International Journal of Bipolar Disorders最新文献

{"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":"12 1","pages":"29"},"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}

{"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":"12 1","pages":"28"},"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}

{"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":"1 1","pages":""},"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}

{"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":"12 1","pages":"26"},"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}

{"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":"12 1","pages":"24"},"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}

{"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":"12 1","pages":"25"},"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}

{"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":"12 1","pages":"23"},"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}

{"title":"The research landscape of bipolar disorder in Germany: productive, but underfunded.","authors":"Cindy Eckart, Andreas Reif","doi":"10.1186/s40345-024-00344-9","DOIUrl":"10.1186/s40345-024-00344-9","url":null,"abstract":"<p><strong>Background: </strong>The recurrent mental illness bipolar disorder is a major burden on the healthcare system, which underlines the importance of research into this disease. Germany is one of the most productive countries in this research activity. This bibliometric analysis aims to outline the social and conceptual structure of the German research landscape on bipolar disorder over the last decade. Furthermore, we provide a short overview over current public funding.</p><p><strong>Results: </strong>Concerning the social structure, most of the German publications were collaboration projects, both with a national but also international orientation, in the latter case predominantly with countries of the global North. Analysis of the conceptual structure of German research activity identified psychiatric genetics, early recognition of bipolar disorder, neuroimaging, and pharmacological interventions as important topics within the field. In the context of a survey, only few publicly funded research projects were reported, many of which did not exclusively investigate bipolar disorder but followed a transdiagnostic approach.</p><p><strong>Conclusions: </strong>Our bibliometric analysis revealed internationally well-networked German research activities on bipolar disorder. In stark contrast to its high prevalence and correspondingly high financial burden to the healthcare system, current grant support for research on this illness is strikingly low, particularly concerning the development of novel treatments.</p>","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":"12 1","pages":"22"},"PeriodicalIF":4.0,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327499","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}

{"title":"Pilot study of circulating cell-free mitochondrial DNA in relation to brain structure in youth bipolar disorder.","authors":"Suyi Shao, Yi Zou, Kody G Kennedy, Mikaela K Dimick, Ana C Andreazza, L Trevor Young, Vanessa F Goncalves, Bradley J MacIntosh, Benjamin I Goldstein","doi":"10.1186/s40345-024-00334-x","DOIUrl":"10.1186/s40345-024-00334-x","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial dysfunction is implicated in the neuropathology of bipolar disorder (BD). Higher circulating cell-free mitochondrial DNA (ccf-mtDNA), generally reflecting poorer mitochondrial health, has been associated with greater symptoms severity in BD. The current study examines the association of serum ccf-mtDNA and brain structure in relation to youth BD. We hypothesized that higher ccf-mtDNA will be associated with measures of lower brain structure, particularly in the BD group.</p><p><strong>Methods: </strong>Participants included 40 youth (BD, n = 19; Control group [CG], n = 21; aged 13-20 years). Serum ccf-mtDNA levels were assayed. T1-weighted brain images were acquired using 3T-MRI. Region of interest (ROI) analyses examined prefrontal cortex (PFC) and whole brain gray matter, alongside exploratory vertex-wise analyses. Analyses examined ccf-mtDNA main-effects and ccf-mtDNA-by-diagnosis interaction effects controlling for age, sex, and intracranial volume.</p><p><strong>Results: </strong>There was no significant difference in ccf-mtDNA levels between BD and CG. In ROI analyses, higher ccf-mtDNA was associated with higher PFC surface area (SA) (β = 0.32 p < 0.001) and PFC volume (β = 0.32 p = 0.002) in the overall sample. In stratified analyses, higher ccf-mtDNA was associated with higher PFC SA within both subgroups (BD: β = 0.39 p = 0.02; CG: β = 0.24 p = 0.045). Higher ccf-mtDNA was associated with higher PFC volume within the BD group (β = 0.39 p = 0.046). In vertex-wise analyses, higher ccf-mtDNA was associated with higher SA and volume in frontal clusters within the overall sample and within the BD group. There were significant ccf-mtDNA-by-diagnosis interactions in three frontal and parietal clusters, whereby higher ccf-mtDNA was associated with higher neurostructural metrics in the BD group but lower neurostructural metrics in CG.</p><p><strong>Conclusions: </strong>Contrasting our hypothesis, higher ccf-mtDNA was consistently associated with higher, rather than lower, regional neuralstructural metrics among youth with BD. While this finding may reflect a compensatory mechanism, future repeated-measures prospective studies evaluating the inter-relationship among ccf-mtDNA, mood, and brain structure across developmental epochs and illness stages are warranted.</p>","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":"12 1","pages":"21"},"PeriodicalIF":4.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11178693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317249","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}

{"title":"Exploring the genetics of lithium response in bipolar disorders.","authors":"Marisol Herrera-Rivero, Mazda Adli, Kazufumi Akiyama, Nirmala Akula, Azmeraw T Amare, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Abesh Kumar Bhattacharjee, Joanna M Biernacka, Armin Birner, Micah Cearns, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Scott R Clark, Francesc Colom, Cristiana Cruceanu, Piotr M Czerski, Nina Dalkner, Franziska Degenhardt, Maria Del Zompo, J Raymond DePaulo, Bruno Etain, Peter Falkai, Ewa Ferensztajn-Rochowiak, Andreas J Forstner, Josef Frank, Louise Frisén, Mark A Frye, Janice M Fullerton, Carla Gallo, Sébastien Gard, Julie S Garnham, Fernando S Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Roland Hasler, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Po-Hsiu Kuo, Ichiro Kusumi, Barbara König, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G Leckband, Mario Maj, Mirko Manchia, Cynthia Marie-Claire, Lina Martinsson, Michael J McCarthy, Susan L McElroy, Vincent Millischer, Marina Mitjans, Francis M Mondimore, Palmiero Monteleone, Caroline M Nievergelt, Tomas Novák, Markus M Nöthen, Claire O'Donovan, Norio Ozaki, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B Potash, Andreas Reif, Eva Reininghaus, Hélène Richard-Lepouriel, Gloria Roberts, Guy A Rouleau, Janusz K Rybakowski, Martin Schalling, Peter R Schofield, Klaus Oliver Schubert, Eva C Schulte, Barbara W Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fabian Streit, Fasil Tekola-Ayele, Anbupalam Thalamuthu, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Biju Viswanath, Stephanie H Witt, Peter P Zandi, Martin Alda, Michael Bauer, Francis J McMahon, Philip B Mitchell, Marcella Rietschel, Thomas G Schulze, Bernhard T Baune","doi":"10.1186/s40345-024-00341-y","DOIUrl":"10.1186/s40345-024-00341-y","url":null,"abstract":"<p><strong>Background: </strong>Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.</p><p><strong>Results: </strong>We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.</p><p><strong>Conclusions: </strong>Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.</p>","PeriodicalId":13944,"journal":{"name":"International Journal of Bipolar Disorders","volume":"12 1","pages":"20"},"PeriodicalIF":2.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305870","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}