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Face and predictive validity of the ClockΔ19 mouse as an animal model for bipolar disorder: a systematic review

Molecular Psychiatry volume 23, pages 70–80 (2018)Cite this article

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Abstract

Mice carrying the circadian locomotor output cycles Kaput delta 19 N-ethyl-N-nitrosoure (ENU) mutation (ClockΔ19) are used as an animal model for bipolar disorder (BD). We aimed to systematically review the face validity (phenotypical and pathophysiological resemblance with BD) and predictive validity (responsiveness to treatments used in BD) of this model in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We carried out a systematic search of the databases PubMed and Embase, combining search terms covering BD and ClockΔ19. The 22 studies included in the review (from a total of 1281 identified records) show that the behavioral phenotype of the ClockΔ19 mouse is characterized by hyperactivity, decreased anxiety-like behavior, decreased depression-like behavior and increased preference for rewarding stimuli. This is highly consistent with mania in humans. Moreover, the ClockΔ19 mouse exhibits rapid mood cycling (a manic-like phenotype during the day followed by euthymia at night), which is consistent with BD. Chronic administration of lithium, a drug with well established mood-stabilizing effect in humans with BD, reverses the majority of the bipolar-like traits and most of the neurobiological abnormalities observed in the ClockΔ19 mouse. In conclusion, the ClockΔ19 mouse has substantial face validity as an animal model for BD. The predictive validity of the ClockΔ19 mouse has primarily been investigated via studies using lithium challenge. Therefore, further studies are needed to determine how the ClockΔ19 mouse responds to other mood-stabilizing treatments of BD such as valproate, lamotrigine, carbamazepine, oxcarbazepine, antipsychotics, electroconvulsive therapy and various light interventions.

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References

  1. Grande I, Berk M, Birmaher B, Vieta E . Bipolar disorder. Lancet 2016; 387: 1561–1572.

    PubMed  Google Scholar 

  2. Phillips ML, Kupfer DJ . Bipolar disorder diagnosis: challenges and future directions. Lancet 2013; 381: 1663–1671.

    PubMed  PubMed Central  Google Scholar 

  3. Mason BL, Brown ES, Croarkin PE . Historical underpinnings of bipolar disorder diagnostic criteria. Behav Sci (Basel) 2016; 6: 3390.

    Google Scholar 

  4. Merikangas KR, He J, Burstein M, Swanson SA, Avenevoli S, Cui L et al. Lifetime prevalence of mental disorders in U.S. adolescents: results from the national comorbidity survey Replication–Adolescent supplement (NCS-A). J Am Acad Child Adolesc Psychiatry 49: 980–989.

    Google Scholar 

  5. Craddock N, Sklar P . Genetics of bipolar disorder. Lancet 2013; 381: 1654–1662.

    CAS  PubMed  Google Scholar 

  6. Nestler EJ, Hyman SE . Animal models of neuropsychiatric disorders. Nat Neurosci 2010; 13: 1161–1169.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Cryan JF, Mombereau C . In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol Psychiatry 2004; 9: 326–357.

    CAS  PubMed  Google Scholar 

  8. Cosgrove VE, Kelsoe JR, Suppes T . Toward a valid animal model of bipolar disorder: how the research domain criteria help bridge the clinical-basic science divide. Biol Psychiatry 2016; 79: 62–70.

    PubMed  Google Scholar 

  9. Gonzalez R . The relationship between bipolar disorder and biological rhythms. J Clin Psychiatry 2014; 75: e323–e331.

    PubMed  Google Scholar 

  10. Etain B, Milhiet V, Bellivier F, Leboyer M . Genetics of circadian rhythms and mood spectrum disorders. Eur Neuropsychopharmacol 2011; 21 (Suppl 4): S676–S682.

    CAS  PubMed  Google Scholar 

  11. Benedetti F, Serretti A, Colombo C, Barbini B, Lorenzi C, Campori E et al. Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness recurrence in bipolar depression. Am J Med Genet B Neuropsychiatr Genet 2003; 123B: 23–26.

    PubMed  Google Scholar 

  12. Benedetti F, Dallaspezia S, Fulgosi MC, Lorenzi C, Serretti A, Barbini B et al. Actimetric evidence that CLOCK 3111 T/C SNP influences sleep and activity patterns in patients affected by bipolar depression. Am J Med Genet B Neuropsychiatr Genet 2007; 144B: 631–635.

