Role of TGFb1 gene as possible pharmacogenomic biomarker for response effectiveness to lithium treatment in Sardinian patients with bipolar disorder

Pharmacogenetic research aims to elucidate associations of genetic variants and individual effects of pharmacotherapy. Personalised expected response to medications might be useful in prognosis for polygenetically determined disorders. In bipolar disorder (BP), that is partly hereditary polygenic disorder, a subgroup of patients excellently responding to lithium prophylaxis was described. During the last 20 years molecular technology allowed to investigate genome of patients treated with lithium and candidate association studies characterised them more precisely than clinical features. The role of several neurotransmitters’ pathways, second messengers, neuroprotection involved genes and clock genes associations were discovered. Further laboratory technics development enables us to perform genome-wide association studies (GWAS) and polygenic risk score (PRS) analyses. We aimed to review research on genes involved in lithium treatment efficacy and safety. PubMed for English papers, articles published in Polish and reference lists from full-text available papers were searched. Pharmacogenetic findings for lithium treatment effects might help develop new personalised strategies and consequently better symptom reduction. So far, chronicity and recurrent course of bipolar disorder impair the functioning of numerous patients and strongly increase the risk of suicide.

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Differences in telomere length between patients with bipolar disorder and controls are influenced by lithium treatment

Pharmacogenomics ◽

10.2217/pgs-2020-0028 ◽

2020 ◽

Vol 21 (8) ◽

pp. 533-540 ◽

Cited By ~ 1

Author(s):

Claudia Pisanu ◽

Donatella Congiu ◽

Mirko Manchia ◽

Paola Caria ◽

Cristina Cocco ◽

...

Keyword(s):

Bipolar Disorder ◽

Telomere Length ◽

Lithium Treatment ◽

Telomere Shortening ◽

Genome Wide ◽

History Of ◽

Genetically Determined ◽

The Relationship

Aim: To assess the role of lithium treatment in the relationship between bipolar disorder (BD) and leukocyte telomere length (LTL). Materials & methods: We compared LTL between 131 patients with BD, with or without a history of lithium treatment, and 336 controls. We tested the association between genetically determined LTL and BD in two large genome-wide association datasets. Results: Patients with BD with a history lithium treatment showed longer LTL compared with never-treated patients (p = 0.015), and similar LTL compared with controls. Patients never treated with lithium showed shorter LTL compared with controls (p = 0.029). Mendelian randomization analysis showed no association between BD and genetically determined LTL. Conclusion: Our data support previous findings showing that long-term lithium treatment might protect against telomere shortening.

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Female vulnerability for thyroid function abnormality in bipolar disorder: role of lithium treatment

Bipolar Disorders ◽

10.1111/bdi.12163 ◽

2013 ◽

Vol 16 (1) ◽

pp. 72-82 ◽

Cited By ~ 19

Author(s):

Ayşegül Özerdem ◽

Zeliha Tunca ◽

Dilek Çımrın ◽

Ceren Hıdıroğlu ◽

Gül Ergör

Keyword(s):

Bipolar Disorder ◽

Thyroid Function ◽

Lithium Treatment

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The Concentration of the Factors Involved in Trafficking of Stem Cells in Long-Term Treated Bipolar Disorder Patients

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.2165 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S206-S206

Author(s):

J. Kucharska-Mazur ◽

A. Reginia ◽

M. Jabłoński ◽

B. Dołęgowska ◽

J. Rybakowski ◽

...

Keyword(s):

Stem Cells ◽

Bipolar Disorder ◽

Peripheral Blood ◽

Lithium Treatment ◽

Control Group ◽

Complement Cascade ◽

Regeneration System ◽

Sphingosine 1 Phosphate

IntroductionAfter analysis of biological and pharmacological data, we formulated the hypothesis that the factors involved in trafficking of stem cells could be engaged in aetiology of bipolar disorder (BP).AimsIn this study, we considered the role of complement cascade proteins, stromal derived factor-1 (SDF-1), and sphingosine-1-phosphate (S1P) in long-term treated BP.MethodsA group of 30 patients with BP, without the history of lithium treatment, was examined in remission and compared with a group of 30 healthy volunteers. In peripheral blood, we have analysed the concentration of stromal derived factor-1 (SDF-1), sphingosine-1-phosphate (S1P), and some proteins of the complement cascade (C3a, C5a, C5b-9).ResultsPeripheral blood concentration of C3a, C5a, C5b-9 and SDF-1 was significantly higher in BP group compared to control group. The concentration of S1P does not distinguish BP patients from controls.ConclusionOur results suggest the possible role of the regeneration system in aetiology of BP.This work was supported by grant POIG.01.01.02-00-109/09.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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The role of lithium in modulation of brain genes: relevance for aetiology and treatment of bipolar disorder

Biochemical Society Transactions ◽

10.1042/bst0371090 ◽

2009 ◽

Vol 37 (5) ◽

pp. 1090-1095 ◽

Cited By ~ 16

Author(s):

S. Hossein Fatemi ◽

Teri J. Reutiman ◽

Timothy D. Folsom

Keyword(s):

Bipolar Disorder ◽

Chronic Treatment ◽

Association Studies ◽

Lithium Treatment ◽

Protein A ◽

Microarray Dataset ◽

Bipolar Ii Disorder ◽

Bipolar Ii ◽

Microarray Studies

Bipolar disorder is a debilitating disorder of the brain with a lifetime prevalence of 1.0% for bipolar I, 1.1% for bipolar II disorder and 2.4–4.7% for subthreshold bipolar disorder. Medications, including lithium, have demonstrated efficacy in the treatment of bipolar disorder, but their molecular targets and mode of action are largely unknown. A few studies have begun to shed light on potential targets of lithium treatment that may be involved in lithium's therapeutic effect. We have recently conducted a microarray study of rat frontal cortex following chronic treatment (21 days) with lithium. Chronic treatment with lithium led to a significant (at least 1.5-fold) down-regulation of 151 genes and up-regulation of 57 genes. We discuss our results in the context of previous microarray studies involving lithium and gene-association studies to identify key genes associated with chronic lithium treatment. A number of genes associated with bipolar disorder, including Comt (catechol-O-methyltransferase), Vapa (vesicle-associated membrane protein-associated protein A), Dtnb (dystrobrevin β) and Pkd1 (polycystic kidney disease 1), were significantly altered in our microarray dataset along with genes associated with synaptic transmission, apoptosis and transport among other functions.

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