Differences in cognitive impairment and its correlation with circulating cell-free mitochondrial DNA in medication-free depression and bipolar depression patients.

OBJECTIVE: This study aimed to investigate whether there are differences in cognitive impairment between medication-free patients with bipolar depression (BD) and major depressive disorder (MDD) and whether these differences are related to circulating cell-free mtDNA (ccf-mtDNA). METHODS: For this cross-sectional study, 76 outpatients with BD, 86 outpatients with MDD and 70 healthy controls (HCs) were enrolled. Sociodemographic and clinical data were collected. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test were used to assess cognitive function. Plasma ccf-mtDNA levels were measured via qPCR. RESULTS: BD and MDD patients had similar scores for immediate memory, language, attention, delayed memory, the RBANS total score, Stroop color, Stroop word, and Stroop total score, which were significantly lower than the HCs. The visuospatial/constructive scores of the BD patients were significantly lower than those of the HCs (p < 0.001) and MDD patients (p = 0.008), but there was no difference between the HCs and MDD patients. The ccf-mtDNA levels in the BD and MDD patient groups were significantly higher than those in the HC group, and those in the MDD group were higher than those in the BD group (p = 0.016). Multiple stepwise regression analysis showed that ccf-mtDNA was negatively correlated with language in patients with depression (t = -2.11, p = 0.039). CONCLUSION: There were differences in specific cognitive dimensions between patients with BD and MDD. Increased ccf-mtDNA levels were found in BD and MDD patients, suggesting ccf-mtDNA may be involved in the pathophysiology of MDD and BD.

Aripiprazole/Sertraline Combination: Clinical and Cost-Effectiveness in Comparison With Quetiapine for the Treatment of Bipolar Depression (ASCEnD Trial)-Protocol for a Nested Qualitative Study.

INTRODUCTION: Bipolar disorder is a recurrent mental health disorder with a prevalence rate of 1.4%. On average, there can be a delay of 9.5 years from the initial presentation of symptoms to a confirmed diagnosis. Individuals living with bipolar disorder have a reduced life expectancy. There is limited evidence regarding the effectiveness of antidepressants in treating bipolar disorder. The ASCEnD clinical trial will test the clinical and cost-effectiveness of the aripiprazole/sertraline combination in comparison with quetiapine for the treatment of bipolar depression (individuals who suffer from depressive episodes in bipolar disorder) and will include a nested qualitative study. METHODS: The qualitative study will use semi-structured interviews to explore pilot trial participants' and clinicians' perspectives on recruitment procedures, the acceptability of the intervention, the management of bipolar disorder and attitudes to medication combinations. CONCLUSION: Findings will inform recruitment strategies and optimise training for the participating sites in the ASCEnD full trial. They will also help to illuminate the lived experience of people with bipolar disorder and the clinicians who work with people with bipolar disorder. The discussion will explore perspectives on the delay in diagnosis, having a diagnosis, the impact of living with bipolar disorder and attitudes to treatment, including drug combinations. PATIENT OR PUBLIC CONTRIBUTION: A Lived Experience Advisory Panel (LEAP) has been convened with the support of the McPin Foundation, which will contribute to the ASCEnD trial and its nested qualitative study to provide input on the design and delivery of the trial and qualitative study, analysis of qualitative data and dissemination of findings.

Well-Being Therapy for Depression.

Well-being therapy (WBT) is a short-term psychotherapeutic strategy, based on the technique of self-observation via the use of a structured diary and the guide of a therapist, with the goal of increasing psychological well-being, thus reaching euthymia and a balance among psychic forces. WBT showed to be suitable for application in residual symptoms of unipolar and bipolar depression, since the sequential combination with cognitive-behavioural therapy (CBT) led to a decrease in the relapse rate of recurrent depression. WBT also showed clinical utility in the treatment of cyclothymia, which represents one of the stages of bipolar disorder. Further, WBT seems to have efficacy in treatment-resistant depression and in case of withdrawal syndromes (in particular the so-called persistent post-withdrawal disorder) following antidepressant decrease, switch or discontinuation. In brief, WBT is a rather new but promising therapeutic strategy in the management of unipolar and bipolar depression. This chapter offers an overview of WBT possible applications.

