Manuel Gardea-Resendez, Manuel Fuentes-Salgado, Francisco Romo-Nava, Miguel L. Prieto, David J. Bond, Aysegul Ozerdem, Hannah K. Betcher, Katherine M. Moore, Melissa Solares-Bravo, Mete Ercis, Alessandro Miola, Jorge A. Sanchez-Ruiz, Marin Veldic, Balwinder Singh, Alfredo B. Cuellar-Barboza, Brandon J. Coombes, Joanna M. Biernacka, Susan L. McElroy, Monica J. Taylor-Desir, Mark A. Frye
Objectives
To explore the clinical impact of social determinants of health (SDoH) stress in bipolar disorder (BD) course of illness and to explore potential gender differences in SDoH stress endorsement.
Methods
2280 individuals living with BD type I or II (62% women; 67.5% BD-I) participating in the Mayo Clinic Bipolar Biobank who completed a questionnaire assessing positive and negative-valent stressors in the 12 months prior to study enrollment were included for this analysis. Six negative stressors were used as proxies of SDoH. Generalized linear models were used to test the association between SDoH stressors and markers of illness severity as well as potential differences by sex by including an interaction term.
Results
After adjusting for age, sex, and recruitment site, SDoH-related stressors were significantly associated with a more severe course of illness in both men and women. Except for unemployment rates, women reported more frequently SDoH-related stress (i.e., lack of family support, financial problems, health coverage and access problems).
Conclusions
The study found significant gender differences in both the endorsement of specific SDoH stressors and in the prevalence of specific illness severity markers; however, it did not directly test the predictive relationship between gender differences in SDoH and illness severity markers. Future studies aiming to achieve health equity in mental health care should continue assessing social determinants of health stressors, incorporating a gender perspective to better understand their influence on bipolar disorder.
目的：探讨健康社会决定因素（social factors of health, SDoH）应激在双相情感障碍（bipolar disorder， BD）病程中的临床影响，并探讨SDoH应激认可的潜在性别差异。方法：2280名I型或II型双相障碍患者（62%为女性，67.5%为BD-I型）参加梅奥诊所双相障碍生物库，在研究入组前12个月完成了一份评估正价和负价压力源的问卷。以6个负性应激源作为SDoH的替代指标。我们使用广义线性模型来检验SDoH应激源与疾病严重程度标记之间的关联，以及通过包括一个相互作用项来检验性别之间的潜在差异。结果：在调整了年龄、性别和招募地点后，sdoh相关压力源与男性和女性更严重的病程显著相关。除失业率外，妇女更多地报告了与特别保健工作有关的压力（即缺乏家庭支持、经济问题、医疗保险和获得服务的问题）。结论：研究发现，在特定SDoH压力源的认可和特定疾病严重程度标记的患病率方面，性别差异显著；然而，它没有直接测试SDoH性别差异与疾病严重程度标志物之间的预测关系。未来旨在实现精神卫生保健健康公平的研究应继续评估健康压力源的社会决定因素，并纳入性别观点，以更好地了解其对双相情感障碍的影响。
{"title":"A Cross-Sectional Analysis of Social Determinants of Health in Bipolar Disorder: Exploring Gender-Related Differences","authors":"Manuel Gardea-Resendez, Manuel Fuentes-Salgado, Francisco Romo-Nava, Miguel L. Prieto, David J. Bond, Aysegul Ozerdem, Hannah K. Betcher, Katherine M. Moore, Melissa Solares-Bravo, Mete Ercis, Alessandro Miola, Jorge A. Sanchez-Ruiz, Marin Veldic, Balwinder Singh, Alfredo B. Cuellar-Barboza, Brandon J. Coombes, Joanna M. Biernacka, Susan L. McElroy, Monica J. Taylor-Desir, Mark A. Frye","doi":"10.1111/bdi.70062","DOIUrl":"10.1111/bdi.70062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To explore the clinical impact of social determinants of health (SDoH) stress in bipolar disorder (BD) course of illness and to explore potential gender differences in SDoH stress endorsement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>2280 individuals living with BD type I or II (62% women; 67.5% BD-I) participating in the Mayo Clinic Bipolar Biobank who completed a questionnaire assessing positive and negative-valent stressors in the 12 months prior to study enrollment were included for this analysis. Six negative stressors were used as proxies of SDoH. Generalized linear models were used to test the association between SDoH stressors and markers of illness severity as well as potential differences by sex by including an interaction term.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After adjusting for age, sex, and recruitment site, SDoH-related stressors were significantly associated with a more severe course of illness in both men and women. Except for unemployment rates, women reported more frequently SDoH-related stress (i.e., lack of family support, financial problems, health coverage and access problems).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The study found significant gender differences in both the endorsement of specific SDoH stressors and in the prevalence of specific illness severity markers; however, it did not directly test the predictive relationship between gender differences in SDoH and illness severity markers. Future studies aiming to achieve health equity in mental health care should continue assessing social determinants of health stressors, incorporating a gender perspective to better understand their influence on bipolar disorder.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"27 8","pages":"545-550"},"PeriodicalIF":4.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bdi.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Søren L. Jacobsen, Christian L. Kraft, Andrew A. Nierenberg, Torben A. Devantier, Ole Köhler-Forsberg
Background
Lithium blood levels are measured routinely 12 h after lithium dosing, but no study has evaluated the actual compliance of patients with the 12-h levels.
