Mapping the global, regional and national burden of bipolar disorder from 1990 to 2019: trend analysis on the Global Burden of Disease Study 2019.

BACKGROUND: Data on trends in the epidemiological burden of bipolar disorder are scarce. AIMS: To provide an overview of trends in bipolar disorder burden from 1990 to 2019. METHOD: Revisiting the Global Burden of Disease Study 2019, we analysed the number of cases, calculated the age-standardised rate (per 100 000 population) and estimated annual percentage change (EAPC) of incidence, prevalence and years lived with disability (YLDs) for bipolar disorder from 1990 to 2019. The independent effects of age, period and cohort were estimated by the age-period-cohort modelling. RESULTS: Globally, the bipolar disorder-related prevalent cases, incident cases and number of YLDs all increased from 1990 to 2019. Regionally, the World Health Organization Region of the Americas accounted for the highest estimated YLD number and rate, with the highest age-standardised prevalence rate in 1990 and 2019 and highest EAPC of prevalence. By sociodemographic index (SDI) quintiles, all five SDI regions saw an increase in estimated incident cases. Nationally, New Zealand reported the highest age-standardised rate of incidence, prevalence and YLDs in 1990 and 2019. The most prominent age effect on incidence rate was in those aged 15-19 years. Decreased effects of period on incidence, prevalence and YLD rates was observed overall and in females, not in males. The incidence, prevalence and YLD rates showed an unfavourable trend in the younger cohorts born after 1990, with males reporting a higher cohort risk than females. CONCLUSIONS: From 1990 to 2019, the overall trend of bipolar disorder burden presents regional and national variations and differs by age, sex, period and cohort.

Psychological and physical side effects during G-CSF mobilization in related donors of allo-HCT.

The psychological side effects of granulocyte colony-stimulating factor mobilization in related donors of allogeneic hematopoietic cell transplantation (allo-HCT) and impacts of psychological/physical side effects on harvest outcomes remain largely unknown. We prospectively analyzed 349 consecutive related peripheral blood stem cell (PBSC) donors for allo-HCT at the First Affiliated Hospital, Zhejiang University, School of Medicine from March 2021 to August 2023. Higher baseline peripheral blood white blood cell counts (p = 0.046), monocyte counts (p < 0.001), platelet counts (p = 0.001), and hemoglobin (p < 0.001) had a positive correlation to CD34+ cell counts in the first leukapheresis, while female donors (male vs. female, p < 0.001) and older age (> 40 vs. < = 40, p = 0.003) were negatively related to CD34+ cell counts. Bone pain was the most observed physical side effect and was more frequent in female donors (p = 0.032). The incidence of fatigue was higher in female donors and older donors (female vs. male, p = 0.016; > 40 vs. < = 40, p = 0.015). Donor depression (pre vs. during mobilization, p < 0.001), anxiety (pre vs. during mobilization, p = 0.043) and insomnia (pre vs. during mobilization, p = 0.011) scores increased during the mobilization period. Donors with higher depression, anxiety and stress scores at admission were more likely to experience nausea. At 1 month after the last leukapheresis, the counts of white blood cell, neutrophil, monocyte and hemoglobin were significant lower than baseline counts, while the platelet counts recovered to baseline. The mobilization and harvest process can increase the depression, anxiety and insomnia scores. Poor psychological status of the donor can aggravate the occurrence of physical side effects.

Multi-omics analyses of serum metabolome, gut microbiome and brain function reveal dysregulated microbiota-gut-brain axis in bipolar depression.

