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Orexin and Circadian Influences in Sleep and Psychiatric Disorders: A Review of Experimental and Computational Modelling Studies

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Abstract

Psychiatric disorders such as unipolar depression have complex pathologies, which include disruptions in circadian and sleep-wake cycles. At the neurochemical level, psychiatric diseases can also be accompanied by changes in neuromodulator systems such as orexin/hypocretin and the monoamines. Indeed, for decades the monoamine hypothesis of depression has been instrumental in driving discoveries and developments of antidepressant drugs. Recent preclinical and clinical advancement strongly suggests that neuropeptides such as orexin can play an important part in the pathophysiology of depression. Due to the complexity and extensive connectedness of neurobiological systems, understanding the biological causes and mechanisms of psychiatric disorders present major research challenges. In this chapter, we review experimental and computational studies investigating the complex relationship between orexinergic, monoaminergic, circadian oscillators, and sleep-wake neural circuitry. Our main aim is to understand how these physiological systems interact and how alteration in any of these factors can contribute to the behaviours commonly observed in depressive patients. Further, we examine how modelling across different levels of neurobiological organization enables insight into these interactions. We propose that a multiscale systems approach is necessary to understand the complex neurobiological systems whose dysfunctions are the underlying causes of psychiatric disorders. Such an approach could illuminate future treatments.

Keywords

Psychiatric disorders Sleep Neuromodulators Orexin (hypocretin) Monoamines Circadian rhythms Computational models 

Notes

Acknowledgements

This work was supported by the Human Frontier Science Program (AJ, HDP), BBSRC (MDCB, HDP), and Northern Ireland Functional Brain Mapping Facility (1303/101154803) funded by InvestNI and the University of Ulster, Innovate UK (102161), and The Royal Society—NSFC International Exchanges (KFW-L). The authors would like to thank Daniel B. Forger, Beatriz Baño Otálora, Joseph Timothy, Jaishree Jalewa, Christian Hölscher, T. Martin McGinnity and Girijesh Prasad for previous discussions in helping to generate some of the presented ideas.

References

  1. Abrahamson E, Leak R, Moore R (2001) The suprachiasmatic nucleus projects to posterior hypothalamic arousal systems. Neuroreport 12:435–440Google Scholar
  2. Anzalone A, Lizardi-Ortiz JE, Ramos M, De Mei C, Hopf FW, Iaccarino C, Halbout B, Jacobsen J, Kinoshita C, Welter M (2012) Dual control of dopamine synthesis and release by presynaptic and postsynaptic dopamine D2 receptors. J Neurosci 32:9023–9034Google Scholar
  3. Arango V, Underwood MD, Boldrini M, Tamir H, Kassir SA, Hsiung S-C, Chen JJ, Mann JJ (2001) Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology 25:892–903PubMedCrossRefGoogle Scholar
  4. Aston-Jones G, Rajkowski J, Cohen J (2000) Locus coeruleus and regulation of behavioral flexibility and attention. Prog Brain Res 126:165–182PubMedCrossRefGoogle Scholar
  5. Aston-Jones G, Smith RJ, Moorman DE, Richardson KA (2009) Role of lateral hypothalamic orexin neurons in reward processing and addiction. Neuropharmacology 56:112–121PubMedCentralPubMedCrossRefGoogle Scholar
  6. Backberg M, Hervieu G, Wilson S, Meister B (2002) Orexin receptor-1 (OX-R1) immunoreactivity in chemically identified neurons of the hypothalamus: focus on orexin targets involved in control of food and water intake. Eur J Neurosci 15:315–328PubMedCrossRefGoogle Scholar
  7. Behn CG, Brown EN, Scammell TE, Kopell NJ (2007) Mathematical model of network dynamics governing mouse sleep-wake behavior. J Neurophysiol 97:3828–3840PubMedCentralPubMedCrossRefGoogle Scholar
  8. Behn CD, Kopell N, Brown EN, Mochizuki T, Scammell TE (2008) Delayed orexin signaling consolidates wakefulness and sleep: physiology and modeling. J Neurophysiol 99:3090–3103CrossRefGoogle Scholar
  9. Behn CGD, Klerman EB, Mochizuki T, Lin S-C, Scammell TE (2010) Abnormal sleep/wake dynamics in orexin knockout mice. Sleep 33:297Google Scholar
  10. Belle MD, Hughes AT, Bechtold DA, Cunningham P, Pierucci M, Burdakov D, Piggins HD (2014) Acute suppressive and long-term phase modulation actions of orexin on the mammalian circadian clock. J Neurosci 34:3607–3621PubMedCentralPubMedCrossRefGoogle Scholar
  11. Boldrini M, Underwood MD, Mann JJ, Arango V (2005) More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides. Brain Res 1041:19–28PubMedCrossRefGoogle Scholar
  12. Booth V, Behn CGD (2014) Physiologically-based modeling of sleep–wake regulatory networks. Math Biosci 250:54–68PubMedCrossRefGoogle Scholar
  13. Borbély AA (1982) A two process model of sleep regulation. Hum Neurobiol 1:195–204Google Scholar
  14. Bowden CL (2005) A different depression: clinical distinctions between bipolar and unipolar depression. J Affect Disord 84:117–125PubMedCrossRefGoogle Scholar
  15. Bromberg-Martin ES, Matsumoto M, Hikosaka O (2010) Dopamine in motivational control: rewarding, aversive, and alerting. Neuron 68:815–834PubMedCentralPubMedCrossRefGoogle Scholar
  16. Brown RE, Sergeeva O, Eriksson KS, Haas HL (2001) Orexin A excites serotonergic neurons in the dorsal raphe nucleus of the rat. Neuropharmacology 40:457–459PubMedCrossRefGoogle Scholar
  17. Brundin L, Bjorkqvist M, Petersen A, Traskman-Bendz L (2007a) Reduced orexin levels in the cerebrospinal fluid of suicidal patients with major depressive disorder. Eur Neuropsychopharmacol 17:573–579PubMedCrossRefGoogle Scholar