    CAS  PubMed  Google Scholar 

  13. Bollettini I, Melloni EM, Aggio V, Poletti S, Lorenzi C, Pirovano A et al. Clock genes associate with white matter integrity in depressed bipolar patients. Chronobiol Int 2017; 34: 212–224.

    CAS  PubMed  Google Scholar 

  14. Roybal K, Theobold D, Graham A, DiNieri JA, Russo SJ, Krishnan V et al. Mania-like behavior induced by disruption of CLOCK. Proc Natl Acad Sci USA 2007; 104: 6406–6411.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Vitaterna MH, King DP, Chang AM, Kornhauser JM, Lowrey PL, McDonald JD et al. Mutagenesis and mapping of a mouse gene, clock, essential for circadian behavior. Science 1994; 264: 719–725.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. King DP, Vitaterna MH, Chang AM, Dove WF, Pinto LH, Turek FW et al. The mouse clock mutation behaves as an antimorph and maps within the W19H deletion, distal of kit. Genetics 1997; 146: 1049–1060.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. King DP, Zhao Y, Sangoram AM, Wilsbacher LD, Tanaka M, Antoch MP et al. Positional cloning of the mouse circadian clock gene. Cell 1997; 89: 641–653.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. McClung CA, Sidiropoulou K, Vitaterna M, Takahashi JS, White FJ, Cooper DC et al. Regulation of dopaminergic transmission and cocaine reward by the clock gene. Proc Natl Acad Sci USA 2005; 102: 9377–9381.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097.

    PubMed  PubMed Central  Google Scholar 

  20. Naylor E, Bergmann BM, Krauski K, Zee PC, Takahashi JS, Vitaterna MH et al. The circadian clock mutation alters sleep homeostasis in the mouse. J Neurosci 2000; 20: 8138–8143.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. van Enkhuizen J, Minassian A, Young JW . Further evidence for ClockDelta19 mice as a model for bipolar disorder mania using cross-species tests of exploration and sensorimotor gating. Behav Brain Res 2013; 249: 44–54.

    PubMed  PubMed Central  Google Scholar 

  22. Gold AK, Sylvia LG . The role of sleep in bipolar disorder. Nat Sci Sleep 2016; 8: 207–214.

    PubMed  PubMed Central  Google Scholar 

  23. Moon J-, Cho C-, Son GH, Geum D, Chung S, Kim H et al. Advanced circadian phase in mania and delayed circadian phase in mixed mania and depression returned to normal after treatment of bipolar disorder. EBioMedicine 2016; 11: 285–295.

    PubMed  PubMed Central  Google Scholar 

  24. Bernardi RE, Spanagel R . The ClockDelta19 mutation in mice fails to alter the primary and secondary reinforcing properties of nicotine. Drug Alcohol Depend 2013; 133: 733–739.

    CAS  PubMed  Google Scholar 

  25. Bernardi RE, Spanagel R . Enhanced extinction of contextual fear conditioning in ClockDelta19 mutant mice. Behav Neurosci 2014; 128: 468–473.

    PubMed  Google Scholar 

  26. Kozikowski AP, Gunosewoyo H, Guo S, Gaisina IN, Walter RL, Ketcherside A et al. Identification of a glycogen synthase kinase-3beta inhibitor that attenuates hyperactivity in CLOCK mutant mice. ChemMedChem 2011; 6: 1593–1602.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Arey R, McClung CA . An inhibitor of casein kinase 1 epsilon/delta partially normalizes the manic-like behaviors of the ClockDelta19 mouse. Behav Pharmacol 2012; 23: 392–396.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Easton A, Arbuzova J, Turek FW . The circadian clock mutation increases exploratory activity and escape-seeking behavior. Genes Brain Behav 2003; 2: 11–19.