The intricate processes of microbiota-gut-brain communication in modulating human cognition and emotion, especially in the context of mood disorders, have remained elusive. Here we performed faecal metagenomic, serum metabolomics and neuroimaging studies on a cohort of 109 unmedicated patients with depressed bipolar disorder (BD) patients and 40 healthy controls (HCs) to characterise the microbial-gut-brain axis in BD. Across over 12,000 measured metabolic features, we observed a large discrepancy (73.54%) in the serum metabolome between BD patients and HCs, spotting differentially abundant microbial-derived neuroactive metabolites including multiple B-vitamins, kynurenic acid, gamma-aminobutyric acid and short-chain fatty acids. These metabolites could be linked to the abundance of gut microbiota presented with corresponding biosynthetic potentials, including Akkermansia muciniphila, Citrobacter spp. (Citrobacter freundii and Citrobacter werkmanii), Phascolarctobacterium spp., Yersinia spp. (Yersinia frederiksenii and Yersinia aleksiciae), Enterobacter spp. (Enterobacter cloacae and Enterobacter kobei) and Flavobacterium spp. Based on functional neuroimaging, BD-related neuroactive microbes and metabolites were discovered as potential markers associated with BD-typical features of functional connectivity of brain networks, hinting at aberrant cognitive function, emotion regulation, and interoception. Our study combines gut microbiota and neuroactive metabolites with brain functional connectivity, thereby revealing potential signalling pathways from the microbiota to the gut and the brain, which may have a role in the pathophysiology of BD.

Shifting levels of peripheral inflammatory profiles as an indicator for comorbid multiple autoimmune diseases and bipolar disorder: a case report.

Autoimmune diseases (AID) cause inflammatory changes in the peripheral blood, which might be a predisposing factor for the development of comorbid bipolar disorder (BD). The levels of peripheral inflammatory indicators and cytokines may also serve as potential biomarkers for predicting BD susceptibility and the efficacy of antipsychotics in patients with AID. Herein, we present the case of a 43-year-old female who has suffered from AID for over 16 years and was recently diagnosed with "bipolar and related disorder due to another medical condition".

Effect of aggressive versus conservative hydration for early phase of acute pancreatitis in adult patients: A meta-analysis of 3,127 cases.

BACKGROUND: The advantages of aggressive hydration compared to conservative hydration within 24 h for acute pancreatitis (AP) remain controversial in adult patients. A meta-analysis was undertaken to investigate whether aggressive strategies are more beneficial. METHODS: We searched (on February 1, 2021) PubMed, Embase, and the Cochrane Library for eligible trials that assessed the two therapies and performed a meta-analysis. The primary endpoint was in-hospital mortality. Secondary outcomes were adverse events (e.g., renal failure and pancreatic necrosis) within 24 h of treatment. RESULTS: Five randomized controlled trials and 8 observational trials involving 3127 patients were identified. Patients with severe pancreatitis showed significant difference of in-hospital mortality (OR 1.75; 95% CI 1.32-2.33) in aggressive hydration group, which were less susceptible to study type and age. Patients with severe pancreatitis were likely to develop respiratory failure (OR 5.08; 95% CI 2.31-11.15), persistent SIRS (OR 2.83; 95% CI 1.58-5.04), renal failure (OR 2.58; 95% CI 1.90-3.50) with significant difference. A longer hospital stay was observed in patients with severe pancreatitis (WMD 7.61; 95% CI 5.51-9.71; P < 0.05) in the aggressive hydration group. Higher incidence of pancreatic necrosis (OR 2.34; 95% CI 1.60-3.42; P < 0.05) was major susceptible to observational studies, old patients and mild pancreatitis. CONCLUSIONS: Compared to conservative hydration, aggressive hydration increases in-hospital mortality and the incidence of renal failure, pancreatic necrosis with relatively strong evidence. Further investigation should be designed with a definitive follow-up period and therapeutic goals to address reverse causation bias.

Impaired blood-brain barrier in the microbiota-gut-brain axis: Potential role of bipolar susceptibility gene TRANK1.

