Skip to main content Accessibility help
  • Print publication year: 2014
  • Online publication date: October 2014

23 - Bipolar disorder

from Section 5 - Anxiety and mood disorders


Agam, G., Bersudsky, Y., Berry, G.T., et al. (2009) Knockout mice in understanding the mechanism of action of lithium. Biochem Soc Trans 37: 1121–1125.
Andreazza, A.C., Shao, L., Wang, J.F., and Young, L.T. (2010) Mitochondrial complex I activity and oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder. Arch Gen Psychiatry 67: 360–368.
Angst, J., Gamma, A., Sellaro, R., Lavori, P.W., and Zhang, H. (2003) Recurrence of bipolar disorders and major depression. A life-long perspective. Eur Arch Psychiatry Clin Neurosci 253: 236–240.
Avale, M.E., Falzone, T.L., Gelman, D.M., et al. (2004) The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperactivity disorder. Mol Psychiatry 9: 718–726.
Bachmann, R.F., Schloesser, R.J., Gould, T.D., and Manji, H.K. (2005) Mood stabilizers target cellular plasticity and resilience cascades: implications for the development of novel therapeutics. Mol Neurobiol 32: 173–202.
Bai, O., Zhang, H., and Li, X.M. (2004) Antipsychotic drugs clozapine and olanzapine upregulate bcl-2 mRNA and protein in rat frontal cortex and hippocampus. Brain Res 1010: 81–86.
Barbier, E. and Wang, J.B. (2009) Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level. BMC Neurosci 10: 132.
Beaulieu, J.M. (2012) A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health. J Psychiatry Neurosci 37: 7–16.
Begley, C.E., Annegers, J.F., Swann, A.C., et al. (2001) The lifetime cost of bipolar disorder in the US: an estimate for new cases in 1998. Pharmacoeconomics 19: 483–495.
Bello, E.P., Mateo, Y., Gelman, D.M., et al. (2011) Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors. Nat Neurosci 14: 1033–1038.
Belmaker, R.H., Livne, A., Agam, G., et al. (1990) Role of inositol-1-phosphatase inhibition in the mechanism of action of lithium. Pharmacol Toxicol 66: 76–83.
Belmaker, R.H., Revazov, A., Bersudskey, Y., and Kofman, O. (1992) Inositol passes the blood brain behavior sufficiently to reverse lithium effects on behavior in rats. Clin Neuropharmacol 15: 606A–607A.
Benedetti, F., Barbini, B., Campori, E., et al. (2001) Sleep phase advance and lithium to sustain the antidepressant effect of total sleep deprivation in bipolar depression: new findings supporting the internal coincidence model? J Psychiatr Res 35: 323–329.
Benedetti, F., Fresi, F., Maccioni, P., and Smeraldi, E. (2008) Behavioural sensitization to repeated sleep deprivation in a mice model of mania. Behav Brain Res 187: 221–217.
Berridge, M.J. (1989) The Albert Lasker Medical Awards. Inositol trisphosphate, calcium, lithium, and cell signaling. JAMA 262: 1834–1841.
Bersudsky, Y., Shaldubina, A., Agam, G., Berry, G.T., and Belmaker, R.H. (2008) Homozygote inositol transporter knockout mice show a lithium-like phenotype. Bipolar Disord 10: 453–459.
Bigos, K.L., Mattay, V.S., Callicott, J.H., et al. (2010) Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch Gen Psychiatry 67: 939–945.
Bloch, P.J., Weller, A.E., Doyle, G.A., et al. (2010) Association analysis between polymorphisms in the myo-inositol monophosphatase 2 (IMPA2) gene and bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 34: 1515–1519.
Bowers, B.J., Collins, A.C., Tritto, T., and Wehner, J.M. (2000) Mice lacking PKC gamma exhibit decreased anxiety. Behav Genet 30: 111–121.
Brown, E.S. (2009) Effects of glucocorticoids on mood, memory, and the hippocampus. Treatment and preventive therapy. Ann NY Acad Sci 1179: 41–55.
Brown, E.S. and Chandler, P.A. (2001) Mood and cognitive changes during systemic corticosteroid therapy. Prim Care Companion J Clin Psychiatry 3: 17–21.
Calabrese, J.R., Hirschfeld, R.M., Reed, M., et al. (2003) Impact of bipolar disorder on a U.S. community sample. J Clin Psychiatry 64: 425–432.
