The International Consortium on Lithium Genetics (ConLiGen): An Initiative by the NIMH and IGSLI to Study the Genetic Basis of Response to Lithium Treatment

Schulze, Thomas G.; Alda, Martin; Adli, Mazda; Akula, Nirmala; Ardau, Raffaella; Bui, Elise; Chillotti, Caterina; Cichon, Sven; Czerski, Piotr M.; Zompo, Maria Del; Detera‐Wadleigh, Sevilla D.; Grof, Paul; Gruber, Oliver; Hashimoto, Ryota; Hauser, Joanna; Hoban, Rebecca; Iwata, Nakao; Kassem, Layla; Kato, Takeshi; Kittel‐Schneider, Sarah; Kliwicki, Sebastian; Kelsoe, John R.; Kusumi, Ichiro; Laje, Gonzalo; Leckband, Susan G.; Manchia, Mirko; MacQueen, Glenda; Masui, Takuya; Ozaki, Norio; Perlis, Roy H.; Pfennig, Andrea; Piccardi, Paola; Richardson, Sara; Rouleau, Guy A.; Reif, Andreas; Rybakowski, Janusz; Sasse, Johanna; Schumacher, Johannes; Severino, Giovanni; Smoller, Jordan W.; Squassina, Alessio; Turecki, Gustavo; Young, L. Trevor; Yoshikawa, Takeo; Bauer, Michael; McMahon, Francis J.

doi:10.1159/000314708

Cited by 146 publications

(104 citation statements)

References 58 publications

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“…Since then, it has been used as a first-line treatment of BPD and as prophylaxis to prevent its recurrence [99]. The rate of lithium treatment response [105] and prophylactic efficacy [39] in BPD is relatively high compared to placebo.…”

Section: Lithium Treatment For Bipolar Disordermentioning

confidence: 99%

“…The ConLi + Gen Consortium (www.ConLiGen.org) is an initiative by the National Institute of Mental Health (NIMH) and the International Group for the Study of Lithium-Treated Patients (IGSLI) (www.IGSLI.org) [99]. The ConLiGen has compiled genetic and clinical data from 3193 patients with BPD who had undergone lithium treatment in Europe, USA, Asia, and Australia [56].…”

Section: Collaborations To Study the Pharmacogenomics Of Lithiummentioning

confidence: 99%

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Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

2017

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Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry. So far, the progress of uncovering single nucleotide polymorphisms (SNPs) underpinning treatment efficacy in mood disorders (e.g., SNPs associated with selective serotonin re-uptake inhibitors or lithium treatment response in patients with bipolar disorder and major depressive disorder) are encouraging, but not adequate. Genetic studies have pointed to a number of SNPs located at candidate genes that possibly influence response to; (a) antidepressants COMT, HTR2A, HTR1A, CNR1, SLC6A4, NPY, MAOA, IL1B, GRIK4, BDNF, GNB3, FKBP5, CYP2D6, CYP2C19, and ABCB1 and (b) mood stabilizers (lithium) 5-HTT, TPH, DRD1, FYN, INPP1, CREB1, BDNF, GSK3β, ARNTL, TIM, DPB, NR3C1, BCR, XBP1, and CACNG2. We suggest three alternative and complementary strategies to implement knowledge gained from pharmacogenomic studies. The first strategy can be to implement diagnostic, therapeutic, or prognostic genetic testing based on candidate genes or gene products. The second alternative is an integrative analysis (systems genomics approach) to combine omics data obtained from the different pillars of omics investigation, including genomics, epigenomes, proteomics, metabolomics and microbiomes. The main goal of system genomics is an identification and understanding of biological pathways, networks, and modules underlying drug-response. The third strategy aims to the development of multivariable diagnostic or prognostic algorithms (tools) combining individual's genomic information (polygenic score) with other predictors (e.g., omics pillars, neuroimaging, and clinical characteristics) to finally predict therapeutic outcomes. An integration of molecular science with that of traditional clinical practice is the way forward to drug discoveries and novel therapeutic approaches and to characterize psychiatric disorders leading to a better predictive, preventive, and personalized medicine (PPPM) in psychiatry. With future advances in the omics technology and methodological developments for data integration, the goal of PPPM in psychiatry is promising.

