Skip to main content
SpringerLink
Log in

Lithium Response Variability: New Avenues and Hypotheses

  • Chapter
  • First Online:
The Science and Practice of Lithium Therapy

Abstract

Lithium is the leading treatment for relapse prevention in bipolar disorders, but response prediction remains an important challenge for clinicians. Clinical predictors have poor sensitivity and specificity, and biomarkers predicting lithium response are lacking. This chapter reviews future research directions that may improve the prediction of lithium response. One important area for research is investigation of the blood and brain pharmacokinetics of lithium in humans, in particular the identification of the brain regions where lithium exerts its therapeutic action. Consistent data suggest the existence of variations in the lithium concentration between brain regions, but the association between brain lithium distribution and therapeutic response remains to be studied. It is also reasonable to think that active mechanisms at brain barriers underlie the brain distribution of lithium. Finally, a growing body of scientific data is available on the molecular signature of the lithium response, as well as lithium-targeted signalling pathways. All these areas of research are likely to open new avenues for identifying predictive biomarkers of the prophylactic response of lithium, thus facilitating the development of personalized therapeutic strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abe M, Herzog ED, Block GD (2000) Lithium lengthens the circadian period of individual suprachiasmatic nucleus neurons. Neuroreport 11(14):3261–3264

    Article  CAS  PubMed  Google Scholar 

  • Abou-Auda HS, Al-Yamani MJ, Abou-Shaaban RR, Khoshhal SI (2008) A new accurate method for predicting lithium clearance and daily dosage requirements in adult psychiatric patients. Bipolar Disord 10(3):369–376. doi:10.1111/j.1399-5618.2007.00549.x

    Article  CAS  PubMed  Google Scholar 

  • Ahluwalia P, Grewaal DS, Singhal RL (1981) Brain gabaergic and dopaminergic systems following lithium treatment and withdrawal. Prog Neuropsychopharmacol 5(5–6):527–530

    Article  CAS  PubMed  Google Scholar 

  • Amdisen A (1977) Serum level monitoring and clinical pharmacokinetics of lithium. Clin Pharmacokinet 2(2):73–92

    Article  CAS  PubMed  Google Scholar 

  • Backlund L, Ehnvall A, Hetta J, Isacsson G, Agren H (2009) Identifying predictors for good lithium response – a retrospective analysis of 100 patients with bipolar disorder using a life-charting method. Eur Psychiatry J Assoc Eur Psychiatr 24(3):171–177. doi:10.1016/j.eurpsy.2008.12.009

    Article  Google Scholar 

  • Baldessarini RJ, Tondo L (2000) Does lithium treatment still work? Evidence of stable responses over three decades. Arch Gen Psychiatry 57(2):187–190

    Article  CAS  PubMed  Google Scholar 

  • Beech RD, Leffert JJ, Lin A, Sylvia LG, Umlauf S, Mane S, Zhao H, Bowden C, Calabrese JR, Friedman ES, Ketter TA, Iosifescu DV, Reilly-Harrington NA, Ostacher M, Thase ME, Nierenberg A (2014) Gene-expression differences in peripheral blood between lithium responders and non-responders in the lithium treatment-moderate dose use study (litmus). Pharmacogenomics J 14(2):182–191. doi:10.1038/tpj.2013.16

    Article  CAS  PubMed  Google Scholar 

  • Chen C, Veronese L, Yin Y (2000) The effects of lamotrigine on the pharmacokinetics of lithium. Br J Clin Pharmacol 50(3):193–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen H, Wang N, Burmeister M, Mcinnis MG (2009) Microrna expression changes in lymphoblastoid cell lines in response to lithium treatment. Int J Neuropsychopharmacol 12(7):975–981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen HM, Delong CJ, Bame M, Rajapakse I, Herron TJ, Mcinnis MG, O’shea KS (2014) Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients. Transl Psychiatry 4:e375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiu CC, Shen WW, Chen KP, Lu ML (2007) Application of the cockcroft-gault method to estimate lithium dosage requirement. Psychiatry Clin Neurosci 61(3):269–274. doi:10.1111/j.1440-1819.2007.01654.x

    Article  CAS  PubMed  Google Scholar 

  • Colin SF, Chang HC, Mollner S, Pfeuffer T, Reed RR, Duman RS, Nestler EJ (1991) Chronic lithium regulates the expression of adenylate cyclase and gi-protein alpha subunit in rat cerebral cortex. Proc Natl Acad Sci U S A 88(23):10634–10637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coppen A, Peet M, Bailey J, Noguera R, Burns BH, Swani MS, Maggs R, Gardner R (1973) Double-blind and open prospective studies on lithium prophylaxis in affective disorders. Psychiatr Neurol Neurochir 76(6):501–510

    CAS  PubMed  Google Scholar 

  • Corena-Mcleod Mdel P, Oliveros A, Charlesworth C, Madden B, Liang YQ, Boules M, Shaw A, Williams K, Richelson E (2008) Paliperidone as a mood stabilizer: a pre-frontal cortex synaptoneurosomal proteomics comparison with lithium and valproic acid after chronic treatment reveals similarities in protein expression. Brain Res 1233:8–19. doi:10.1016/j.brainres.2008.07.021