Carlson, P.J., Singh, J.B., Zarate, C.A., Jr., Drevets, W.C., and Manji, H.K. (2006) Neural circuitry and neuroplasticity in mood disorders: insights for novel therapeutic targets. NeuroRx 3: 22–41.
Chan, J.P., Unger, T.J., Byrnes, J., and Rios, M. (2006) Examination of behavioral deficits triggered by targeting Bdnf in fetal or postnatal brains of mice. Neuroscience 142: 49–58.
Chang, F., Steelman, L.S., Shelton, J.G., et al. (2003) Regulation of cell cycle progression and apoptosis by the Ras/Raf/MEK/ERK pathway (review). Int J Oncol 22: 469–480.
Chen, G., Henter, I.D., and Manji, H.K. (2010) Translational research in bipolar disorder: emerging insights from genetically based models. Mol Psychiatry 15: 883–895.
Chen, G. and Manji, H.K. (2006) The extracellular signal-regulated kinase pathway: an emerging promising target for mood stabilizers. Curr Opin Psychiatry 19: 313–323.
Chen, G., Zeng, W.Z., Yuan, P.X., et al. (1999) The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS. J Neurochem 72: 879–882.
Cleary, C., Linde, J.A., Hiscock, K.M., et al. (2008) Antidepressive-like effects of rapamycin in animal models: implications for mTOR inhibition as a new target for treatment of affective disorders. Brain Res Bull 76: 469–473.
Cousins, D.A. and Young, A.H. (2007) The armamentarium of treatments for bipolar disorder: a review of the literature. Int J Neuropsychopharmacol 10: 411–431.
Crawley, J.N. (2000) What’s Wrong with My Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice. New York: Wiley-Liss.
Cryns, K., Shamir, A., Shapiro, J., et al. (2007) Lack of lithium-like behavioral and molecular effects in IMPA2 knockout mice. Neuropsychopharmacology 32: 881–891.
Cryns, K., Shamir, A., Van Acker, N., et al. (2008) IMPA1 is essential for embryonic development and lithium-like pilocarpine sensitivity. Neuropsychopharmacology 33: 674–684.
Dao, D.T., Mahon, P.B., Cai, X., et al. (2010) Mood disorder susceptibility gene CACNA1C modifies mood-related behaviors in mice and interacts with sex to influence behavior in mice and diagnosis in humans. Biol Psychiatry 68: 801–810.
Diazgranados, N., Ibrahim, L., Brutsche, N.E., et al. (2010) A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch 67: 793–802.
Dluzen, D.E., Gao, X., Story, G.M., et al. (2001) Evaluation of nigrostriatal dopaminergic function in adult +/+ and +/– BDNF mutant mice. Exp Neurol 170: 121–128.
Dzirasa, K., Coque, L., Sidor, M.M., et al. (2010) Lithium ameliorates nucleus accumbens phase-signaling dysfunction in a genetic mouse model of mania. J Neurosci 30: 16314–16323.
Einat, H. (2007) Different behaviors and different strains: potential new ways to model bipolar disorder. Neurosci Biobehav Rev 31: 850–857.
Einat, H. (2010) Strategies for the development of animal models for bipolar disorder: new opportunities and new challenges. In C. Zarate and K.H. Manji (eds) Behavioral Neurobiology of Bipolar Disorder and its Treatment. Berlin: Springer.
Einat, H., Kofman, O., Itkin, O., Lewitan, R.J., and Belmaker, R.H. (1998) Augmentation of lithium’s behavioral effect by inositol uptake inhibitors. J Neural Transm 105: 31–38.
Einat, H. and Manji, H.K. (2006) Cellular plasticity cascades: gene to behavior pathways in animal models of bipolar disorder. Biol Psychiatry 59: 1960–1971.
Einat, H., Manji, H.K., Gould, T.D., Du, J., and Chen, G. (2003a) Possible involvement of the ERK signaling cascade in bipolar disorder: behavioral leads from the study of mutant mice. Drug News Perspect 16: 453–563.
Einat, H., Shaldubina, A., Bersudskey, Y., and Belmaker, R.H. (2007a) Prospects for the development of animal models for the study of bipolar disorder. In J.C. Soares and A. Young (eds) Bipolar Disorder: Basic Mechanisms and Therapeutic Implications, 2nd edn. New York: Taylor & Francis.
