Depression: An Evolutionarily Conserved Mechanism to Terminate Separation Distress? A Review of Aminergic, Peptidergic, and Neural Network Perspectives

Neuropsychoanalysis

Volumn 11, Issue 1, 2009, Pages 7-51

  Watt, Douglas F ^a   Panksepp, Jaak ^b  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b WASHINGTON STATE UNIVERSITY   (United States)

Author keywords

Attachment; Corticotropin releasing factor; Depression; Dynorphin; Neuropeptides; Opioids; Separation distress; Stress

Indexed keywords

EID: 78650678814     PISSN: 15294145     EISSN: 20443978     Source Type: Journal    
DOI: 10.1080/15294145.2009.10773593     Document Type: Article

References (248)

1. Alcaro, A., Huber, R., & Panksepp, J., (2007). Behavioral functions of the mesolimbic dopaminergic system:An affective neuroethological perspective. Brain Research Reviews, 56:283–321.
2. Allen, N. B., & Badcock, P. B. T., (2006). Darwinian models of depression:A review of evolutionary accounts of mood and mood disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 30:815–826.
3. Anand, A., Li, Y., Wang, Y., Gardner, K., & Lowe, M. J., (2007). Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit:An fMRI study. Journal of Neuropsychiatry and Clinical Neuroscience, 19:274–282.
4. Apa (1994). Diagnostic and Statistical Manual of Mental Disorders (4th edition). Washington, DC:American Psychiatric Association.
5. Baker, G. B., Coutts, R. T., & Greenshaw, A. J., (2000). Neuro-chemical and metabolic aspects of antidepressants:An overview. Journal of Psychiatry & Neuroscience 25:481–496.
6. Bale, T. L., & Vale, W. W., (2004). CRF and CRF receptors:Role in stress responsivity and other behaviors. Annual Review of Pharmacology and Toxicology, 44:525–557.
7. Bals-Kubik, R., Ableitner, A., Herz, A., & Shippenberg, T. S., (1993). Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats. Journal of Pharmacology and Experimental Therapeutics, 264 (1):489–495.
8. Barden, N., (2004). Implication of the hypothalamic–pituitary–adrenal axis in the physiopathology of depression. Journal of Psychiatry & Neuroscience, 29:185–193.
9. Barr, A. M., & Markou, A., (2005). Psychostimulant withdrawal as an inducing condition in animal models of depression. Neuroscience and Biobehavioral Reviews, 29:675–706
10. Barr, A. M., Markou, A., & Phillips, A. G., (2002). A “crash” course on psychostimulant withdrawal as a model of depression. Trends in Pharmacological Sciences, 23:475–482.
11. Barr, C. S., Schwandt, M. L., Lindell, S. G., Higley, J. D., Maestripieri, D., Goldman, D., (2008). Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates. Proceedings of the National Academy of Sciences, USA, 105:52777–52781.
12. Becker, C., Thiebot, M., Touitou, Y., Hamon, M., Cesselin, F., & Benoliel, J. J., (2001). Enhanced cortical extracellular levels of cholecystokinin-like material in a model of anticipation of social defeat in the rat. Journal of Neuroscience, 21 (1):262–269.
13. Becker, C., Zeau, B., Rivat, C., Blugeot, A., Hamon, M., & Benoliel, J. J., (2008). Repeated social defeat-induced depression-like behavioral and biological alterations in rats:Involvement of cholecystokinin. Molecular Psychiatry, 13 (12):1079–1092.
14. Berridge, K. C., (2004). Motivation concepts in behavioral neuroscience. Physiology & Behavior, 81:179–209.
15. Berridge, K. C., (2007). The debate over dopamine’s role in reward:The case for incentive salience. Psychopharmacology, 191:391–431.
16. Berton, O., & Nestler, E. J., (2006). New approaches to anti-depressant drug discovery:Beyond monoamines. Nature Reviews. Neuroscience, 7:137–151.
17. Bevins, R. A., & Besheer, J., (2005). Novelty reward as a measure of anhedonia. Neuroscience & Biobehavioral Reviews, 29:707–714.
18. Bhagwagar, Z., Whale, R., & Cowen, P. J., (2002). State and trait abnormalities in serotonin function in major depression. British Journal of Psychiatry, 180:24–28.