    Article  PubMed  CAS  Google Scholar 

  • Coryell W, Akiskal H, Leon AC, Turvey C, Solomon D, Endicott J (2000) Family history and symptom levels during treatment for bipolar i affective disorder. Biol Psychiatry 47(12):1034–1042

    Article  CAS  PubMed  Google Scholar 

  • Cruceanu C, Alda M, Grof P, Rouleau GA, Turecki G (2012) Synapsin ii is involved in the molecular pathway of lithium treatment in bipolar disorder. PLoS ONE 7(2), e32680. doi:10.1371/journal.pone.0032680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuffi ML, Artells R, Navarro A, Ciruela F, Carbonell L (2010) Regulation of alpha(2)-adrenoceptor gene expression by chronic lithium treatment in rat brain. Methods Find Exp Clin Pharmacol 32(10):721–725. doi:10.1358/mf.2010.32.10.1545783

    Article  CAS  PubMed  Google Scholar 

  • Cunha AB, Frey BN, Andreazza AC, Goi JD, Rosa AR, Goncalves CA, Santin A, Kapczinski F (2006) Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes. Neurosci Lett 398(3):215–219. doi:10.1016/j.neulet.2005.12.085

    Article  CAS  PubMed  Google Scholar 

  • D’addario C, Dell’osso B, Palazzo MC, Benatti B, Lietti L, Cattaneo E, Galimberti D, Fenoglio C, Cortini F, Scarpini E, Arosio B, Di Francesco A, Di Benedetto M, Romualdi P, Candeletti S, Mari D, Bergamaschini L, Bresolin N, Maccarrone M, Altamura AC (2012) Selective DNA methylation of bdnf promoter in bipolar disorder: differences among patients with bdi and bdii. Neuropsychopharmacology 37(7):1647–1655. doi:10.1038/npp.2012.10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Damkier HH, Praetorius J (2012) Genetic ablation of slc4a10 alters the expression pattern of transporters involved in solute movement in the mouse choroid plexus. Am J Physiol Cell Physiol 302(10):C1452–C1459. doi:10.1152/ajpcell.00285.2011

    Article  CAS  PubMed  Google Scholar 

  • Dasso L, Campanini T, De Risio C (1977) Electroencephalographic changes during lithium salt therapy: correlation with the erythrocyte lithium content. Ateneo Parmense Acta Biomed Organo Soc Med Sci Nat Parma 48(5):417–423

    CAS  Google Scholar 

  • De Oliveira GS, Cereser KM, Fernandes BS, Kauer-Sant’anna M, Fries GR, Stertz L, Aguiar B, Pfaffenseller B, Kapczinski F (2009) Decreased brain-derived neurotrophic factor in medicated and drug-free bipolar patients. J Psychiatr Res 43(14):1171–1174

    Article  PubMed  Google Scholar 

  • Dols A, Sienaert P, Van Gerven H, Schouws S, Stevens A, Kupka R, Stek ML (2013) The prevalence and management of side effects of lithium and anticonvulsants as mood stabilizers in bipolar disorder from a clinical perspective: a review. Int Clin Psychopharmacol 28(6):287–296. doi:10.1097/YIC.0b013e32836435e2

    Article  PubMed  Google Scholar 

  • Duffy A, Horrocks J, Doucette S, Keown-Stoneman C, Mccloskey S, Grof P (2014) The developmental trajectory of bipolar disorder. Br J Psychiatr J Ment Sci 204(2):122–128. doi:10.1192/bjp.bp.113.126706

    Article  Google Scholar 

  • Dunner DL, Fieve RR (1974) Clinical factors in lithium carbonate prophylaxis failure. Arch Gen Psychiatry 30(2):229–233

    Article  CAS  PubMed  Google Scholar 

  • Dwivedi T, Zhang H (2014) Lithium-induced neuroprotection is associated with epigenetic modification of specific BDNF gene promoter and altered expression of apoptotic-regulatory proteins. Front Neurosci 8:457. doi:10.3389/fnins.2014.00457

  • Dwivedi T, Zhang H (2015) Lithium-induced neuroprotection is associated with epigenetic modification of specific BDNF gene promoter and altered expression of apoptotic-regulatory proteins. Front Neurosci 14;8:457

    Google Scholar 

  • Dysken MW, Comaty JE, Pandey GN, Davis JM (1979) Asterixis associated with a high rbc lithium concentration. Am J Psychiatry 136(12):1610

    Article  CAS  PubMed  Google Scholar 

  • ElDesoky ES, Kumar V, Alorainy MS, Hamdi MM, Derendorf H (2008) Estimation of lithium clearance from routine clinical data in Egyptian bipolar patients. A population pharmacokinetic approach. Int J Clin Pharmacol Ther 46(12):617–626

    Google Scholar 

  • Elizur A, Yeret A, Segal Z, Graff E (1982) Lithium and electrolytes plasma/rbc ratio and paradoxical lithium neurotoxicity. Prog Neuro-Psychopharmacol Biol Psychiatry 6(3):235–241

    Article  CAS  Google Scholar 

  • Fatemi SH, Folsom TD, Reutiman TJ, Braun NN, Lavergne LG (2010) Levels of phosphodiesterase 4a and 4b are altered by chronic treatment with psychotropic medications in rat frontal cortex. Synapse 64(7):550–555. doi:10.1002/syn.20762

