scholarly journals Starting lithium prophylaxis earlyv.late in bipolar disorder

2014 ◽  
Vol 205 (3) ◽  
pp. 214-220 ◽  
Author(s):  
Lars Vedel Kessing ◽  
Eleni Vradi ◽  
Per Kragh Andersen
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Hospital ◽  
Lithium Treatment ◽  
Preventive Treatment ◽  
Hazard Ratio ◽  
Mixed Episode ◽  
Start Up ◽  
Late Intervention ◽  
Lithium Response ◽  
First Contact

BackgroundNo study has investigated when preventive treatment with lithium should be initiated in bipolar disorder.AimsTo compare response rates among patients with bipolar disorder starting treatment with lithium earlyv.late.MethodNationwide registers were used to identify all patients with a diagnosis of bipolar disorder in psychiatric hospital settings who were prescribed lithium during the period 1995–2012 in Denmark (n= 4714). Lithium responders were defined as patients who, following a stabilisation lithium start-up period of 6 months, continued lithium monotherapy without being admitted to hospital. Earlyv.late intervention was defined in two ways: (a) start of lithium following first contact; and (b) start of lithium following a diagnosis of a single manic/mixed episode.ResultsRegardless of the definition used, patients who started lithium early had significantly decreased rates of nonresponse to lithium compared with the rate for patients starting lithium later (adjusted analyses: firstv.later contact:P<0.0001; hazard ratio (HR) = 0.87, 95% CI 0.76–0.91; single manic/mixed episodev.bipolar disorder:P<0.0001; HR = 0.75, 95% CI 0.67–0.84).ConclusionsStarting lithium treatment early following first psychiatric contact or a single manic/mixed episode is associated with increased probability of lithium response.

scholarly journals Valproate v. lithium in the treatment of bipolar disorder in clinical practice: observational nationwide register-based cohort study

2011 ◽  
Vol 199 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Lars Vedel Kessing ◽  
Gunnar Hellmund ◽  
John R. Geddes ◽  
Guy M. Goodwin ◽  
Per Kragh Andersen
Keyword(s):  
Bipolar Disorder ◽  
Cohort Study ◽  
Clinical Practice ◽  
Hospital Admission ◽  
Psychiatric Hospital ◽  
Hospital Admissions ◽  
Observational Cohort Study ◽  
Hazard Ratio ◽  
Daily Clinical Practice ◽  
Observational Cohort

BackgroundValproate is one of the most used mood stabilisers for bipolar disorder, although the evidence for the effectiveness of valproate is sparse.AimsTo compare the effect of valproate v. lithium for treatment of bipolar disorder in clinical practice.MethodAn observational cohort study with linkage of nationwide registers of all people with a diagnosis of bipolar disorder in psychiatric hospital settings who were prescribed valproate or lithium in Denmark during a period from 1995 to 2006.ResultsA total of 4268 participants were included among whom 719 received valproate and 3549 received lithium subsequent to the diagnosis of bipolar disorder. The rate of switch/add on to the opposite drug (lithium or valproate), antidepressants, antipsychotics or anticonvulsants (other than valproate) was increased for valproate compared with lithium (hazard ratio (HR) = 1.86, 95% CI 1.59–2.16). The rate of psychiatric hospital admissions was increased for valproate v. lithium (HR = 1.33, 95% CI 1.18–1.48) and regardless of the type of episode leading to a hospital admission (depressive or manic/mixed). Similarly, for participants with a depressive index episode (HR = 1.87, 95% CI 1.40–2.48), a manic index episode (HR = 1.24, 95% CI 1.01–1.51) and a mixed index episode (HR = 1.44, 95% CI 1.04–2.01), the overall rate of hospital admissions was significantly increased for valproate compared with lithium.ConclusionsIn daily clinical practice, treatment with lithium seems in general to be superior to treatment with valproate.

scholarly journals Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Klaus Oliver Schubert ◽  
Anbupalam Thalamuthu ◽  
Azmeraw T. Amare ◽  
Joseph Frank ◽  
Fabian Streit ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Treatment Response ◽  
Molecular Mechanisms ◽  
Lithium Treatment ◽  
Meta Analysis ◽  
Risk Scores ◽  
Poor Responders ◽  
Genetic Trait ◽  
Polygenic Risk ◽  
Lithium Response

AbstractLithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium’s therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.

scholarly journals A 7 Tesla Amygdalar-Hippocampal Shape Analysis of Lithium Response in Bipolar Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Thomas L. Athey ◽  
Can Ceritoglu ◽  
Daniel J. Tward ◽  
Kwame S. Kutten ◽  
J. Raymond DePaulo ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Shape Analysis ◽  
Lithium Treatment ◽  
Structural Mri ◽  
Ventral Surface ◽  
7 Tesla ◽  
Surface Anatomy ◽  
Response Status ◽  
Lithium Response

Research to discover clinically useful predictors of lithium response in patients with bipolar disorder has largely found them to be elusive. We demonstrate here that detailed neuroimaging may have the potential to fill this important gap in mood disorder therapeutics. Lithium treatment and bipolar disorder have both been shown to affect anatomy of the hippocampi and amygdalae but there is no consensus on the nature of their effects. We aimed to investigate structural surface anatomy changes in amygdala and hippocampus correlated with treatment response in bipolar disorder. Patients with bipolar disorder (N = 14) underwent lithium treatment, were classified by response status at acute and long-term time points, and scanned with 7 Tesla structural MRI. Large Deformation Diffeomorphic Metric Mapping was applied to detect local differences in hippocampal and amygdalar anatomy between lithium responders and non-responders. Anatomy was also compared to 21 healthy comparison participants. A patch of the ventral surface of the left hippocampus was found to be significantly atrophied in non-responders as compared to responders at the acute time point and was associated at a trend-level with long-term response status. We did not detect an association between response status and surface anatomy of the right hippocampus or amygdala. To the best of our knowledge, this is the first shape analysis of hippocampus and amygdala in bipolar disorder using 7 Tesla MRI. These results can inform future work investigating possible neuroimaging predictors of lithium response in bipolar disorder.

scholarly journals Studying cellular functions in bipolar disorder: Are there specific predictors of lithium response?

2019 ◽  
Author(s):  
Pradip Paul ◽  
Shruti Iyer ◽  
Ravi Kumar Nadella ◽  
Rashmitha Nayak ◽  
Anirudh S. Chellappa ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Lithium Treatment ◽  
Healthy Population ◽  
Outpatient Services ◽  
Mitochondrial Potential ◽  
Lithium Response ◽  
Cellular Phenotypes

ABSTRACTBackgroundLithiumis the first-line mood stabilizer for the treatment of bipolar disorder (BD). In order to interrogate cellular phenotypes related to disease and lithium treatment response, this study used neural precursor cells (NPCs) and lymphoblastoid cell lines (LCLs) from BD patients who are well characterized for clinical lithium response.MethodsBDpatientsdiagnosed according to the DSM-IV criteria; were recruited from the outpatient services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Clinical lithium response was assessed using the “Alda scale” and “NIMH Retrospective Life chart method”. The controls were ethnically matched healthy subjects with no family history of neuropsychiatric illness. NPCs from two BD patients from the same family who clearly differed in their clinical response to lithium were chosen, and compared with healthy population controls. Whole transcriptome sequencing (RNA-Seq) and analysis were performed, with and withoutin vitrolithium (1mM for 7 days). In addition, mitochondrial membrane potential (MMP), cell viability and cell proliferation parameters were examined. Experiments were also performed in 25 LCLs from BD patients (16 lithium responders and 9 lithium non-responders), and 12 healthy control LCLs, to evaluate them in a system amenable to clinical translation.ResultsRNA-Sequencingand analysis did not reveal differences in NPCs onin vitrolithium treatment. MMP was lower in BD, both in NPCs and LCLs; reversal within vitrolithium happened only in LCLs and was unrelated to lithium response. Cell proliferation was higher in BD compared to controls, and there was no change on lithium addition. Cell viability assays indicated greater cell death in BD; which could only be rescued in LCLs of clinical lithium responders. The latter finding was associated with enhancedBCL2andGSK3Bexpression within vitrolithium.DiscussionOverall, our study findings indicate that there are cellular phenotypes related to the disease (mitochondrial potential, cell proliferation) in NPCs and LCLs. We also observed clinical lithium response related phenotypes (cell viability,BCL2/ GSK3Bexpression) in LCLs. The next step would be to evaluate a larger set of PBMCs from clinical lithium response groups of BD to derive cellular phenotypes related to direct clinical application.