19. Bhatt, S., Gregg, T. R., & Siegel, A., (2003). NK1 receptors in the medial hypothalamus potentiate defensive rage behavior elicited from the midbrain periaqueductal gray of the cat. Brain Research, 966:54–64.
20. Bibring, E., (1953). The mechanism of depression. In:Affective Disorders, ed. P., Greenacre. New York:International Universities Press, pp. 13–48.
21. Bilkei-Gorzo, A., Michel, K., Noble, F., Roques, B. P., & Zimmer, A., (2008). Preproenkephalin knockout mice show no depression-related phenotype. Neuropsychopharmacology, 196:327–335.
22. Bleuler, M., (1919). The Internal Secretions and the Nervous System. Nervous and Mental Disease Monograph Series, No. 30. New York:Nervous and Mental Disease Publishing Company.
23. Bodkin, J. A., Zornberg, G. L., Lukas, S. E., & Cole, J. O., (1995). Buprenorphine treatment of refractory depression. Journal of Clinical Psychopharmacology, 15 (1):49–57.
24. Bowlby, J., (1969). Attachment, Vol. 1:Attachment and Loss (2nd edition). New York:Basic Books, 1999.
25. Bowlby, J., (1980). Attachment and Loss, Vol. 3. Loss:Sadness and Depression. New York:Basic Books.
26. Boyle, M. P., Brewer, J. A., Funatsu, M., Wozniak, D. F., Tsien, J. Z., Izumi, Y., (2005). Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior. Proceedings of the National Academy of Sciences, USA, 102 (2):473–478.
27. Bremner, J. D., Narayan, M., Anderson, E. R., Staib, L. H., Miller, H. L., & Charney, D. S., (2000). Hippocampal volume reduction in major depression. Americqn Journal of Psychiatry, 157:115–117.
28. Brudzynski, S., (2007). Ultrasonic calls of rats as indicator variables of negative or positive states:Acetylcholine–dopamine interaction and acoustic coding. Behavioural Brain Research, 182:261–273.
29. Burke, H. M., Davis, M. C., Ottec, C., & Mohra, D. C., (2005). Depression and cortisol responses to psychological stress:A meta-analysis. Psychoneuroendocrinology, 30:846–856.
30. Cai, C., & Leonard, B. E., (2006). The olfactory bulbectomised rat as a model of depression. Neuroscience and Biobehavioral Reviews, 29:627–647.
31. Calabrese, F., Molteni, R., Maj, P. F, Cattaneo, A., Gennarelli, M., Racagni, G., (2007). Chronic duloxetine treatment induces specific changes in the expression of BDNF transcripts and in the subcellular localization of the neurotrophin protein. Neuropsychopharmacology, 32:2351–2359.
32. Callaway, E., (1996). Buprenorphine for depression:The unadoptable orphan. Biological Psychiatry, 39 (12):989–990.
33. Cameron, N. M., Champagne, F. A., Parent, C., Fish, E. W., Ozaki-Kuroda, K., & Meaney, M. J., (2005). The programming of individual differences in defensive responses and reproductive strategies in the rat through variations in maternal care. Neuroscience and Biobehavioral Reviews, 29:843–865.
34. Carlezon, W. A., Beguin, C., DiNieri, J. A., Baumann, M. H., Richards, M. R., Todtenkopf, M. S., (2006). Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats. Journal of Pharmacology and Experimental Therapeutics, 316:440–447.
35. Castrén, E., (2005). Is mood chemistry? Nature Reviews. Neuroscience, 6:241–246.
36. Celada, P., Puig, M., Amargós-Bosch, M., Adell, A., & Artigas, F., (2004). The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. Journal of Psychiatry & Neuroscience, 29:252–265.
37. Charmandari, E., Tsigos, C., & Chrousos, G., (2005). Endocrinology of the stress response. Annual Review of Neuroscience, 6:463–475.
38. Charney, D. S., Nestler, E. J., & Bunney, B. S., (1999). Neurobiology of Mental Illness. New York:Oxford University Press.
39. Coppen, A., Eccleston, E., Craft, I., & Bye, P., (1973). Total and free plasma-tryptophan concentration and oral contraception [Letter]. Lancet, 2:1498.
