Genetic and clinical factors predict lithium's effects on PER2 gene expression rhythms in cells from bipolar disorder patients
| العنوان: | Genetic and clinical factors predict lithium's effects on PER2 gene expression rhythms in cells from bipolar disorder patients |
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| المؤلفون: | Michael McCarthy, R M Darvish, Donna L. McPhie, Bruce M. Cohen, Z Marnoy, David K. Welsh, Heather Wei |
| المصدر: | Translational Psychiatry Translational psychiatry, vol 3, iss 10 McCarthy, MJ; Wei, H; Marnoy, Z; Darvish, RM; McPhie, DL; Cohen, BM; et al.(2013). Genetic and clinical factors predict lithium's effects on PER2 gene expression rhythms in cells from bipolar disorder patients. Translational Psychiatry, 3. doi: 10.1038/tp.2013.90. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/30s4r5m1Test |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Bipolar Disorder, Circadian clock, Gene Expression, Glycogen Synthase Kinase 3, 0302 clinical medicine, Group F, Antimanic Agents, Psychology, Cells, Cultured, bipolar disorder, 0303 health sciences, Cultured, Nuclear Receptor Subfamily 1, Group F, Member 1, Period Circadian Proteins, Middle Aged, Serious Mental Illness, 3. Good health, CLOCK, PER2, Psychiatry and Mental health, PER3, Mental Health, lithium, Public Health and Health Services, Lithium Compounds, Female, Original Article, Sleep Research, Adult, circadian rhythm, medicine.medical_specialty, Member 1, Nuclear Receptor Subfamily 1, Period (gene), Cells, Clinical Sciences, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, Clinical Research, Internal medicine, Genetics, medicine, Humans, Circadian rhythm, Bipolar disorder, Biological Psychiatry, 030304 developmental biology, Glycogen Synthase Kinase 3 beta, Fibroblasts, medicine.disease, Brain Disorders, Endocrinology, Case-Control Studies, 030217 neurology & neurosurgery |
| الوصف: | Bipolar disorder (BD) is associated with abnormal circadian rhythms. In treatment responsive BD patients, lithium (Li) stabilizes mood and reduces suicide risk. Li also affects circadian rhythms and expression of 'clock genes' that control them. However, the extent to which BD, Li and the circadian clock share common biological mechanisms is unknown, and there have been few direct measurements of clock gene function in samples from BD patients. Hence, the role of clock genes in BD and Li treatment remains unclear. Skin fibroblasts from BD patients (N=19) or healthy controls (N=19) were transduced with Per2::luc, a rhythmically expressed, bioluminescent circadian clock reporter gene, and rhythms were measured for 5 consecutive days. Rhythm amplitude and period were compared between BD cases and controls with and without Li. Baseline period was longer in BD cases than in controls. Li 1 mM increased amplitude in controls by 36%, but failed to do so in BD cases. Li 10 mM lengthened period in both BD cases and controls. Analysis of clock gene variants revealed that PER3 and RORA genotype predicted period lengthening by Li, whereas GSK3β genotype predicted rhythm effects of Li, specifically among BD cases. Analysis of BD cases by clinical history revealed that cells from past suicide attempters were more likely to show period lengthening with Li 1 mM. Finally, Li enhanced the resynchronization of damped rhythms, suggesting a mechanism by which Li could act therapeutically in BD. Our work suggests that the circadian clock's response to Li may be relevant to molecular pathology of BD. © 2013 Macmillan Publishers Limited All rights reserved. |
| وصف الملف: | application/pdf |
| تدمد: | 2158-3188 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cc8d758b32cc8f34c34b55d7bddcdf99Test https://pubmed.ncbi.nlm.nih.gov/24150227Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....cc8d758b32cc8f34c34b55d7bddcdf99 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21583188 |
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