Pub Date : 2024-08-30DOI: 10.1186/s40345-024-00348-5
Julia Fraiha-Pegado, Vanessa J Rodrigues de Paula, Tariq Alotaibi, Orestes Forlenza, Tomas Hajek
Background: Since its debut in 1949, lithium (Li) has been regarded as a gold standard therapy for mood stabilization. Neuroprotective effects of Li have been replicated across many different paradigms ranging from tissue cultures to human studies. This has generated interest in potentially repurposing this drug. However, the optimal dosage required for neuroprotective effects remains unclear and may be different than the doses needed for treatment of bipolar disorders. Recent studies on trace-Li levels in the water suggest that Li, could slow cognitive decline and prevent dementia with long-term use even at very low doses. The current review aims to synthesize the data on the topic and challenge the conventional high-dose paradigm.
Results: We systematically reviewed five available studies, which reported associations between trace-Li in water and incidence or mortality from dementia. Association between trace-Li levels and a lower risk or mortality from dementia were observed at concentrations of Li in drinking water as low as 0.002 mg/L and 0.056 mg/L. Meanwhile, levels below 0.002 mg/L did not elicit this effect. Although three of the five studies found dementia protective properties of Li in both sexes, a single study including lower Li levels (0.002 mg/l) found such association only in women. CONCLUSION: The reviewed evidence shows that trace-Li levels in the water are sufficient to lower the incidence or mortality from dementia. Considering the lack of options for the prevention or treatment of dementia, we should not ignore these findings. Future trials of Li should focus on long term use of low or even micro doses of Li in the prevention or treatment of dementia.
{"title":"Trace lithium levels in drinking water and risk of dementia: a systematic review.","authors":"Julia Fraiha-Pegado, Vanessa J Rodrigues de Paula, Tariq Alotaibi, Orestes Forlenza, Tomas Hajek","doi":"10.1186/s40345-024-00348-5","DOIUrl":"https://doi.org/10.1186/s40345-024-00348-5","url":null,"abstract":"<p><strong>Background: </strong>Since its debut in 1949, lithium (Li) has been regarded as a gold standard therapy for mood stabilization. Neuroprotective effects of Li have been replicated across many different paradigms ranging from tissue cultures to human studies. This has generated interest in potentially repurposing this drug. However, the optimal dosage required for neuroprotective effects remains unclear and may be different than the doses needed for treatment of bipolar disorders. Recent studies on trace-Li levels in the water suggest that Li, could slow cognitive decline and prevent dementia with long-term use even at very low doses. The current review aims to synthesize the data on the topic and challenge the conventional high-dose paradigm.</p><p><strong>Results: </strong>We systematically reviewed five available studies, which reported associations between trace-Li in water and incidence or mortality from dementia. Association between trace-Li levels and a lower risk or mortality from dementia were observed at concentrations of Li in drinking water as low as 0.002 mg/L and 0.056 mg/L. Meanwhile, levels below 0.002 mg/L did not elicit this effect. Although three of the five studies found dementia protective properties of Li in both sexes, a single study including lower Li levels (0.002 mg/l) found such association only in women. CONCLUSION: The reviewed evidence shows that trace-Li levels in the water are sufficient to lower the incidence or mortality from dementia. Considering the lack of options for the prevention or treatment of dementia, we should not ignore these findings. Future trials of Li should focus on long term use of low or even micro doses of Li in the prevention or treatment of dementia.</p>","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107099","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}
Pub Date : 2024-08-23DOI: 10.1186/s40345-024-00353-8
Paul Rensch, Teodor T Postolache, Nina Dalkner, Tatjana Stross, Niel Constantine, Aline Dagdag, Abhishek Wadhawan, Farooq Mohyuddin, Christopher A Lowry, Joshua Joseph, Armin Birner, Frederike T Fellendorf, Alexander Finner, Melanie Lenger, Alexander Maget, Annamaria Painold, Robert Queissner, Franziska Schmiedhofer, Stefan Smolle, Adelina Tmava-Berisha, Eva Z Reininghaus
Background: Alongside affective episodes, cognitive dysfunction is a core symptom of bipolar disorder. The intracellular parasite T. gondii has been positively associated with both, the diagnosis of bipolar disorder and poorer cognitive performance, across diagnostic boundaries. This study aims to investigate the association between T. gondii seropositivity, serointensity, and cognitive function in an euthymic sample of bipolar disorder.
