appears to relate to the severity of the depressive episode for both conditions.

New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data.

Tetratricopeptide repeat and ankyrin repeat containing 1 (TRANK1) is a robust risk gene of bipolar disorder (BD). However, little is known on the role of TRANK1 in the pathogenesis of BD and whether the gut microbiota is capable of regulating TRANK1 expression. In this study, we first investigated the serum mRNA level of TRANK1 in medication-free patients with a depressive episode of BD, then a mice model was constructed by fecal microbiota transplantation (FMT) to explore the effects of gut microbiota on brain TRANK1 expression and neuroinflammation, which was further verified by in vitro Lipopolysaccharide (LPS) treatment in BV-2 microglial cells and neurons. 22 patients with a depressive episode and 28 healthy individuals were recruited. Serum level of TRANK1 mRNA was higher in depressed patients than that of healthy controls. Mice harboring ‘BD microbiota’ following FMT presented depression-like phenotype. mRNA levels of inflammatory cytokines and TRANK1 were elevated in mice hippocampus and prefrontal cortex. In vitro, LPS treatment activated the secretion of pro-inflammatory factors in BV-2 cells, which was capable of upregulating the neuronal expression of TRANK1 mRNA. Moreover, primary cortical neurons transfected with plasmid Cytomegalovirus DNA (pcDNA3.1(+)) vector encoding human TRANK1 showed decreased dendritic spine density. Together, these findings add new evidence to the microbiota-gut-brain regulation in BD, indicating that microbiota is possibly involved in the neuropathogenesis of BD by modulating the expression of TRANK1.

Variants in COMT, CYP3A5, CYP2B6, and ABCG2 Alter Quetiapine Pharmacokinetics.

Quetiapine is an atypical antipsychotic widely used for the treatment of schizophrenia and the depressive episodes of bipolar disorder. The aim of this work was to investigate the effect of variants in relevant pharmacogenes in the pharmacokinetics of quetiapine and to exploratorily evaluate adverse drug reaction (ADR) incidence based on genetic polymorphism. Specifically, 49 healthy volunteers enrolled in two bioequivalence clinical trials were included in this study. In addition, 80 variants in 19 relevant pharmacogenes were genotyped, including cytochrome P450 (CYP) genes, catechol-O-methyl transferase (COMT), other enzymes (e.g., UGT1A1 or UGT1A4), and transporters (e.g., SLCO1B1, ABCB1, or ABCG2). The COMT rs13306278 T allele was significantly related to quetiapine-increased exposure. We demonstrated the existence of quetiapine derivatives with a catechol-like structure (7,8-dihydroxi-quetiapine and 7,8-dihydroxi-N-desalkyl-quetiapine), which would be COMT metabolites and would explain quetiapine accumulation through CYP2D6 and CYP3A4 negative feedback. Moreover, CYP3A5 and CYP2B6 phenotypes were related to quetiapine exposure variability, which confirms (for CYP3A5) and suggests (for CYP2B6) that these enzymes play an important role in quetiapine’s metabolism. Finally, the ABCG2 rs2231142 T allele was related to quetiapine accumulation. Further studies are required to confirm the clinical relevance of our findings.