Methods
First, we used the US multicenter clinical trial “Bipolar CHOICE” (n = 145 patients treated with lithium with N = 287 lithium blood tests), where participants reported the time since the last lithium dose at lithium blood tests. Second, we included all lithium blood tests (3179 individuals, 52,837 blood tests) from hospitals and private practitioners in the Central Denmark Region (CDR, approximate population 1.3 million) during 2012–2022, including the time of lithium blood tests and the registered time when patients were supposed to take their lithium dose.
Results
In Bipolar CHOICE, participants took the lithium blood test at a mean/median of 12.8/12 h (SD = 9.1, IQR = 10.5–14) after the lithium dose, but the range was 0.5–120 h and 44.9% had the blood test taken < 10 or > 14 h after the lithium dose. Those with a blood test > 14 h after the lithium dose had significantly lower lithium levels (0.41 vs. 0.64). In the CDR, the mean/median time was 14.5/13.7 (SD = 3.8, IQR = 12.0–15.8) and 49.7% had the blood test taken < 10 or > 14 h after the supposed intake of lithium. Those with > 16 h between lithium intake and the lithium blood test were more often followed by general practitioners and showed higher creatinine concentrations.
Conclusions
Approximately half of lithium blood tests do not comply with guideline-based recommendations for 12-h trough levels, emphasizing the need for solutions to solve this clinical need.
{"title":"Do Patients Comply With 12-h Lithium Blood Level Timing? Findings From a Controlled Clinical Trial and a Real-World Clinical Setting","authors":"Søren L. Jacobsen, Christian L. Kraft, Andrew A. Nierenberg, Torben A. Devantier, Ole Köhler-Forsberg","doi":"10.1111/bdi.70060","DOIUrl":"10.1111/bdi.70060","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lithium blood levels are measured routinely 12 h after lithium dosing, but no study has evaluated the actual compliance of patients with the 12-h levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>First, we used the US multicenter clinical trial “Bipolar CHOICE” (<i>n</i> = 145 patients treated with lithium with <i>N</i> = 287 lithium blood tests), where participants reported the time since the last lithium dose at lithium blood tests. Second, we included all lithium blood tests (3179 individuals, 52,837 blood tests) from hospitals and private practitioners in the Central Denmark Region (CDR, approximate population 1.3 million) during 2012–2022, including the time of lithium blood tests and the registered time when patients were supposed to take their lithium dose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In Bipolar CHOICE, participants took the lithium blood test at a mean/median of 12.8/12 h (SD = 9.1, IQR = 10.5–14) after the lithium dose, but the range was 0.5–120 h and 44.9% had the blood test taken < 10 or > 14 h after the lithium dose. Those with a blood test > 14 h after the lithium dose had significantly lower lithium levels (0.41 vs. 0.64). In the CDR, the mean/median time was 14.5/13.7 (SD = 3.8, IQR = 12.0–15.8) and 49.7% had the blood test taken < 10 or > 14 h after the supposed intake of lithium. Those with > 16 h between lithium intake and the lithium blood test were more often followed by general practitioners and showed higher creatinine concentrations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Approximately half of lithium blood tests do not comply with guideline-based recommendations for 12-h trough levels, emphasizing the need for solutions to solve this clinical need.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"27 7","pages":"519-526"},"PeriodicalIF":4.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bdi.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayal Schaffer, Prudence Po Ming Chan, Vera Yu Men, Rosalie Steinberg, Rachel HB. Mitchell, Gin Malhi, Lakshmi N. Yatham, Mark Sinyor
Objectives
This study aimed to compare suicide deaths in those with or without bipolar disorder (BD), taking into particular consideration the degree to which treatment at the time of death, according to toxicology data, reflects evidence-based pharmacotherapy.
