Correction of depression‐associated circadian rhythm abnormalities is associated with lithium‐response in bipolar disorder

2021 ◽  
Author(s):  
Monica Federoff ◽  
Michael J. McCarthy ◽  
Amit Anand ◽  
Wade H. Berrettini ◽  
Holli Bertram ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Circadian Rhythm ◽  
Lithium Response

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

scholarly journals Prevalence of Circadian Rhythm Sleep-Wake Disorders and Associated Factors in Euthymic Patients with Bipolar Disorder

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0159578 ◽  
Author(s):  
Yoshikazu Takaesu ◽  
Yuichi Inoue ◽  
Akiko Murakoshi ◽  
Yoko Komada ◽  
Ayano Otsuka ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Circadian Rhythm ◽  
Associated Factors ◽  
Sleep Wake Disorders

scholarly journals Network-based integrative analysis of lithium response in bipolar disorder using transcriptomic and GWAS data

2022 ◽  
Author(s):  
Vipavee Niemsiri ◽  
Sarah Brin Rosenthal ◽  
Caroline M. Nievergelt ◽  
Adam X. Maihofer ◽  
Maria C. Marchetto ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Focal Adhesion ◽  
Gene Networks ◽  
Gene List ◽  
Integrative Analysis ◽  
Functional Enrichment ◽  
Network Propagation ◽  
Lithium Response ◽  
The Difference ◽  
Effective Drugs

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric=1.28E-09 and 4.10E-18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.

scholarly journals Sleep and Circadian Rhythm Disturbance in Remitted Schizophrenia and Bipolar Disorder: A Systematic Review and Meta-analysis

2020 ◽  
Vol 46 (5) ◽  
pp. 1126-1143 ◽  
Author(s):  
Nicholas Meyer ◽  
Sophie M Faulkner ◽  
Robert A McCutcheon ◽  
Toby Pillinger ◽  
Derk-Jan Dijk ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Circadian Rhythm ◽  
Motor Activity ◽  
Sleep Latency ◽  
Total Sleep Time ◽  
Sleep Time ◽  
Mean Difference ◽  
Effect Sizes ◽  
Time In Bed ◽  
Modifiable Factors

Abstract Background Sleep and circadian rhythm disturbances in schizophrenia are common, but incompletely characterized. We aimed to describe and compare the magnitude and heterogeneity of sleep-circadian alterations in remitted schizophrenia and compare them with those in interepisode bipolar disorder. Methods EMBASE, Medline, and PsycINFO were searched for case–control studies reporting actigraphic parameters in remitted schizophrenia or bipolar disorder. Standardized and absolute mean differences between patients and controls were quantified using Hedges’ g, and patient–control differences in variability were quantified using the mean-scaled coefficient of variation ratio (CVR). A wald-type test compared effect sizes between disorders. Results Thirty studies reporting on 967 patients and 803 controls were included. Compared with controls, both schizophrenia and bipolar groups had significantly longer total sleep time (mean difference [minutes] [95% confidence interval {CI}] = 99.9 [66.8, 133.1] and 31.1 [19.3, 42.9], respectively), time in bed (mean difference = 77.8 [13.7, 142.0] and 50.3 [20.3, 80.3]), but also greater sleep latency (16.5 [6.1, 27.0] and 2.6 [0.5, 4.6]) and reduced motor activity (standardized mean difference [95% CI] = −0.86 [−1.22, −0.51] and −0.75 [−1.20, −0.29]). Effect sizes were significantly greater in schizophrenia compared with the bipolar disorder group for total sleep time, sleep latency, and wake after sleep onset. CVR was significantly elevated in both diagnoses for total sleep time, time in bed, and relative amplitude. Conclusions In both disorders, longer overall sleep duration, but also disturbed initiation, continuity, and reduced motor activity were found. Common, modifiable factors may be associated with these sleep-circadian phenotypes and advocate for further development of transdiagnostic interventions that target them.

scholarly journals Agomelatine: Its Role in the Management of Major Depressive Disorder

2012 ◽  
Vol 4 ◽  
pp. CMPsy.S7989 ◽  
Author(s):  
Daniel P. Cardinali ◽  
María F. Vidal ◽  
Daniel E. Vigo
Keyword(s):  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Circadian Rhythm ◽  
Depressive Disorder ◽  
Seasonal Affective Disorder ◽  
Rapid Onset ◽  
Depressive Illness ◽  
Melatonin Secretion ◽  
Major Depressive ◽  
Onset Of Action

Circadian rhythm abnormalities, as shown by sleep/wake cycle disturbances, constitute one the most prevalent signs of depressive illness; advances or delays in the circadian phase are documented in patients with major depressive disorder (MDD), bipolar disorder, and seasonal affective disorder (SAD). The disturbances in the amplitude and phase of rhythm in melatonin secretion that occur in patients with depression resemble those seen in chronobiological disorders, thus suggesting a link between disturbed melatonin secretion and depressed mood. Based on this, agomelatine, the first MT1/MT2 melatonergic agonist displaying also 5-HT2C serotonergic antagonism, has been introduced as an antidepressant. Agomelatine has been shown to be effective in several animal models of depression and anxiety and it has beneficial effects in patients with MDD, bipolar disorder, or SAD. Among agomelatine's characteristics are a rapid onset of action and a pronounced effectiveness for correcting circadian rhythm abnormalities and improving the sleep/wake cycle. Agomelatine also improves the 3 functional dimensions of depression—emotional, cognitive, and social—thus aiding in the full recovery of patients to a normal life.

SU100INTEGRATIVE ANALYSIS OF OMICS SUMMARY DATA TO IDENTIFY GENES ASSOCIATED WITH LITHIUM RESPONSE AND RELATED PHENOTYPES IN PATIENTS WITH BIPOLAR DISORDER

2019 ◽  
Vol 29 ◽  
pp. S1319
Author(s):  
Claudia Pisanu ◽  
Nirmala Akula ◽  
Maria Del Zompo ◽  
Alessio Squassina ◽  
Francis J. McMahon
Keyword(s):  
Bipolar Disorder ◽  
Lithium Response ◽  
Summary Data
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