40. Cowen, P. J., Parry-Billings, M., & Newsholme, E. A., (1989). Decreased plasma tryptophan levels in major depression. Journal of Affective Disorders, 16:27–31.
41. de Kloet, E. R., Joëls, M., & Holsboer, F., (2005). Stress and the brain:From adaptation to disease. Nature Reviews. Neuroscience, 6, 463–475.
42. De La Garza, R., II (2005). Endotoxin- or pro-inflammatory cytokine-induced sickness behavior as an animal model of depression:Focus on anhedonia. Neuroscience and Biobehavioral Reviews, 29:761–770.
43. Delgado, P. L., (2000). Depression:The case for a monoamine deficiency. Journal of Clinical Psychiatry, 61 (Suppl. 6):7–11.
44. Delgado, P. L., (2004). Treatment of mood disorders. In:Textbook of Biological Psychiatry, ed. J., Panksepp. New York:Wiley, pp. 231–266.
45. Delgado, P. L., Charney, D. S., Price, L. H., Aghajanian, G. K., Landis, H., & Heninger. G. R., (1990). Serotonin function and the mechanism of antidepressant action:Reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Archives of General Psychiatry, 47:411–418.
46. Delgado, P. L., Price, L. H., Heninger, G. R., & Charney, D. S., (1992). Neurochemistry of affective disorders. In:Handbook of Affective Disorders, ed. E. S., Paykel. New York:Churchill Livingstone, pp. 219–253.
47. Dortch-Carnes, J., & Potter, D. E., (2005). Bremazocine:A kappa-opioid agonist with potent analgesic and other pharmacologic properties. CNS Drug Reviews, 11:195–212.
48. Dranovsky, A., & Hen, R., (2006). Hippocampal neurogenesis:Regulation by stress and antidepressants. Biological Psychiatry, 59:1136–1143.
49. Drevets, W. C., Frank, E., Price, J. C., Kupfer, D. J., Holt, D., Greer, P. J., (1999). PET imaging of serotonin 1A receptor binding in depression. Biological Psychiatry, 46:1375–1387.
50. Drew, M. R., & Hen, R., (2007). Adult hippocampal neurogenesis as target for the treatment of depression. CNS Neurological Disorders Drug Targets, 6 (3):205–218.
51. Dubrovsky, B., (2006). Neurosteroids, neuroactive steroids, and symptoms of affective disorders. Pharmacology Biochemistry and Behavior, 84:644–655.
52. Duman, R. S., Heninger, G. R., & Nestler, E. J., (1997). A molecular and cellular theory of depression. Archives of General Psychiatry, 54:607–608.
53. Duman, R. S., & Monteggia, L. M., (2006). A neurotrophic model for stress-related mood disorders. Biological Psychiatry, 59:1116–1127.
54. Duval, F., Mokrani, M. C., Ortiz, J. A., Schulz, P., Champeval, C., & Macher, J. P., (2005). Neuroendocrine predictors of the evolution of depression. Dialogues in Clinical Neuroscience, 7:273–282.
55. Ehrensing, R. H., Kastin, A. J., Wurzlow, G. F., Michell, G. F., & Mebane, A. H., (1994). Improvement in major depression after low subcutaneous doses of MIF-1. Journal of Affective Disorders, 31 (4):227–233.
56. Elliot, O., & Scott, J. P., (1961). The development of emotional distress reactions to separation, in puppies. Journal of Genetic Psychology, 99:3–22.
57. Etkin, A., Pittenger, C., Polan, H. J., & Kandel, E. R., (2005). Toward a neurobiology of psychotherapy:Basic science and clinical applications. Journal of Neuropsychiatry Clinical Neuroscience, 17:145–158.
58. Fink, M., & Taylor, M. A., (2007). Resurrecting melancholia. Acta Psychiatrica Scandinavica, 433 (Suppl.):14–20.
59. Fitzgerald, P. B., Oxley, T. J., Laird, A. R., Kulkarni, J., Egan, G. F., & Daskalakis, Z. J., (2006). An analysis of functional neuroimaging studies of dorsolateral prefrontal cortical activity in depression. Psychiatry Research, 148:33–45.
60. Flory, J. D., Mann, J. J., Manuck, S. B., & Muldoon, M. F., (1998). Recovery from major depression is not associated with normalization of serotonergic function. Biological Psychiatry, 43:320–326.
61. Flory, J. D., Manuck, S. B., Matthews, K. A., & Muldoon, M. F., (2004). Serotonergic function in the central nervous system is associated with daily ratings of positive mood. Psychiatry Research, 129:11–19.