Sociodemographic and clinical characteristics of suspected difficult-to-treat depression.

Introduction: Difficult-to-treat depression (DTD) represents a broad spectrum of patients with persistent depression where standard treatment modalities are insufficient, yet specific characteristics of this group remain insufficiently understood. This investigation aims to delineate the sociodemographic and clinical profiles of suspected DTD patients in real-world clinical settings. Method: We conducted a retrospective analysis of data from patients comprehensively evaluated for suspected DTD at Kyorin University Hospital, Tokyo, Japan, between October 2014 and September 2018. The study participants consisted of individuals with persistent depression unresponsive to conventional antidepressant treatments during the current episode. Diagnoses adhered to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Additional evaluations included the Montgomery-Åsberg Depression Rating Scale (MADRS) and other pertinent measures. The analysis focused on comparing demographic and clinical characteristics across diagnosed groups. Results: The analysis encompassed 122 patients, with diagnoses of major depressive disorder (MDD) in 41.8%, bipolar disorder (BD) in 28.7%, and subthreshold depression in 29.5%. Notably, high incidences of psychiatric comorbidities were present across all groups, with anxiety disorders exceeding 30% and personality disorders surpassing 50%. The only significant distinction among the three groups was observed in the MADRS scores, with the MDD group exhibiting the highest values (20.9 ± 9.7 vs. 18.6 ± 9.3 vs. 11.3 ± 7.4, p<0.01). Conclusions: This study sheds light on the intricate nature of suspected DTD, emphasizing the coexistence of MDD, BD, and subthreshold depression within this category. Our findings underscore the necessity for thorough evaluations and tailored treatment approaches for managing suspected DTD.

Enhanced network synchronization connectivity following transcranial direct current stimulation (tDCS) in bipolar depression: Effects on EEG oscillations and deep learning-based predictors of clinical remission.

AIM: To investigate oscillatory networks in bipolar depression, effects of a home-based tDCS treatment protocol, and potential predictors of clinical response. METHODS: 20 participants (14 women) with bipolar disorder, mean age 50.75 ±â€¯10.46 years, in a depressive episode of severe severity (mean Montgomery-Åsberg Rating Scale (MADRS) score 24.60 ±â€¯2.87) received home-based transcranial direct current stimulation (tDCS) treatment for 6 weeks. Clinical remission defined as MADRS score < 10. Resting-state EEG data were acquired at baseline, prior to the start of treatment, and at the end of treatment, using a portable 4-channel EEG device (electrode positions: AF7, AF8, TP9, TP10). EEG band power was extracted for each electrode and phase locking value (PLV) was computed as a functional connectivity measure of phase synchronization. Deep learning was applied to pre-treatment PLV features to examine potential predictors of clinical remission. RESULTS: Following treatment, 11 participants (9 women) attained clinical remission. A significant positive correlation was observed with improvements in depressive symptoms and delta band PLV in frontal and temporoparietal regional channel pairs. An interaction effect in network synchronization was observed in beta band PLV in temporoparietal regions, in which participants who attained clinical remission showed increased synchronization following tDCS treatment, which was decreased in participants who did not achieve clinical remission. Main effects of clinical remission status were observed in several PLV bands: clinical remission following tDCS treatment was associated with increased PLV in frontal and temporal regions and in several frequency bands, including delta, theta, alpha and beta, as compared to participants who did not achieve clinical remission. The highest deep learning prediction accuracy 69.45 % (sensitivity 71.68 %, specificity 66.72 %) was obtained from PLV features combined from theta, beta, and gamma bands. CONCLUSIONS: tDCS treatment enhances network synchronization, potentially increasing inhibitory control, which underscores improvement in depressive symptoms. Baseline EEG-based measures might aid predicting clinical response.

Treatment of bipolar depression: clinical practice vs. adherence to guidelines-data from a Bavarian drug surveillance project.