Methods
Coroner data were coded for all verified suicide deaths in the City of Toronto, Canada (1998–2020). Suicide decedents with BD (n = 340) were compared to the non-BD group (n = 4948) on demographic, clinical, and suicide-related variables. In a subsample of decedents, the presence and/or lethality of medications or substances at the time of death was identified from toxicology data and compared between groups and across time (two 11.5 year epochs). Data were analyzed using univariate analyses.
Results
Several noteworthy demographic, clinical, and suicide-specific differences between BD and non-BD suicide groups emerged. Antidepressants (48.9%) and benzodiazepines (46.7%) were the most commonly present medications among people with BD, at a proportion similar to the non-BD group. There was a significant decrease in the presence of mood stabilizers across time (33.3% vs. 13.5%, p = 0.006), and lithium was present in only 5.8% of decedents with BD. Opioids (22.1%) and antipsychotics (22.1%) were the most common substances detected in lethal amounts in the BD group.
Conclusions
The findings of this study suggest that a substantial proportion of people with BD who die by suicide are not receiving first-line treatments at the time of death. While causality cannot be established, further exploration of pharmacotherapy at the time of death would ideally link to living controls to address issues of risk and lethality.
{"title":"Suicide Deaths in People With Bipolar Disorder: Characteristics and Treatments at Time of Death","authors":"Ayal Schaffer, Prudence Po Ming Chan, Vera Yu Men, Rosalie Steinberg, Rachel HB. Mitchell, Gin Malhi, Lakshmi N. Yatham, Mark Sinyor","doi":"10.1111/bdi.70061","DOIUrl":"10.1111/bdi.70061","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to compare suicide deaths in those with or without bipolar disorder (BD), taking into particular consideration the degree to which treatment at the time of death, according to toxicology data, reflects evidence-based pharmacotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Coroner data were coded for all verified suicide deaths in the City of Toronto, Canada (1998–2020). Suicide decedents with BD (<i>n</i> = 340) were compared to the non-BD group (<i>n</i> = 4948) on demographic, clinical, and suicide-related variables. In a subsample of decedents, the presence and/or lethality of medications or substances at the time of death was identified from toxicology data and compared between groups and across time (two 11.5 year epochs). Data were analyzed using univariate analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Several noteworthy demographic, clinical, and suicide-specific differences between BD and non-BD suicide groups emerged. Antidepressants (48.9%) and benzodiazepines (46.7%) were the most commonly present medications among people with BD, at a proportion similar to the non-BD group. There was a significant decrease in the presence of mood stabilizers across time (33.3% vs. 13.5%, <i>p</i> = 0.006), and lithium was present in only 5.8% of decedents with BD. Opioids (22.1%) and antipsychotics (22.1%) were the most common substances detected in lethal amounts in the BD group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings of this study suggest that a substantial proportion of people with BD who die by suicide are not receiving first-line treatments at the time of death. While causality cannot be established, further exploration of pharmacotherapy at the time of death would ideally link to living controls to address issues of risk and lethality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"27 7","pages":"527-537"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bdi.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bipolar and ADHD are two diseases that exhibit similar traits but at different levels of severity. Understanding this behavior can help treatment of these disorders.
Method
We hypothesize that there is a common partial genetic cause for both attention-deficit/hyperactivity disorder (ADHD) and bipolar disorders (BD), which is the reversal function of the dopamine neurotransporter DAT gate (see Figure 1) into an efflux mode. We analyze the dopamine chemistry in the neuron synapse under this assumption.