Einat, H., Yuan, P., Gould, T.D., et al. (2003b) The role of the extracellular signal-regulated kinase signaling pathway in mood modulation. J Neurosci 23: 7311–7316.
Einat, H., Yuan, P., and Manji, H.K. (2005) Increased anxiety-like behaviors and mitochondrial dysfunction in mice with targeted mutation of the Bcl-2 gene: further support for the involvement of mitochondrial function in anxiety disorders. Behav Brain Res 165: 172–180.
Einat, H., Yuan, P., Szabo, S.T., Dogra, S., and Manji, H.K. (2007b) Protein kinase C inhibition by tamoxifen antagonizes manic-like behavior in rats: implications for the development of novel therapeutics for bipolar disorder. Neuropsychobiology 55: 123–131.
Ellenbroek, B.A. and Cools, A.R. (1990) Animal models with construct validity for schizophrenia. Behav Pharmacol 1: 469–490.
Engel, S.R., Creson, T.K., Hao, Y., et al. (2009) The extracellular signal-regulated kinase pathway contributes to the control of behavioral excitement. Mol Psychiatry 14: 448–461.
Fitzgerald, P.J., Barkus, C., Feyder, M., et al. (2010) Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder? Neurobiol Dis 40: 608–621.
Flaisher-Grinberg, S. and Einat, H. (2010) Strain-specific battery of tests for domains of mania: effects of valproate, lithium and imipramine. Front Psychopharmacology 1: 1–10.
Flaisher-Grinberg, S., Kronfeld-Schor, N., and Einat, H. (2010) Models of mania: from facets to domains and from animal models to model animals. J Psychopharmacology 24: 437–438.
Friedman, E., Hoau Yan, W., Levinson, D., Connell, T.A., and Singh, H. (1993) Altered platelet protein kinase C activity in bipolar affective disorder, manic episode. Biol Psychiatry 33: 520–525.
Fukada, M., Hanai, A., Nakayama, A., et al. (2012) Loss of deacetylation activity of Hdac6 affects emotional behavior in mice. PLoS One 7: e30924.
Gessa, G.L., Pani, L., Fadda, P., and Fratta, W. (1995) Sleep deprivation in the rat: an animal model of mania. Eur Neuropsychopharmacol 5: 89–93.
Geyer, M.A., Krebs-Thomson, K., Braff, D.L., and Swerdlow, N.R. (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 156: 117–154.
Goodwin, F.K. and Jamison, K.R. (1990) Manic Depressive Illness. New York: Oxford University Press.
Gould, T.D. and Einat, H. (2007) Animal models of bipolar disorder and mood stabilizer efficacy: a critical need for improvement. Neurosci Biobehav Rev 31: 825–831.
Gould, T.D., Einat, H., Bhat, R., and Manji, H.K. (2004) AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol 7: 387–390.
Gould, T.D., Einat, H., O’Donnell, K.C., et al. (2007a) Beta-catenin overexpression in the mouse brain phenocopies lithium-sensitive behaviors. Neuropsychopharmacology 32: 2173–2183.
Gould, T.D. and Gottesman, I.I. (2006) Psychiatric endophenotypes and the development of valid animal models. Genes Brain Behav 5: 113–119.
Gould, T.D. and Manji, H.K. (2004) The molecular medicine revolution and psychiatry: bridging the gap between basic neuroscience research and clinical psychiatry. J Clin Psychiatry 65: 598–604.
Gould, T.D., O’Donnell, K.C., Picchini, A.M., and Manji, H.K. (2007b) Strain differences in lithium attenuation of d-amphetamine-induced hyperlocomotion: a mouse model for the genetics of clinical response to lithium. Neuropsychopharmacology 32: 1321–1333.
Gould, T.D., O’Donnell, K.C., Picchini, A.M., et al. (2008) Generation and behavioral characterization of [beta]-catenin forebrain-specific conditional knock-out mice. Behav Brain Res 189: 117.
Gould, T.D., Picchini, A.M., Einat, H., and Manji, H.K. (2006) Targeting glycogen synthase kinase-3 in the CNS: implications for the development of new treatments for mood disorders. Curr Drug Targets 7: 1399–1409.
Greenlund, L.J., Korsmeyer, S.J., and JohnsonE.M., Jr. (1995) Role of BCL-2 in the survival and function of developing and mature sympathetic neurons. Neuron 15: 649–661.
Hara, A., Hirose, Y., Wang, A., et al. (1996) Localization of Bax and Bcl-2 proteins, regulators of programmed cell death, in the human central nervous system. Virchows Arch 429: 249–253.