    Article  CAS  PubMed  Google Scholar 

  • Ferrie L, Young AH, Mcquade R (2005) Effect of chronic lithium and withdrawal from chronic lithium on presynaptic dopamine function in the rat. J Psychopharmacol 19(3):229–234. doi:10.1177/0269881105051525

    Article  CAS  PubMed  Google Scholar 

  • Ferrie L, Young AH, Mcquade R (2006) Effect of lithium and lithium withdrawal on potassium-evoked dopamine release and tyrosine hydroxylase expression in the rat. Int J Neuropsychopharmacol 9(6):729–735. doi:10.1017/S1461145705006243

    Article  CAS  PubMed  Google Scholar 

  • Frazer A, Mendels J, Secunda SK, Cochrane CM, Bianchi CP (1973) The prediction of brain lithium concentrations from plasma or erythrocyte measures. J Psychiatr Res 10(1):1–7

    Article  CAS  PubMed  Google Scholar 

  • Fukumoto T, Morinobu S, Okamoto Y, Kagaya A, Yamawaki S (2001) Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain. Psychopharmacology 158(1):100–106. doi:10.1007/s002130100871

    Article  CAS  PubMed  Google Scholar 

  • Gaillot J, Steimer JL, Mallet AJ, Thebault JJ, Bieder A (1979) A priori lithium dosage regimen using population characteristics of pharmacokinetic parameters. J Pharmacokinet Biopharm 7(6):579–628

    Article  CAS  PubMed  Google Scholar 

  • Garnham J, Munro A, Slaney C, Macdougall M, Passmore M, Duffy A, O’donovan C, Teehan A, Alda M (2007) Prophylactic treatment response in bipolar disorder: results of a naturalistic observation study. J Affect Disord 104(1–3):185–190. doi:10.1016/j.jad.2007.03.003

    Article  PubMed  Google Scholar 

  • Geddes JR, Burgess S, Hawton K, Jamison K, Goodwin GM (2004) Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials. Am J Psychiatry 161(2):217–222

    Article  PubMed  Google Scholar 

  • Gould TD, Manji HK (2002) The wnt signaling pathway in bipolar disorder. Neuroscientist Rev J Bringing Neurobiol Neurol Psychiatry 8(5):497–511

    CAS  Google Scholar 

  • Greil W, Stoltzenburg MC, Mairhofer ML, Haag M (1985) Lithium dosage in the elderly. A study with matched age groups. J Affect Disord 9(1):1–4

    Article  CAS  PubMed  Google Scholar 

  • Grof P, Alda M, Grof E, Zvolsky P, Walsh M (1994) Lithium response and genetics of affective disorders. J Affect Disord 32(2):85–95

    Article  CAS  PubMed  Google Scholar 

  • Grof P, Duffy A, Alda M, Hajek T (2009) Lithium response across generations. Acta Psychiatr Scand 120(5):378–385. doi:10.1111/j.1600-0447.2009.01454.x

    Article  CAS  PubMed  Google Scholar 

  • Guarnieri DJ, Dileone RJ (2008) Micrornas: a new class of gene regulators. Ann Med 40(3):197–208. doi:10.1080/07853890701771823

    Article  CAS  PubMed  Google Scholar 

  • Hewick DS, Murray N (1976) Red-blood-cell levels and lithium toxicity. Lancet 2(7983):473

    Article  CAS  PubMed  Google Scholar 

  • Higuchi S, Fukuoka R, Aoyama T, Horioka M (1988) Predicting serum lithium concentration using bayesian method: a comparison with other methods. J Pharmacobiodyn 11(3):158–174

    Article  CAS  PubMed  Google Scholar 

  • Hoegberg LC, Jurgens G, Zederkof VW, Holgersson B, Andersson JE, Dalhoff KP, Larsen EB, Angelo HR (2012) A computerised sampling strategy for therapeutic drug monitoring of lithium provides precise estimates and significantly reduces dose-finding time. Basic Clin Pharmacol Toxicol 110(3):259–263. doi:10.1111/j.1742-7843.2011.00800.x

    Article  CAS  PubMed  Google Scholar 

  • Huang HC, Chang YL, Lan TH, Chiu HJ, Liu WM, Lee TJ (2008) Prediction of optimal lithium doses for Taiwanese psychiatric patients. J Clin Pharm Ther 33(2):115–121. doi:10.1111/j.1365-2710.2007.00888.x

    Article  CAS  PubMed  Google Scholar 

  • Huang TL, Hung YY, Lee CT, Chen RF (2012) Serum protein levels of brain-derived neurotrophic factor and tropomyosin-related kinase b in bipolar disorder: effects of mood stabilizers. Neuropsychobiology 65(2):65–69. doi:10.1159/000328991

    Article  CAS  PubMed  Google Scholar 

  • Hunsberger JG, Chibane FL, Elkahloun AG, Henderson R, Singh R, Lawson J, Cruceanu C, Nagarajan V, Turecki G, Squassina A, Medeiros CD, Del Zompo M, Rouleau GA, Alda M, Chuang DM (2015) Novel integrative genomic tool for interrogating lithium response in bipolar disorder. Transl Psychiatry 5, e504. doi:10.1038/tp.2014.139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hunter R (1988) Steady-state pharmacokinetics of lithium carbonate in healthy subjects. Br J Clin Pharmacol 25(3):375–380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jermain DM, Crismon ML, Martin ES 3rd (1991) Population pharmacokinetics of lithium. Clin Pharm 10(5):376–381