Results
The difference between ADHD and BD phenotypes is due either to the dopamine receptor (D2R) operation or to the threshold levels of the dopamine homeostatic control and the intensity of its operation.
Significance
The common cause of the two disorders could explain the frequent phenomenon of ADHD symptoms preceding BD beginning and the high comorbidity between these disorders.
{"title":"A Common Cause of ADHD and Bipolar Disorder (BD)","authors":"Rabinovitch Avinoam, Rabinovitch Revital, Braunstein Doron, Smolik Ella, Biton Yaacov","doi":"10.1111/bdi.70057","DOIUrl":"10.1111/bdi.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Bipolar and ADHD are two diseases that exhibit similar traits but at different levels of severity. Understanding this behavior can help treatment of these disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We hypothesize that there is a common partial genetic cause for both attention-deficit/hyperactivity disorder (ADHD) and bipolar disorders (BD), which is the reversal function of the dopamine neurotransporter DAT gate (see Figure 1) into an efflux mode. We analyze the dopamine chemistry in the neuron synapse under this assumption.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The difference between ADHD and BD phenotypes is due either to the dopamine receptor (D2R) operation or to the threshold levels of the dopamine homeostatic control and the intensity of its operation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>The common cause of the two disorders could explain the frequent phenomenon of ADHD symptoms preceding BD beginning and the high comorbidity between these disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"27 6","pages":"472-475"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bdi.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Russell Franco D'Souza, Krishna Mohan Surapaneni, Mary Mathew, Shabbir Amanullah, Rajiv Tandon
Background
Bipolar disorders present complex ethical challenges to patient care due to the delicate balance between patient autonomy and safety. The use of artificial intelligence (AI), particularly ChatGPT, holds the potential to address these dilemmas by providing personalized treatment plans, monitoring patient well-being, and reducing stigma associated with mental health issues. However, the application of AI in this context requires a deep understanding of the unique needs and vulnerabilities of individuals with bipolar disorder.
Methods
This experimental study evaluated ChatGPT's (Version 3.5) responses to ethical dilemmas in bipolar disorder care using three clinical case scenarios reported in an open-access publication. The study compared ChatGPT's answers to an original answer key from the article. ChatGPT's responses were cross-checked and analyzed for alignment with the explanation given in the article.
Results
ChatGPT provided mostly congruent responses with the original answer key, demonstrating its potential to offer insights and considerations for ethical dilemmas. However, there were variations in some responses, emphasizing the complexity of ethical decision-making in healthcare. These findings underscore the importance of combining AI-generated insights with human expertise in complex medical and ethical situations.
Conclusion
ChatGPT, and similar AI systems, can be valuable resources for addressing ethical concerns in bipolar disorder care. They offer guidance and information to clinicians, patients, and stakeholders, contributing to shared decision-making in healthcare. Nonetheless, the study highlights the essential role of human judgment and expertise in navigating intricate ethical dilemmas. Continuous research and development are necessary to enhance ChatGPT's capabilities and ensure responsible use, aligning AI assistance with the highest standards of patient care and ethical conduct.