Genetics of Lithium Response in Bipolar Disorder

2018 ◽  
Vol 51 (05) ◽  
pp. 206-211 ◽  
Author(s):  
Sergi Papiol ◽  
Thomas Schulze ◽  
Martin Alda
Keyword(s):  
Bipolar Disorder ◽  
Genetic Architecture ◽  
Association Studies ◽  
Lithium Treatment ◽  
Genetic Association Studies ◽  
Term Treatment ◽  
Individual Response ◽  
Long Term Treatment ◽  
Lithium Response

Abstract Introduction Lithium remains the best-established long-term treatment for bipolar disorder because of its efficacy in maintaining periods of remission and reducing the risk of suicide. Not all patients successfully respond to lithium treatment, and the individual response, including the occurrence of side effects, is highly variable and not easy to predict. The genetic basis of lithium response is supported by the fact that the response clusters in families. Likewise, recent high-throughput genomic analyses have shed light on its genetic architecture. Methods This nonsystematic review summarizes the main results obtained in genetic association studies using lithium response as target trait. Results These studies suggest that several genetic loci might modulate the way a patient responds to lithium maintenance treatment. Further studies to fully characterize the genetic architecture of lithium response are warranted. Discussion The identification of genetic factors associated with lithium response will be important for (1) better understanding of lithium’s mode of action and (2) development of a predictive model for optimization of long-term treatment of bipolar disorder.

scholarly journals Pharmacogenomics of Lithium Response in Bipolar Disorder

2021 ◽  
Vol 14 (4) ◽  
pp. 287
Author(s):  
Courtney M. Vecera ◽  
Gabriel R. Fries ◽  
Lokesh R. Shahani ◽  
Jair C. Soares ◽  
Rodrigo Machado-Vieira
Keyword(s):  
Bipolar Disorder ◽  
Association Studies ◽  
Mood Stabilizer ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Lithium Response ◽  
Genetic Loading ◽  
Long Non Coding Rna

Despite being the most widely studied mood stabilizer, researchers have not confirmed a mechanism for lithium’s therapeutic efficacy in Bipolar Disorder (BD). Pharmacogenomic applications may be clinically useful in the future for identifying lithium-responsive patients and facilitating personalized treatment. Six genome-wide association studies (GWAS) reviewed here present evidence of genetic variations related to lithium responsivity and side effect expression. Variants were found on genes regulating the glutamate system, including GAD-like gene 1 (GADL1) and GRIA2 gene, a mutually-regulated target of lithium. In addition, single nucleotide polymorphisms (SNPs) discovered on SESTD1 may account for lithium’s exceptional ability to permeate cell membranes and mediate autoimmune and renal effects. Studies also corroborated the importance of epigenetics and stress regulation on lithium response, finding variants on long, non-coding RNA genes and associations between response and genetic loading for psychiatric comorbidities. Overall, the precision medicine model of stratifying patients based on phenotype seems to derive genotypic support of a separate clinical subtype of lithium-responsive BD. Results have yet to be expounded upon and should therefore be interpreted with caution.

Involvement of microRNAs in Lithium Response in Patients With Bipolar Disorder and Related Phenotypes

2021 ◽  
Vol 89 (9) ◽  
pp. S13
Author(s):  
Claudia Pisanu ◽  
Donatella Congiu ◽  
Giovanni Severino ◽  
Paola Niola ◽  
Juan Pablo Lopez ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Lithium Response

scholarly journals Functional genetic variation in the Rev-Erbαpathway and lithium response in the treatment of bipolar disorder

2011 ◽  
Vol 10 (8) ◽  
pp. 852-861 ◽  
Author(s):  
M. J. McCarthy ◽  
C. M. Nievergelt ◽  
T. Shekhtman ◽  
D. F. Kripke ◽  
D. K. Welsh ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Genetic Variation ◽  
Functional Genetic Variation ◽  
Lithium Response
Sign in / Sign up

Export Citation Format

Share Document