  18. Brundin L, Petersen A, Bjorkqvist M, Traskman-Bendz L (2007b) Orexin and psychiatric symptoms in suicide attempters. J Affect Disord 100:259–263PubMedCrossRefGoogle Scholar
  19. Brundin L, Bjorkqvist M, Traskman-Bendz L, Petersen A (2009) Increased orexin levels in the cerebrospinal fluid the first year after a suicide attempt. J Affect Disord 113:179–182PubMedCrossRefGoogle Scholar
  20. Carter ME, Brill J, Bonnavion P, Huguenard JR, Huerta R, de Lecea L (2012) Mechanism for Hypocretin-mediated sleep-to-wake transitions. Proc Natl Acad Sci U S A 109:E2635–E2644PubMedCentralPubMedCrossRefGoogle Scholar
  21. Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98:437–451PubMedCrossRefGoogle Scholar
  22. Chien Y-L, Liu C-M, Shan J-C, Lee H-J, Hsieh MH, Hwu H-G, Chiou L-C (2015) Elevated plasma orexin A levels in a subgroup of patients with schizophrenia associated with fewer negative and disorganized symptoms. Psychoneuroendocrinology 53:1–9PubMedCrossRefGoogle Scholar
  23. Cools R, Roberts AC, Robbins TW (2008) Serotoninergic regulation of emotional and behavioural control processes. Trends Cogn Sci 12:31–40PubMedCrossRefGoogle Scholar
  24. Cullen M, Wong-Lin K (2014) Analysis of a computational model of dopamine synthesis and release through perturbation. In: 2014 IEEE international conference on bioinformatics and biomedicine (BIBM), pp 1–7Google Scholar
  25. Czeisler C (1978) Internal organization of temperature, sleep-wake, and neuroendocrine rhythms monitored in an environment free of time cues. Stanford University, StanfordGoogle Scholar
  26. Czeisler CA, Weitzman E, Moore-Ede MC, Zimmerman JC, Knauer RS (1980) Human sleep: its duration and organization depend on its circadian phase. Science 210:1264–1267PubMedCrossRefGoogle Scholar
  27. Daan S, Beersma D, Borbély AA (1984) Timing of human sleep: recovery process gated by a circadian pacemaker. Am J Physiol-Regul Integr Comp Physiol 246:R161–R183Google Scholar
  28. Dada JO, Mendes P (2011) Multi-scale modelling and simulation in systems biology. Integr Biol (Camb) 3:86–96CrossRefGoogle Scholar
  29. Dalal MA, Schuld A, Pollmacher T (2003) Lower CSF orexin A (hypocretin-1) levels in patients with schizophrenia treated with haloperidol compared to unmedicated subjects. Mol Psychiatry 8:836–837PubMedCrossRefGoogle Scholar
  30. Dayan P, Huys QJ (2008) Serotonin, inhibition, and negative mood. PLoS Comput Biol 4:e4PubMedCentralPubMedCrossRefGoogle Scholar
  31. de Lecea L, Kilduff T, Peyron C, Gao X-B, Foye P, Danielson P, Fukuhara C, Battenberg E, Gautvik V, Bartlett FN (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci 95:322–327PubMedCentralPubMedCrossRefGoogle Scholar
  32. de Lecea L, Jones BE, Boutrel B, Borgland SL, Nishino S, Bubser M, Dileone R (2006) Addiction and arousal: alternative roles of hypothalamic peptides. J Neurosci 26:10372–10375PubMedCrossRefGoogle Scholar
  33. Deboer T, Vansteensel MJ, Detari L, Meijer JH (2003) Sleep states alter activity of suprachiasmatic nucleus neurons. Nat Neurosci 6:1086–1090PubMedCrossRefGoogle Scholar
  34. Deboer T, Overeem S, Visser NA, Duindam H, Frolich M, Lammers GJ, Meijer JH (2004) Convergence of circadian and sleep regulatory mechanisms on hypocretin-1. Neuroscience 129:727–732PubMedCrossRefGoogle Scholar
  35. Delgado PL (2000) Depression: the case for a monoamine deficiency. J Clin Psychiatry 61(Suppl 6):7–11PubMedGoogle Scholar
  36. Den Boer JA (2006) Looking beyond the monoamine hypothesisGoogle Scholar
  37. Deutch AY, Goldstein M, Roth RH (1986) Activation of the locus coeruleus induced by selective stimulation of the ventral tegmental area. Brain Res 363:307–314PubMedCrossRefGoogle Scholar
  38. Deutch AY, Fadel J, Bubser M (2005) Dopamine-hypocretin/orexin interactions. In: Hypocretins. Springer, BerlinGoogle Scholar
  39. Dijk D-J, Lockley SW (2002) Invited review: integration of human sleep-wake regulation and circadian rhythmicity. J Appl Physiol 92:852–862PubMedCrossRefGoogle Scholar
  40. Dorocic IP, Fürth D, Xuan Y, Johansson Y, Pozzi L, Silberberg G, Carlén M, Meletis K (2014) A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei. Neuron 83:663–678Google Scholar
  41. Drevets WC (2001) Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol 11:240–249PubMedCrossRefGoogle Scholar
  42. Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C (1999) PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 46:1375–1387PubMedCrossRefGoogle Scholar
  43. Dunlop BW, Nemeroff CB (2007) The role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry 64:327–337PubMedCrossRefGoogle Scholar
  44. Eckhoff P, Wong-Lin KF, Holmes P (2009) Optimality and robustness of a biophysical decision-making model under norepinephrine modulation. J Neurosci 29:4301–4311PubMedCentralPubMedCrossRefGoogle Scholar
  45. Eckhoff P, Wong-Lin K, Holmes P (2011) Dimension reduction and dynamics of a spiking neural network model for decision making under neuromodulation. SIAM J Appl Dyn Syst 10:148–188PubMedCentralPubMedCrossRefGoogle Scholar
  46. Ericson H, Blomqvist A, Köhler C (1989) Brainstem afferents to the tuberomammillary nucleus in the rat brain with special reference to monoaminergic innervation. J Comp Neurol 281:169–192Google Scholar
  47. España RA, Scammell TE (2011) Sleep neurobiology from a clinical perspective. Sleep 34:845PubMedCentralPubMedCrossRefGoogle Scholar
  48. Estabrooke IV, McCarthy MT, Ko E, Chou TC, Chemelli RM, Yanagisawa M, Saper CB, Scammell TE (2001) Fos expression in orexin neurons varies with behavioral state. J Neurosci 21:1656–1662PubMedGoogle Scholar