{"title":"Choices of Artificial Intelligence (AI): ChatGPT's Solutions to Ethical Dilemmas in Bipolar Disorder Care","authors":"Russell Franco D'Souza, Krishna Mohan Surapaneni, Mary Mathew, Shabbir Amanullah, Rajiv Tandon","doi":"10.1111/bdi.70059","DOIUrl":"10.1111/bdi.70059","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bipolar disorders present complex ethical challenges to patient care due to the delicate balance between patient autonomy and safety. The use of artificial intelligence (AI), particularly ChatGPT, holds the potential to address these dilemmas by providing personalized treatment plans, monitoring patient well-being, and reducing stigma associated with mental health issues. However, the application of AI in this context requires a deep understanding of the unique needs and vulnerabilities of individuals with bipolar disorder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This experimental study evaluated ChatGPT's (Version 3.5) responses to ethical dilemmas in bipolar disorder care using three clinical case scenarios reported in an open-access publication. The study compared ChatGPT's answers to an original answer key from the article. ChatGPT's responses were cross-checked and analyzed for alignment with the explanation given in the article.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ChatGPT provided mostly congruent responses with the original answer key, demonstrating its potential to offer insights and considerations for ethical dilemmas. However, there were variations in some responses, emphasizing the complexity of ethical decision-making in healthcare. These findings underscore the importance of combining AI-generated insights with human expertise in complex medical and ethical situations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ChatGPT, and similar AI systems, can be valuable resources for addressing ethical concerns in bipolar disorder care. They offer guidance and information to clinicians, patients, and stakeholders, contributing to shared decision-making in healthcare. Nonetheless, the study highlights the essential role of human judgment and expertise in navigating intricate ethical dilemmas. Continuous research and development are necessary to enhance ChatGPT's capabilities and ensure responsible use, aligning AI assistance with the highest standards of patient care and ethical conduct.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"27 7","pages":"511-518"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shiyun Wu, Zhongwan Liu, Robin Shao, Wenjin Zou, Xiaoyue Li, Weicong Lu, Jinyong Chen, Suk-Yu Yau, Kangguang Lin
Objective
Accumulative research indicates key roles of the peripheral inflammation system and hippocampal function in major mood disorders. The complement system modulates inflammatory function and is abnormal in mood disorders, but its precise neural pathway remains unclear. This study investigates the interrelations among complement component 3 (C3) levels, hippocampal function, and mood symptoms among offspring of bipolar disorder (BD) parents who carry familial risk of mood disorders.
Method
We recruited unaffected BD offspring with (symptomatic offspring, SO, N = 31) or without (asymptomatic offspring, AO, N = 39) subthreshold symptoms, and matched healthy controls (HC, N = 41). Peripheral C3 levels were measured, and resting-state fMRI was conducted to assess hippocampal functional connectivity (FC). Spectral dynamic causal modeling (spDCM) was conducted to verify the directionality of the hippocampal FC.
Results
The SO group exhibited significantly lower peripheral C3 levels (F2,108 = 23.651, p < 0.001) and reduced left hippocampus-left cerebellum FC (F2,108 = 8.541, p < 0.001) compared to both the AO and HC groups. Furthermore, the left hippocampus-left cerebellum FC partially mediated the relationship between C3 levels and depressive symptoms in the SO group (bootstrapping 95% CI = −4.1168 to −0.1569), but not in AO (bootstrapping 95% CI = −0.3479 to 0.1317) or HC (bootstrapping 95% CI = −0.3297 to 0.0885). The left hippocampus-left cerebellum FC was bidirectional in all 3 groups.
Conclusion
Our findings indicate a C3-hippocampus-depressive symptom pathway might underpin the particular high vulnerability of individuals with both familial and symptomatic risks of mood disorders. This evidence provides new neuroinflammatory markers and targets for early identification and intervention of these individuals.