Methods: A total of 76 participants with bipolar disorder in remission were tested for T. gondii-specific IgG and IgM antibodies and for cognitive performance using neuropsychological test battery. Cognitive parameters were categorized into three cognitive domains (attention and processing speed, verbal memory, and executive function). Statistical analysis of associations between continuous indicators of cognitive function as dependent variables in relationship to T. gondii, included multivariate analyses of co-variance for seropositivity, and partial correlations with IgG serointensity in IgG seropositives. All analyses were controlled for age and premorbid IQ.
Results: In seropositives (n = 27), verbal memory showed significant inverse partial correlations with IgG antibody levels (short delay free recall (r=-0.539, p = 0.005), long delay free recall (r=-0.423, p = 0.035), and immediate recall sum trial 1-5 (r=-0.399, p = 0.048)). Cognitive function did not differ between IgG seropositive and seronegative individuals in any of the cognitive domains (F (3,70) = 0.327, p = 0.806, n = 76). IgM positives (n = 7) were too few to be analyzed.
Conclusions: This investigation is the first to show an association between T. gondii IgG serointensity and memory function in a well-diagnosed bipolar disorder sample. It adds to the existing literature on associations between latent T. gondii infection and cognition in bipolar disorder, while further research is needed to confirm and expand our findings, eliminate potential sources of bias, and establish cause-effect relationships.
{"title":"Toxoplasma gondii IgG serointensity and cognitive function in bipolar disorder.","authors":"Paul Rensch, Teodor T Postolache, Nina Dalkner, Tatjana Stross, Niel Constantine, Aline Dagdag, Abhishek Wadhawan, Farooq Mohyuddin, Christopher A Lowry, Joshua Joseph, Armin Birner, Frederike T Fellendorf, Alexander Finner, Melanie Lenger, Alexander Maget, Annamaria Painold, Robert Queissner, Franziska Schmiedhofer, Stefan Smolle, Adelina Tmava-Berisha, Eva Z Reininghaus","doi":"10.1186/s40345-024-00353-8","DOIUrl":"10.1186/s40345-024-00353-8","url":null,"abstract":"<p><strong>Background: </strong>Alongside affective episodes, cognitive dysfunction is a core symptom of bipolar disorder. The intracellular parasite T. gondii has been positively associated with both, the diagnosis of bipolar disorder and poorer cognitive performance, across diagnostic boundaries. This study aims to investigate the association between T. gondii seropositivity, serointensity, and cognitive function in an euthymic sample of bipolar disorder.</p><p><strong>Methods: </strong>A total of 76 participants with bipolar disorder in remission were tested for T. gondii-specific IgG and IgM antibodies and for cognitive performance using neuropsychological test battery. Cognitive parameters were categorized into three cognitive domains (attention and processing speed, verbal memory, and executive function). Statistical analysis of associations between continuous indicators of cognitive function as dependent variables in relationship to T. gondii, included multivariate analyses of co-variance for seropositivity, and partial correlations with IgG serointensity in IgG seropositives. All analyses were controlled for age and premorbid IQ.</p><p><strong>Results: </strong>In seropositives (n = 27), verbal memory showed significant inverse partial correlations with IgG antibody levels (short delay free recall (r=-0.539, p = 0.005), long delay free recall (r=-0.423, p = 0.035), and immediate recall sum trial 1-5 (r=-0.399, p = 0.048)). Cognitive function did not differ between IgG seropositive and seronegative individuals in any of the cognitive domains (F (3,70) = 0.327, p = 0.806, n = 76). IgM positives (n = 7) were too few to be analyzed.</p><p><strong>Conclusions: </strong>This investigation is the first to show an association between T. gondii IgG serointensity and memory function in a well-diagnosed bipolar disorder sample. It adds to the existing literature on associations between latent T. gondii infection and cognition in bipolar disorder, while further research is needed to confirm and expand our findings, eliminate potential sources of bias, and establish cause-effect relationships.</p>","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046636","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}
Pub Date : 2024-08-20DOI: 10.1186/s40345-024-00352-9
Ali-Reza Ghazi-Noori, Rachel D Woodham, Hakimeh Rezaei, Mhd Saeed Sharif, Elvira Bramon, Philipp Ritter, Michael Bauer, Allan H Young, Cynthia H Y Fu
Background: Current treatments for bipolar depression have limited effectiveness, tolerability and acceptability. Transcranial direct current stimulation (tDCS) is a novel non-invasive brain stimulation method that has demonstrated treatment efficacy for major depressive episodes. tDCS is portable, safe, and individuals like having sessions at home. We developed a home-based protocol with real-time remote supervision. In the present study, we have examined the clinical outcomes, acceptability and feasibility of home-based tDCS treatment in bipolar depression.