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Section: Lithium Treatment For Bipolar Disordermentioning

confidence: 99%

Section: Collaborations To Study the Pharmacogenomics Of Lithiummentioning

confidence: 99%

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

2017

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“…Genetic factors and clinical characteristics contribute to the failure of a favourable treatment outcome [4,5]. A large number of genes are likely to influence the toxicity and response of an individual medication of antidepressant response [1][2][3][4][5][6][7][8][9][10][11][12][13][14]15]. A recent study focused on determination of the effect of the CYP2D6 genotype on the length of hospitalization stay for patients treated for major depressive disorder and found that the hospital stay was significantly longer in deficient CYP2D6 metabolizers compared with functional or supra-functional metabolizers [16].…”

Section: Current Findingsmentioning

confidence: 99%

Pharmacogenetics of Antidepressants, A Review of Significant Genetic Variants in Different Populations

Reyes-Barron¹,

Tonarelli²,

Delozier³

et al. 2017

Clin Depress

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Major depressive disorder is a highly prevalent disease that is challenging to treat, often requiring medication and dose adjustments. Genetic factors play an important role in psychotropic medication responses. However, the translation of pharmacogenetics findings to clinical recommendations with regards to antidepressant responses is still in its early stages. We reviewed recent primary research articles, meta-analyses, and reviews on the pharmacogenetics of antidepressant treatment for major depressive disorder in different populations. We identified eight genes with likely associations with treatment responses and summarized genetic variants most likely to influence treatment responses. We determined the frequency of these variants in Caucasian, Asian, Hispanic, and African American populations. The genes are related to functions in drug metabolism, transport, signalling, stress response, and neuroplasticity. Clinical recommendations already exist for CYP2D6 and CYP2C19 cytochrome P450 drug metabolism genes. The other genes are: ABCB1 with single nucleotide polymorphisms (SNPs) rs2032583 and rs2235015; FKBP5 with SNPs rs1360780, rs3800373, and rs4713916; GNB3 with SNP rs5443; BDNF with SNP rs6265; HTR2A with SNPs rs7997012 and rs6313; and SLC6A4 with polymorphisms 5-HTTLPR and STin2. There is significant variability of the frequencies of these polymorphisms in the different populations we reviewed. There is also variability in the antidepressant responses between populations carrying the same polymorphism in some cases, indicating a likely polygenic influence. Future studies in the pharmacogenetics of antidepressants would benefit from including more subjects from underrepresented ethnic groups and stratifying results.

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“…Several genome scans and meta-analyses have been completed, mostly in international cooperation; others are on the way [52] . The genetic studies of lithium response have offered much promise and I cannot do justice to this exciting, quickly expanding area while staying within the assigned space.…”

Section: Search For Genetic Culpritsmentioning

confidence: 99%

Sixty Years of Lithium Responders

Grof¹

2010

Neuropsychobiology

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It has been 60 years since Cade first described patients who responded to antimanic lithium treatment. Two decades later, responders to lithium stabilization emerged in larger numbers. The responses of many severely ill bipolar patients to lithium were striking and called for an explanation. Remarkable reactions to a simple ion generated hope for an uncomplicated laboratory test of response and an extensive search for suitable biological markers ensued. But despite promising reports, particularly from molecular genetics, we are still waiting for a biological elucidation of the stabilizing effects of lithium. The most useful predictor of lithium stabilization has to date been the patient’s clinical profile, based on a comprehensive clinical assessment: complete remissions and other characteristics of episodic clinical course, bipolar family history, low psychiatric comorbidity and a characteristic presenting psychopathology. In brief, the responders approximate the classical Kraepelinian description of a manic-depressive patient. But the most intriguing findings have recently emerged from prospective observations of the next generation: the children of lithium responders, their counterparts coming from parents who did not respond to lithium and controls. Overall, they indicate that parents and offspring suffer from a comparable brain dysfunction that manifests clinically in distinct stages. If the child’s predicament starts early in childhood, it presents with varied, nonaffective or subclinical manifestations that are usually nonresponsive to standard treatments prescribed according to the symptoms. The next stage then unfolds in adolescence, first with depressive and later with activated episodes. The observations have a potential to markedly enrich the prevailing understanding and management of mood disorders.

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The International Consortium on Lithium Genetics (ConLiGen): An Initiative by the NIMH and IGSLI to Study the Genetic Basis of Response to Lithium Treatment

Cited by 146 publications

References 58 publications

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

Pharmacogenetics of Antidepressants, A Review of Significant Genetic Variants in Different Populations

Sixty Years of Lithium Responders

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