    CAS  PubMed  Google Scholar 

  • Johnston BB, Dick EG, Naylor GJ, Dick DA (1979) Lithium side effects in a routine lithium clinic. Br J Psychiatry J Ment Sci 134:482–487

    Article  CAS  Google Scholar 

  • Kato T, Shioiri T, Inubushi T, Takahashi S (1993) Brain lithium concentrations measured with lithium-7 magnetic resonance spectroscopy in patients with affective disorders: relationship to erythrocyte and serum concentrations. Biol Psychiatry 33(3):147–152

    Article  CAS  PubMed  Google Scholar 

  • Kato T, Fujii K, Shioiri T, Inubushi T, Takahashi S (1996) Lithium side effects in relation to brain lithium concentration measured by lithium-7 magnetic resonance spectroscopy. Prog Neuro-Psychopharmacol Biol Psychiatry 20(1):87–97

    Article  CAS  Google Scholar 

  • Kato T, Inubushi T, Kato N (2000) Prediction of lithium response by 31p-mrs in bipolar disorder. Int J Neuropsychopharmacol 3(1):83–85. doi:10.1017/S1461145799001674

    Article  CAS  PubMed  Google Scholar 

  • Kato T, Hayashi-Takagi A, Toyota T, Yoshikawa T, Iwamoto K (2011) Gene expression analysis in lymphoblastoid cells as a potential biomarker of bipolar disorder. J Hum Genet 56(11):779–783. doi:10.1038/jhg.2011.101

    Article  CAS  PubMed  Google Scholar 

  • Keshavarz M, Emamghoreishi M, Nekooeian AA, Warsh J, Zare HR (2013) Increased bcl-2 protein levels in rat primary astrocyte culture following chronic lithium treatment. Iran J Med Sci 38(3):255–262

    PubMed  PubMed Central  Google Scholar 

  • Kim SH, Yu HS, Park HG, Ahn YM, Kim YS, Lee YH, Ha K, Shin SY (2013) Egr1 regulates lithium-induced transcription of the period 2 (per2) gene. Biochim Biophys Acta 1832(12):1969–1979. doi:10.1016/j.bbadis.2013.06.010

    Article  CAS  PubMed  Google Scholar 

  • Kittel-Schneider S, Schreck S, Ziegler C, Weissflog L, Hilscher M, Schwarz R, Schnetzler L, Neuner M, Reif A (2015) Lithium-induced clock gene expression in lymphoblastoid cells of bipolar affective patients. Pharmacopsychiatry 48(4–5):145–149. doi:10.1055/s-0035-1549946

    CAS  PubMed  Google Scholar 

  • Klein PS, Melton DA (1996) A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A 93(16):8455–8459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kleindienst N, Engel R, Greil W (2005) Which clinical factors predict response to prophylactic lithium? A systematic review for bipolar disorders. Bipolar Disord 7(5):404–417. doi:10.1111/j.1399-5618.2005.00244.x

    Article  CAS  PubMed  Google Scholar 

  • Komoroski RA, Pearce JM, Newton JE (1997) The distribution of lithium in rat brain and muscle in vivo by 7lithium nmr imaging. Magn Reson Med Off J Soc Magn Reson Med Soc Magn Reson Med 38(2):275–278

    Article  CAS  Google Scholar 

  • Kristoff CA, Hayes PE, Barr WH, Small RE, Townsend RJ, Ettigi PG (1986) Effect of ibuprofen on lithium plasma and red blood cell concentrations. Clin Pharm 5(1):51–55

    Google Scholar 

  • Lee JY, Lee JH, Moon YW, Chun BG, Jahng JW (2009) Proteomic analysis of lithium-induced gene expression in the rat hypothalamus. Int J Neurosc 119(9):1267–1281

    Article  CAS  Google Scholar 

  • Lee JH, Adler C, Norris M, Chu WJ, Fugate EM, Strakowski SM, Komoroski RA (2012) 4-t 7lithium 3d mr spectroscopy imaging in the brains of bipolar disorder subjects. Magn Reson Med Off J Soc Magn Reson Med Soc Magn Reson Med 68(2):363–368. doi:10.1002/mrm.24361

    Article  Google Scholar 

  • Lee RS, Pirooznia M, Guintivano J, Ly M, Ewald ER, Tamashiro KL, Gould TD, Moran TH, Potash JB (2015) Search for common targets of lithium and valproic acid identifies novel epigenetic effects of lithium on the rat leptin receptor gene. Transl Psychiatry 5, e600. doi:10.1038/tp.2015.90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lehmann W, Kanarkowski R, Matkowski K, Rybakowski J (1988) Studies of lithium pharmacokinetics in patients with affective illness. Pol J Pharmacol Pharm 40(1):47–54

    CAS  PubMed  Google Scholar 

  • Lenox RH, Wang L (2003) Molecular basis of lithium action: integration of lithium-responsive signaling and gene expression networks. Mol Psychiatry 8(2):135–144. doi:10.1038/sj.mp.4001306

    Article  CAS  PubMed  Google Scholar 

  • Lenox RH, Watson DG, Patel J, Ellis J (1992) Chronic lithium administration alters a prominent pkc substrate in rat hippocampus. Brain Res 570(1–2):333–340