Objectives: Pharmacotherapy of bipolar depression (BPD) is confronted with major clinical challenges, like limited evidence-based treatment options, regular cases of treatment resistance, and risk of treatment-emergent affective switches. Medical guidelines can support practitioners to make decisions based on current scientific evidence. The objective of this study is to evaluate to what extent recommendations of the 2019 German S3 guidelines "Diagnosis and Treatment of Bipolar Disorders" are reflected in clinical practice in inpatient treatment. Methods: We conducted a descriptive analysis of prescription numbers in 2,627 patients with BPD in a naturalistic inpatient setting analyzing data from the ongoing Bavarian multicenter drug safety project Pharmaco-Epidemiology and Vigilance (Pharmako-EpiVig) from the years 2014-2022. Results: Of the patients, 38% were not administered any drug explicitly recommended for treatment of BPD, that is, quetiapine, lamotrigine, carbamazepine, or olanzapine. Only 6% of the patients received monotherapy with one of those drugs. Of the patients, 34% were administered ≥4 psychotropic drugs simultaneously. Patients received 912 different therapy regimens of mono or combination therapy with mood stabilizers (MS), atypical antipsychotics (AAP), and antidepressants. Of the patients, 72% received an antidepressant and 6% without concomitant prescription of an AAP or MS. Prescription rates of venlafaxine (21% to 14%) and tricyclic antidepressants (9% to 6%) decreased significantly from the first (2014-2016) to the last (2020-2022) observed time period. Of the patients, 60% received an MS. Prescription rate of valproate (22% to 14%) decreased significantly, while lithium prescription increased significantly (29% to 35%). Of the patients, 71% were administered an AAP. Quetiapine was the most prescribed drug overall (43%). Only two patients were administered a combination of olanzapine and fluoxetine. Conclusion: Our results demonstrate a substantial gap between guideline recommendations and current clinical practice. The remarkable heterogeneity in treatment regimens, with no discernible dominant treatment approach, is in part a reflection of the complexity of bipolar disorder but also substantiates the need of comprehensive recommendations regarding combination therapies. Increase in lithium prescription is an encouraging development due to its unique efficacy in maintenance treatment. To improve the quality of clinical practice guideline implementation, more randomized controlled trials should be conducted in the future to prospectively investigate different implementation strategies.

Treatment-emergent symptoms during short-term ketamine administration in treatment-resistant bipolar depression: A retrospective cross-sectional descriptive study.

Symptoms that emerge during pharmacological treatment of bipolar depression are frequently observed, underscoring the necessity for comprehensive treatment monitoring. This observational study sought to observe the correlation of eight intravenous ketamine infusions with treatment-emergent depressive symptoms in treatment-resistant bipolar depression patients who maintained their baseline psychotropic and chronic somatic treatments. Depressive symptoms were evaluated using the Inventory of Depressive Symptomatology Self-Report 30 (IDS-SR30). Treatment-emergent symptoms TES were defined as symptoms absent at baseline but present at the conclusion of the study. The most common TES included decreased appetite, increased weight, hypersomnia, and diurnal mood variation. Conversely, feelings of sadness, altered perceptions of the future, decreased interest in sex, and physical discomfort were absent in all patients. Notably, 13.6 % of patients reported thoughts of death or suicide. Larger-scale studies, integrating clinician-rated and patient-reported outcome measures, are essential to deepen our understanding of treatment-emergent symptoms. Establishing regulatory or professional definitions for treatment-emergent symptoms is warranted to improve the robustness of future research endeavors.

Peripheral biomarkers to differentiate bipolar depression from major depressive disorder: a real-world retrospective study.

BACKGROUND: Bipolar depression (BPD) is often misdiagnosed as a major depressive disorder (MDD) in clinical practice, which may be attributed to a lack of robust biomarkers indicative of differentiated diagnosis. This study analysed the differences in various hormones and inflammatory markers to explore peripheral biomarkers that differentiate BPD from MDD patients. METHODS: A total of 2,048 BPD and MDD patients were included. A panel of blood tests was performed to determine the levels of sex hormones, stress hormones, and immune-related indicators. Propensity score matching (PSM) was used to control for the effect of potential confounders between two groups and further a receiver operating characteristic (ROC) curve was used to analyse the potential biomarkers for differentiating BPD from MDD. RESULTS: Compared to patients with MDD, patients with BPD expressed a longer duration of illness, more hospitalisations within five years, and an earlier age of onset, along with fewer comorbid psychotic symptoms. In terms of biochemical parameters, MDD patients presented higher IgA and IgM levels, while BPD patients featured more elevated neutrophil and monocyte counts. ROC analysis suggested that combined biological indicators and clinical features could moderately distinguish between BPD and MDD. In addition, different biological features exist in BPD and MDD patients of different ages and sexes. CONCLUSIONS: Differential peripheral biological parameters were observed between BPD and MDD, which may be age-sex specific, and a combined diagnostic model that integrates clinical characteristics and biochemical indicators has a moderate accuracy in distinguishing BPD from MDD.