  49. Fang P, Min W, Sun Y, Guo L, Shi M, Bo P, Zhang Z (2014) The potential antidepressant and antidiabetic effects of galanin system. Pharmacol Biochem Behav 120:82–87PubMedCrossRefGoogle Scholar
  50. Feng P, Vurbic D, Wu Z, Hu Y, Strohl KP (2008) Changes in brain orexin levels in a rat model of depression induced by neonatal administration of clomipramine. J Psychopharmacol 22:784–791PubMedCentralPubMedCrossRefGoogle Scholar
  51. Flower G, Wong-Lin K (2014) Reduced computational models of serotonin synthesis, release, and reuptake. IEEE Trans Biomed Eng 61:1054–1061PubMedCrossRefGoogle Scholar
  52. Forger DB, Peskin CS (2003) A detailed predictive model of the mammalian circadian clock. Proc Natl Acad Sci 100:14806–14811PubMedCentralPubMedCrossRefGoogle Scholar
  53. Fukunaka Y, Shinkai T, Hwang R, Hori H, Utsunomiya K, Sakata S, Naoe Y, Shimizu K, Matsumoto C, Ohmori O, Nakamura J (2007) The orexin 1 receptor (HCRTR1) gene as a susceptibility gene contributing to polydipsia-hyponatremia in schizophrenia. Neuromolecular Med 9:292–297PubMedCrossRefGoogle Scholar
  54. Fulcher BD, Phillips AJ, Postnova S, Robinson PA (2014) A physiologically based model of orexinergic stabilization of sleep and wake. PLoS ONE 9:e91982PubMedCentralPubMedCrossRefGoogle Scholar
  55. Germain A, Kupfer DJ (2008) Circadian rhythm disturbances in depression. Human Psychopharmacol Clin Exp 23:571–585CrossRefGoogle Scholar
  56. Goldbeter A (1995) A model for circadian oscillations in the Drosophila period protein (PER). Proc Roy Soc Lond Ser B Biol Sci 261:319–324Google Scholar
  57. Goncalves L, Sego C, Metzger M (2012) Differential projections from the lateral habenula to the rostromedial tegmental nucleus and ventral tegmental area in the rat. J Comp Neurol 520:1278–1300PubMedCrossRefGoogle Scholar
  58. Gonzalez R (2014) The relationship between bipolar disorder and biological rhythms. J Clin Psychiatry 75:e323–e331PubMedCrossRefGoogle Scholar
  59. Gonze D, Bernard S, Waltermann C, Kramer A, Herzel H (2005) Spontaneous synchronization of coupled circadian oscillators. Biophys J 89:120–129PubMedCentralPubMedCrossRefGoogle Scholar
  60. Gradin VB, Kumar P, Waiter G, Ahearn T, Stickle C, Milders M, Reid I, Hall J, Steele JD (2011) Expected value and prediction error abnormalities in depression and schizophrenia. Brain 134:1751–1764PubMedCrossRefGoogle Scholar
  61. Grzanna R, Molliver M (1980) The locus coeruleus in the rat: an immunohistochemical delineation. Neuroscience 5:21–40Google Scholar
  62. Guilding C, Piggins HD (2007) Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian oscillators present throughout the mammalian brain? Eur J Neurosci 25:3195–3216PubMedCrossRefGoogle Scholar
  63. Hasler G (2010) Pathophysiology of depression: do we have any solid evidence of interest to clinicians? World Psychiatry 9:155–161PubMedCentralPubMedCrossRefGoogle Scholar
  64. Hassani OK, Lee MG, Henny P, Jones BE (2009) Discharge profiles of identified GABAergic in comparison to cholinergic and putative glutamatergic basal forebrain neurons across the sleep–wake cycle. J Neurosci 29:11828–11840PubMedCentralPubMedCrossRefGoogle Scholar
  65. Hassani OK, Henny P, Lee MG, Jones BE (2010) GABAergic neurons intermingled with orexin and MCH neurons in the lateral hypothalamus discharge maximally during sleep. Eur J Neurosci 32:448–457PubMedCentralPubMedCrossRefGoogle Scholar
  66. Hattar S, Kumar M, Park A, Tong P, Tung J, Yau KW, Berson DM (2006) Central projections of melanopsin‐expressing retinal ganglion cells in the mouse. Journal of Comparative Neurology 497:326–349Google Scholar
  67. Herkenham M, Nauta WJ (1979) Efferent connections of the habenular nuclei in the rat. J Comp Neurol 187:19-47Google Scholar
  68. Herkenham M, Nauta WJ (1993) Afferent connections of the habenular nuclei in the rat. A horseradish peroxidase study, with a note on the fiber-of-passage problem. Neuroanatomy Springer 277–299Google Scholar
  69. Huang ZL, Zhang Z, Qu WM (2014) Roles of adenosine and its receptors in sleep-wake regulation. Int Rev Neurobiol 119:349–371PubMedCrossRefGoogle Scholar
  70. Hughes AT, Piggins HD (2012) Feedback actions of locomotor activity to the circadian clock. Prog Brain Res 199:305–336PubMedCrossRefGoogle Scholar
  71. Huys QJ, Pizzagalli DA, Bogdan R, Dayan P (2013) Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis. Biol Mood Anxiety Disord 3:12PubMedCentralPubMedCrossRefGoogle Scholar
  72. Iitaka C, Miyazaki K, Akaike T, Ishida N (2005) A role for glycogen synthase kinase-3beta in the mammalian circadian clock. J Biol Chem 280:29397–29402PubMedCrossRefGoogle Scholar
  73. Ito N, Yabe T, Gamo Y, Nagai T, Oikawa T, Yamada H, Hanawa T (2008) Icv administration of orexin-A induces an antidepressive-like effect through hippocampal cell proliferation. Neuroscience 157:720–732PubMedCrossRefGoogle Scholar
  74. Jalewa J, Joshi A, McGinnity TM, Prasad G, Wong-Lin K, Holscher C (2014a) Neural circuit interactions between the dorsal raphe nucleus and the lateral hypothalamus: an experimental and computational study. PLoS ONE 9:e88003PubMedCentralPubMedCrossRefGoogle Scholar
  75. Jalewa J, Wong-Lin K, McGinnity TM, Prasad G, Hölscher C (2014b) Increased number of orexin/hypocretin neurons with high and prolonged external stress-induced depression. Behav Brain Res 272:196–204PubMedCrossRefGoogle Scholar
  76. Jankowski MP, Sesack SR (2004) Prefrontal cortical projections to the rat dorsal raphe nucleus: ultrastructural features and associations with serotonin and gamma-aminobutyric acid neurons. J Comp Neurol 468:518–529PubMedCrossRefGoogle Scholar
  77. Jones BE, Moore RY (1977) Ascending projections of the locus coeruleus in the rat II. Autoradiographic study. Brain Res 127:25–53PubMedGoogle Scholar