Harvey, A.G. (2008) Sleep and circadian rhythms in bipolar disorder: seeking synchrony, harmony, and regulation. Am J Psychiatry 165: 820–829.
Howell, M.P. and Muglia, L.J. (2006) Effects of genetically altered brain glucocorticoid receptor action on behavior and adrenal axis regulation in mice. Front Neuroendocrinol 27: 275–284.
Huang, E.J. and Reichardt, L.F. (2001) Neurotrophins: roles in neuronal development and function. Ann Rev Neurosci 24: 677–736.
Huang, Y.Y., Peng, C.H., Yang, Y.P., et al. (2007) Desipramine activated Bcl-2 expression and inhibited lipopolysaccharide-induced apoptosis in hippocampus-derived adult neural stem cells. J Pharmacol Sci 104: 61–72.
Insel, T.R. (2007) From animal models to model animals. Biol Psychiatry 62: 1337–1339.
Jasmin, L., Narasaiah, M., and Tien, D. (2006) Noradrenaline is necessary for the hedonic properties of addictive drugs. Vascul Pharmacol 45: 243–250.
Kaidanovich-Beilin, O., Milman, A., Weizman, A., Pick, C.G., and Eldar-Finkelman, H. (2004) Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on beta-catenin in mouse hippocampus. Biol Psychiatry 55: 781–784.
Kakefuda, K., Oyagi, A., Ishisaka, M., et al. (2010) Diacylglycerol kinase beta knockout mice exhibit lithium-sensitive behavioral abnormalities. PLoS One 5: e13447.
Kalinichev, M. and Dawson, L.A. (2011) Evidence for antimanic efficacy of glycogen synthase kinase-3 (GSK-3) inhibitors in a strain specific model of acute mania. Int J Neuropsychopharmacol 6: 1–17.
Karin, M. (1996) The regulation of AP-1 activity by mitogen-activated protein kinases. Philos Trans R Soc Lond B Biol Sci 351: 127–134.
Kasahara, T., Kubota, M., Miyauchi, T., et al. (2006) Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes. Mol Psychiatry 11: 577–593.
Kernie, S.G., Liebl, D.J., and Parada, L.F. (2000) BDNF regulates eating behavior and locomotor activity in mice. EMBO J 19: 1290–1300.
Klein, P.S. and Melton, D.A. (1996) A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci USA 93: 8455–8459.
Kofman, O., Belmaker, R.H., Grisaru, N., et al. (1991) Myo-inositol attenuates two specific behavioral effects of acute lithium in rats. Psychopharmacol Bull 27: 185–190.
Kripke, D., Nievergelt, C., Joo, E.J., Shekhtman, T., and Kelsoe, J. (2009) Circadian polymorphisms associated with affective disorders. J Circad Rhythm 7: 2.
Kronfeld-Schor, N. and Einat, H. (2012) Circadian rhythms and depression: human psychopathology and animal models. Neuropharmacology 62: 101–114.
Kupfer, D.J. (2005) The increasing medical burden in bipolar disorder. JAMA 293: 2528–2530.
Large, C.H., Einat, H., and Mahableshwarkar, A.R. (2008) Developing therapeutics for bipolar disorder: from animal models to the clinic. In R.A. McArthur and F. Borsini (eds) Animal and Translational Models for CNS Drug Discovery. Amsterdam: Elsevier.
Le-Niculescu, H., McFarland, M.J., Ogden, C.A., et al. (2008) Phenomic, convergent functional genomic, and biomarker studies in a stress-reactive genetic animal model of bipolar disorder and co-morbid alcoholism. Am J Med Genet B Neuropsychiatr Genet 147B: 134–166.
Lee, S.Y., Chen, S.L., Chang, Y.H., et al. (2012) The ALDH2 and 5-HT2A genes interacted in bipolar-I but not bipolar-II disorder. Prog Neuropsychopharmacol Biol Psychiatry 38: 247–251.
Li, X., Liu, M., Cai, Z., and Wang, G. (2010) Regulation of glycogen synthase kinase-3 during bipolar mania treatment. Bipolar Disord 12: 741–752.
Lien, R., Flaisher-Grinberg, S., Cleary, C., Hejny, M., and Einat, H. (2008) Behavioral effects of Bcl-2 deficiency: implications for affective disorders. Pharmacol Rep 60: 490–498.