    CAS  PubMed  Google Scholar 

  29. Dzirasa K, Coque L, Sidor MM, Kumar S, Dancy EA, Takahashi JS et al. Lithium ameliorates nucleus accumbens phase-signaling dysfunction in a genetic mouse model of mania. J Neurosci 2010; 30: 16314–16323.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Coque L, Mukherjee S, Cao JL, Spencer S, Marvin M, Falcon E et al. Specific role of VTA dopamine neuronal firing rates and morphology in the reversal of anxiety-related, but not depression-related behavior in the ClockDelta19 mouse model of mania. Neuropsychopharmacology 2011; 36: 1478–1488.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Dzirasa K, McGarity DL, Bhattacharya A, Kumar S, Takahashi JS, Dunson D et al. Impaired limbic gamma oscillatory synchrony during anxiety-related behavior in a genetic mouse model of bipolar mania. J Neurosci 2011; 31: 6449–6456.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Sidor MM, Spencer SM, Dzirasa K, Parekh PK, Tye KM, Warden MR et al. Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice. Mol Psychiatry 2015; 20: 1406–1419.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Perry W, Minassian A, Henry B, Kincaid M, Young JW, Geyer MA . Quantifying over-activity in bipolar and schizophrenia patients in a human open field paradigm. Psychiatry Res 2010; 178: 84–91.

    PubMed  PubMed Central  Google Scholar 

  34. Minassian A, Henry BL, Young JW, Masten V, Geyer MA, Perry W . Repeated assessment of exploration and novelty seeking in the human behavioral pattern monitor in bipolar disorder patients and healthy individuals. PLoS ONE 2011; 6: e24185.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Kim SW, Grant JE, Eckert ED, Faris PL, Hartman BK . Pathological gambling and mood disorders: clinical associations and treatment implications. J Affect Disord 2006; 92: 109–116.

    PubMed  Google Scholar 

  36. Perry W, Minassian A, Feifel D, Braff DL . Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania. Biol Psychiatry 2001; 50: 418–424.

    CAS  PubMed  Google Scholar 

  37. Acheson DT, Eyler LT, Resovsky J, Tsan E, Risbrough VB . Fear extinction memory performance in a sample of stable, euthymic patients with bipolar disorder. J Affect Disord 2015; 185: 230–238.

    PubMed  Google Scholar 

  38. Di Nicola M, De Risio L, Pettorruso M, Caselli G, De Crescenzo F, Swierkosz-Lenart K et al. Bipolar disorder and gambling disorder comorbidity: current evidence and implications for pharmacological treatment. J Affect Disord 2014; 167: 285–298.

    PubMed  Google Scholar 

  39. Fletcher K, Parker G, Paterson A, Synnott H . High-risk behaviour in hypomanic states. J Affect Disord 2013; 150: 50–56.

    PubMed  Google Scholar 

  40. Kopeykina I, Kim HJ, Khatun T, Boland J, Haeri S, Cohen LJ et al. Hypersexuality and couple relationships in bipolar disorder: a review. J Affect Disord 2016; 195: 1–14.

    PubMed  Google Scholar 

  41. Marengo E, Martino DJ, Igoa A, Fassi G, Scapola M, Urtueta Baamonde M et al. Sexual risk behaviors among women with bipolar disorder. Psychiatry Res 2015; 230: 835–838.

    PubMed  Google Scholar 

  42. MacCabe JH, Lambe MP, Cnattingius S, Sham PC, David AS, Reichenberg A et al. Excellent school performance at age 16 and risk of adult bipolar disorder: National Cohort Study. Br J Psychiatry 2010; 196: 109–115.

    PubMed  Google Scholar 

  43. Power RA, Steinberg S, Bjornsdottir G, Rietveld CA, Abdellaoui A, Nivard MM et al. Polygenic risk scores for schizophrenia and bipolar disorder predict creativity. Nat Neurosci 2015; 18: 953–955.

    CAS  PubMed  Google Scholar 

  44. Vreeker A, Boks MP, Abramovic L, Verkooijen S, van Bergen AH, Hillegers MH et al. High educational performance is a distinctive feature of bipolar disorder: a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls. Psychol Med 2016; 46: 807–818.

    CAS  PubMed  Google Scholar 

  45. Ozburn AR, Falcon E, Mukherjee S, Gillman A, Arey R, Spencer S et al. The role of clock in ethanol-related behaviors. Neuropsychopharmacology 2013; 38: 2393–2400.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Ozburn AR, Larson EB, Self DW, McClung CA . Cocaine self-administration behaviors in ClockDelta19 mice. Psychopharmacology (Berl) 2012; 223: 169–177.

    CAS  Google Scholar 

  47. Cassidy F, Ahearn EP, Carroll BJ . Substance abuse in bipolar disorder. Bipolar Disord 2001; 3: 181–188.

    CAS  PubMed  Google Scholar 

  48. Elmslie JL, Mann JI, Silverstone JT, Williams SM, Romans SE . Determinants of overweight and obesity in patients with bipolar disorder. J Clin Psychiatry 2001; 62: 492–493, 486,91; quiz.