Early symptom improvement and other clinical predictors of response to repetitive transcranial magnetic stimulation for depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a rapidly emerging treatment for depression, but outcome prediction is still a challenge. This study aimed to identify predictors of response to rTMS among baseline clinical factors and early symptomatic improvements. METHODS: This cohort study comprised 136 patients with a unipolar or bipolar depressive episode referred for clinical intermittent theta-burst stimulation or right-sided 1 Hz rTMS at the Uppsala Brain Stimulation Unit. The co-primary outcomes used for logistic regression were response, defined as ≥50 % reduction of Montgomery and Åsberg Depression Rating Scale Self-assessment (MADRS-S) total score, and 1-2 points on the Clinical Global Impression Improvement (CGI-I) scale. Early improvement was defined as ≥20 % reduction in the MADRS-S total score, or ≥ 1 point reduction in each MADRS-S item, after two weeks of treatment. RESULTS: The response rates were 21 % for MADRS-S and 45 % for CGI-I. A depressive episode >24 months had lower odds for MADRS-S response compared to ≤12 months. Early improvement of the MADRS-S total score predicted CGI-I response (95 % CI = 1.35-9.47, p = 0.011), Initiative6 predicted MADRS-S response (95 % CI = 1.08-9.05, p = 0.035), and Emotional involvement7 predicted CGI-I response (95 % CI = 1.03-8.66, p = 0.044). LIMITATIONS: No adjustment for concurrent medication. CONCLUSIONS: A depressive episode ≤12 months and early improvement in overall depressive symptoms, as well as the individual items, Initiative6 and Emotional involvement7, predicted subsequent rTMS response in a naturalistic sample of depressed patients. This could facilitate the early identification of patients who will benefit from further rTMS sessions.

Continuous theta burst stimulation for bipolar depression: A multicenter, double-blind randomized controlled study exploring treatment efficacy and predictive potential of kynurenine metabolites.

BACKGROUND: While theta burst stimulation (TBS) shows promise in Major Depressive Disorder (MDD), its effectiveness in bipolar depression (BD-D) remains uncertain. Optimizing treatment parameters is crucial in the pursuit of rapid symptom relief. Moreover, aligning with personalized treatment strategies and increased interest in immunopsychiatry, biomarker-based stratification of patients most likely to benefit from TBS might improve remission rates. We investigated treatment effectiveness of continuous TBS (cTBS) compared to sham in BD-D, and assessed the capacity of plasma kynurenine pathway metabolites to predict treatment outcome. METHODS: Thirty-seven patients with BD-D underwent accelerated active or sham cTBS treatment in a multicenter, double-blind, randomized controlled trial. Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before treatment (T0), 3-4 days posttreatment (T1) and 10-11 days posttreatment (T2). Plasma tryptophan, kynurenine, kynurenic acid and quinolinic acid concentrations were quantified with ELISA. Linear mixed models were used for statistical analyses. RESULTS: Although the total sample showed depressive symptom improvement, active cTBS did not demonstrate greater symptom alleviation compared to sham. However, higher baseline quinolinic acid significantly predicted symptom improvement in the active treatment group, not in sham-stimulated patients. LIMITATIONS: The modest sample size limited the power to detect significant differences with regard to treatment effect. Also, the follow-up period was 10-11 days, whereas similar studies usually follow up for at least one month. CONCLUSION: More research is required to optimize cTBS for BD-D and explore the involvement of quinolinic acid in treatment outcome.