    Article  CAS  PubMed  Google Scholar 

  • Liang Y, Ridzon D, Wong L, Chen C (2007) Characterization of microrna expression profiles in normal human tissues. BMC Genomics 8:166. doi:10.1186/1471-2164-8-166

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lowthert L, Leffert J, Lin A, Umlauf S, Maloney K, Muralidharan A, Lorberg B, Mane S, Zhao H, Sinha R, Bhagwagar Z, Beech R (2012) Increased ratio of anti-apoptotic to pro-apoptotic bcl2 gene-family members in lithium-responders one month after treatment initiation. Biol Mood Anxiety Disord 2(1):15. doi:10.1186/2045-5380-2-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Machado-Vieira R, Dietrich MO, Leke R, Cereser VH, Zanatto V, Kapczinski F, Souza DO, Portela LV, Gentil V (2007) Decreased plasma brain derived neurotrophic factor levels in unmedicated bipolar patients during manic episode. Biol Psychiatry 61(2):142–144. doi:10.1016/j.biopsych.2006.03.070

    Article  CAS  PubMed  Google Scholar 

  • Machado-Vieira R, Manji HK, Zarate CA Jr (2009) The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord 11(Suppl 2):92–109. doi:10.1111/j.1399-5618.2009.00714.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maj M, Starace F, Nolfe G, Kemalithium D (1986) Minimum plasma lithium levels required for effective prophylaxis in dsm iii bipolar disorder: a prospective study. Pharmacopsychiatry 19(6):420–423. doi:10.1055/s-2007-1017280

    Article  CAS  PubMed  Google Scholar 

  • Maj M, Pirozzi R, Magliano L (1995) Nonresponse to reinstituted lithium prophylaxis in previously responsive bipolar patients: prevalence and predictors. Am J Psychiatry 152(12):1810–1811

    Article  CAS  PubMed  Google Scholar 

  • Mann L, Heldman E, Bersudsky Y, Vatner SF, Ishikawa Y, Almog O, Belmaker RH, Agam G (2009) Inhibition of specific adenylyl cyclase isoforms by lithium and carbamazepine, but not valproate, may be related to their antidepressant effect. Bipolar Disord 11(8):885–896. doi:10.1111/j.1399-5618.2009.00762.x

    Article  CAS  PubMed  Google Scholar 

  • Marmol F (2008) Lithium: bipolar disorder and neurodegenerative diseases possible cellular mechanisms of the therapeutic effects of lithium. Prog Neuro-Psychopharmacol Biol Psychiatry 32(8):1761–1771. doi:10.1016/j.pnpbp.2008.08.012

    Article  CAS  Google Scholar 

  • Matigian N, Windus L, Smith H, Filippich C, Pantelis C, Mcgrath J, Mowry B, Hayward N (2007) Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the wnt signalling pathway. Mol Psychiatry 12(9):815–825. doi:10.1038/sj.mp.4001998

    Article  CAS  PubMed  Google Scholar 

  • Mcgrath BM, Greenshaw AJ, Mckay R, Slupsky CM, Silverstone PH (2006) Lithium alters regional rat brain myo-inositol at 2 and 4 weeks: an ex-vivo magnetic resonance spectroscopy study at 18.8 t. Neuroreport 17(12):1323–1326. doi:10.1097/01.wnr.0000230501.40349.41

    Article  CAS  PubMed  Google Scholar 

  • McKnew DH, Cytryn L, Buchsbaum MS, Hamovit J, Lamour M, Rapoport JL, Gershon ES (1981) Lithium in children of lithium-responding parents. Psychiatry Res 4(2):171–180

    Article  CAS  PubMed  Google Scholar 

  • Mcquillin A, Rizig M, Gurling HM (2007) A microarray gene expression study of the molecular pharmacology of lithium carbonate on mouse brain mrna to understand the neurobiology of mood stabilization and treatment of bipolar affective disorder. Pharmacogenet Genomics 17(8):605–617. doi:10.1097/FPC.0b013e328011b5b2

    Article  CAS  PubMed  Google Scholar 

  • Mendels J, Frazer A (1973) Intracellular lithium concentration and clinical response: towards a membrane theory of depression. J Psychiatr Res 10(1):9–18

    Article  CAS  PubMed  Google Scholar 

  • Mukherjee BP, Bailey PT, Pradhan SN (1976) Temporal and regional differences in brain concentrations of lithium in rats. Psychopharmacology 48(1):119–121

    Article  CAS  PubMed  Google Scholar 

  • Okuma T (1993) Effects of carbamazepine and lithium on affective disorders. Neuropsychobiology 27(3):138–145, doi:118969

    Article  CAS  PubMed  Google Scholar 

  • Olie JP, Gay C, Loo H, Zarifian E, Poirier-Littre MF, Deniker P (1982) The value of the measurement of intra-erythrocytic lithium in the bio-clinical surveillance of lithium therapy (author’s transl). Ann Biol Clin 40(1):3–10

    CAS  Google Scholar 

  • Ong YL (1983) Lithium levels in white blood cells and their relationship to observed side effects. Br J Psychiatry J Ment Sci 143:36–39

    Article  CAS  Google Scholar 

  • Osland TM, Ferno J, Havik B, Heuch I, Ruoff P, Laerum OD, Steen VM (2011) Lithium differentially affects clock gene expression in serum-shocked nih-3 t3 cells. J Psychopharmacol 25(7):924–933. doi:10.1177/0269881110379508