    Google Scholar 

  49. Heffner JL, Strawn JR, DelBello MP, Strakowski SM, Anthenelli RM . The co-occurrence of cigarette smoking and bipolar disorder: phenomenology and treatment considerations. Bipolar Disord 2011; 13: 439–453.

    PubMed  PubMed Central  Google Scholar 

  50. Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E et al. Obesity and metabolic syndrome in circadian clock mutant mice. Science 2005; 308: 1043.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Vancampfort D, Vansteelandt K, Correll CU, Mitchell AJ, De Herdt A, Sienaert P et al. Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators. Am J Psychiatry 2013; 170: 265–274.

    PubMed  Google Scholar 

  52. McElroy SL, Keck PE Jr . Metabolic syndrome in bipolar disorder: a review with a focus on bipolar depression. J Clin Psychiatry 2014; 75: 46–61.

    CAS  PubMed  Google Scholar 

  53. Sidor MM, Spencer S, Tye K, Warden M, Dzirasa K, Deisseroth K et al. Optogenetic control of mesolimbic dopamine neural activity recapitulates the anxiety-related phenotype of the clock-δ19 mouse model of mania. Neuropsychopharmacology 2011; 36: S92.

    Google Scholar 

  54. Spencer S, Torres-Altoro MI, Falcon E, Arey R, Marvin M, Goldberg M et al. A mutation in CLOCK leads to altered dopamine receptor function. J Neurochem 2012; 123: 124–134.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Cousins DA, Butts K, Young AH . The role of dopamine in bipolar disorder. Bipolar Disord 2009; 11: 787–806.

    CAS  PubMed  Google Scholar 

  56. de Bartolomeis A, Buonaguro EF, Iasevoli F, Tomasetti C . The emerging role of dopamine-glutamate interaction and of the postsynaptic density in bipolar disorder pathophysiology: implications for treatment. J Psychopharmacol 2014; 28: 505–526.

    CAS  PubMed  Google Scholar 

  57. Whitton AE, Treadway MT, Pizzagalli DA . Reward processing dysfunction in major depression, bipolar disorder and schizophrenia. Curr Opin Psychiatry 2015; 28: 7–12.

    PubMed  PubMed Central  Google Scholar 

  58. Zhan L, Kerr JR, Lafuente MJ, Maclean A, Chibalina MV, Liu B et al. Altered expression and coregulation of dopamine signalling genes in schizophrenia and bipolar disorder. Neuropathol Appl Neurobiol 2011; 37: 206–219.

    CAS  PubMed  Google Scholar 

  59. Arey RN, Enwright JF 3rd, Spencer SM, Falcon E, Ozburn AR, Ghose S et al. An important role for cholecystokinin, a CLOCK target gene, in the development and treatment of manic-like behaviors. Mol Psychiatry 2014; 19: 342–350.

    CAS  PubMed  Google Scholar 

  60. Beaule C, Swanstrom A, Leone MJ, Herzog ED . Circadian modulation of gene expression, but not glutamate uptake, in mouse and rat cortical astrocytes. PLoS ONE 2009; 4: e7476.

    PubMed  PubMed Central  Google Scholar 

  61. Hashimoto K, Sawa A, Iyo M . Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry 2007; 62: 1310–1316.

    CAS  PubMed  Google Scholar 

  62. Eastwood SL, Harrison PJ . Markers of glutamate synaptic transmission and plasticity are increased in the anterior cingulate cortex in bipolar disorder. Biol Psychiatry 2010; 67: 1010–1016.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Ehrlich A, Schubert F, Pehrs C, Gallinat J . Alterations of cerebral glutamate in the euthymic state of patients with bipolar disorder. Psychiatry Res 2015; 233: 73–80.

    PubMed  Google Scholar 

  64. Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S et al. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry 2010; 67: 793–802.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Zarate CA Jr, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A et al. Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry 2012; 71: 939–946.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Hong M, Chen DC, Klein PS, Lee VM . Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. J Biol Chem 1997; 272: 25326–25332.

    CAS  PubMed  Google Scholar 

  67. Chen G, Huang LD, Jiang YM, Manji HK . The mood-stabilizing agent valproate inhibits the activity of glycogen synthase kinase-3. J Neurochem 1999; 72: 1327–1330.