Role of Electroconvulsive Therapy, Ketamine Infusion, and Deep Repetitive Transcranial Magnetic Stimulation in Treatment-Resistant Bipolar Depression: A Case Report.

Background and Objectives: Options for treatment-resistant bipolar depression (TRBPD) are limited. Electroconvulsive therapy (ECT) has shown efficacy in TRBPD. However, the cognitive deficits and memory concerns associated with ECT are problematic for a significant number of patients. It remains unclear what the next step is for patients with TRBPD who fail ECT. Materials and Methods: In this case report, we present a patient with TRBPD who sequentially received 12 sessions of brief-pulse right unilateral ECT, 22 sessions of ketamine infusion at 0.5-0.75 mg/kg for 40 min, and 39 sessions of deep repetitive transcranial magnetic stimulation (dTMS). Results: The patient had some benefit from ECT, but declined continuation of ECT due to memory concerns. The patient tolerated ketamine infusion well but had limited benefit. However, the patient responded well to acute treatment with dTMS and maintained relative stability for more than 2 years. Conclusions: This case suggests that patients with TRBPD who fail ECT and/or ketamine infusion might benefit from dTMS.

Ketamine treatment for anhedonia in unipolar and bipolar depression: a systematic review.

Ketamine, an N-methyl-D-aspartate receptor antagonist, is a racemic mixture of esketamine and arketamine used to treat unipolar and bipolar depression. Preliminary reports indicate that it may be beneficial for depressed patients reporting symptoms of anhedonia. In this systematic review we aim to assess and analyze the existing body of evidence regarding the therapeutic effects of ketamine on the domain of anhedonia. Electronic databases (PubMed, APA Psycinfo and Web of Science) were searched from inception to November 2023. Protocol was registered in PROSPERO under the identifier CRD42023476603. A total of twenty-two studies, including four randomized-controlled trials and eighteen open-label trials were included. All studies reported alleviation of anhedonia symptoms following ketamine or esketamine administration, regardless of the number of infusions. Several important limitations were included, first and foremost low number of placebo-controlled randomized-controlled trials. This review indicates a potential anti-anhedonic effect of ketamine in patients with depression. Several trials used neuroimaging techniques which confirm ketamine's effect on functional connectivity correlating with the improvement in anhedonia. Despite considerable variations in methodology and the specific brain regions investigated, these studies collectively point towards ketamine's neuroplastic effects in mitigating anhedonia.

Real-world case series of maintenance theta burst stimulation therapy following response to acute theta burst stimulation therapy for difficult-to-treat depression.

OBJECTIVE: Treatment and management for difficult-to-treat depression are challenging, especially in a subset of patients who are at high risk for relapse and recurrence. The conditions that represent this subset are recurrent depressive disorder (RDD) and bipolar disorder (BD). In this context, we aimed to examine the effectiveness of maintenance transcranial magnetic stimulation (TMS) on a real-world clinical basis by retrospectively extracting data from the TMS registry data in Tokyo, Japan. METHODS: Data on patients diagnosed with treatment-resistant RDD and BD who received maintenance intermittent theta burst stimulation (iTBS) weekly after successful treatment with acute iTBS between March 2020 and October 2023 were extracted from the registry. RESULTS: All patients (21 cases: 10 cases with RDD and 11 cases with BD) could sustain response, and 19 of them further maintained remission. In this study, maintenance iTBS did not exacerbate depressive symptoms in any of the cases, but may rather have the effect of stabilizing the mental condition and preventing recurrence. CONCLUSIONS: This case series is of great clinical significance because it is the first study to report on the effectiveness of maintenance iTBS for RDD and BD, with a follow-up of more than 2 years. Further validation with a randomized controlled trial design with a larger sample size is warranted.

Serum Levels of Zinc, Albumin, Interleukin-6 and CRP in Patients with Unipolar and Bipolar Depression: Cross Sectional Study.