Bipolar disorder (BD) is a common psychiatric illness with high prevalence and disease burden. Accumulating susceptibility genes for BD have been identified in recent years. However, the exact functions of these genes remain largely unknown. Despite its high heritability, gene and environment interaction is commonly accepted as the major contributing factor to BD pathogenesis. Intestine microbiota is increasingly recognized as a critical environmental factor for human health and diseases via the microbiota-gut-brain axis. BD individuals showed altered diversity and compositions in the commensal microbiota. In addition to pro-inflammatory factors, such as interleukin-6 and tumour necrosis factor-α, type 1 interferon signalling pathway is also modulated by specific intestinal bacterial strains. Disruption of the microbiota-gut-brain axis contributes to peripheral and central nervous system inflammation, which accounts for the BD aetiology. Administration of type 1 interferon can induce the expression of TRANK1, which is associated with elevated circulating biomarkers of the impaired blood-brain barrier in BD patients. In this review, we focus on the influence of intestine microbiota on the expression of bipolar gene TRANK1 and propose that intestine microbiota-dependent type 1 interferon signalling is sufficient to induce the over-expression of TRANK1, consequently causing the compromise of BBB integrity and facilitating the entrance of inflammatory mediators into the brain. Activated neuroinflammation eventually contributes to the occurrence and development of BD. This review provides a new perspective on how gut microbiota participate in the pathogenesis of BD. Future studies are needed to validate these assumptions and develop new treatment targets for BD.

Differing default mode network activities in men with homosexual or heterosexual preferences.

INTRODUCTION: Neuroimaging studies have reported differences in brain structure and function between homosexual and heterosexual men. The neural basis for homosexual orientation, however, is still unknown. AIM: This study characterized the association of homosexual preference with measures of fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) in the resting state. METHODS: We collected echo planar magnetic resonance imaging data in 26 healthy homosexual men and 26 age-matched heterosexual men in the resting state. MAIN OUTCOME MEASURES: Sexual orientation was evaluated using the Kinsey scale. We assessed group differences in fALFF and then, taking the identified group differences as seed regions, we compared groups on measures of FC from those seeds. The behavioral significance of the group differences in fALFF and FC was assessed by examining their associations with the Kinsey scores. RESULTS: Compared with heterosexual participants, homosexual men showed significantly increased fALFF in the right middle frontal gyrus and right anterior cerebellum, and decreased fALFF in the left postcentral gyrus, left lingual gyrus, right pallidum, right postcentral gyrus, left interior parietal gyrus, right superior temporal gyrus, left cuneus, and left inferior frontal gyrus. Additionally, fALFF in the left postcentral gyrus and left cuneus correlated positively with Kinsey scores in the homosexual participants. When the seeds in the left cuneus, left cuneus, and left superior parietal gyrus also had reduced FC in homosexual participants, FC correlated positively with the Kinsey scores. CONCLUSIONS: Differences in fALFF and FC suggest male sexual preference may influence the pattern activity in the default mode network.

The impact of quetiapine monotherapy or in combination with lithium on the thyroid function in patients with bipolar depression: A retrospective study.

OBJECTIVE: This study aims to investigate whether quetiapine monotherapy or in combination with lithium significantly disturbs thyroid function in depressed patients with bipolar disorder (BD), and whether difference exists in the post-treatment thyroid function between the two therapies. METHODS: Based on the electric medical records, outpatients and inpatients with a current depressive episode of BD from January 2016 to December 2022 were screened. All patients were treated with quetiapine monotherapy or in combination with lithium. In addition to the demographic data and depression scale, thyroid profiles including total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TGAb) were recorded, analyzed, and compared before and after the treatment. RESULTS: Totally, 73 eligible patients were enrolled, including 53 in the monotherapy group (MG) and 20 in the combined therapy group (CG). No significant differences in thyroid profiles were detected between the two groups at the baseline (p > 0.05). After one-month treatment, in the MG, serum levels of TT4, TT3, FT4, and FT3 reduced significantly (p < 0.05), while TSH, TPOAb, and TGAb increased significantly (p < 0.05). In the CG, serum levels of TT4, TT3, and FT4 reduced and TSH increased following one-month treatment (p < 0.05), with no significant change in FT3, TPOAb, or TGAb (p > 0.05). After one-month treatment, no difference of TT4, TT3, FT4, FT3, and TSH was found between the two groups (p > 0.05). CONCLUSION: Both quetiapine monotherapy and a combined therapy with lithium significantly disturbed thyroid function in patients with bipolar depression, while quetiapine monotherapy seems to be associated with immune dysregulation in the thyroid.