    CAS  PubMed  Google Scholar 

  68. Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Moller HJ et al. The world federation of societies of biological psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2009 on the treatment of acute mania. World J Biol Psychiatry 2009; 10: 85–116.

    PubMed  Google Scholar 

  69. Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Moller HJ et al. The world federation of societies of biological psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2010 on the treatment of acute bipolar depression. World J Biol Psychiatry 2010; 11: 81–109.

    PubMed  Google Scholar 

  70. Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Moller HJ et al. The world federation of societies of biological psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2012 on the long-term treatment of bipolar disorder. World J Biol Psychiatry 2013; 14: 154–219.

    PubMed  Google Scholar 

  71. Bech P, Thomsen J, Rafaelsen OJ . Long-term lithium treatment: effect on simulated driving and other psychological tests. Eur J Clin Pharmacol 1976; 10: 331–335.

    CAS  PubMed  Google Scholar 

  72. Schou M., Amdisen A, Thornsen K. The effect of lithium on the normal mindIn Baudis P, Peterova E, Sedievec V eds. De Psychiatrica Pregrediente II 1968.

  73. Mukherjee S, Coque L, Cao J-, Kumar J, Chakravarty S, Asaithamby A et al. Knockdown of clock in the ventral tegmental area through RNA interference results in a mixed state of mania and depression-like behavior. Biol Psychiatry 2010; 68: 503–511.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Edgar N, Hoffman D, McClung C . Clock mutant mice are susceptible to developing a depression-like state following unpredictable chronic mild stress. Biol Psychiatry 2013; 73: 150S.

    Google Scholar 

  75. Johnson SL . Life events in bipolar disorder: towards more specific models. Clin Psychol Rev 2005; 25: 1008–1027.

    PubMed  PubMed Central  Google Scholar 

  76. Goldstein BI, Strober M, Axelson D, Goldstein TR, Gill MK, Hower H et al. Predictors of first-onset substance use disorders during the prospective course of bipolar spectrum disorders in adolescents. J Am Acad Child Adolesc Psychiatry 2013; 52: 1026–1037.

    PubMed  PubMed Central  Google Scholar 

  77. Naglich A, Adinoff B, Brown ES . Pharmacological treatment of bipolar disorder with comorbid alcohol use disorder. CNS Drugs 2017; 31: 665–674.

    CAS  PubMed  Google Scholar 

  78. Prisciandaro JJ, Brown DG, Brady KT, Tolliver BK . Comorbid anxiety disorders and baseline medication regimens predict clinical outcomes in individuals with co-occurring bipolar disorder and alcohol dependence: Results of a randomized controlled trial. Psychiatry Res 2011; 188: 361–365.

    PubMed  PubMed Central  Google Scholar 

  79. Bowden CL, Calabrese JR, Ketter TA, Sachs GS, White RL, Thompson TR . Impact of lamotrigine and lithium on weight in obese and nonobese patients with bipolar I disorder. Am J Psychiatry 2006; 163: 1199–1201.

    PubMed  Google Scholar 

  80. Gitlin M . Lithium side effects and toxicity: prevalence and management strategies. Int J Bipolar Disord 2016; 4: 27.

    PubMed  PubMed Central  Google Scholar 

  81. Sachs G, Bowden C, Calabrese JR, Ketter T, Thompson T, White R et al. Effects of lamotrigine and lithium on body weight during maintenance treatment of bipolar I disorder. Bipolar Disord 2006; 8: 175–181.

    CAS  PubMed  Google Scholar 

  82. Teixeira PJ, Rocha FL . The prevalence of metabolic syndrome among psychiatric inpatients in brazil. Rev Bras Psiquiatr 2007; 29: 330–336.

    PubMed  Google Scholar 

  83. Logan R, Ozburn A, Arey R, Zhang H, Zhu X, McClung C . Class I histone deacetylase (HDAC) inhibition reduces the mania-like behavioral phenotype of clockδ19 mutant mice. Neuropsychopharmacology 2014; 39: S603.

    Google Scholar 

  84. Perugi G, Medda P, Toni C, Mariani MG, Socci C, Mauri M . The role of electroconvulsive therapy (ECT) in bipolar disorder: fffectiveness in 522 patients with bipolar depression, mixed-state, mania and catatonic features. Curr Neuropharmacol 2017; 15: 359–371.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Henriksen TE, Skrede S, Fasmer OB, Schoeyen H, Leskauskaite I, Bjørke-Bertheussen J et al. Blue-blocking glasses as additive treatment for mania: a randomized placebo-controlled trial. Bipolar Disord 2016; 18: 221–232.