62. Flügge, G., van Kampen, M., Meyer, H., & Fuchs, E., (2003). Alpha2A and alpha2C-adrenoceptor regulation in the brain:Alpha2a changes persist after chronic stress. European Journal of Neuroscience, 17:917–928.
63. Freed, P. J., & Mann, J. J., (2007). Sadness and loss:A neurobiopsychosocial model. American Journal of Psychiatry, 164:28–34.
64. Freud, S., (1914g). Remembering, repeating and working-through. Standard Edition, 12.
65. Freud, S., (1917e [1915]). Mourning and melancholia. Standard Edition, 14.
66. Freud, S., (1920g) Beyond the Pleasure Principle. Standard Edition, 18.
67. Furey, M. L., & Drevets, W. C., (2006). Antidepressant efficacy of the antimuscarinic drug scopolamine:A randomized, placebo-controlled clinical trial. Archives of General Psychiatry, 63:1121–1129.
68. Gallagher, S., (2008). Brainstorming:Views and Interviews on the Mind. Exeter:Academic Press.
69. Grimm, S., Beck, J., Schuepbach, D., Hell, D., Boesiger P., Bermpohl, (2008). Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment:An fMRI study in severe major depressive disorder. Biological Psychiatry, 63:369–376.
70. Grimm, S., Grimm, S., Boesiger, P., Beck, J., Schuepbach, D., Bermpohl, F., et al. (in press). Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology.
71. Groves, J. O., (2007). Is it time to reassess the BDNF hypothesis of depression. Molecular Psychiatry, 12:1079–1088.
72. Haggendal, J., & Lindqvist, M., (1964). Disclosure of labile monoamine fractions in brain and their correlation to behaviour. Acta Physiologica Scandinavica, 60:351–357.
73. Harris, G. C., & Aston-Jones, G., (2006). Arousal and reward:A dichotomy in orexin function. Trends in Neurosciences, 29:571–577.
74. Harris, J. C., (1989). Experimental animal modeling of depression and anxiety. Psychiatric Clinics of North America, 18:815–836.
75. Harro, J., & Oreland, L., (2001). Depression as a spreading adjustment disorder of monoaminergic neurons:A case for primary implications of the locus coeruleus. Brain Research Reviews, 38:79–128.
76. Harro, J., Vasar, E., & Bradwejin, J., (1993). Cholecystokinin in animal and human research on anxiety. Trends in Pharmacological Sciences, 14:244–249.
77. Hasebe, K., Kawai, K., Suzuki, T., Kawamura, K., Tanaka, T., Narita, M., (2004). Possible pharmacotherapy of the opioid kappa receptor agonist for drug dependence. Annals of the New York Academy of Sciences, 1025:404–413.
78. Healy, D., (1996). The Psychopharmacologists:Interviews. London:Altman.
79. Healy, D., (1997). The Antidepressant Era. Cambridge, MA:Harvard University.
80. Heim, C., & Nemeroff, C. B., (1999). The impact of early adverse experiences on brain systems involved in the pathophysiology of anxiety and affective disorders. Biological Psychiatry, 46:1509–1522.
81. Heinrichs, M., Baumgartner, T., Kirschbaum, C., & Ehlert, U., (2003). Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biological Psychiatry, 54 (12):1389–1398.
82. Henn, F. A., & Vollmayr, B., (2005). Stress models of depression:Forming genetically vulnerable strains. Neuroscience and Biobehavioral Reviews, 29:799–804.
83. Hennessy, M. B., Deak, T., & Schiml-Webb, P. A., (2001). Stress-induced sickness behaviors:An alternative hypothesis for responses during maternal separation. Developmental Psychobiology, 39:76–83.
84. Heuser, I. J., Schweiger, U., Gotthardt, U., Schmider, J., Lammers, C. H., (1996). Pituitary-adrenal system regulation and psychopathology during amitriptyline treatment in elderly depressed patients and normal comparison subjects. American Journal of Psychiatry, 153 (1):93–99.
85. Heuser, I., Yassouridis, A., & Holsboer, F., (1994). The combined dexamethasone/CRH test:A refined laboratory test for psychiatric disorders. Journal of Psychiatric Research, 28 (4):341–356.