Efficacy and tolerability of FDA-approved atypical antipsychotics for the treatment of bipolar depression: a systematic review and network meta-analysis.

We employed a Bayesian network meta-analysis for comparison of the efficacy and tolerability of US Food and Drug Administration (FDA)-approved atypical antipsychotics (AAPs) for the treatment of bipolar patients with depressive episodes. Sixteen randomized controlled trials with 7234 patients treated by one of the five AAPs (cariprazine, lumateperone, lurasidone, olanzapine, and quetiapine) were included. For the response rate (defined as an improvement of ≥50% from baseline on the Montgomery-Åsberg Depression Rating Scale [MADRS]), all AAPs were more efficacious than placebo. For the remission rate (defined as the endpoint of MADRS ≤12 or ≤ 10), cariprazine, lurasidone, olanzapine, and quetiapine had higher remission rates than placebo. In terms of tolerability, olanzapine was unexpectedly associated with lower odds of all-cause discontinuation in comparison with placebo, whereas quetiapine was associated with higher odds of discontinuation due to adverse events than placebo. Compared with placebo, lumateperone, olanzapine, and quetiapine showed higher odds of somnolence. Lumateperone had a lower rate of ≥ weight gain of 7% than placebo and other treatments. Olanzapine was associated with a significant increase from baseline in total cholesterol and triglycerides than placebo. These findings inform individualized prescriptions of AAPs for treating bipolar depression in clinical practice.

Latent Profile Analysis of Suicidal Ideation in Chinese Individuals with Bipolar Disorder.

Individuals with bipolar disorder (BD) have a greater suicide risk than the general population. In this study, we employed latent profile analysis (LPA) to explore whether Chinese individuals with different phases of BD differed at the levels of suicidal ideation. We recruited 517 patients. Depressive symptoms were measured using the 24-item Hamilton Depression Rating Scale (HAMD-24), and manic symptoms were evaluated using the Young Mania Rating Scale (YMRS). The extent of suicidal thoughts was determined through the Beck Scale for Suicide Ideation (BSSI). The scores of HAMD and YMRS were used to perform LPA. LPA categorized participants into three classes: one exhibiting severe depressive and mild manic symptomatology, another showing severe depressive and severe manic symptomatology, and the third one displaying severe depressive and intermediate manic symptomatology. Suicidal ideation levels were found to be remarkably elevated across all three classes. Additionally, the three classes showed no significant differences in terms of suicidal ideation. Our research confirms the link between depressive symptoms and suicide, independent of the manic symptoms. These findings carry meaning as they provide insight into the suicide risk profiles within different phases of BD.

Progress and Implications from Genetic Studies of Bipolar Disorder.

With the advancements in gene sequencing technologies, including genome-wide association studies, polygenetic risk scores, and high-throughput sequencing, there has been a tremendous advantage in mapping a detailed blueprint for the genetic model of bipolar disorder (BD). To date, intriguing genetic clues have been identified to explain the development of BD, as well as the genetic association that might be applied for the development of susceptibility prediction and pharmacogenetic intervention. Risk genes of BD, such as CACNA1C, ANK3, TRANK1, and CLOCK, have been found to be involved in various pathophysiological processes correlated with BD. Although the specific roles of these genes have yet to be determined, genetic research on BD will help improve the prevention, therapeutics, and prognosis in clinical practice. The latest preclinical and clinical studies, and reviews of the genetics of BD, are analyzed in this review, aiming to summarize the progress in this intriguing field and to provide perspectives for individualized, precise, and effective clinical practice.