Unipolar (UD) and bipolar depression (BDD) show a high degree of similarity in clinical presentations, which complicates the differential diagnosis of these disorders. The aim of this study was to investigate the serum levels of interleukin 6 (IL-6), C-reactive protein (CRP), albumin (Alb), and zinc (Zn) in patients with UD, BDD, and healthy controls (HC). A total of 211 samples were collected: 131 patient samples (65 UD and 68 BDD) and 80 HC. The Montgomery-Asberg Depression Rating Scale (MADRS), along with the Hamilton Depression Rating Scale (HAMD-17), were administered to patient groups to evaluate symptoms. A cross-sectional study was performed to analyse the serum levels of IL-6, CRP, albumin, and zinc. The concentration of CRP was determined using the immunoturbidimetry method, zinc using the colorimetric method, and albumin using the colorimetric method with bromocresol green on the Alinity c device. IL-6 cytokine concentration in serum samples was ascertained using a commercial enzyme immunoassay, ELISA. We found no significant differences in serum concentrations of zinc, albumin, CRP, and IL-6 between the groups of patients with unipolar and bipolar depression. There was a significant statistical difference (p < 0.001) between serum levels of all investigated parameters in both groups of depressed patients in comparison with HC. Furthermore, correlations with specific items on HAMD-17; (namely, hypochondrias, work and activities, somatic symptoms-general, and weight loss) and on MADRS (concentration difficulties, lassitude) were observed in both patient groups. These findings confirm the presence of low-grade inflammation in depression, thus adding better insight into the inflammation hypothesis directed to explain the aetiology of depressive disorders. Our results do not indicate potential biomarkers for distinguishing between unipolar and bipolar depression.

Latent profile analysis of vitamin D and its association with depression severity of hospitalized patients with bipolar depression.

OBJECTIVE: Vitamin D is thought to be deficient in patients with bipolar disorder. The purpose of this study is to use latent profile analysis to identify the patterns of vitamin D levels in patients with episodes of bipolar depression, and to examine the relationship among these latent profiles and demographic and clinical characteristics. METHODS: A total of 149 patients diagnosed with bipolar depression were selected in Guangzhou, China. Depression was evaluated by Zung Self-Rating Depression Scale. Serum 25-hydroxyvitamin D levels tested at baseline and after two weeks of psychiatric treatment were included in the latent profile analysis to identify subgroups. P-trend analysis was used to assess the association between subgroups and depression improvement. Multinomial logistic regression analysis was used to assess the influencing factors of subgroups. RESULTS: A three-profiles solution was found to demonstrate the best fit [low-level profile (32.9%), medium-level profile (51.0%), and high-level profile (16.1%)]. There was a significant nonlinear relationship between depression improvement and vitamin D high-level profile, compared to medium-level profile (P for trend <0.05). In multinomial logistic regression analysis, baseline and post-treatment SDS scores, admission season, age, and body mass index significantly affect the profile membership. CONCLUSIONS: This study found that individuals with high levels of vitamin D showed a significant improvement in depression severity. However, those with low levels of vitamin D remained deficient, indicating a need for targeted vitamin D supplementation. Our findings may provide valuable insights for designing tailored vitamin D supplement interventions to address vitamin D deficiency in bipolar depression.

Prevalence and correlates of manic/hypomanic and depressive predominant polarity in bipolar disorder: systematic review and meta-analysis.