目的：研究表明外周炎症系统和海马功能在重大情绪障碍中的关键作用。补体系统调节炎症功能，在情绪障碍中异常，但其确切的神经通路尚不清楚。本研究探讨了具有情绪障碍家族风险的双相情感障碍（BD）父母后代补体成分3 （C3）水平、海马功能和情绪症状之间的相互关系。方法：我们招募了未受影响的双相障碍后代（有症状的后代，SO, N = 31）或没有（无症状的后代，AO, N = 39）阈下症状，并匹配健康对照（HC, N = 41）。测量外周C3水平，静息状态fMRI评估海马功能连通性（FC）。采用频谱动态因果模型（spDCM）验证海马FC的方向性。结果：SO组外周血C3水平明显降低（f2108 = 23.651, p 2108 = 8.541, p）。结论：C3-海马-抑郁症状通路可能是具有家族性和症状性情绪障碍风险个体特别高易感性的基础。这一证据为这些个体的早期识别和干预提供了新的神经炎症标志物和靶点。
{"title":"The Role of the Complement C3-Hippocampus Pathway in Relation With Mood Symptoms in Offspring of Parents With Bipolar Disorder","authors":"Shiyun Wu, Zhongwan Liu, Robin Shao, Wenjin Zou, Xiaoyue Li, Weicong Lu, Jinyong Chen, Suk-Yu Yau, Kangguang Lin","doi":"10.1111/bdi.70056","DOIUrl":"10.1111/bdi.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Accumulative research indicates key roles of the peripheral inflammation system and hippocampal function in major mood disorders. The complement system modulates inflammatory function and is abnormal in mood disorders, but its precise neural pathway remains unclear. This study investigates the interrelations among complement component 3 (C3) levels, hippocampal function, and mood symptoms among offspring of bipolar disorder (BD) parents who carry familial risk of mood disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We recruited unaffected BD offspring with (symptomatic offspring, SO, <i>N</i> = 31) or without (asymptomatic offspring, AO, <i>N</i> = 39) subthreshold symptoms, and matched healthy controls (HC, <i>N</i> = 41). Peripheral C3 levels were measured, and resting-state fMRI was conducted to assess hippocampal functional connectivity (FC). Spectral dynamic causal modeling (spDCM) was conducted to verify the directionality of the hippocampal FC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The SO group exhibited significantly lower peripheral C3 levels (<i>F</i><sub>2,108</sub> = 23.651, <i>p</i> < 0.001) and reduced left hippocampus-left cerebellum FC (<i>F</i><sub>2,108</sub> = 8.541, <i>p</i> < 0.001) compared to both the AO and HC groups. Furthermore, the left hippocampus-left cerebellum FC partially mediated the relationship between C3 levels and depressive symptoms in the SO group (bootstrapping 95% CI = −4.1168 to −0.1569), but not in AO (bootstrapping 95% CI = −0.3479 to 0.1317) or HC (bootstrapping 95% CI = −0.3297 to 0.0885). The left hippocampus-left cerebellum FC was bidirectional in all 3 groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings indicate a C3-hippocampus-depressive symptom pathway might underpin the particular high vulnerability of individuals with both familial and symptomatic risks of mood disorders. This evidence provides new neuroinflammatory markers and targets for early identification and intervention of these individuals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"27 6","pages":"461-471"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bdi.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qian Zhao, Hongbao Cao, Ancha Baranova, Fuquan Zhang
Background
Previous studies have shown that gut microbiome dysbiosis has pathogenic significance in the development of bipolar disorder (BD), but the direct causal relationship remains unclear. We aimed to investigate this potential correlation.
Methods
Using a two-sample Mendelian randomization (TSMR) analysis, we examined the potential causal effects of gut microbiota on BD. Summary results for gut microbiota were derived from two large genome-wide association studies (GWAS) on gut microbiota: the MibioGen consortium (N = 18,340) and the Dutch Microbiome Project (N = 8208), as well as one GWAS summary result for BD (N = 413,466).
Results
Our TSMR analysis revealed that the levels of 12 taxa were associated with a reduced risk of BD. These included the phylum Bacteroidetes, its class Bacteroidia, its order Bacteroidales, its species Parabacteroides johnsonii and Paraprevotella unclassified, and genus Faecalibacterium (OR: 0.85 ~ 0.96, p ≤ 0.043). Conversely, 11 gut bacterial taxa were linked to an increased risk of BD. These comprised the class Betaproteobacteria, its order Burkholderiales, and its family Sutterellaceae (OR: 1.06 ~ 1.25, p ≤ 0.049).
Conclusions
Our study further identifies a genetic link between BD and gut microbiota. The causal effects of certain gut microbiota on BD may bring potential clinical benefits and provide a new paradigm for the prevention and treatment of BD.
{"title":"Evaluating Causal Effects of Gut Microbiome on Bipolar Disorder","authors":"Qian Zhao, Hongbao Cao, Ancha Baranova, Fuquan Zhang","doi":"10.1111/bdi.70063","DOIUrl":"10.1111/bdi.70063","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous studies have shown that gut microbiome dysbiosis has pathogenic significance in the development of bipolar disorder (BD), but the direct causal relationship remains unclear. We aimed to investigate this potential correlation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using a two-sample Mendelian randomization (TSMR) analysis, we examined the potential causal effects of gut microbiota on BD. Summary results for gut microbiota were derived from two large genome-wide association studies (GWAS) on gut microbiota: the MibioGen consortium (<i>N</i> = 18,340) and the Dutch Microbiome Project (<i>N</i> = 8208), as well as one GWAS summary result for BD (<i>N</i> = 413,466).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our TSMR analysis revealed that the levels of 12 taxa were associated with a reduced risk of BD. These included the phylum <i>Bacteroidetes</i>, its class <i>Bacteroidia</i>, its order <i>Bacteroidales</i>, its species <i>Parabacteroides johnsonii</i> and <i>Paraprevotella unclassified</i>, and genus <i>Faecalibacterium</i> (OR: 0.85 ~ 0.96, <i>p</i> ≤ 0.043). Conversely, 11 gut bacterial taxa were linked to an increased risk of BD. These comprised the class <i>Betaproteobacteria</i>, its order <i>Burkholderiales</i>, and its family <i>Sutterellaceae</i> (OR: 1.06 ~ 1.25, <i>p</i> ≤ 0.049).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study further identifies a genetic link between BD and gut microbiota. The causal effects of certain gut microbiota on BD may bring potential clinical benefits and provide a new paradigm for the prevention and treatment of BD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"27 8","pages":"551-556"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeff Zarp, Hanne Lie Kjærstad, Maria Nesje Porten, Lars Vedel Kessing, Kamilla Woznica Miskowiak
Objectives
Cognitive impairment during remission in bipolar disorder (BD) hampers functional recovery. While diverse factors can impact these impairments, sleep disturbance is considered a key component. This cross-sectional report aimed to analyze the association between subjective sleep characteristics and objective cognitive impairment in two independent samples of remitted outpatients with BD.
Methods
Baseline data, including neuropsychological test performances and questionnaire-based sleep quality, subjective cognitive complaints, and mood ratings, were pooled from two clinical trials. Eighteen- to sixty-four-year-old fully or partially remitted outpatients with BD were divided into two independent cohorts: (i) newly diagnosed patients classified as cognitively impaired (n = 40) or normal (n = 58) according to hierarchical cluster analysis and matching healthy controls (HC) (n = 80), as well as (ii) patients with longer duration of illness prescreened for cognitive impairment (n = 115) and matching HC (n = 75). Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Correlational and multiple linear regression analyses investigated associations between cognition and sleep.
Results
In age-, sex-, and medication-adjusted regression analyses, subjectively reported sleep quality (PSQI total score) was not associated with objective cognitive impairment globally or across domains in any cohort. Instead, worse subjective sleep quality was associated with more subjective cognitive complaints, greater subsyndromal depression symptoms, and receiving antipsychotic medication.
Conclusions
Our findings support the view that objective cognitive impairments in remitted patients with BD, whether newly diagnosed or with longer illness duration, may not be solely attributable to subjectively reported sleep disturbances. This adds to emerging evidence suggesting cognition as a relevant treatment target in BD.
{"title":"Disentangling Subjective Sleep and Objective Cognition: Insights From Two Independent Cross-Sectional Cohorts of Remitted Bipolar Disorder","authors":"Jeff Zarp, Hanne Lie Kjærstad, Maria Nesje Porten, Lars Vedel Kessing, Kamilla Woznica Miskowiak","doi":"10.1111/bdi.70051","DOIUrl":"10.1111/bdi.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Cognitive impairment during remission in bipolar disorder (BD) hampers functional recovery. While diverse factors can impact these impairments, sleep disturbance is considered a key component. This cross-sectional report aimed to analyze the association between subjective sleep characteristics and objective cognitive impairment in two independent samples of remitted outpatients with BD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Baseline data, including neuropsychological test performances and questionnaire-based sleep quality, subjective cognitive complaints, and mood ratings, were pooled from two clinical trials. Eighteen- to sixty-four-year-old fully or partially remitted outpatients with BD were divided into two independent cohorts: (i) newly diagnosed patients classified as cognitively impaired (<i>n</i> = 40) or normal (<i>n</i> = 58) according to hierarchical cluster analysis and matching healthy controls (HC) (<i>n</i> = 80), as well as (ii) patients with longer duration of illness prescreened for cognitive impairment (<i>n</i> = 115) and matching HC (<i>n</i> = 75). Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Correlational and multiple linear regression analyses investigated associations between cognition and sleep.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In age-, sex-, and medication-adjusted regression analyses, subjectively reported sleep quality (PSQI total score) was not associated with objective cognitive impairment globally or across domains in any cohort. Instead, worse subjective sleep quality was associated with more subjective cognitive complaints, greater subsyndromal depression symptoms, and receiving antipsychotic medication.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings support the view that objective cognitive impairments in remitted patients with BD, whether newly diagnosed or with longer illness duration, may not be solely attributable to subjectively reported sleep disturbances. This adds to emerging evidence suggesting cognition as a relevant treatment target in BD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"27 6","pages":"435-448"},"PeriodicalIF":4.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Ulrichsen, Esther Mühlbauer, Lisa-Marie Hartnagel, Emanuel Severus, Anthony Cleare, Sameer Jauhar, Michael Bauer, Ulrich Ebner-Priemer
Background
Bipolar disorder (BD) is a recurrent disorder, characterised by episodes of (hypo)mania, depression and euthymia with variation in mood, cognition and sleep. Many patients identify changes in sleep before an episode; using daily sleep logs could help identify these changes. Such early warning signs can be a valuable tool for patients and clinicians alike in predicting and preparing for changes in mood.
Methods
In the BipoSense study, we followed patients with BD, who were in remission at the start of the study, daily for 1 year. Patients reported for each hour if they were awake or asleep through an app and received fortnightly clinical assessments of bipolar symptoms. We used statistical analyses applying person-centred data in multilevel logit models to investigate if sleep patterns could differentiate between the period before an episode (prodromal stage) and euthymia, looking at both mean changes and variability of sleep. Bonferroni-Holm corrections were applied to avoid inflation of type I errors from multiple testing.
Results
Twenty-nine participants were included (mean age 44.0 years [SD = 11.9], female 55% and BD-I 59%). Waking up later was associated with prodromal depression and was the only significant finding for prodromal mood episodes. Greater variability of sleep duration, total time spent in bed and time waking up were associated with prodromal depression; less variability of time falling asleep and time waking up were linked with prodromal (hypo)mania.
Conclusion
Using self-assessed sleep changes and especially variability can be potential tools in helping patients identify early warning signs of mood recurrence; however, these analyses were explorative and further investigations are warranted.
{"title":"Can Sleep Parameters Predict Upcoming Mood Episodes in Bipolar Disorder?","authors":"Andrea Ulrichsen, Esther Mühlbauer, Lisa-Marie Hartnagel, Emanuel Severus, Anthony Cleare, Sameer Jauhar, Michael Bauer, Ulrich Ebner-Priemer","doi":"10.1111/bdi.70054","DOIUrl":"10.1111/bdi.70054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bipolar disorder (BD) is a recurrent disorder, characterised by episodes of (hypo)mania, depression and euthymia with variation in mood, cognition and sleep. Many patients identify changes in sleep before an episode; using daily sleep logs could help identify these changes. Such early warning signs can be a valuable tool for patients and clinicians alike in predicting and preparing for changes in mood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the BipoSense study, we followed patients with BD, who were in remission at the start of the study, daily for 1 year. Patients reported for each hour if they were awake or asleep through an app and received fortnightly clinical assessments of bipolar symptoms. We used statistical analyses applying person-centred data in multilevel logit models to investigate if sleep patterns could differentiate between the period before an episode (prodromal stage) and euthymia, looking at both mean changes and variability of sleep. Bonferroni-Holm corrections were applied to avoid inflation of type I errors from multiple testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-nine participants were included (mean age 44.0 years [SD = 11.9], female 55% and BD-I 59%). Waking up later was associated with prodromal depression and was the only significant finding for prodromal mood episodes. Greater variability of sleep duration, total time spent in bed and time waking up were associated with prodromal depression; less variability of time falling asleep and time waking up were linked with prodromal (hypo)mania.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Using self-assessed sleep changes and especially variability can be potential tools in helping patients identify early warning signs of mood recurrence; however, these analyses were explorative and further investigations are warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"27 6","pages":"449-460"},"PeriodicalIF":4.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bdi.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144941470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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