Longoni, R., Spina, L., Vinci, S., and Acquas, E. (2011) The MEK inhibitor SL327 blocks acquisition but not expression of lithium-induced conditioned place aversion: a behavioral and immunohistochemical study. Psychopharmacology 216: 63–73.
Lucki, I., Dalvi, A., and Mayorga, A.J. (2001) Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology 155: 315–322.
Luo, C., Xu, H., and Li, X.M. (2004) Post-stress changes in BDNF and Bcl-2 immunoreactivities in hippocampal neurons: effect of chronic administration of olanzapine. Brain Res 1025: 194–202.
Lyon, M. (1991) Animal models of mania and schizophrenia. In P. Willner (ed.) Behavioral Models in Psychopharmacology: Theoretical, Industrial and Clinical Perspectives. Cambridge: Cambridge University Press.
Lyons, W.E., Mamounas, L.A., Ricaurte, G.A., et al. (1999) Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc Natl Acad Sci USA 96: 15239–15244.
Machado-Vieira, R., Ibrahim, L., Henter, I.D., and Zarate, C.A., Jr. (2012) Novel glutamatergic agents for major depressive disorder and bipolar disorder. Pharmacol Biochem Behav 100: 678–687.
Machado-Vieira, R., Kapczinski, F., and Soares, J.C. (2004) Perspectives for the development of animal models of bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 28: 209–224.
Maeng, S., Hunsberger, J.G., Pearson, B., et al. (2008) BAG1 plays a critical role in regulating recovery from both manic-like and depression-like behavioral impairments. Proc Natl Acad Sci USA 105: 8766–8771.
Malkesman, O., Austin, D.R., Chen, G., and Manji, H.K. (2009a) Reverse translational strategies for developing animal models of bipolar disorder. Dis Model Mech 2: 238–245.
Malkesman, O., Scattoni, M.L., Paredes, D., et al. (2009b) The female urine sniffing test: a novel approach for assessing reward-seeking behavior in rodents. Biol Psychiatry 67: 864–871.
Manji, H.K. and Duman, R.S. (2001) Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeutics. Psychopharmacol Bull 35: 5–49.
Manji, H.K., Moore, G.J., and Chen, G. (2000) Lithium up-regulates the cytoprotective protein Bcl-2 in the CNS in vivo: a role for neurotrophic and neuroprotective effects in manic depressive illness. J Clin Psychiatry 61: 82–96.
McEachron, D.L., Kripke, D.F., Sharp, F.R., Lewy, A.J., and McClellan, D.E. (1985) Lithium effects on selected circadian rhythms in rats. Brain Res Bull 15: 347–350.
McIntyre, R.S. (2010) Pharmacology and efficacy of asenapine for manic and mixed states in adults with bipolar disorder. Expert Rev Neurother 10: 645–649.
McIsaac, S.A. and Young, A.H. (2009) The role of hypothalamic pituitary-adrenal axis dysfunction in the etiology of depressive disorders. Drugs Today 45: 127–133.
McKinney, W.T., Jr. and Bunney, W.E., Jr. (1969) Animal model of depression. I. Review of evidence: implications for research. Arch Gen Psychiatry 21: 240–248.
Meltzer, H.Y., Arora, R.C., and Goodnick, P. (1983) Effect of lithium carbonate on serotonin uptake in blood platelets of patients with affective disorders. J Affect Disord 5: 215–221.
Mendels, J., Frazer, A., Fitzgerald, R.G., Ramsey, T.A., and Stokes, J.W. (1972) Biogenic amine metabolites in cerebrospinal fluid of depressed and manic patients. Science 175: 1380–1382.
Merikangas, K.R., Akiskal, H.S., Angst, J., et al. (2007) Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry 64: 543–552.
Michaud, C.M., Murray, C.J., and Bloom, B.R. (2001) Burden of disease – implications for future research. JAMA 285: 535–539.
Mitchell, K.J., Huang, Z.J., Moghaddam, B., and Sawa, A. (2011) Following the genes: a framework for animal modeling of psychiatric disorders. BMC Biol 9: 76.
Mitchell, P.J. and Redfern, P.H. (2005) Animal models of depressive illness: the importance of chronic drug treatment. Curr Pharm Des 11: 171–203.
Mokry, J. (1995) Experimental models and behavioural tests used in the study of Parkinson’s disease. Physiol Res 44: 143–150.