    Article  CAS  PubMed  Google Scholar 

  • Palomino A, Vallejo-Illarramendi A, Gonzalez-Pinto A, Aldama A, Gonzalez-Gomez C, Mosquera F, Gonzalez-Garcia G, Matute C (2006) Decreased levels of plasma bdnf in first-episode schizophrenia and bipolar disorder patients. Schizophr Res 86(1–3):321–322. doi:10.1016/j.schres.2006.05.028

    Article  PubMed  Google Scholar 

  • Parthasarathy LK, Seelan RS, Wilson MA, Vadnal RE, Parthasarathy RN (2003) Regional changes in rat brain inositol monophosphatase 1 (impase 1) activity with chronic lithium treatment. Prog Neuro-Psychopharmacol Biol Psychiatry 27(1):55–60

    Article  CAS  Google Scholar 

  • Passmore MJ, Garnham J, Duffy A, Macdougall M, Munro A, Slaney C, Teehan A, Alda M (2003) Phenotypic spectra of bipolar disorder in responders to lithium versus lamotrigine. Bipolar Disord 5(2):110–114

    Article  CAS  PubMed  Google Scholar 

  • Price LH, Heninger GR (1994) Lithium in the treatment of mood disorders. N Engl J Med 331(9):591–598. doi:10.1056/NEJM199409013310907

    Article  CAS  PubMed  Google Scholar 

  • Pulford DJ, Adams F, Henry B, Mallinson DJ, Reid IC, Stewart CA (2006) Chronic lithium administration down regulates transthyretin mrna expression in rat choroid plexus. Neuropsychiatr Dis Treat 2(4):549–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quiroz JA, Machado-Vieira R, Zarate CA Jr, Manji HK (2010) Novel insights into lithium’s mechanism of action: neurotrophic and neuroprotective effects. Neuropsychobiology 62(1):50–60. doi:10.1159/000314310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramaprasad S (2004) Lithium spectroscopic imaging of rat brain at therapeutic doses. Magn Reson Imaging 22(5):727–734. doi:10.1016/j.mri.2004.01.063

    Article  CAS  PubMed  Google Scholar 

  • Ramaprasad S, Newton JE, Cardwell D, Fowler AH, Komoroski RA (1992) In vivo 7lithium nmr imaging and localized spectroscopy of rat brain. Magn Reson Med Off J Soc Magn Reson Med Soc Magn Reson Med 25(2):308–318

    Article  CAS  Google Scholar 

  • Ramaprasad S, Ripp E, Pi J, Lyon M (2005) Pharmacokinetics of lithium in rat brain regions by spectroscopic imaging. Magn Reson Imaging 23(8):859–863. doi:10.1016/j.mri.2005.07.007

    Article  CAS  PubMed  Google Scholar 

  • Renshaw PF, Haselgrove JC, Leigh JS, Chance B (1985) In vivo nuclear magnetic resonance imaging of lithium. Magn Reson Med Off J Soc Magn Reson Med Soc Magn Reson Med 2(5):512–516

    Article  CAS  Google Scholar 

  • Rios C, Guzman-Mendez R (1990) Determination of lithium in rat brain regions and synaptosomes by graphite furnace atomic absorption spectrophotometry. J Pharmacol Methods 24(4):327–332

    Article  CAS  PubMed  Google Scholar 

  • Rohayem J, Bayle JF, Richa S (2008) Predictors of prophylactic response to lithium. L'Encéphale 34(4):394–399. doi:10.1016/j.encep.2007.05.002

    Article  CAS  PubMed  Google Scholar 

  • Rong H, Liu TB, Yang KJ, Yang HC, Wu DH, Liao CP, Hong F, Yang HZ, Wan F, Ye XY, Xu D, Zhang X, Chao CA, Shen QJ (2011) Microrna-134 plasma levels before and after treatment for bipolar mania. J Psychiatr Res 45(1):92–95

    Article  PubMed  Google Scholar 

  • Rybakowski JK (2013) Genetic influences on response to mood stabilizers in bipolar disorder: current status of knowledge. CNS Drugs 27(3):165–173. doi:10.1007/s40263-013-0040-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rybakowski JK, Suwalska A, Skibinska M, Dmitrzak-Weglarz M, Leszczynska-Rodziewicz A, Hauser J (2007) Response to lithium prophylaxis: interaction between serotonin transporter and bdnf genes. Am J Med Genet B Neuropsychiatr Genet 144B(6):820–823. doi:10.1002/ajmg.b.30420

    Article  CAS  PubMed  Google Scholar 

  • Sarantidis D, Waters B (1981) Predictors of lithium prophylaxis effectiveness. Prog Neuropsychopharmacol 5(5–6):507–510

    Article  CAS  PubMed  Google Scholar 

  • Seelan RS, Khalyfa A, Lakshmanan J, Casanova MF, Parthasarathy RN (2008) Deciphering the lithium transcriptome: microarray profiling of lithium-modulated gene expression in human neuronal cells. Neuroscience 151(4):1184–1197. doi:10.1016/j.neuroscience.2007.10.045

    Article  CAS  PubMed  Google Scholar 

  • Simard M, Gumbiner B, Lee A, Lewis H, Norman D (1989) Lithium carbonate intoxication. A case report and review of the literature. Arch Intern Med 149(1):36–46