Clinical Characteristics of Asymptomatic Thromboembolism in Psychiatric Inpatients: A Retrospective Study.

Purpose: Venous thromboembolism (VTE) poses a significant threat to individuals' health, yet its correlation with mental disorders remains underappreciated. Here, we conducted a retrospective analysis to explore the characteristics of psychiatric patients presenting with VTE. Methods: We retrospectively analyzed psychiatric inpatients with elevated plasma D-dimer levels at the Mental Health Center, First Affiliated Hospital, Zhejiang University School of Medicine, from January 2014 to January 2022. The inclusion criteria comprised comprehensive demographic and clinical profiles, including laboratory and imaging findings. Results: A cohort of 33 eligible patients was included, with plasma D-dimer levels ranging from 880 to 10,700 µg/L FEU. Significantly higher D-dimer levels were observed in patients diagnosed with severe mental disorders (SMD), such as schizophrenia and bipolar disorder, compared to those with mild mental disorders (MMD), including depression and anxiety disorders (p = 0.007). Furthermore, individuals receiving antipsychotic medications for less than one year exhibited elevated D-dimer levels compared to those on treatment for over one year (p = 0.005). However, normalization of D-dimer levels did not demonstrate a significant association with psychiatric diagnosis or treatment duration (p > 0.05). Conclusion: Our findings suggest that patients diagnosed with SMD or those undergoing antipsychotic treatment for less than one year may have elevated D-dimer levels, indicating a potential predisposition to VTE severity. This underscores the importance of recognizing VTE risk in individuals with severe mental disorders and warrants further investigation into the impact of antipsychotic treatment duration on thrombotic risk.

Task-state skin potential abnormalities can distinguish major depressive disorder and bipolar depression from healthy controls.

Early detection of bipolar depression (BPD) and major depressive disorder (MDD) has been challenging due to the lack of reliable and easily measurable biological markers. This study aimed to investigate the accuracy of discriminating patients with mood disorders from healthy controls based on task state skin potential characteristics and their correlation with individual indicators of oxidative stress. A total of 77 patients with BPD, 53 patients with MDD, and 79 healthy controls were recruited. A custom-made device, previously shown to be sufficiently accurate, was used to collect skin potential data during six emotion-inducing tasks involving video, pictorial, or textual stimuli. Blood indicators reflecting individual levels of oxidative stress were collected. A discriminant model based on the support vector machine (SVM) algorithm was constructed for discriminant analysis. MDD and BPD patients were found to have abnormal skin potential characteristics on most tasks. The accuracy of the SVM model built with SP features to discriminate MDD patients from healthy controls was 78% (sensitivity 78%, specificity 82%). The SVM model gave an accuracy of 59% (sensitivity 59%, specificity 79%) in classifying BPD patients, MDD patients, and healthy controls into three groups. Significant correlations were also found between oxidative stress indicators in the blood of patients and certain SP features. Patients with depression and bipolar depression have abnormalities in task-state skin potential that partially reflect the pathological mechanism of the illness, and the abnormalities are potential biological markers of affective disorders.

Serum signature of antibodies to Toxoplasma gondii, rubella virus, and cytomegalovirus in females with bipolar disorder: A cross-sectional study.