Muller, M.B., Zimmermann, S., Sillaber, I., et al. (2003) Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress. Nat Neurosci 6: 1100–1107.
Murphy, D.L., Colburn, R.W., Davis, J.M., and Bunney, W.E., Jr. (1969) Stimulation by lithium of monoamine uptake in human platelets. Life Sci 8: 1187–1193.
Nestler, E.J., Gould, E., Manji, H., et al. (2002) Preclinical models: status of basic research in depression. Biol Psychiatry 52: 503–528.
Nestler, E.J. and Hyman, S.E. (2010) Animal models of neuropsychiatric disorders. Nat Neurosci 13: 1161–1169.
Ng, W.X., Lau, I.Y., Graham, S., and Sim, K. (2009) Neurobiological evidence for thalamic, hippocampal and related glutamatergic abnormalities in bipolar disorder: a review and synthesis. Neurosci Biobehav Rev 33: 336–354.
Nievergelt, C.M., Kripke, D.F., Remick, R.A., et al. (2005) Examination of the clock gene Cryptochrome 1 in bipolar disorder: mutational analysis and absence of evidence for linkage or association. Psychiatr Genet 15: 45–52.
O’Brien, W.T., Harper, A.D., Jove, F., et al. (2004) Glycogen synthase kinase-3 beta haploinsufficiency mimics the behavioral and molecular effects of lithium. J Neurosci 24: 6791–6798.
Offord, J. (2012) Genetic approaches to a better understanding of bipolar disorder. Pharmacol Ther 133: 133–141.
Ohnishi, T., Watanabe, A., Ohba, H., et al. (2010) Behavioral analyses of transgenic mice harboring bipolar disorder candidate genes, IMPA1 and IMPA2. Neurosci Res 67: 86–94.
Pandey, G.N., Pandey, S.C., Ren, X., Dwivedi, Y., and Janicak, P.G. (2003) Serotonin receptors in platelets of bipolar and schizoaffective patients: effect of lithium treatment. Psychopharmacology 170: 115–123.
Perona, M.T., Waters, S., Hall, F.S., et al. (2008) Animal models of depression in dopamine, serotonin, and norepinephrine transporter knockout mice: prominent effects of dopamine transporter deletions. Behav Pharmacol 19: 566–574.
Post, R.M., Uhde, T.W., Roy-Byrne, P.P., and Joffe, R.T. (1987) Correlates of antimanic response to carbamazepine. Psychiatry Res 21: 71–83.
Prickaerts, J., Moechars, D., Cryns, K., et al. (2006) Transgenic mice overexpressing glycogen synthase kinase 3 beta: a putative model of hyperactivity and mania. J Neurosci 26: 9022–9029.
Redei, E.E., Ahmadiyeh, N., Baum, A.E., et al. (2001) Novel animal models of affective disorders. Semin Clin Neuropsychiatry 6: 43–67.
Rondi-Reig, L., Lemaigre Dubreuil, Y., Martinou, J.C., et al. (1997) Fear decrease in transgenic mice overexpressing bcl-2 in neurons. Neuroreport 8: 2429–2432.
Roybal, K., Theobold, D., Graham, A., et al. (2007) Mania-like behavior induced by disruption of CLOCK. Proc Natl Acad Sci USA 104: 6406–6411.
Rozeboom, A.M., Akil, H., and Seasholtz, A.F. (2007) Mineralocorticoid receptor overexpression in forebrain decreases anxiety-like behavior and alters the stress response in mice. Proc Natl Acad Sci USA 104: 4688–4693.
Schank, J.R., Liles, L.C., and Weinshenker, D. (2008) Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety. Biol Psychiatry 63: 1007–1012.
Schildkraut, J.J. (1974) Biogenic amines and affective disorders. Ann Rev Med 25: 333–348.
Schober, A. (2004) Classic toxin-induced animal models of Parkinson’s disease: 6-OHDA and MPTP. Cell Tissue Res 318: 215–224.
Seeman, P. (1987) Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse 1: 133–152.
Serretti, A. and Mandelli, L. (2008) The genetics of bipolar disorder: genome “hot regions,” genes, new potential candidates and future directions. Mol Psychiatry 13: 742–771.
Shaldubina, A., Buccafusca, R., Johanson, R.A. et al. (2007) Behavioural phenotyping of sodium-myo-inositol cotransporter heterozygous knockout mice with reduced brain inositol. Genes Brain Behav 6: 253–259.