    Article  CAS  PubMed  Google Scholar 

  • Solomon DA, Keitner GI, Miller IW, Shea MT, Keller MB (1995) Course of illness and maintenance treatments for patients with bipolar disorder. J Clin Psychiatry 56(1):5–13

    CAS  PubMed  Google Scholar 

  • Sproule B (2002) Lithium in bipolar disorder: can drug concentrations predict therapeutic effect? Clin Pharmacokinet 41(9):639–660. doi:10.2165/00003088-200241090-00002

    Article  PubMed  Google Scholar 

  • Squassina A, Costa M, Congiu D, Manchia M, Angius A, Deiana V, Ardau R, Chillotti C, Severino G, Calza S, Del Zompo M (2013) Insulin-like growth factor 1 (igf-1) expression is up-regulated in lymphoblastoid cell lines of lithium responsive bipolar disorder patients. Pharmacol Res Off J Ital Pharmacol Soc 73:1–7. doi:10.1016/j.phrs.2013.04.004

    CAS  Google Scholar 

  • Subramanian P, Menon VP, Arokiam FV, Rajakrishnan V, Balamurugan E (1998) Lithium modulates biochemical circadian rhythms in wistar rats. Chronobiol Int 15(1):29–38

    Article  CAS  PubMed  Google Scholar 

  • Sugawara H, Iwamoto K, Bundo M, Ishiwata M, Ueda J, Kakiuchi C, Ishigooka J, Kato T (2010) Effect of mood stabilizers on gene expression in lymphoblastoid cells. J Neural Transm 117(2):155–164. doi:10.1007/s00702-009-0340-8

    Article  CAS  PubMed  Google Scholar 

  • Sullivan PF, Fan C, Perou CM (2006) Evaluating the comparability of gene expression in blood and brain. Am J Med Genet B Neuropsychiatr Genet 141(3):261–268

    Article  Google Scholar 

  • Sun X, Young LT, Wang JF, Grof P, Turecki G, Rouleau GA, Alda M (2004) Identification of lithium-regulated genes in cultured lymphoblasts of lithium responsive subjects with bipolar disorder. Neuropsychopharmacology 29(4):799–804. doi:10.1038/sj.npp.1300383

    Article  CAS  PubMed  Google Scholar 

  • Swartz CM (1987) Correction of lithium levels for dose and blood sampling times. J Clin Psychiatry 48(2):60–64

    CAS  PubMed  Google Scholar 

  • Tajes M, Yeste-Velasco M, Zhu X, Chou SP, Smith MA, Pallas M, Camins A, Casadesus G (2009) Activation of akt by lithium: pro-survival pathways in aging. Mech Ageing Dev 130(4):253–261. doi:10.1016/j.mad.2008.12.006

    Article  CAS  PubMed  Google Scholar 

  • Terao T, Okuno K, Okuno T, Nakano H, Shinkai T, Ohmori O, Yoshimura R, Suzuki T, Abe K (1999) A simpler and more accurate equation to predict daily lithium dose. J Clin Psychopharmacol 19(4):336–340

    Article  CAS  PubMed  Google Scholar 

  • Tondo L, Baldessarini RJ, Floris G (2001) Long-term clinical effectiveness of lithium maintenance treatment in types i and ii bipolar disorders. Br J Psychiatry J Ment Sci 178(Suppl 41):S184–S190

    Article  Google Scholar 

  • Tramontina J, Frey BN, Andreazza AC, Zandona M, Santin A, Kapczinski F (2007) Val66met polymorphism and serum brain-derived neurotrophic factor levels in bipolar disorder. Mol Psychiatry 12(3):230–231. doi:10.1038/sj.mp.4001941

    Article  CAS  PubMed  Google Scholar 

  • Tramontina JF, Andreazza AC, Kauer-Sant’anna M, Stertz L, Goi J, Chiarani F, Kapczinski F (2009) Brain-derived neurotrophic factor serum levels before and after treatment for acute mania. Neurosci Lett 452(2):111–113

    Article  CAS  PubMed  Google Scholar 

  • Tseng M, Alda M, Xu L, Sun X, Wang JF, Grof P, Turecki G, Rouleau G, Young LT (2008) Bdnf protein levels are decreased in transformed lymphoblasts from lithium-responsive patients with bipolar disorder. J Psychiatry Neurosci JPN 33(5):449–453

    PubMed  Google Scholar 

  • Turck D, Heinzel G, Luik G (2000) Steady-state pharmacokinetics of lithium in healthy volunteers receiving concomitant meloxicam. Br J Clin Pharmacol 50(3):197–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vargas C, Tannhauser M, Barros HM (1998) Dissimilar effects of lithium and valproic acid on gaba and glutamine concentrations in rat cerebrospinal fluid. Gen Pharmacol 30(4):601–604

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Liu X, Lenox RH (2001) Transcriptional down-regulation of marcks gene expression in immortalized hippocampal cells by lithium. J Neurochem 79(4):816–825

    Article  CAS  PubMed  Google Scholar 

  • Williams MB, Jope RS (1995) Circadian variation in rat brain ap-1 DNA binding activity after cholinergic stimulation: modulation by lithium. Psychopharmacology 122(4):363–368