BACKGROUND: Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management of bipolar disorder. AIMS: We performed a systematic review and meta-analysis to estimate prevalence and correlates of mPP and dPP in bipolar disorder. METHOD: The protocol was registered in the Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/8S2HU). We searched main electronic databases up to December 2023 and performed random-effects meta-analyses of weighted prevalence of mPP and dPP. Odds ratios and weighted mean differences (WMDs) were used for relevant correlates. RESULTS: We included 28 studies, providing information on rates and/or correlates of mPP and dPP. We estimated similar rates of mPP (weighted prevalence = 30.0%, 95% CI: 23.1 to 37.4%) and dPP (weighted prevalence = 28.5%, 95% CI: 23.7 to 33.7%) in bipolar disorder. Younger age (WMD = -3.19, 95% CI: -5.30 to -1.08 years), male gender (odds ratio = 1.39, 95% CI: 1.10 to 1.76), bipolar-I disorder (odds ratio = 4.82, 95% CI: 2.27 to 10.24), psychotic features (odds ratio = 1.56, 95% CI: 1.01 to 2.41), earlier onset (WMD = -1.57, 95% CI: -2.88 to -0.26 years) and manic onset (odds ratio = 13.54, 95% CI: 5.83 to 31.46) were associated with mPP (P < 0.05). Depressive onset (odds ratio = 12.09, 95% CI: 6.38 to 22.90), number of mood episodes (WMD = 0.99, 95% CI: 0.28 to 1.70 episodes), history of suicide attempts (odds ratio = 2.09, 95% CI: 1.49 to 2.93) and being in a relationship (odds ratio = 1.98, 95% CI: 1.22 to 3.22) were associated with dPP (P < 0.05). No differences were estimated for other variables. CONCLUSIONS: Despite some limitations, our findings support the hypothesis that predominant polarity might be a useful specifier of bipolar disorder. Evidence quality was mixed, considering effects magnitude, consistency, precision and publication bias. Different predominant polarities may identify subgroups of patients with specific clinical characteristics.

Lipid and Glucose Profile across Different Mental Disorders.

Objectives: Schizophrenia, unipolar depression, bipolar disorder, bipolar mania, and bipolar depression are a few of the severe psychiatric diseases that affect millions of individuals and their overall life quality. This study aimed to look at differences in TGA, TC, HDL, LDL, and FPG levels in people who were going through acute episodes of listed diseases. Materials and methods: A cross-sectional prospective study was carried out in Jordan between January and November of 2023, involving all patients with the aforementioned diseases who attended three psychiatric clinics. This study encompassed results from 1187 patients (women N = 675, 56.87%) who were classified into the following ranges: <25, 25-45, 45-65, and >65. Results: The average level of LDL was the highest in bipolar depression (112.442 ± 36.178 mg/dL) and the lowest in bipolar mania (111.25 ± 33.14 mg/dL). The average level of HDL was the highest in schizophrenia (58.755 ± 16.198 mg/dL) and the lowest in bipolar depression (45.584 ± 12.128 mg/dL). Both average levels of TC and TGA were the highest in patients with bipolar depression (188.403 ± 37.396 mg/dL and 149.685 ± 96.951 mg/dL, respectively) and the lowest in bipolar mania (164.790 ± 40.488 mg/dL and 100.679 ± 54.337 mg/dL, respectively). The average level of FPG was the highest in unipolar depression (94.00 ± 21.453 mg/dL) and the lowest in bipolar mania (89.492 ± 14.700 mg/dL). Conclusions: The results confirmed that lipid and glucose abnormalities were more common in people with schizophrenia and mood disorders (unipolar and bipolar).

Treatment of Refractory Bipolar Depression With Stereotactic Radiosurgery Targeting the Subgenual Cingulate Cortex.

Background The subgenual cingulate cortex (SGC) has been identified as a key structure within multiple neural circuits whose dysfunction is implicated in the neurobiology of depression. Deep brain stimulation in the SGC is thought to reduce and normalize local metabolism, causing normalization of circuit behavior and an improvement in depressive symptoms. We hypothesized that nonablative stereotactic radiosurgery (SRS) to the SGC would reduce local metabolism and reduce the severity of depression in patients with treatment-resistant bipolar depression. Methods Under the FDA's Humanitarian Device Exemption program, patients were screened for inclusion and exclusion criteria. Three volunteers meeting the criteria provided informed consent. Bilateral SGC targets were irradiated to a maximum dose of 75 Gy in one fraction. Subjects were followed for one year following the procedure with mood assessments (Hamilton Depression Rating Scale (HDRS), Clinical Global Impression-Improvement, Clinical Global Impression-Severity, and Young Mania Rating Scale), neurocognitive testing (Delis-Kaplan Executive Function System, Wechsler Adult Intelligence Scale III digit span, and California Verbal Learning Test II), and imaging. Further imaging was completed approximately two years after the procedure. Clinical improvement was defined as a ≥50% reduction in HDRS. Results Two of the three subjects showed clinical improvement in depressive symptoms during the follow-up period, while one subject showed no change in symptom severity. One of three subjects was hospitalized for the emergence of an episode of psychotic mania after discontinuing antipsychotic medications against medical advice but promptly recovered with the reinstitution of an antipsychotic. Sequential assessments did not reveal impairment in any cognitive domain assessed. For one of the three subjects, MRI imaging showed evidence of edema at 12 months post-SRS, which resolved at 22 months post-procedure. In a second of three patients, there was evidence of local edema at the target site at long-term follow-up. All imaging changes were asymptomatic. Conclusion Radiosurgical targeting of the SGC may be a noninvasive strategy for the reduction of severe depression in treatment-resistant bipolar disorder. Two out of three patients showed clinical improvement. While these results are promising, further study, including improvements in target selection and dosing considerations, is needed.