Shaltiel, G., Chen, G., and Manji, H.K. (2007) Neurotrophic signaling cascades in the pathophysiology and treatment of bipolar disorder. Curr Opin Pharmacol 7: 22–26.
Shaltiel, G., Maeng, S., Malkesman, O., et al. (2008) Evidence for the involvement of the kainate receptor subunit GluR6 (GRIK2) in mediating behavioral displays related to behavioral symptoms of mania. Mol Psychiatry 13: 858–872.
Shaltiel, G., Shamir, A., Shapiro, J., et al. (2004) Valproate decreases inositol biosynthesis. Biol Psychiatry 56: 868–874.
Sjoholt, G., Ebstein, R.P., Lie, R.T., et al. (2004) Examination of IMPA1 and IMPA2 genes in manic-depressive patients: association between IMPA2 promoter polymorphisms and bipolar disorder. Mol Psychiatry 9: 621–629.
Sjoholt, G., Gulbrandsen, A.K., Lovlie, R., et al. (2000) A human myo-inositol monophosphatase gene (IMPA2) localized in a putative susceptibility region for bipolar disorder on chromosome 18p11.2: genomic structure and polymorphism screening in manic-depressive patients. Mol Psychiatry 5: 172–180.
Smith, G.T. (2005) On construct validity: issues of method and measurement. Psychol Assess 17: 396–408.
Smith, G.W., Aubry, J.M., Dellu, F., et al. (1998) Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development. Neuron 20: 1093–1102.
Soria, V., Martinez-Amoros, E., Escaramis, G., et al. (2010) Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder. Neuropsychopharmacology 35: 1279–1289.
Srinivasan, V., Smits, M., Spence, W., et al. (2006) Melatonin in mood disorders. World J Biol Psychiatry 7: 138–151.
Steketee, J.D. (1993) Injection of the protein kinase inhibitor H7 into the A10 dopamine region blocks the acute responses to cocaine: behavioral and in vivo microdialysis studies. Neuropharmacology 32: 1289–1297.
Stork, C. and Renshaw, P.F. (2005) Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol Psychiatry 10: 900–919.
Strauss, M.E. and Smith, G.T. (2008) Construct validity: advances in theory and methodology. Ann Rev Clin Psychol 16: 16.
Taniguchi, S., Nakazawa, T., Tanimura, A., et al. (2009) Involvement of NMDAR2A tyrosine phosphorylation in depression-related behaviour. EMBO J 28: 3717–3729.
Tecott, L.H. and Nestler, E.J. (2004) Neurobehavioral assessment in the information age. Nat Neurosci 7: 462–466.
Timpl, P., Spanagel, R., Sillaber, I., et al. (1998) Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1. Nat Genet 19: 162–166.
Van Riezen, H., Schnieden, H., and Wren, A.F. (1977) Olfactory bulb ablation in the rat: behavioural changes and their reversal by antidepressant drugs. Br J Pharmacol 60: 521–528.
Varadarajulu, J., Lebar, M., Krishnamoorthy, G., et al. (2011) Increased anxiety-related behaviour in Hint1 knockout mice. Behav Brain Res 220: 305–311.
Watson, S., Gallagher, P., Ritchie, J.C., Ferrier, I.N., and Young, A.H. (2004) Hypothalamic–pituitary–adrenal axis function in patients with bipolar disorder. Br J Psychiatry 184: 496–502.
Wehr, T.A., Goodwin, F.K., Wirz-Justice, A., Breitmaier, J., and Craig, C. (1982) 48-hour sleep–wake cycles in manic-depressive illness: naturalistic observations and sleep deprivation experiments. Arch Gen Psychiatry 39: 559–565.
Wehr, T.A., Sack, D.A., and Rosenthal, N.E. (1987) Sleep reduction as a final common pathway in the genesis of mania. Am J Psychiatry 144: 201–204.
Wei, Q., Fentress, H.M., Hoversten, M.T., et al. (2012) Early-life forebrain glucocorticoid receptor overexpression increases anxiety behavior and cocaine sensitization. Biol Psychiatry 71: 224–231.
Wei, Q., Lu, X.Y., Liu, L., et al. (2004) Glucocorticoid receptor overexpression in forebrain: a mouse model of increased emotional lability. Proc Natl Acad Sci USA 101: 11851–11856.
