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bipolar disorder lithium biomarkers

Caroline Vintergaard Ott, Claire Bergstrom Johnson, Julian Macoveanu, Kamilla Miskowiak
Cognitive impairments are a core feature of several neuropsychiatric disorders. A common biomarker for pro-cognitive effects may provide a much-needed tool to select amongst candidate treatments targeting cognition. The hippocampus is a promising biomarker for target-engagement due to the illness-associated morphological hippocampal changes across unipolar disorder (UD), bipolar disorder (BD) and schizophrenia (SCZ). Following the PRISMA guidelines, we searched PubMed and Embase, for clinical trials targeting cognition across neuropsychiatric disorders, with longitudinal structural magnetic resonance imaging (MRI) measures of the hippocampus...
January 14, 2019: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Fiona Coutts, Alish B Palmos, Rodrigo R R Duarte, Simone de Jong, Cathryn M Lewis, Danai Dima, Timothy R Powell
Telomere length is a promising biomarker for age-related disease and a potential anti-ageing drug target. Here, we study the genetic architecture of telomere length and the repositioning potential of lithium as an anti-ageing medication. LD score regression applied to the largest telomere length genome-wide association study to-date, revealed SNP-chip heritability estimates of 7.29%, with polygenic risk scoring capturing 4.4% of the variance in telomere length in an independent cohort (p = 6.17 × 10-5 )...
December 18, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Johannes Petzold, Michael Bauer, Emanuel Severus
Lithium is the gold standard in the long-term treatment of bipolar disorders and the only substance with a convincing antisuicidal effect in affective disorders. Under regular monitoring, lithium represents mostly a well-tolerated and safe medication. Balancing risk and benefits shows that lithium can also be an off-label therapeutic option during pregnancy and breast feeding. Lithium may exhibit neuroprotective effects and has been linked to a reduced risk of Alzheimer's disease and stroke. In the future, biomarkers of lithium response may be available that enable development of more personalized therapies...
November 12, 2018: Fortschritte der Neurologie-Psychiatrie
Claudia Pisanu, Donatella Congiu, Marta Costa, Caterina Chillotti, Raffaella Ardau, Giovanni Severino, Andrea Angius, Urs Heilbronner, Liping Hou, Francis J McMahon, Thomas G Schulze, Maria Del Zompo, Alessio Squassina
Lithium is the mainstay treatment in bipolar disorder (BD) for its effectiveness in the acute phases of illness and in prevention of recurrences. Lithium's mechanism of action is complex, and while it modulates the function of hundreds of molecular targets, most of these effects could be unspecific and not relevant for its clinical efficacy. In this study, we applied an integrated analytical approach using genome-wide expression and genotyping data from BD patients to identify lithium-responsive genes that may serve as biomarkers of its efficacy...
October 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Michele Fornaro, Domenico De Berardis, Annalisa Anastasia, Stefano Novello, Andrea Fusco, Carlo Ignazio Cattaneo, Marco Solmi, Francesco Monaco, Nicola Veronese, Yong-Ku Kim, Andrea de Bartolomeis
The prediction of acute and maintenance lithium treatment response carries major clinical and neurobiological implications, warranting systematic review. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant review searched major electronic databases from inception until December 2017 for studies documenting a clinical diagnosis of bipolar disorder (BD) made according to the mainstream diagnostic manuals and confirmed by a structured interview. Eligible studies allowed a quantitative comparison of endpoint vs baseline mean values of a given biomarker, regardless of the mood phase of patients with BD, and the disorder was assessed for severity using validated rating tool(s)...
November 2018: Psychiatry Research
Jan Scott, Bruno Etain, Frank Bellivier
Clinical practice guidelines identify lithium as a first line treatment for mood stabilization and reduction of suicidality in bipolar disorders (BD); however, most individuals show sub-optimal response. Identifying biomarkers for lithium response could enable personalization of treatment and refine criteria for stratification of BD cases into treatment-relevant subgroups. Existing systematic reviews identify potential biomarkers of lithium response, but none directly address the conceptual issues that need to be addressed to enhance translation of research into precision prescribing of lithium...
2018: Frontiers in Psychiatry
Linling Li, Erni Ji, Xue Han, Fei Tang, Yuanhan Bai, Daihui Peng, Yiru Fang, Shengli Zhang, Zhiguo Zhang, Haichen Yang
Reported structural abnormalities of patients with bipolar disorder (BD) are inconsistent and the use of psychotropic medication is one of the sources of heterogeneity. A fairly small number of morphometric studies have involved comparison of BD on different mood stabilizers. Here in this study, we aimed to investigate the cortical thickness and subcortical volumes in euthymic BD patients on lithium and valproate and healthy controls (HC), and to elucidate the relationship between the use of medication and brain structure variations...