BACKGROUND AND AIM: Immunity alterations have been observed in bipolar disorder (BD). However, whether serum positivity of antibodies to Toxoplasma gondii (T gondii), rubella, and cytomegalovirus (CMV) shared clinical relevance with BD, remains controversial. This study aimed to investigate this association. METHODS: Antibody seropositivity of IgM and IgG to T gondii, rubella virus, and CMV of females with BD and controls was extracted based on medical records from January 2018 to January 2023. Family history, type of BD, onset age, and psychotic symptom history were also collected. RESULTS: 585 individuals with BD and 800 healthy controls were involved. Individuals with BD revealed a lower positive rate of T gondii IgG in the 10-20 aged group (OR = 0.10), and a higher positive rate of rubella IgG in the 10-20 (OR = 5.44) and 20-30 aged group (OR = 3.15). BD with family history preferred a higher positive rate of T gondii IgG (OR = 24.00). Type-I BD owned a decreased positive rate of rubella IgG (OR = 0.37) and an elevated positive rate of CMV IgG (OR = 2.12) compared to type-II BD, while BD with early onset showed contrast results compared to BD without early onset (Rubella IgG, OR = 2.54; CMV IgG, OR = 0.26). BD with psychotic symptom history displayed a lower positive rate of rubella IgG (OR = 0.50). LIMITATIONS: Absence of male evidence and control of socioeconomic status and environmental exposure. CONCLUSIONS: Differential antibody seropositive rates of T gondii, rubella, and cytomegalovirus in BD were observed.

Circulating T-cell subsets discrepancy between bipolar disorder and major depressive disorder during mood episodes: A naturalistic, retrospective study of 1015 cases.

AIMS: We aimed to investigate whether peripheral T-cell subsets could be a biomarker to distinguish major depressive disorder (MDD) and bipolar disorder (BD). METHODS: Medical records of hospitalized patients in the Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2015 to September 2020 with a discharge diagnosis of MDD or BD were reviewed. Patients who underwent peripheral blood examination of T-cell subtype proportions, including CD3+, CD4+, CD8+ T-cell, and natural killer (NK) cells, were enrolled. The Chi-square test, t-test, or one-way analysis of variance were used to analyze group differences. Demographic profiles and T-cell data were used to construct a random forest classifier-based diagnostic model. RESULTS: Totally, 98 cases of BD mania, 459 cases of BD depression (BD-D), and 458 cases of MDD were included. There were significant differences in the proportions of CD3+, CD4+, CD8+ T-cell, and NK cells among the three groups. Compared with MDD, the BD-D group showed higher CD8+ but lower CD4+ T-cell and a significantly lower ratio of CD4+ and CD8+ proportions. The random forest model achieved an area under the curve of 0.77 (95% confidence interval: 0.71-0.83) to distinguish BD-D from MDD patients. CONCLUSION: These findings imply that BD and MDD patients may harbor different T-cell inflammatory patterns, which could be a potential diagnostic biomarker for mood disorders.

Hippocampal mitophagy contributes to spatial memory via maintaining neurogenesis during the development of mice.

BACKGROUND: Impaired mitochondrial dynamics have been identified as a significant contributing factor to reduced neurogenesis under pathological conditions. However, the relationship among mitochondrial dynamics, neurogenesis, and spatial memory during normal development remains unclear. This study aims to elucidate the role of mitophagy in spatial memory mediated by neurogenesis during development. METHODS: Adolescent and adult male mice were used to assess spatial memory performance. Immunofluorescence staining was employed to evaluate levels of neurogenesis, and mitochondrial dynamics were assessed through western blotting and transmission electron microscopy. Pharmacological interventions further validated the causal relationship among mitophagy, neurogenesis, and behavioral performance during development. RESULTS: The study revealed differences in spatial memory between adolescent and adult mice. Diminished neurogenesis, accompanied by reduced mitophagy, was observed in the hippocampus of adult mice compared to adolescent subjects. Pharmacological induction of mitophagy in adult mice with UMI-77 resulted in enhanced neurogenesis and prolonged spatial memory retention. Conversely, inhibition of mitophagy with Mdivi-1 in adolescent mice led to reduced hippocampal neurogenesis and impaired spatial memory. CONCLUSION: The observed decline in spatial memory in adult mice is associated with decreased mitophagy, which affects neurogenesis in the dentate gyrus. This underscores the therapeutic potential of enhancing mitophagy to counteract age- or disease-related cognitive decline.