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are thankful to research librarian Helene Sognstrup, Aarhus University Library–Psychiatry, Aarhus, Denmark. SDØ is supported by a grant from the Lundbeck Foundation (R165-2013-15320).

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  1. Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark

    M Kristensen & S D Østergaard

  2. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

    M Kristensen & S D Østergaard

  3. Bipolar Clinic and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    A A Nierenberg

  4. Aarhus Institute of Advanced Studies, Aarhus University, Aarhus, Denmark

    S D Østergaard

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Ms Kristensen and Dr Østergaard reports no conflicts of interest. Dr Nierenberg reports the following conflicts of interest: Consultancy: Abbott Laboratories, Alkermes, American Psychiatric Association, Appliance Computing (Mindsite), Basliea, Brain Cells, Brandeis University, Bristol Myers Squibb, Clintara, Corcept, Dey Pharmaceuticals, Dainippon Sumitomo (now Sunovion), Eli Lilly and Company, EpiQ, L.P./Mylan, Forest, Genaissance, Genentech, GlaxoSmithKline, Healthcare Global Village, Hoffman LaRoche, Infomedic, Intra-Cellular Therapies, Lundbeck, Janssen Pharmaceutica, Jazz Pharmaceuticals, Medavante, Merck, Methylation Sciences, NeuroRx, Naurex, Novartis, PamLabs, Parexel, Pfizer, PGx Health, Otsuka, Ridge Diagnostics Shire, Schering-Plough, Somerset, Sunovion, Takeda Pharmaceuticals, Targacept and Teva; consulted through the MGH Clinical Trials Network and Institute (CTNI) for Astra Zeneca, Brain Cells, Dianippon Sumitomo/Sepracor, Johnson and Johnson, Labopharm, Merck, Methylation Science, Novartis, PGx Health, Shire, Schering-Plough, Targacept and Takeda/Lundbeck Pharmaceuticals, NeuroRx Pharma, Pfizer and Physician’s Postgraduate Press. Grants/Research support: American Foundation for Suicide Prevention, AHRQ, Brain and Behavior Research Foundation, Bristol-Myers Squibb, Cederroth, Cephalon, Cyberonics, Elan, Eli Lilly & Company, Forest, GlaxoSmithKline, Intra-Cellular Therapies, Janssen Pharmaceuticals, Lichtwer Pharma, Marriott Foundation, Mylan, NIMH, PamLabs, Patient Centered Outcomes Research Institute (PCORI), Pfizer Pharmaceuticals, Shire, Stanley Foundation, Takeda/Lundbeck and Wyeth-Ayerst. Honoraria: Belvoir Publishing, University of Texas Southwestern Dallas, Brandeis University, Bristol-Myers Squibb, Hillside Hospital, American Drug Utilization Review, American Society for Clinical Psychopharmacology, Baystate Medical Center, Columbia University, CRICO, Dartmouth Medical School, Health New England, Harold Grinspoon Charitable Foundation, IMEDEX, International Society for Bipolar Disorder, Israel Society for Biological Psychiatry, Johns Hopkins University, MJ Consulting, New York State, Medscape, MBL Publishing, MGH Psychiatry Academy, National Association of Continuing Education, Physicians Postgraduate Press, SUNY Buffalo, University of Wisconsin, University of Pisa, University of Michigan, University of Miami, University of Wisconsin at Madison, APSARD, ISBD, SciMed, Slack Publishing and Wolters Klower Publishing, ASCP, NCDEU, Rush Medical College, Yale University School of Medicine, NNDC, Nova Southeastern University, NAMI, Institute of Medicine, CME Institute, ISCTM, World Congress on Brain Behavior and Emotion, Congress of the Hellenic Society for Basic and Clinical Pharmacology and ADAA. Stock: Appliance Computing (MindSite), Brain Cells, Medavante. Copyrights: Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute (CTNI). Speaker Bureaus: none since 2003.

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Kristensen, M., Nierenberg, A. & Østergaard, S. Face and predictive validity of the ClockΔ19 mouse as an animal model for bipolar disorder: a systematic review. Mol Psychiatry 23, 70–80 (2018). https://doi.org/10.1038/mp.2017.192

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