August 25, 2018: Brain Imaging and Behavior
Frank Bellivier, Cynthia Marie-Claire
Lithium (Li) is the key mood stabilizer in the prevention of mood recurrences and suicide in bipolar disorders. However, only one-third of patients become asymptomatic with Li treatment, and to date, no clinical markers can predict this response variability. Li is a multitargeting drug, complicating an understanding of its mechanisms of action. The present article reviews Li's various biological effects, including those obtained in transcriptomic and epigenetic studies, in both humans and animal models. A molecular signature of the therapeutic response to Li is urgently required, including possibly from the circulation...
September 2018: Pharmacopsychiatry
Wenjing Zhang, Yuan Xiao, Huaiqiang Sun, L Rodrigo Patino, Maxwell J Tallman, Wade A Weber, Caleb M Adler, Christina Klein, Jeffrey R Strawn, Fabiano G Nery, Qiyong Gong, John A Sweeney, Su Lui, Melissa P DelBello
The need for treatment response predictive biomarkers is being increasingly recognized in children and adolescents with psychiatric disorders. Structural gray matter abnormalities as a predictor of treatment outcome in pediatric bipolar disorder have not been systematically investigated, especially early in the illness course. With a prospective longitudinal study design, the present study enrolled 52 bipolar adolescents with no history of treatment with mood stabilizers or a therapeutic dose of antipsychotic drugs and 31 healthy controls...
October 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Jeverson Moreira, Gaëlle Noé, Savithri Rangarajan, Cindie Courtin, Bruno Etain, Pierre A Geoffroy, Jean-Louis Laplanche, Michel Vidal, Frank Bellivier, Cynthia Marie-Claire
OBJECTIVES: Lithium is the leading mood stabiliser for maintenance treatment in bipolar disorder (BD). However, response to lithium is heterogeneous with more than 60% of patients experiencing partial or no response. In vitro and in vivo molecular studies have reported the implication of kinases in the pathophysiology of BD. METHODS: Since kinases are putative targets for lithium therapeutic action, we conducted the first pilot study using kinase array technology to evaluate the global serine/threonine kinases (STK) profiles in cell lines from BD I subtype patients classified as lithium excellent-responders (ER) and non-responder (NR) to lithium treatment...
July 23, 2018: World Journal of Biological Psychiatry
Claudia Pisanu, Urs Heilbronner, Alessio Squassina
Bipolar disorder (BD) is a common and disabling psychiatric condition with a severe socioeconomic impact. BD is treated with mood stabilizers, among which lithium represents the first-line treatment. Lithium alone or in combination is effective in 60% of chronically treated patients, but response remains heterogenous and a large number of patients require a change in therapy after several weeks or months. Many studies have so far tried to identify molecular and genetic markers that could help us to predict response to mood stabilizers or the risk for adverse drug reactions...
August 2018: Molecular Diagnosis & Therapy
Georgina P Ossani, Diego J Martino, Jorge E Toblli
Lithium has been approved for the treatment of bipolar disorder since the 1970s and even today it is considered a first-line drug for the treatment of this disease. As bipolar disorder often begins between 15-35 years of age and requires long-term treatment, the assessment of the adverse effects of the drugs used is critical. Recently, there has been renewed interest on the risk of chronic kidney disease and kidney failure induced by lithium, with findings suggesting that both complications could be more frequent than previously considered...
September 2017: Vertex: Revista Argentina de Psiquiatriá
Rodrigo Machado-Vieira
BACKGROUND: Lithium is the lightest metal and the only mood stabilizer that has been used for over half a century for the treatment of bipolar disorder (BD). As a small ion, lithium is omnipresent, and consequently, its molecular mechanisms and targets are widespread. Currently, lithium is a crucial pharmacotherapy for the treatment of acute mood episodes, prophylactic therapy, and suicide prevention in BD. Besides, lithium blood level is the most widely used biomarker in clinical psychiatry...
June 2018: Journal of Affective Disorders
Tess Maria Rajan, Balaji Bharadwaj, Ravi Philip Rajkumar, Prashant Shankarrao Adole
BACKGROUND: Patients with Bipolar Disorder (BD) may have higher risk of Tardive Dyskinesia (TD). Theories for TD include inflammatory or oxidative stress and altered iron metabolism. The current frequency and clinical and biochemical correlates of TD in BD needs exploration. OBJECTIVES: To assess: (1) the frequency of TD in BD; (2) clinical correlates of TD in BD; (3) oxidative stress markers, inflammatory markers and hepcidin in TD in BD. MATERIALS & METHODS: In this cross-sectional study, 170 patients with BD were assessed for clinical characteristics using structured assessments...
February 2018: Asian Journal of Psychiatry
Claudia Pisanu, Theodora Katsila, George P Patrinos, Alessio Squassina
Mood stabilizers are the cornerstone in treatment of mood disorders, but their use is characterized by high interindividual variability. This feature has stimulated intensive research to identify predictive biomarkers of response and disentangle the molecular bases of their clinical efficacy. Nevertheless, findings from studies conducted so far have only explained a small proportion of the observed variability, suggesting that factors other than DNA variants could be involved. A growing body of research has been focusing on the role of epigenetics and metabolomics in response to mood stabilizers, especially lithium salts...
January 2018: Pharmacogenomics
In Hee Shim, Young Sup Woo, Moon-Doo Kim, Won-Myong Bahk
The concept of the bipolar-spectrum and of mixed features being a bridge between major depressive disorders and bipolar disorders (BDs) has become increasingly important in mood-disorder diagnoses. Under these circumstances, antidepressants (ADs) and mood stabilizers (MSs) should be used with caution in the treatment of major depressive episodes (MDEs) and to obtain long-term stability in BDs. Before treating MDEs, screening tools, specific symptom evaluation and medical history should be used to distinguish between bipolarity and mixed features in patients for whom AD monotherapy may present a risk...
November 13, 2017: International Journal of Molecular Sciences
Shuang-Jiang Zhou, Li-Gang Zhang, Hong-Mei Chen, Ju-Yan Li, Ran Li, Xi-Mei Zhang, Ning Wang, Jair C Soares, Ryan M Cassidy, Yingjun Zheng, Yuping Ning, Shao-Li Wang, Jing-Xu Chen, Xiang-Yang Zhang
Recent studies have reported that hyperhomocystinemia (HHcy) is highly prevalent in patients with bipolar disorder (BD), placing them at greater risk of cardiovascular disease and possibly serving as a disease biomarker. However, the correlation of HHcy with demographic or clinical parameters is not well known. In this study, we examined the prevalence of HHcy and its association with these parameters in a sample of Chinese BD patients. Fasting plasma homocysteine (Hcy) levels were determined in 198 BD inpatients and 84 healthy controls...
January 2018: Psychiatry Research
Massimiliano Buoli, Marta Serati, A Carlo Altamura
Rapid-cycling bipolar disorder represents a frequent severe subtype of illness which has been associated with poor response to pharmacological treatment. Aim of the present article is to provide an updated review of biological markers associated with rapid-cycling bipolar disorder. A research in the main database sources has been conducted to identify relevant papers about the topic. Rapid-cycling bipolar disorder patients seem to have a more frequent family history for bipolar spectrum disorders (d range: 0...
December 2017: Psychiatry Research
Elena Milanesi, Irena Voinsky, Adva Hadar, Ala Srouji, Carlo Maj, Tatyana Shekhtman, Michael Gershovits, Shlomit Gilad, Caterina Chillotti, Alessio Squassina, James B Potash, Thomas G Schulze, Fernando S Goes, Peter Zandi, John R Kelsoe, David Gurwitz
OBJECTIVES: Lithium remains the oldest and most effective treatment for mood stabilisation in bipolar disorder (BD), even though at least half of patients are only partially responsive or do not respond. This study aimed to identify biomarkers associated with lithium response in BD, based on comparing RNA sequencing information derived from lymphoblastoid cell lines (LCLs) of lithium-responsive (LR) versus lithium non-responsive (LNR) BD patients, to assess gene expression variations that might bear on treatment outcome...
September 22, 2017: World Journal of Biological Psychiatry
Eleni Merkouri Papadima, Paola Niola, Carla Melis, Claudia Pisanu, Donatella Congiu, Cristiana Cruceanu, Juan Pablo Lopez, Gustavo Turecki, Raffaella Ardau, Giovanni Severino, Caterina Chillotti, Maria Del Zompo, Alessio Squassina
Lithium has been used for more than six decades for the management of bipolar disorder (BD). In a previous transcriptomic study, we showed that patients affected by either BD or cluster headache, both disorders characterized by circadian disturbances and response to lithium in a subgroup of patients, have higher expression of the RNA binding motif (RNP1, RRM) protein 3 (RBM3) gene compared to controls. To investigate whether RBM3 could represent a biomarker of lithium response, we screened raw microarray expression data from lymphoblastoid cell lines (LCLs) derived from 20 BD patients, responders or non-responders to lithium...
August 2017: Journal of Molecular Neuroscience: MN
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