    Article  CAS  PubMed  Google Scholar 

  • Willmroth F, Drieling T, Lamla U, Marcushen M, Wark HJ, Van Calker D (2007) Sodium-myo-inositol co-transporter (smit-1) mrna is increased in neutrophils of patients with bipolar 1 disorder and down-regulated under treatment with mood stabilizers. Int J Neuropsychopharmacol 10(1):63–71. doi:10.1017/S1461145705006371

    Article  CAS  PubMed  Google Scholar 

  • Wright R, Crismon ML (2000) Comparison of three a priori methods and one empirical method in predicting lithium dosage requirements. Am J Health Syst Pharm AJHP Off J Am Soc Health Syst Pharm 57(18):1698–1702

    CAS  Google Scholar 

  • Yang YY (1985) Prophylactic efficacy of lithium and its effective plasma levels in Chinese bipolar patients. Acta Psychiatr Scand 71(2):171–175

    Article  CAS  PubMed  Google Scholar 

  • Yang YY, Yeh EK, Chang SS, Deng HC, Lee CF (1991) Maintenance lithium levels could be lowered: based on Taiwanese and Danish studies. J Formos Med Assoc Taiwan Yi Zhi 90(5):509–513

    CAS  PubMed  Google Scholar 

  • Yasuda S, Liang MH, Marinova Z, Yahyavi A, Chuang DM (2009) The mood stabilizers lithium and valproate selectively activate the promoter iv of brain-derived neurotrophic factor in neurons. Mol Psychiatry 14(1):51–59. doi:10.1038/sj.mp.4002099

    Article  CAS  PubMed  Google Scholar 

  • Yazici O, Kora K, Ucok A, Tunalithium D, Turan N (1999) Predictors of lithium prophylaxis in bipolar patients. J Affect Disord 55(2–3):133–142

    Article  CAS  PubMed  Google Scholar 

  • Yildiz A, Vieta E, Leucht S, Baldessarini RJ (2011) Efficacy of antimanic treatments: meta-analysis of randomized, controlled trials. Neuropsychopharmacology 36(2):375–389. doi:10.1038/npp.2010.192

    Article  CAS  PubMed  Google Scholar 

  • Yu Z, Ono C, Aiba S, Kikuchi Y, Sora I, Matsuoka H, Tomita H (2015) Therapeutic concentration of lithium stimulates complement c3 production in dendritic cells and microglia via gsk-3 inhibition. Glia 63(2):257–270. doi:10.1002/glia.22749

    Article  PubMed  Google Scholar 

  • Yukawa E, Nomiyama N, Higuchi S, Aoyama T (1993) Lithium population pharmacokinetics from routine clinical data: role of patient characteristics for estimating dosing regimens. Ther Drug Monit 15(2):75–82

    Article  CAS  PubMed  Google Scholar 

  • Zakowska-Dabrowska T, Rybakowski J (1973) Lithium-induced eeg changes: relation to lithium levels in serum and red blood cells. Acta Psychiatr Scand 49(4):457–465

    Article  CAS  PubMed  Google Scholar 

  • Zarate CA, Manji HK (2009) Protein kinase c inhibitors: rationale for use and potential in the treatment of bipolar disorder. CNS Drugs 23(7):569–582. doi:10.2165/00023210-200923070-00003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou R, Yuan P, Wang Y, Hunsberger JG, Elkahloun A, Wei Y, Damschroder-Williams P, Du J, Chen G, Manji HK (2009) Evidence for selective micrornas and their effectors as common long-term targets for the actions of mood stabilizers. Neuropsychopharmacology 34(6):1395–1405

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM UMR-S1144, Paris Descartes University & Paris Diderot University, PRES Sorbonne Paris Cité, Paris, France

    Frank Bellivier MD, PhD

  2. UFR de Médecine, Denis Diderot University, Paris, France

    Frank Bellivier MD, PhD

  3. FondaMental Foundation, Creteil, France

    Frank Bellivier MD, PhD

  4. Psychiatry Department, AP-HP GH Saint-Louis – Lariboisiere – F. Widal & INSERM UMR-S 1144, 200, rue du Fg Saint-Denis, Paris, 75475, Cedex 10, France

    Frank Bellivier MD, PhD

  5. INSERM UMR-S1144, Paris Descartes University & Paris Diderot University, PRES Sorbonne Paris Cité, Paris, France

    Cynthia Marie-Claire PhD

Authors
  1. Frank Bellivier MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cynthia Marie-Claire PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frank Bellivier MD, PhD .

Editor information

Editors and Affiliations

  1. Academic Department of Psychiatry, Sydney Medical School The University of Sydney, Sydney, Australia

    Gin S. Malhi

  2. Nightingale Hospitals Paris-Clinique du Château de Garches, Consultant Service Hospitalo-Universitaire Centre Hospitalier Sainte-Anne, Paris, France

    Marc Masson

  3. Publique – Hôpitaux de Paris, INSERM UMR-S1144 Paris-Diderot University, Paris, France

    Frank Bellivier

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Bellivier, F., Marie-Claire, C. (2017). Lithium Response Variability: New Avenues and Hypotheses. In: Malhi, G., Masson, M., Bellivier, F. (eds) The Science and Practice of Lithium Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-45923-3_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-45923-3_9

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-45921-9

  • Online ISBN: 978-3-319-45923-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation