Genetic Predictors of Lithium Response
https://doi.org/10.31363/2313-7053-2019-4-1-26-27
Abstract
Lithium remains a first-line pharmacological treatment of bipolar disorder (BD). However, treatment response is heterogeneous, with several lines of evidence implicating genetic factors. Unfortunately, neither hypothesis-driven approaches nor initial genome-wide association studies (GWAS) were successful in identifying genetic drivers of response heterogeneity, probably due to low statistical power and different phenotype measurements. Recently, a GWAS of the Consortium of Lithium Genetics (ConLiGen) has identified four single nucleotide polymorphisms (SNPs) mediating response to lithium, located in genes for two long non-coding RNAs. This success was only possible by international collaboration and the use of an established lithium response scale. The findings await further replication.
About the Author
U. Heilbronner
Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich
Germany
Urs Heilbronner — PhD
Germany
Urs Heilbronner — PhD
References
1. Alda M., Manchia M. Personalized management of bipolar disorder. Neuroscience Lettersю 2018;669:3 – 9. https://doi.org/10.1016/j.neulet.2017.12.005
2. Garnham J., Munro A., Slaney C., Macdougall M., Passmore M., Duffy A., Alda M. Prophylactic treatment response in bipolar disorder: Results of a naturalistic observation study. Journal of Affective Disorders. 2007;104(1–3):185–190. https://doi. org/10.1016/j.jad.2007.03.003
3. Grof P., Duffy A., Cavazzoni P., Grof E., Garnham J., MacDougall M., Alda M. Is response to prophylactic lithium a familial trait? The Journal of Clinical Psychiatry. 2002;63(10):942–947. https:// doi.org/10.4088/jcp.v63n1013
4. Hou L., Heilbronner U., Degenhardt F., Adli M., Akiyama K., Akula N., Schulze, T. G. Genetic variants associated with response to lithium treatment in bipolar disorder: A genome-wide association study. The Lancet. 2016;387(10023):1085–1093. https://doi.org/10.1016/S0140-6736(16)00143-4
5. Papiol S., Schulze T. G., Alda M. Genetics of Lithium Response in Bipolar Disorder. Pharmacopsychiatry. 2018;51(5):206–211. https://doi. org/10.1055/a-0590-4992
6. Perlis R.H., Smoller J.W., Ferreira M.A.R., McQuillin A., Bass N., Lawrence J., Purcell S. A genomewide association study of response to lithium for prevention of recurrence in bipolardisorder. The American Journal of Psychiatry. 2009;166(6):718–725. https://doi.org/10.1176/appi. ajp.2009.08111633
7. Pisanu C., Heilbronner U., Squassina A. The Role of Pharmacogenomics in Bipolar Disorder: Moving Towards Precision Medicine. Mol Diagn Ther. 2018;22(4):409–420. https://doi.org/10.1007/ s40291-018-0335-y
8. Schulze T.G., Alda M., Adli M., Akula N., Ardau R., Bui E. T., … McMahon, F.J. The International Consortium on Lithium Genetics (ConLiGen): An initiative by the NIMH and IGSLI to study the genetic basis of response to lithium treatment. Neuropsychobiology. 2010;62(1):72–78. https://doi. org/10.1159/000314708
9. Song J., Bergen S. E., Di Florio A., Karlsson R., Charney A., Ruderfer D. M., Landén M. Genomewide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder. Molecular Psychiatry. 2017;22(8):1223. https://doi. org/10.1038/mp.2016.246
10. Squassina A., Manchia M., Borg J., Congiu D., Costa M., Georgitsi M., Patrinos G.P. Evidence for association of an ACCN1 gene variant with response to lithium treatment in Sardinian patients with bipolar disorder. Pharmacogenomics. 2011;12(11):1559–1569. https://doi.org/10.2217/ pgs.11.102
Review
For citations:
Heilbronner U. Genetic Predictors of Lithium Response. V.M. BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY. 2019;(4-1):26-27. https://doi.org/10.31363/2313-7053-2019-4-1-26-27
Views:
811
Email this article 