  78. Joshi A, Wong-Lin K, Mcginnity TM, Prasad G (2011) A mathematical model to explore the interdependence between the serotonin and orexin/hypocretin systems. In: Proceedings of conference on IEEE engineering in medicine and biology society, pp 7270–7273Google Scholar
  79. Kalen P, Skagerberg G, Lindvall O (1988) Projections from the ventral tegmental area and mesencephalic raphe to the dorsal raphe nucleus in the rat. Exp Brain Res 73:69–77PubMedCrossRefGoogle Scholar
  80. Kantor S, Mochizuki T, Janisiewicz AM, Clark E, Nishino S, Scammell TE (2009) Orexin neurons are necessary for the circadian control of REM sleep. Sleep 32:1127–1134PubMedCentralPubMedGoogle Scholar
  81. Kawato M, Fujita K, Suzuki R, Winfree AT (1982) A three-oscillator model of the human circadian system controlling the core temperature rhythm and the sleep-wake cycle. J Theor Biol 98:369–392PubMedCrossRefGoogle Scholar
  82. Keers R, Pedroso I, Breen G, Aitchison KJ, Nolan PM, Cichon S, Nothen MM, Rietschel M, Schalkwyk LC, Fernandes C (2012) Reduced anxiety and depression-like behaviours in the circadian period mutant mouse afterhours. PLoS ONE 7:e38263PubMedCentralPubMedCrossRefGoogle Scholar
  83. Kim MA, Lee HS, Lee BY, Waterhouse BD (2004) Reciprocal connections between subdivisions of the dorsal raphe and the nuclear core of the locus coeruleus in the rat. Brain research 1026:56–67Google Scholar
  84. Klimek V, Stockmeier C, Overholser J, Meltzer HY, Kalka S, Dilley G, Ordway GA (1997) Reduced levels of norepinephrine transporters in the locus coeruleus in major depression. J Neurosci 17:8451–8458PubMedGoogle Scholar
  85. Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455:894–902PubMedCentralPubMedCrossRefGoogle Scholar
  86. Kronauer RE, Czeisler CA, Pilato SF, Moore-Ede MC, Weitzman ED (1982) Mathematical model of the human circadian system with two interacting oscillators. Am J Physiol-Regul Integr Comp Physiol 242:R3–R17Google Scholar
  87. Kronauer R, Czeisler C, Pilato S, Moore-Ede M, Weitzman E (1983) Mathematical representation of the human circadian system: two interacting oscillators which affect sleep. Sleep Dis Basic Clin Res 173–194Google Scholar
  88. Kumar R, Bose A, Mallick BN (2012) A mathematical model towards understanding the mechanism of neuronal regulation of wake-NREMS-REMS states. PLoS ONE 7:e42059PubMedCentralPubMedCrossRefGoogle Scholar
  89. Kuru M, Ueta Y, Serino R, Nakazato M, Yamamoto Y, Shibuya I, Yamashita H (2000) Centrally administered orexin/hypocretin activates HPA axis in rats. NeuroReport 11:1977–1980PubMedCrossRefGoogle Scholar
  90. Laasonen-Balk T, Kuikka J, Viinamaki H, Husso-Saastamoinen M, Lehtonen J, Tiihonen J (1999) Striatal dopamine transporter density in major depression. Psychopharmacology 144:282–285PubMedCrossRefGoogle Scholar
  91. Lambe EK, Liu RJ, Aghajanian GK (2007) Schizophrenia, hypocretin (orexin), and the thalamocortical activating system. Schizophr Bull 33:1284–1290PubMedCentralPubMedCrossRefGoogle Scholar
  92. Landgraf D, McCarthy MJ, Welsh DK (2014) The role of the circadian clock in animal models of mood disorders. Behav Neurosci 128:344–359PubMedCrossRefGoogle Scholar
  93. Lanni C, Govoni S, Lucchelli A, Boselli C (2009) Depression and antidepressants: molecular and cellular aspects. Cell Mol Life Sci 66:2985–3008PubMedCrossRefGoogle Scholar
  94. Laposky A, Easton A, Dugovic C, Walisser J, Bradfield C, Turek F (2005) Deletion of the mammalian circadian clock gene BMAL1/Mop3 alters baseline sleep architecture and the response to sleep deprivation. Sleep 28:395–409PubMedGoogle Scholar
  95. Laviale A, Weiss T, Veh RW, Mcginnity T, Maguire L, Wong-Lin K (2013) A single spiking neuronal model to account for the diverse spontaneous firing patterns of lateral habenula neurons. Society for Neuroscience, Washington DCGoogle Scholar
  96. Lee HS, Lee BY, Waterhouse BD (2005a) Retrograde study of projections from the tuberomammillary nucleus to the dorsal raphe and the locus coeruleus in the rat. Brain Res 1043:65–75PubMedCrossRefGoogle Scholar
  97. Lee MG, Hassani OK, Jones BE (2005b) Discharge of identified orexin/hypocretin neurons across the sleep-waking cycle. J Neurosci 25:6716–6720PubMedCrossRefGoogle Scholar
  98. Leibowitz SF, Shor-Posner G (1986) Brain serotonin and eating behavior. Appetite 7:1–14PubMedCrossRefGoogle Scholar
  99. Leloup J-C, Goldbeter A (2003) Toward a detailed computational model for the mammalian circadian clock. Proc Natl Acad Sci 100:7051–7056PubMedCentralPubMedCrossRefGoogle Scholar
  100. Li J, Lu WQ, Beesley S, Loudon AS, Meng QJ (2012) Lithium impacts on the amplitude and period of the molecular circadian clockwork. PLoS ONE 7:e33292PubMedCentralPubMedCrossRefGoogle Scholar
  101. Lin L, Faraco J, Li R, Kadotani H, Rogers W, Lin X, Qiu X, de Jong PJ, Nishino S, Mignot E (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell 98:365–376PubMedCrossRefGoogle Scholar
  102. López M, Tena-Sempere M, Diéguez C (2010) Cross-talk between orexins (hypocretins) and the neuroendocrine axes (hypothalamic–pituitary axes). Front Neuroendocrinol 31:113–127PubMedCrossRefGoogle Scholar
  103. Madaan V, Wilson DR (2009) Neuropeptides: relevance in treatment of depression and anxiety disorders. Drug News Perspect 22:319–324PubMedCrossRefGoogle Scholar
  104. Mahler SV, Moorman DE, Smith RJ, James MH, Aston-Jones G (2014) Motivational activation: a unifying hypothesis of orexin/hypocretin function. Nat Neurosci 17:1298–1303PubMedCentralPubMedCrossRefGoogle Scholar
  105. Malison RT, Price LH, Berman R, van Dyck CH, Pelton GH, Carpenter L, Sanacora G, Owens MJ, Nemeroff CB, Rajeevan N (1998) Reduced brain serotonin transporter availability in major depression as measured by [123 I]-2β-carbomethoxy-3β-(4-iodophenyl) tropane and single photon emission computed tomography. Biol Psychiatry 44:1090–1098PubMedCrossRefGoogle Scholar
  106. Mang GM, Durst T, Burki H, Imobersteg S, Abramowski D, Schuepbach E, Hoyer D, Fendt M, Gee CE (2012) The dual orexin receptor antagonist almorexant induces sleep and decreases orexin-induced locomotion by blocking orexin 2 receptors. Sleep 35:1625–1635PubMedCentralPubMedGoogle Scholar
  107. Manns ID, Alonso A, Jones BE (2000) Discharge profiles of juxtacellularly labeled and immunohistochemically identified GABAergic basal forebrain neurons recorded in association with the electroencephalogram in anesthetized rats. J Neurosci 20:9252–9263PubMedGoogle Scholar
  108. Marston OJ, Williams RH, Canal MM, Samuels RE, Upton N, Piggins HD (2008) Circadian and dark-pulse activation of orexin/hypocretin neurons. Mol Brain 1:19PubMedCentralPubMedCrossRefGoogle Scholar
  109. Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS medicine 3:e442PubMedCentralPubMedCrossRefGoogle Scholar
  110. Mazzocchi G, Malendowicz LK, Gottardo L, Aragona F, Nussdorfer GG (2001) Orexin A stimulates cortisol secretion from human adrenocortical cells through activation of the adenylate cyclase-dependent signaling cascade. J Clin Endocrinol Metab 86:778–782PubMedCrossRefGoogle Scholar
  111. McCarthy MJ, Welsh DK (2012) Cellular circadian clocks in mood disorders. J Biol Rhythms 27:339–352PubMedCrossRefGoogle Scholar
  112. McClung CA, Sidiropoulou K, Vitaterna M, Takahashi JS, White FJ, Cooper DC, Nestler EJ (2005) Regulation of dopaminergic transmission and cocaine reward by the Clock gene. Proc Natl Acad Sci U S A 102:9377–9381PubMedCentralPubMedCrossRefGoogle Scholar
  113. McGranaghan PA, Piggins HD (2001) Orexin A-like immunoreactivity in the hypothalamus and thalamus of the Syrian hamster (Mesocricetus auratus) and Siberian hamster (Phodopus sungorus), with special reference to circadian structures. Brain Res 904:234–244PubMedCrossRefGoogle Scholar
  114. Menet JS, Rosbash M (2011) When brain clocks lose track of time: cause or consequence of neuropsychiatric disorders. Curr Opin Neurobiol 21:849–857PubMedCentralPubMedCrossRefGoogle Scholar
  115. Meyer JH, Kruger S, Wilson AA, Christensen BK, Goulding VS, Schaffer A, Minifie C, Houle S, Hussey D, Kennedy SH (2001) Lower dopamine transporter binding potential in striatum during depression. NeuroReport 12:4121–4125PubMedCrossRefGoogle Scholar
  116. Mieda M, Hasegawa E, Kisanuki YY, Sinton CM, Yanagisawa M, Sakurai T (2011) Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep. J Neurosci 31:6518–6526PubMedCentralPubMedCrossRefGoogle Scholar
  117. Mikrouli E, Wörtwein G, Soylu R, Mathé AA, Petersén Å (2011) Increased numbers of orexin/hypocretin neurons in a genetic rat depression model. Neuropeptides 45:401–406PubMedCrossRefGoogle Scholar
  118. Mileykovskiy BY, Kiyashchenko LI, Siegel JM (2005) Behavioral correlates of activity in identified hypocretin/orexin neurons. Neuron 46:787–798Google Scholar
  119. Mintun MA, Sheline YI, Moerlein SM, Vlassenko AG, Huang Y, Snyder AZ (2004) Decreased hippocampal 5-HT 2A receptor binding in major depressive disorder: in vivo measurement with [18 F] altanserin positron emission tomography. Biol Psychiatry 55:217–224PubMedCrossRefGoogle Scholar
  120. Mohawk JA, Takahashi JS (2011) Cell autonomy and synchrony of suprachiasmatic nucleus circadian oscillators. Trends Neurosci 34:349–358PubMedCentralPubMedCrossRefGoogle Scholar
  121. Moret C, Briley M (2011) The importance of norepinephrine in depression. Neuropsychiatric Dis Treat 7:9Google Scholar
  122. Mosqueiro T, De Lecea L, Huerta R (2014) Control of sleep-to-wake transitions via fast aminoacid and slow neuropeptide transmission. New J Phys 16Google Scholar
  123. Mukherjee S, Coque L, Cao JL, Kumar J, Chakravarty S, Asaithamby A, Graham A, Gordon E, Enwright JF, 3RD, Dileone RJ, Birnbaum SG, Cooper DC, Mcclung CA (2010) Knockdown of Clock in the ventral tegmental area through RNA interference results in a mixed state of mania and depression-like behavior. Biol Psychiatry 68:503–511Google Scholar
  124. Murray G, Harvey A (2010) Circadian rhythms and sleep in bipolar disorder. Bipolar Disord 12:459–472PubMedCrossRefGoogle Scholar
  125. Muschamp JW, Hollander JA, Thompson JL, Voren G, Hassinger LC, Onvani S, Kamenecka TM, Borgland SL, Kenny PJ, Carlezon WA Jr (2014) Hypocretin (orexin) facilitates reward by attenuating the antireward effects of its cotransmitter dynorphin in ventral tegmental area. Proc Natl Acad Sci U S A 111:E1648–E1655Google Scholar
  126. Nakamura K, Wong-Lin K (2014) Functions and computational principles of serotonergic and related systems at multiple scales. Front Integr Neurosci 8:23PubMedCentralPubMedGoogle Scholar
  127. Nambu T, Sakurai T, Mizukami K, Hosoya Y, Yanagisawa M, Goto K (1999) Distribution of orexin neurons in the adult rat brain. Brain Res 827:243–260PubMedCrossRefGoogle Scholar
  128. Naylor E, Bergmann BM, Krauski K, Zee PC, Takahashi JS, Vitaterna MH, Turek FW (2000) The circadian clock mutation alters sleep homeostasis in the mouse. J Neurosci 20:8138–8143PubMedGoogle Scholar
  129. Nemeroff CB (1998) The neurobiology of depression. Sci Am-Am Edit 278:42–49Google Scholar
  130. Nollet M, Leman S (2013) Role of orexin in the pathophysiology of depression: potential for pharmacological intervention. CNS Drugs 27:411–422PubMedCrossRefGoogle Scholar
  131. Nollet M, Gaillard P, Tanti A, Girault V, Belzung C, Leman S (2012) Neurogenesis-independent antidepressant-like effects on behavior and stress axis response of a dual orexin receptor antagonist in a rodent model of depression. Neuropsychopharmacology 37:2210–2221PubMedCentralPubMedCrossRefGoogle Scholar
  132. Ogawa SK, Cohen JY, Hwang D, Uchida N, Watabe-Uchida M (2014) Organization of monosynaptic inputs to the serotonin and dopamine neuromodulatory systems. Cell reports 8:1105–1118Google Scholar
  133. Omelchenko N, Bell R, Sesack SR (2009) Lateral habenula projections to dopamine and GABA neurons in the rat ventral tegmental area. Eur J Neurosci 30:1239–1250PubMedCentralPubMedCrossRefGoogle Scholar
  134. Onge JRS, Stopper CM, Zahm DS, Floresco SB (2012) Separate prefrontal-subcortical circuits mediate different components of risk-based decision making. J Neurosci 32:2886–2899CrossRefGoogle Scholar
  135. Ordway GA, Schenk J, Stockmeier CA, May W, Klimek V (2003) Elevated agonist binding to α 2-adrenoceptors in the locus coeruleus in major depression. Biol Psychiatry 53:315–323PubMedCrossRefGoogle Scholar
  136. Overstreet DH (1986) Selective breeding for increased cholinergic function: development of a new animal model of depression. Biol Psychiatry 21:49–58PubMedCrossRefGoogle Scholar
  137. Overstreet DH, Friedman E, Mathé AA, Yadid G (2005) The Flinders Sensitive Line rat: a selectively bred putative animal model of depression. Neurosci Biobehav Rev 29:739–759PubMedCrossRefGoogle Scholar
  138. Owens MJ, Nemeroff CB (1994) Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem 40:288–295PubMedGoogle Scholar
  139. Pandi-Perumal SR, Moscovitch A, Srinivasan V, Spence DW, Cardinali DP, Brown GM (2009) Bidirectional communication between sleep and circadian rhythms and its implications for depression: lessons from agomelatine. Prog Neurobiol 88:264–271PubMedCrossRefGoogle Scholar
  140. Park S, Harrold JA, Widdowson PS, Williams G (1999) Increased binding at 5-HT 1A, 5-HT 1B, and 5-HT 2A receptors and 5-HT transporters in diet-induced obese rats. Brain research 847:90–97Google Scholar
  141. Patriarca M, Postnova S, Braun HA, Hernandez-Garcia E, Toral R (2012) Diversity and noise effects in a model of homeostatic regulation of the sleep-wake cycle. PLoS Comput Biol 8:e1002650PubMedCentralPubMedCrossRefGoogle Scholar
  142. Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18:9996–10015PubMedGoogle Scholar
  143. Peyron C, Faraco J, Rogers W, Ripley B, Overeem S, Charnay Y, Nevsimalova S, Aldrich M, Reynolds D, Albin R, Li R, Hungs M, Pedrazzoli M, Padigaru M, Kucherlapati M, Fan J, Maki R, Lammers GJ, Bouras C, Kucherlapati R, Nishino S, Mignot E (2000) A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med 6:991–997PubMedCrossRefGoogle Scholar
  144. Phillips AJ, Robinson PA (2007) A quantitative model of sleep-wake dynamics based on the physiology of the brainstem ascending arousal system. J Biol Rhythms 22:167–179PubMedCrossRefGoogle Scholar
  145. Pietraszek MH, Takahashi S, Takada Y, Ohara K, Inatomi H, Kondo N, Ohara K, Takada A (1991) Diurnal patterns of serotonin, 5-hydroxyindoleacetic acid, tryptophan and fibrinolytic activity in blood of depressive patients and healthy volunteers. Thromb Res 64:243–252PubMedCrossRefGoogle Scholar
  146. Piggins HD, Guilding C (2011) The neural circadian system of mammals. Essays Biochem 49:1–17PubMedCrossRefGoogle Scholar
  147. Poirier S, Legris G, Tremblay P, Michea R, Viau-Guay L, Merette C, Bouchard RH, Maziade M, Roy MA (2010) Schizophrenia patients with polydipsia and water intoxication are characterized by greater severity of psychotic illness and a more frequent history of alcohol abuse. Schizophr Res 118:285–291PubMedCrossRefGoogle Scholar
  148. Postnova S, Voigt K, Braun HA (2009) A mathematical model of homeostatic regulation of sleep-wake cycles by hypocretin/orexin. J Biol Rhythms 24:523–535PubMedCrossRefGoogle Scholar
  149. Proulx CD, Hikosaka O, Malinow R (2014) Reward processing by the lateral habenula in normal and depressive behaviors. Nat Neurosci 17:1146–1152PubMedCentralPubMedCrossRefGoogle Scholar
  150. Pujara M, Koenigs M (2014) Mechanisms of reward circuit dysfunction in psychiatric illness: prefrontal-striatal interactions. Neuroscientist 20:82–95PubMedCentralPubMedCrossRefGoogle Scholar
  151. Qu Z, Garfinkel A, Weiss JN, Nivala M (2011) Multi-scale modeling in biology: how to bridge the gaps between scales? Prog Biophys Mol Biol 107:21–31PubMedCentralPubMedCrossRefGoogle Scholar
  152. Quintana J (1992) Platelet serotonin and plasma tryptophan decreases in endogenous depression. Clinical, therapeutic, and biological correlations. J Affect Disord 24:55–62PubMedCrossRefGoogle Scholar
  153. Rajkowska G (2000) Histopathology of the prefrontal cortex in major depression: what does it tell us about dysfunctional monoaminergic circuits? Prog Brain Res 126:397–412PubMedCrossRefGoogle Scholar
  154. Rempe MJ, Best J, Terman D (2010) A mathematical model of the sleep/wake cycle. J Math Biol 60:615–644PubMedCrossRefGoogle Scholar
  155. Root DH, Mejias-Aponte CA, Qi J, Morales M (2014) Role of glutamatergic projections from ventral tegmental area to lateral habenula in aversive conditioning. J Neurosci 34:13906–13910PubMedCentralPubMedCrossRefGoogle Scholar
  156. Roybal K, Theobold D, Graham A, Dinieri JA, Russo SJ, Krishnan V, Chakravarty S, Peevey J, Oehrlein N, Birnbaum S, Vitaterna MH, Orsulak P, Takahashi JS, Nestler EJ, Carlezon WA Jr, Mcclung CA (2007) Mania-like behavior induced by disruption of CLOCK. Proc Natl Acad Sci U S A 104:6406–11Google Scholar
  157. Ruhe HG, Mason NS, Schene AH (2007) Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry 12:331–359PubMedCrossRefGoogle Scholar
  158. Saar I, Lahe J, Langel K, Runesson J, Webling K, Jarv J, Rytkonen J, Narvanen A, Bartfai T, Kurrikoff K, Langel U (2013) Novel systemically active galanin receptor 2 ligands in depression-like behavior. J Neurochem 127:114–123PubMedGoogle Scholar
  159. Sakhi K, Belle MD, Gossan N, Delagrange P, Piggins HD, (2014) Daily variation in the electrophysiological activity of mouse medial habenula neurones. J physiol 592:587–603Google Scholar
  160. Sakurai T (2006) Roles of orexins and orexin receptors in central regulation of feeding behavior and energy homeostasis. CNS Neurol Disorders-Drug Targets (Formerly Curr Drug Targets-CNS Neurol Disorders) 5:313–325Google Scholar
  161. Sakurai T (2007) The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci 8:171–181PubMedCrossRefGoogle Scholar
  162. Sakurai T (2014) The role of orexin in motivated behaviours. Nat Rev Neurosci 15:719–731Google Scholar
  163. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573–585PubMedCrossRefGoogle Scholar
  164. Sakurai T, Mieda M, Tsujino N (2010) The orexin system: roles in sleep/wake regulation. Ann N Y Acad Sci 1200:149–161PubMedCrossRefGoogle Scholar
  165. Salomon RM, Ripley B, Kennedy JS, Johnson B, Schmidt D, Zeitzer JM, Nishino S, Mignot E (2003) Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects. Biol Psychiatry 54:96–104PubMedCrossRefGoogle Scholar
  166. Saper CB, Chou TC, Scammell TE (2001) The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci 24:726–731PubMedCrossRefGoogle Scholar
  167. Sarchiapone M, Carli V, Camardese G, Cuomo C, di Giuda D, Calcagni M-L, Focacci C, de Risio S (2006) Dopamine transporter binding in depressed patients with anhedonia. Psychiatry Res Neuroimaging 147:243–248PubMedCrossRefGoogle Scholar
  168. Schmidt FM, Brugel M, Kratzsch J, Strauss M, Sander C, Baum P, Thiery J, Hegerl U, Schonknecht P (2010) Cerebrospinal fluid hypocretin-1 (orexin A) levels in mania compared to unipolar depression and healthy controls. Neurosci Lett 483:20–22PubMedCrossRefGoogle Scholar
  169. Schnell A, Albrecht U, Sandrelli F (2014) Rhythm and mood: relationships between the circadian clock and mood-related behavior. Behav Neurosci 128:326–343PubMedCrossRefGoogle Scholar
  170. Schone C, Apergis-Schoute J, Sakurai T, Adamantidis A, Burdakov D (2014) Coreleased orexin and glutamate evoke nonredundant spike outputs and computations in histamine neurons. Cell Rep 7:697–704PubMedCentralPubMedCrossRefGoogle Scholar
  171. Schwartz MD, Urbanski HF, Nunez AA, Smale L (2011) Projections of the suprachiasmatic nucleus and ventral subparaventricular zone in the Nile grass rat (Arvicanthis niloticus). Brain Res 1367:146–161PubMedCentralPubMedCrossRefGoogle Scholar
  172. Segal M (1979) Serotonergic innervation of the locus coeruleus from the dorsal raphe and its action on responses to noxious stimuli. J Physiol 286:401–415PubMedCentralPubMedCrossRefGoogle Scholar
  173. Sidor MM, Spencer SM, Dzirasa K, Parekh PK, Tye KM, Warden MR, Arey RN, Enwright JF, 3RD, Jacobsen JP, Kumar S, Remillard EM, Caron MG, Deisseroth K, Mcclung CA (2015) Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice. Mol Psychiatry 5Google Scholar
  174. Siegle GJ (1999) A neural network model of attention biases in depression. Prog Brain Res 121:407–432PubMedCrossRefGoogle Scholar
  175. Siegle GJ, Hasselmo ME (2002) Using connectionist models to guide assessment of psychological disorder. Psychol Assess 14:263–278PubMedCrossRefGoogle Scholar
  176. Sim CK, Forger DB (2007) Modeling the electrophysiology of suprachiasmatic nucleus neurons. J Biol Rhythms 22:445–453PubMedCrossRefGoogle Scholar
  177. Sims RE, Wu HH, Dale N (2013) Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents: an in vitro study. PLoS ONE 8:e53814PubMedCentralPubMedCrossRefGoogle Scholar
  178. Smith CM, Walker AW, Hosken IT, Chua BE, Zhang C, Haidar M, Gundlach AL (2014) Relaxin-3/RXFP3 networks: an emerging target for the treatment of depression and other neuropsychiatric diseases? Frontiers Pharmacol 5Google Scholar
  179. Sorooshyari S, Huerta R, De_Lecea L (2015) A framework for quantitative modeling of neural circuits involved in sleep-to-wake transition. Name Frontiers Neurol 6:32Google Scholar
  180. Spinazzi R, Andreis PG, Rossi GP, Nussdorfer GG (2006) Orexins in the regulation of the hypothalamic-pituitary-adrenal axis. Pharmacol Rev 58:46–57PubMedCrossRefGoogle Scholar
  181. Stamatakis AM, Jennings JH, Ung RL, Blair GA, Weinberg RJ, Neve RL, Boyce F, Mattis J, Ramakrishnan C, Deisseroth K (2013) A unique population of ventral tegmental area neurons inhibits the lateral habenula to promote reward. Neuron 80:1039–1053Google Scholar
  182. Strogatz SH (1987) Open peer. Commentary the mathematical structure of the human sleep-wake cycle. In: Strogatz SH (1986) Lecture notes in biomathematics, vol 69. Springer, Berlin. J Biol Rhythms 2:317–329Google Scholar
  183. Strogatz S, Carpenter G (1986) A comparative analysis of models of the human sleep-wake cycle. Lect Math Life Sci 19:1–38Google Scholar
  184. Thase ME, Trivedi MH, Rush AJ (1995) MAOIs in the contemporary treatment of depression. Neuropsychopharmacology 12:185–219PubMedCrossRefGoogle Scholar
  185. Toh KL, Jones CR, He Y, Eide EJ, Hinz WA, Virshup DM, Ptacek LJ, Fu YH (2001) An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science 291:1040–1043PubMedCrossRefGoogle Scholar
  186. Torterolo P, Chase MH (2014) The hypocretins (orexins) mediate the “phasic” components of REM sleep: a new hypothesis. Sleep Sci 7:19–29CrossRefPubMedCentralPubMedGoogle Scholar
  187. Tsujino N, Sakurai T (2009) Orexin/hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, and reward system. Pharmacol Rev 61:162–176PubMedCrossRefGoogle Scholar
  188. Tsuno N, Besset A, Ritchie K (2005) Sleep and depression. J Clin Psychiatry 66:1254–1269PubMedCrossRefGoogle Scholar
  189. Valdizán EM, Díez-Alarcia R, González-Maeso J, Pilar-Cuéllar F, García-Sevilla JA, Meana JJ, Pazos A (2010) α 2-Adrenoceptor functionality in postmortem frontal cortex of depressed suicide victims. Biol Psychiatry 68:869–872PubMedCentralPubMedCrossRefGoogle Scholar
  190. van Oosterhout F, Lucassen EA, Houben T, Vanderleest HT, Antle MC, Meijer JH (2012) Amplitude of the SCN clock enhanced by the behavioral activity rhythm. PLoS ONE 7:e39693PubMedCentralPubMedCrossRefGoogle Scholar
  191. Vasalou C, Henson MA (2010) A multiscale model to investigate circadian rhythmicity of pacemaker neurons in the suprachiasmatic nucleus. PLoS Comput Biol 6:e1000706PubMedCentralPubMedCrossRefGoogle Scholar
  192. Vertes RP, Linley SB (2008) Efferent and afferent connections of the dorsal and median raphe nuclei in the rat. Serotonin and sleep: molecular, functional and clinical aspects Springer 4:69Google Scholar
  193. Vitaterna MH, King DP, Chang AM, Kornhauser JM, Lowrey PL, McDonald JD, Dove WF, Pinto LH, Turek FW, Takahashi JS (1994) Mutagenesis and mapping of a mouse gene, clock, essential for circadian behavior. Science 264:719–725PubMedCentralPubMedCrossRefGoogle Scholar
  194. Vreeburg SA, Hoogendijk WJ, van Pelt J, Derijk RH, Verhagen JC, van Dyck R, Smit JH, Zitman FG, Penninx BW (2009) Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study. Arch Gen Psychiatry 66:617–626PubMedCrossRefGoogle Scholar
  195. Walderhaug E, Varga M, San Pedro M, Hu J, Neumeister A (2011) The role of the aminergic systems in the pathophysiology of bipolar disorder. In: Behavioral neurobiology of bipolar disorder and its treatment. Springer, BerlinGoogle Scholar
  196. Wang DH, Wong-Lin K (2013) Comodulation of dopamine and serotonin on prefrontal cortical rhythms: a theoretical study. Front Integr Neurosci 7:54PubMedCentralPubMedCrossRefGoogle Scholar
  197. Watabe-Uchida M, Zhu L, Ogawa SK, Vamanrao A, Uchida N (2012) Whole-brain mapping of direct inputs to midbrain dopamine neurons. Neuron 74:858–873Google Scholar
  198. Webb IC, Patton DF, Hamson DK, Mistlberger RE (2008) Neural correlates of arousal-induced circadian clock resetting: hypocretin/orexin and the intergeniculate leaflet. Eur J Neurosci 27:828–835PubMedCrossRefGoogle Scholar
  199. Wehr TA, Sack D, Rosenthal N, Duncan W, Gillin JC (1983) Circadian rhythm disturbances in manic-depressive illness. Fed Proc 42:2809–2814PubMedGoogle Scholar
  200. Welsh DK, Moore-Ede MC (1990) Lithium lengthens circadian period in a diurnal primate, Saimiri sciureus. Biol Psychiatry 28:117–126PubMedCrossRefGoogle Scholar
  201. Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, Charlson FJ, Norman RE, Flaxman AD, Johns N (2013) Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet 382:1575–1586PubMedCrossRefGoogle Scholar
  202. Williams KS, Behn CG (2011) Dynamic interactions between orexin and dynorphin may delay onset of functional orexin effects: a modeling study. J Biol Rhythms 26:171–181PubMedCrossRefGoogle Scholar
  203. Wilson HR, Cowan JD (1972) Excitatory and inhibitory interactions in localized populations of model neurons. Biophys J 12:1–24PubMedCentralPubMedCrossRefGoogle Scholar
  204. Winfree AT (1983) Impact of a circadian clock on the timing of human sleep. Am J Physiol-Regul Integr Comp Physiol 245:R497–R504Google Scholar
  205. Wirz-Justice A (2008) Diurnal variation of depressive symptoms. Dialogues Clin Neurosci 10:337–343PubMedCentralPubMedGoogle Scholar
  206. Wong-Lin K, Joshi A, Prasad G, McGinnity TM (2012) Network properties of a computational model of the dorsal raphe nucleus. Neural Netw 32:15–25PubMedCrossRefGoogle Scholar
  207. Wulff K, Gatti S, Wettstein JG, Foster RG (2010) Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease. Nat Rev Neurosci 11:589–599PubMedCrossRefGoogle Scholar
  208. Wulff K, Dijk D-J, Middleton B, Foster RG, Joyce EM (2012) Sleep and circadian rhythm disruption in schizophrenia. Br J Psychiatry 200:308–316PubMedCentralPubMedCrossRefGoogle Scholar
  209. Yamada Y, Forger D (2010) Multiscale complexity in the mammalian circadian clock. Curr Opin Genet Dev 20:626–633PubMedCentralPubMedCrossRefGoogle Scholar
  210. Yeoh JW, Campbell EJ, James MH, Graham BA, Dayas CV (2014) Orexin antagonists for neuropsychiatric disease: progress and potential pitfalls. Front Neurosci 8:36PubMedCentralPubMedCrossRefGoogle Scholar
  211. Yoshida Y, Fujiki N, Nakajima T, Ripley B, Matsumura H, Yoneda H, Mignot E, Nishino S (2001) Fluctuation of extracellular hypocretin‐1 (orexin A) levels in the rat in relation to the light–dark cycle and sleep–wake activities. J Neurosci 14:1075–1081Google Scholar
  212. Yu X, Zecharia A, Zhang Z, Yang Q, Yustos R, Jager P, Vyssotski AL, Maywood ES, Chesham JE, Ma Y, Brickley SG, Hastings MH, Franks NP, Wisden W (2014) Circadian factor BMAL1 in histaminergic neurons regulates sleep architecture. Curr Biol 24:2838–2844PubMedCentralPubMedCrossRefGoogle Scholar
  213. Zhang S, Zeitzer JM, Yoshida Y, Wisor JP, Nishino S, Edgar DM, Mignot E (2004) Lesions of the suprachiasmatic nucleus eliminate the daily rhythm of hypocretin-1 release. Sleep 27:619–627PubMedGoogle Scholar
  214. Ziolkowska A, Spinazzi R, Albertin G, Nowak M, Malendowicz LK, Tortorella C, Nussdorfer GG (2005) Orexins stimulate glucocorticoid secretion from cultured rat and human adrenocortical cells, exclusively acting via the OX1 receptor. J Steroid Biochem Mol Biol 96:423–429PubMedCrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Faculty of Life SciencesUniversity of ManchesterManchesterUK
  2. 2.Intelligent Systems Research CentreUniversity of Ulster, Magee CampusDerryNorthern Ireland, UK

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