Weinshenker, D., Miller, N.S., Blizinsky, K., Laughlin, M.L., and Palmiter, R.D. (2002) Mice with chronic norepinephrine deficiency resemble amphetamine-sensitized animals. Proc Natl Acad Sci USA 99: 13873–13877.
Williams, R.S., Cheng, L., Mudge, A.W., and Harwood, A.J. (2002) A common mechanism of action for three mood-stabilizing drugs. Nature 417: 292–295.
Willner, P. (1984) The validity of animal models of depression. Psychopharmacology 83: 1–16.
Willner, P. (1986) Validation criteria for animal models of human mental disorders: learned helplessness as a paradigm case. Prog Neuropsychopharmacol Biol Psychiatry 10: 677–690.
Willner, P. (1990) Animal models of depression: an overview. Pharmacol Ther 45: 425–455.
Willner, P. (1991a) Animal models as simulations of depression. Trends Pharmacol Sci 12: 131–136.
Willner, P. (1991b) Behavioral models in psychopharmacology. In P. Willner (ed.) Behavioral Models in Psychopharmacology: Theoretical, Industrial and Clinical Perspectives. Cambridge: Cambridge University Press.
Willner, P. (1995a) Animal models of depression: validity and applications. Adv Biochem Psychopharmacol 49: 19–41.
Willner, P. (1995b) Animal models of depression: validity and applications. In G.L. Gessa, W. Fratta, L. Pani, and G. Serra (eds) Depression and Mania: From Neurobiology to Treatment. New York: Raven Press.
Willner, P., Muscat, R., and Papp, M. (1992) Chronic mild stress-induced anhedonia: a realistic animal model of depression. Neurosci Biobehav Rev 16: 525–534.
Wolfson, M., Einat, H., Bersudsky, Y., et al. (2000) Nordidemnin potently inhibits inositol uptake in cultured astrocytes and dose-dependently augments lithium’s proconvulsant effect in vivo. J Neurosci Res 60: 116–121.
Wu, J.B. and Shih, J.C. (2011) Valproic acid induces monoamine oxidase A via Akt/forkhead box O1 activation. Mol Pharmacol 80: 714–723.
Xu, F., Gainetdinov, R.R., Wetsel, W.C., et al. (2000) Mice lacking the norepinephrine transporter are supersensitive to psychostimulants. Nat Neurosci 3: 465–471.
Xu, H., Richardson, S.J., and Li, X.M. (2003) Dose-related effects of chronic antidepressants on neuroprotective proteins BDNF, Bcl-2 and Cu/Zn-SOD in rat hippocampus. Neuropsychopharmacology 28: 53–62.
Yadav, R., Gupta, S.C., Hillman, B.G., et al. (2012) Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors. PLoS One 7: e32969.
Yan, X.B., Hou, H.L., Wu, L.M., Liu, J., and Zhou, J.N. (2007) Lithium regulates hippocampal neurogenesis by ERK pathway and facilitates recovery of spatial learning and memory in rats after transient global cerebral ischemia. Neuropharmacology 53: 487–495.
Yildiz, A., Guleryuz, S., Ankerst, D.P., Ongur, D., and Renshaw, P.F. (2008) Protein kinase C inhibition in the treatment of mania: a double-blind, placebo-controlled trial of tamoxifen. Arch Gen Psychiatry 65: 255–263.
Young, J.W., Minassian, A., Paulus, M.P., Geyer, M.A., and Perry, W. (2007) A reverse-translational approach to bipolar disorder: rodent and human studies in the Behavioral Pattern Monitor. Neurosci Biobehav Rev 31: 882–896.
Yuan, P.X., Huang, L.D., Jiang, Y.M., et al. (2001) The mood stabilizer valproic acid activates mitogen-activated protein kinases and promotes neurite growth. J Biol Chem 276: 31674–31683.
Zarate, C.A., Jr., Du, J., Quiroz, J., et al. (2003) Regulation of cellular plasticity cascades in the pathophysiology and treatment of mood disorders: role of the glutamatergic system. Ann NY Acad Sci 1003: 273–291.
Zarate, C.A., Jr., Singh, J.B., Carlson, P.J., et al. (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63: 856–864.
Zarate, C.A., Jr., Singh, J.B., Carlson, P.J., et al. (2007) Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study. Bipolar Disord 9: 561–570.
Zorner, B., Wolfer, D.P., Brandis, D., et al. (2003) Forebrain-specific trkB-receptor knockout mice: behaviorally more hyperactive than “depressive.”Biol Psychiatry 54: 972–982.