Results: Participants were 44 individuals with bipolar disorder (31 women), mean age 47.27 ± 12.89 years, in current depressive episode of at least moderate severity (mean Montgomery Asberg Depression Rating Scale (MADRS) score 24.59 ± 2.64). tDCS was provided in bilateral frontal montage, F3 anode, F4 cathode, 2 mA, for 30 min, in a 6-week trial, for total 21 sessions, a follow up visit was conducted 5 months from baseline. Participants maintained their current treatment (psychotherapy, antidepressant or mood stabilising medication) or maintained being medication-free. A research team member was present by video conference at each session. 93.2% participants (n = 41) completed the 6-week treatment and 72.7% of participants (n = 32) completed the 5 month follow up. There was a significant improvement in depressive symptoms following treatment (mean MADRS 8.77 ± 5.37) which was maintained at the 5 month follow up (mean MADRS 10.86 ± 6.90), rate of clinical response was 77.3% (MADRS improvement of 50% or greater from baseline), and rate of clinical remission was 47.7% (MADRS rating of 9 or less). Acceptability was endorsed as "very acceptable" or "quite acceptable" by all participants. No participants developed mania or hypomania.
Conclusions: In summary, home-based tDCS with real-time supervision was associated with significant clinical improvements and high acceptability in bipolar depression. Due to the open-label design, efficacy findings are preliminary.
Trial registration: ClinicalTrials.gov number NCT05436613 registered on 23 June 2022 https//www.
{"title":"Home-based transcranial direct current stimulation in bipolar depression: an open-label treatment study of clinical outcomes, acceptability and adverse events.","authors":"Ali-Reza Ghazi-Noori, Rachel D Woodham, Hakimeh Rezaei, Mhd Saeed Sharif, Elvira Bramon, Philipp Ritter, Michael Bauer, Allan H Young, Cynthia H Y Fu","doi":"10.1186/s40345-024-00352-9","DOIUrl":"10.1186/s40345-024-00352-9","url":null,"abstract":"<p><strong>Background: </strong>Current treatments for bipolar depression have limited effectiveness, tolerability and acceptability. Transcranial direct current stimulation (tDCS) is a novel non-invasive brain stimulation method that has demonstrated treatment efficacy for major depressive episodes. tDCS is portable, safe, and individuals like having sessions at home. We developed a home-based protocol with real-time remote supervision. In the present study, we have examined the clinical outcomes, acceptability and feasibility of home-based tDCS treatment in bipolar depression.</p><p><strong>Results: </strong>Participants were 44 individuals with bipolar disorder (31 women), mean age 47.27 ± 12.89 years, in current depressive episode of at least moderate severity (mean Montgomery Asberg Depression Rating Scale (MADRS) score 24.59 ± 2.64). tDCS was provided in bilateral frontal montage, F3 anode, F4 cathode, 2 mA, for 30 min, in a 6-week trial, for total 21 sessions, a follow up visit was conducted 5 months from baseline. Participants maintained their current treatment (psychotherapy, antidepressant or mood stabilising medication) or maintained being medication-free. A research team member was present by video conference at each session. 93.2% participants (n = 41) completed the 6-week treatment and 72.7% of participants (n = 32) completed the 5 month follow up. There was a significant improvement in depressive symptoms following treatment (mean MADRS 8.77 ± 5.37) which was maintained at the 5 month follow up (mean MADRS 10.86 ± 6.90), rate of clinical response was 77.3% (MADRS improvement of 50% or greater from baseline), and rate of clinical remission was 47.7% (MADRS rating of 9 or less). Acceptability was endorsed as \"very acceptable\" or \"quite acceptable\" by all participants. No participants developed mania or hypomania.</p><p><strong>Conclusions: </strong>In summary, home-based tDCS with real-time supervision was associated with significant clinical improvements and high acceptability in bipolar depression. Due to the open-label design, efficacy findings are preliminary.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov number NCT05436613 registered on 23 June 2022 https//www.</p><p><strong>Clinicaltrials: </strong>gov/study/NCT05436613.</p>","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004131","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}
Pub Date : 2024-08-07DOI: 10.1186/s40345-024-00351-w
Frances N Adiukwu, Anastasia K Yocum, Brittany M Wright, Ian Gesler, Melvin G McInnis
Background: There have been case reports of renal dysfunction with lithium toxicity among severely ill COVID-19 patients. Lithium levels may be affected by comorbid conditions and the presence of infective disease states like the SARS-CoV-2 which clearly adds systemic health burden. This study aimed to review the effect SARS-CoV-2 has on serum Li levels and the possible mechanism underlying it.
Methods: Retrospective data from all clinical service encounters within the University of Michigan health system between September 2019 and September 2023 were reviewed. The study cohort included 98 patients with an average age of 45 years (62% female) who were diagnosed with any subtype of bipolar disorder, actively taking Li, and infected with SARS-CoV-2 during the study timeframe.
Results: There was no overarching effect of a SARS-CoV-2 infection on Li chemistry in the overall sample. Higher serum Li levels were not significantly associated with SARS-CoV-2 infection nor total comorbidity index. However, higher Li levels were observed in males while infected with SARS-CoV-2 when compared with no infection. eGFR remained unassociated with serum Li level. Receiving COVID vaccination was associated with lower serum Li levels (Coeff. = - 0.88, p = 0.048).
Conclusions: Patients with a diagnosis of BD, treated with Li, and infected with SARS-CoV-2 were not likely to present with elevated Li levels unless they are male or unvaccinated. Elevated serum Li level was not associated with significant renal dysfunction in this cohort. The case reports of severe renal complications and Li toxicity may be among cases of greater overall clinical severity of COVID-19. These findings are reassuring that Li may be used in the context of a COVID-19 illness but emphasize the ongoing need for clinical vigilance.
背景:在 COVID-19 重症患者中,有肾功能障碍伴锂中毒的病例报告。锂水平可能会受到合并症和感染性疾病(如 SARS-CoV-2)的影响,这显然会增加全身健康负担。本研究旨在探讨 SARS-CoV-2 对血清锂水平的影响及其可能的机制:研究回顾了密歇根大学卫生系统在 2019 年 9 月至 2023 年 9 月期间所有临床服务的数据。研究队列包括98名患者,平均年龄45岁(62%为女性),这些患者被诊断为任何亚型的双相情感障碍,正在服用Li,并在研究期间感染了SARS-CoV-2:在所有样本中,SARS-CoV-2 感染对锂化学成分没有总体影响。血清中较高的 Li 含量与 SARS-CoV-2 感染或总合并症指数无明显关系。然而,与未感染相比,男性在感染 SARS-CoV-2 时血清锂含量更高。接种 COVID 疫苗与较低的血清 Li 水平相关(Coeff:结论:除非是男性或未接种疫苗的患者,否则诊断为 BD、接受过 Li 治疗并感染了 SARS-CoV-2 的患者不太可能出现 Li 水平升高的情况。在这组患者中,血清Li水平升高与严重的肾功能障碍无关。严重肾脏并发症和Li毒性的病例报告可能是COVID-19总体临床严重程度较高的病例之一。这些发现令人欣慰的是,在 COVID-19 病例中可以使用 Li,但强调临床上仍需保持警惕。
{"title":"Lithium in the time of COVID: forever vigilant.","authors":"Frances N Adiukwu, Anastasia K Yocum, Brittany M Wright, Ian Gesler, Melvin G McInnis","doi":"10.1186/s40345-024-00351-w","DOIUrl":"10.1186/s40345-024-00351-w","url":null,"abstract":"<p><strong>Background: </strong>There have been case reports of renal dysfunction with lithium toxicity among severely ill COVID-19 patients. Lithium levels may be affected by comorbid conditions and the presence of infective disease states like the SARS-CoV-2 which clearly adds systemic health burden. This study aimed to review the effect SARS-CoV-2 has on serum Li levels and the possible mechanism underlying it.</p><p><strong>Methods: </strong>Retrospective data from all clinical service encounters within the University of Michigan health system between September 2019 and September 2023 were reviewed. The study cohort included 98 patients with an average age of 45 years (62% female) who were diagnosed with any subtype of bipolar disorder, actively taking Li, and infected with SARS-CoV-2 during the study timeframe.</p><p><strong>Results: </strong>There was no overarching effect of a SARS-CoV-2 infection on Li chemistry in the overall sample. Higher serum Li levels were not significantly associated with SARS-CoV-2 infection nor total comorbidity index. However, higher Li levels were observed in males while infected with SARS-CoV-2 when compared with no infection. eGFR remained unassociated with serum Li level. Receiving COVID vaccination was associated with lower serum Li levels (Coeff. = - 0.88, p = 0.048).</p><p><strong>Conclusions: </strong>Patients with a diagnosis of BD, treated with Li, and infected with SARS-CoV-2 were not likely to present with elevated Li levels unless they are male or unvaccinated. Elevated serum Li level was not associated with significant renal dysfunction in this cohort. The case reports of severe renal complications and Li toxicity may be among cases of greater overall clinical severity of COVID-19. These findings are reassuring that Li may be used in the context of a COVID-19 illness but emphasize the ongoing need for clinical vigilance.</p>","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901702","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}
Pub Date : 2024-08-07DOI: 10.1186/s40345-024-00350-x
Miriam Gerstenberg, Lukasz Smigielski, Anna M Werling, Maria E Dimitriades, Christoph U Correll, Susanne Walitza, Jules Angst
Background: The 33-item Hypomania Checklist (HCL-33) has been shown to distinguish between adolescent bipolar disorder (BD) and unipolar depression. To investigate the utility of the HCL-33 as a screening tool in routine diagnostics, the frequency and psychopathological characteristics of detected individuals in a mixed psychiatric sample necessitate more examination.
Methods: The HCL-33, Children's Depression Inventory, Beck's Anxiety Inventory, and Strengths and Difficulties Questionnaire were completed by 285 children and adolescents (12-18 years) in a mixed psychiatric sample. Applying the proposed HCL-33 cut-off score of ≥ 18, individuals with depressive symptoms were divided into at-risk or not at-risk for BD groups. The factorial structure, sum and factor score correlations with psychopathology, and impact on daily functioning were assessed.
Results: 20.6% of the sample met at-risk criteria for BD. These individuals (n = 55) were older, more anxious, and showed more conduct problems vs the not at-risk group (n = 107). A two- and a three-factor model were pursued with the same Factor 1 ("active-elated"). Factor 2 ("risk-taking/irritable") was separated into 2a ("irritable-erratic") and 2b ("outgoing-disinhibited") in the three-factor model. Whereas higher Factor 2 and 2a scores correlated with a broad range of more severe symptomatology (i.e., depression, anxiety, hyperactivity), higher Factor 1 and 2b scores correlated with more emotional and conduct problems, respectively. 51.7% of the sample reported a negative impact from hypomanic symptoms on daily functioning.
Limitations: Cross-sectional design and data collection in a single mental health service.
Conclusions: The HCL-33 may be a useful tool to improve diagnostics, especially in adolescents with depressive symptoms additionally presenting with anxious symptoms and conduct problems.
{"title":"Hypomania-Checklist-33: risk stratification and factor structure in a mixed psychiatric adolescent sample.","authors":"Miriam Gerstenberg, Lukasz Smigielski, Anna M Werling, Maria E Dimitriades, Christoph U Correll, Susanne Walitza, Jules Angst","doi":"10.1186/s40345-024-00350-x","DOIUrl":"10.1186/s40345-024-00350-x","url":null,"abstract":"<p><strong>Background: </strong>The 33-item Hypomania Checklist (HCL-33) has been shown to distinguish between adolescent bipolar disorder (BD) and unipolar depression. To investigate the utility of the HCL-33 as a screening tool in routine diagnostics, the frequency and psychopathological characteristics of detected individuals in a mixed psychiatric sample necessitate more examination.</p><p><strong>Methods: </strong>The HCL-33, Children's Depression Inventory, Beck's Anxiety Inventory, and Strengths and Difficulties Questionnaire were completed by 285 children and adolescents (12-18 years) in a mixed psychiatric sample. Applying the proposed HCL-33 cut-off score of ≥ 18, individuals with depressive symptoms were divided into at-risk or not at-risk for BD groups. The factorial structure, sum and factor score correlations with psychopathology, and impact on daily functioning were assessed.</p><p><strong>Results: </strong>20.6% of the sample met at-risk criteria for BD. These individuals (n = 55) were older, more anxious, and showed more conduct problems vs the not at-risk group (n = 107). A two- and a three-factor model were pursued with the same Factor 1 (\"active-elated\"). Factor 2 (\"risk-taking/irritable\") was separated into 2a (\"irritable-erratic\") and 2b (\"outgoing-disinhibited\") in the three-factor model. Whereas higher Factor 2 and 2a scores correlated with a broad range of more severe symptomatology (i.e., depression, anxiety, hyperactivity), higher Factor 1 and 2b scores correlated with more emotional and conduct problems, respectively. 51.7% of the sample reported a negative impact from hypomanic symptoms on daily functioning.</p><p><strong>Limitations: </strong>Cross-sectional design and data collection in a single mental health service.</p><p><strong>Conclusions: </strong>The HCL-33 may be a useful tool to improve diagnostics, especially in adolescents with depressive symptoms additionally presenting with anxious symptoms and conduct problems.</p>","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901701","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}
Pub Date : 2024-07-27DOI: 10.1186/s40345-024-00349-4
Florencia Trespalacios, Ariel Boyle, Lisa Serravalle, Sheilagh Hodgins, Mark A. Ellenbogen
The offspring of parents with bipolar disorder (OBD) are at higher risk of developing psychopathology than the offspring of parents with no affective disorder (control). In addition to genetic predisposition, childhood adversity and a stressful family environment are important risk factors for the OBD. Protective factors in parents, such as social support and coping strategies, may buffer the effects of stress on at-risk children. This study tested whether parents’ social support and coping style attenuated the link between risk status (OBD vs. control) and psychopathology in offspring. During offspring’s middle childhood, parents underwent a diagnostic interview and completed social support and coping style questionnaires. Sixty-nine OBD (39 female) and 69 control (29 female) offspring between ages 13 and 29 completed a diagnostic interview approximately 10 years later. Parents’ social support satisfaction moderated the link between offspring risk status and their development of substance use disorder (SUD) symptoms (F(1,131) = 5.90, p = .017). Parents’ social network size moderated the link between offspring risk status and their development of anxiety and depression symptoms in an unexpected direction (F(1,131) = 5.07, p = .026). No effects of parents’ coping style were found. Among the OBD, having parents with greater social support satisfaction and, unexpectedly, a smaller social network buffered their development of SUD and depression and anxiety symptoms by early adulthood. Parents’ social support may thus have a protective function for children in these high-risk families.
父母患有双相情感障碍(OBD)的后代比父母没有情感障碍(对照组)的后代患精神病理学的风险更高。除了遗传易感性之外,童年时期的逆境和紧张的家庭环境也是躁郁症的重要风险因素。父母的保护性因素,如社会支持和应对策略,可以缓冲压力对高危儿童的影响。本研究测试了父母的社会支持和应对方式是否会减轻风险状况(OBD 与对照组)与后代心理病理学之间的联系。在后代的童年中期,父母接受了诊断性访谈,并填写了社会支持和应对方式问卷。年龄在 13 岁至 29 岁之间的 69 名 OBD 患者(39 名女性)和 69 名对照组患者(29 名女性)的后代在大约 10 年后完成了诊断性访谈。父母的社会支持满意度调节了后代的风险状况与其药物使用障碍(SUD)症状发展之间的联系(F(1,131) = 5.90, p = .017)。父母的社会网络规模以意想不到的方向调节了后代的风险状况与其焦虑和抑郁症状发展之间的联系(F(1,131) = 5.07, p = .026)。没有发现父母应对方式的影响。在 OBD 患者中,如果父母的社会支持满意度较高,而社会网络较小,那么到成年早期,他们的 SUD 以及抑郁和焦虑症状的发展就会得到缓冲,这一点出乎意料。因此,父母的社会支持可能对这些高危家庭的儿童具有保护作用。
{"title":"The perceived social support of parents having bipolar disorder impacts their children’s mental health: a 10-year longitudinal study","authors":"Florencia Trespalacios, Ariel Boyle, Lisa Serravalle, Sheilagh Hodgins, Mark A. Ellenbogen","doi":"10.1186/s40345-024-00349-4","DOIUrl":"https://doi.org/10.1186/s40345-024-00349-4","url":null,"abstract":"The offspring of parents with bipolar disorder (OBD) are at higher risk of developing psychopathology than the offspring of parents with no affective disorder (control). In addition to genetic predisposition, childhood adversity and a stressful family environment are important risk factors for the OBD. Protective factors in parents, such as social support and coping strategies, may buffer the effects of stress on at-risk children. This study tested whether parents’ social support and coping style attenuated the link between risk status (OBD vs. control) and psychopathology in offspring. During offspring’s middle childhood, parents underwent a diagnostic interview and completed social support and coping style questionnaires. Sixty-nine OBD (39 female) and 69 control (29 female) offspring between ages 13 and 29 completed a diagnostic interview approximately 10 years later. Parents’ social support satisfaction moderated the link between offspring risk status and their development of substance use disorder (SUD) symptoms (F(1,131) = 5.90, p = .017). Parents’ social network size moderated the link between offspring risk status and their development of anxiety and depression symptoms in an unexpected direction (F(1,131) = 5.07, p = .026). No effects of parents’ coping style were found. Among the OBD, having parents with greater social support satisfaction and, unexpectedly, a smaller social network buffered their development of SUD and depression and anxiety symptoms by early adulthood. Parents’ social support may thus have a protective function for children in these high-risk families.","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783545","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}
Pub Date : 2024-07-25DOI: 10.1186/s40345-024-00343-w
Xabier Pérez de Mendiola, Diego Hidalgo-Mazzei, Eduard Vieta, Ana González-Pinto
{"title":"Correction: Overview of lithium's use: a nationwide survey.","authors":"Xabier Pérez de Mendiola, Diego Hidalgo-Mazzei, Eduard Vieta, Ana González-Pinto","doi":"10.1186/s40345-024-00343-w","DOIUrl":"10.1186/s40345-024-00343-w","url":null,"abstract":"","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758506","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}
Pub Date : 2024-07-11DOI: 10.1186/s40345-024-00347-6
Delfina Janiri, Alessio Simonetti, Mario Luciano, Silvia Montanari, Evelina Bernardi, Giuseppe Carrà, Andrea Fiorillo, Gabriele Sani
{"title":"Correction: Type of cycle, temperament and childhood trauma are associated with lithium response in patients with bipolar disorders.","authors":"Delfina Janiri, Alessio Simonetti, Mario Luciano, Silvia Montanari, Evelina Bernardi, Giuseppe Carrà, Andrea Fiorillo, Gabriele Sani","doi":"10.1186/s40345-024-00347-6","DOIUrl":"10.1186/s40345-024-00347-6","url":null,"abstract":"","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11239618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590263","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}
Background: PER3 is a circadian gene that contains a variable number of tandem repeats (VNTR) which codifies for three genotypes: 4/4; 4/5; and 5/5 and is involved in non-visual response to light, a critical process associated with bipolar disorder onset. Benedetti et al. (Neurosci Lett 445(2):184-7) related this VNTR with bipolar disorder age of onset and linked genotype 5/5 with an earlier onset. In this study, we aimed to investigate these associations of PER3 VNTR genotypes with age of onset in a homogenous sample of German patients with bipolar I disorder through Kaplan-Meier curves.
Methods: 45 patients were enrolled and divided into three groups according to PER3 VNTR genotypes. Recognizing common biological features, we built a combined group of -5 allele carriers (4/5 + 5/5). As a primary outcome, Kaplan-Meier analysis was conducted to delineate the three genotypes' influence on age of onset. The secondary Kaplan-Meier analysis aimed to evaluate the relation between the 4/4 homozygotes group and the combined group (4/5 + 5/5) with age of onset. Finally, we proceeded to compare groups through a Log Rank Test and performed an analysis of covariance (ANCOVA).
Results: The Kaplan-Meier analysis with three separate genotypes didn't replicate the findings of Benedetti's study. The analysis comparing genotype 4/4 with the combined group showed the influence of PER3 VNTR variants on the age of onset and relates genotype 4/4 to an earlier onset. ANCOVA between the combined and the 4/4 genotype groups, correlated genotype 4/4 with an increased number of depressive episodes.
Conclusion: This study showed no significant effect of PER3 VNTR genotypes on the age of onset and in linking genotype 5/5 with an earlier onset age. Contrasting results may arise from intrinsic differences between the two studies but also shed light on hypothetically different levels of functioning of PER3 VNTR genotypes in the context of bipolar pathology. Further studies will require bigger and more homogeneous clinical samples.
{"title":"The influence of PER3 VNTR genotypes on the age of onset in a group of bipolar I disorder patients: an exploratory study.","authors":"Tommaso Barlattani, Bettina Soltmann, Chiara D'Amelio, Valentina Socci, Francesca Pacitti, Maurizio Pompili, Philipp Ritter","doi":"10.1186/s40345-024-00346-7","DOIUrl":"10.1186/s40345-024-00346-7","url":null,"abstract":"<p><strong>Background: </strong>PER3 is a circadian gene that contains a variable number of tandem repeats (VNTR) which codifies for three genotypes: 4/4; 4/5; and 5/5 and is involved in non-visual response to light, a critical process associated with bipolar disorder onset. Benedetti et al. (Neurosci Lett 445(2):184-7) related this VNTR with bipolar disorder age of onset and linked genotype 5/5 with an earlier onset. In this study, we aimed to investigate these associations of PER3 VNTR genotypes with age of onset in a homogenous sample of German patients with bipolar I disorder through Kaplan-Meier curves.</p><p><strong>Methods: </strong>45 patients were enrolled and divided into three groups according to PER3 VNTR genotypes. Recognizing common biological features, we built a combined group of -5 allele carriers (4/5 + 5/5). As a primary outcome, Kaplan-Meier analysis was conducted to delineate the three genotypes' influence on age of onset. The secondary Kaplan-Meier analysis aimed to evaluate the relation between the 4/4 homozygotes group and the combined group (4/5 + 5/5) with age of onset. Finally, we proceeded to compare groups through a Log Rank Test and performed an analysis of covariance (ANCOVA).</p><p><strong>Results: </strong>The Kaplan-Meier analysis with three separate genotypes didn't replicate the findings of Benedetti's study. The analysis comparing genotype 4/4 with the combined group showed the influence of PER3 VNTR variants on the age of onset and relates genotype 4/4 to an earlier onset. ANCOVA between the combined and the 4/4 genotype groups, correlated genotype 4/4 with an increased number of depressive episodes.</p><p><strong>Conclusion: </strong>This study showed no significant effect of PER3 VNTR genotypes on the age of onset and in linking genotype 5/5 with an earlier onset age. Contrasting results may arise from intrinsic differences between the two studies but also shed light on hypothetically different levels of functioning of PER3 VNTR genotypes in the context of bipolar pathology. Further studies will require bigger and more homogeneous clinical samples.</p>","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11239620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590293","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}
Pub Date : 2024-06-24DOI: 10.1186/s40345-024-00345-8
Mirko Manchia, Pasquale Paribello, Martina Pinna, Luca Steardo, Bernardo Carpiniello, Federica Pinna, Claudia Pisanu, Alessio Squassina, Tomas Hajek
Background: Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium's clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations.
Content: This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors' preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections.
Conclusions: Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.
{"title":"Lithium and its effects: does dose matter?","authors":"Mirko Manchia, Pasquale Paribello, Martina Pinna, Luca Steardo, Bernardo Carpiniello, Federica Pinna, Claudia Pisanu, Alessio Squassina, Tomas Hajek","doi":"10.1186/s40345-024-00345-8","DOIUrl":"10.1186/s40345-024-00345-8","url":null,"abstract":"<p><strong>Background: </strong>Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium's clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations.</p><p><strong>Content: </strong>This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors' preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections.</p><p><strong>Conclusions: </strong>Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.</p>","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446112","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}