Comparing Symptoms of Major Depression in Youth with Confirmed Versus Suspected Bipolar Disorder.

Background: While numerous studies have compared symptoms of major depressive episodes (MDEs) associated with bipolar disorder (BD; i.e., bipolar depression) versus major depressive disorder (MDD; i.e., unipolar depression), little is known about this topic in youth. We compared MDE symptoms in youth with BD with youth with suspected BD who have similar clinical and familial characteristics aside from having BD. Methods: MDE symptoms based on Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS) Depression Rating Scale items for the most severe past episode were compared in youth, ages 13-21 years, with BD (n = 208) versus suspected BD (n = 165). Diagnoses were confirmed via semistructured interviews. Symptoms with between-group differences (p < 0.05) in univariate analyses were evaluated in a multivariate forward stepwise regression. All analyses controlled for age and sex. Results: Youth with BD had significantly higher (more severe) ratings on depressed mood (p = 0.001, η2 = 0.05), irritability (p = 0.037, η2 = 0.02), anhedonia (p = 0.004, η2 = 0.04), negative self-image (p < 0.001, η2 = 0.07), hopelessness (p = 0.04, η2 = 0.02), fatigue (p = 0.001, η2 = 0.05), hypersomnia (p = 0.001, η2 = 0.05), suicidal ideation (p = 0.04, η2 = 0.02), and recurrent thoughts of death (p < 0.001, η2 = 0.05). In regression analyses, the only symptom that remained significant in the BD group was depressed mood (p = 0.002). Conclusions: These findings demonstrate greater severity of depressive symptoms in youth with BD versus MDD across mood, and cognitive and neurovegetative symptom domains. These differences are especially noteworthy given that the MDD group was highly similar to the BD group, aside from BD diagnosis. Present findings emphasize the need for novel treatment approaches to bipolar depression in youth, and for studies examining potential mechanisms underlying the increased severity of bipolar depression.

Distinguishing bipolar depression, bipolar mania, and major depressive disorder by gut microbial characteristics.

BACKGROUND: Gut microbial disturbance has been widely confirmed in mood disorders. However, little is known about whether gut microbial characteristics can distinguish major depressive disorder (MDD), bipolar depression (BP-D), and bipolar mania (BP-M). METHODS: This was a prospective case-control study. The composition of gut microbiota was profiled using 16S ribosomal RNA (rRNA) gene sequencing of fecal samples and compared between healthy controls (HC; n = 46), MDD (n = 51), BP-D (n = 44), and patients with BP-M (n = 45). RESULTS: Gut microbial compositions were remarkably changed in the patients with MDD, BP-D, and BP-M. Compared to HC, distinct gut microbiome signatures were found in MDD, BP-D, and BP-M, and some gut microbial changes were overlapping between the three mood disorders. Furthermore, we identified a signature of 7 operational taxonomic units (OUT; Prevotellaceae-related OUT22, Prevotellaceae-related OUT31, Prevotellaceae-related OTU770, Ruminococcaceae-related OUT70, Bacteroidaceae-related OTU1536, Propionibacteriaceae-related OTU97, Acidaminococcaceae-related OTU34) that can distinguish patients with MDD from those with BP-D, BP-M, or HC, with area under the curve (AUC) values ranging from 0.910 to 0.996. CONCLUSION: Our results provide the clinical rationale for the discriminative diagnosis of MDD, BP-D, and BP-M by characteristic gut microbial features.