86. Hobson, J. A., Pace-Schott, E. F., & Stickgold, R., (2000). Dreaming and the brain:Toward a cognitive neuroscience of conscious states. Behavioral and Brain Sciences, 23:793–842.
87. Holsboer, F., (2000). The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology, 23:477–501.
88. Holsboer, F., (2003). The role of peptides in treatment of psychiatric disorders. Journal of Neural Transmission (Suppl.), 64:17–34.
89. Horvath, T. L., & Diano, S., (2004). The floating blueprint of hypothalamic feeding circuits. Nature Reviews. Neuroscience, 5:662–667.
90. Hurd, Y. L., Herman, M. M., Hyde, T. M., Bigelow, L. B., Weinberger, D. R., & Kleinman, J. E., (1997). Prodynorphin mRNA expression is increased in the patch vs matrix compartment of the caudate nucleus in suicide subjects. Molecular Psychiatry, 2:495–500.
91. Hurd, Y. L., Svensson, P., & Ponten, M., (1999). The role of dopamine, dynorphin, and CART systems in the ventral striatum and amygdala in cocaine abuse. Annals of the New York Academy of Sciences, 877:499–506.
92. Ikemoto, S., & Panksepp, J., (1999). The role of nucleus accumbens dopamine in motivated behavior:A unifying interpretation with special reference to reward-seeking. Brain Research Reviews, 31:6–41.
93. Insel, T. R., & Harbaugh, C. R., (1989). Central administration of corticotropin releasing factor alters rat pup isolation calls. Pharmacology, Biochemistry & Behavior, 32:197–201.
94. Jacobs, B. L., Praag, H., & Gage, F. H., (2000). Adult brain neurogenesis and psychiatry:A novel theory of depression. Molecular Psychiatry, 5:262–269.
95. Jacobson, E., (1964). The Self and the Object World. New York:International Universities Press.
96. Jacobson, E., (1971). Depression:Comparative Studies of Normal, Neurotic and Psychotic Conditions. New York:International Universities Press.
97. Janowsky, D. S., El-Yousef, M. K., Davis, J. M., & Sekerke, H. J., (1972). A cholinergic–adrenergic hypothesis of mania and depression. Lancet, 2:632–635.
98. Janowsky, D. S., Overstreet, D. H., & Nurnberger, J. I., Jr. (1994). Is cholinergic sensitivity a genetic marker for the affective disorders? American Journal of Medical Genetics, 54 (4):335–344.
99. Jans, L. A. W., Riedell, W. J., Markus, C. R., & Blokland, A., (2007). Serotonergic vulnerability and depression:Assumptions, experimental evidence and implications. Molecular Psychiatry, 12:522–543.
100. Jones, B. E., (2005). From waking to sleeping:Neuronal and chemical substrates. Trends in Pharmacological Sciences, 26:578–586.
101. Kalin, N. H., (1985). Behavioral effects of ovine corticotropin-releasing factor administered to rhesus monkeys. Federation Proceedings, 44:249–253.
102. Kalin, N. H., Shelton, S. E., & Barksdale, C. M., (1988). Opiate modulation of separation-induced distress in non-human primates. Brain Research, 440:285–292.
103. Kanner, A. M., (2004). Structural MRI changes of the brain in depression. Clinical EEG Neuroscience, 35:46–52.
104. Kapitany, T., Schindl, M., Schindler, S. D., Hesselmann, B., Füreder, T., (1999). The citalopram challenge test in patients with major depression and healthy controls. Psychiatry Research, 88:75–88.
105. Kaufman, J., Martin, A., King, R. A., & Charney, D., (2001). Are child-, adolescent-, and adult-onset depression one and the same disorder? Biological Psychiatry, 49:980–1001.
106. Keck, M. E., Ohl, F., Holsboer, F., & Muller, M. B., (2005). Listening to mutant mice:A spotlight on the role of CRF/CRF receptor systems in affective disorders. Neuroscience and Biobehavioral Reviews, 29:867–889.
107. Kehne, J. H., (2007). The CRF1 receptor, a novel target for the treatment of depression, anxiety, and stress-related disorders. CNS Neurological Disorders and Drug Targets, 6:163–182.
108. Kehoe, P., & Blass, E. M., (1986). Opioid-mediation of separation distress in 10-day-old rats:Reversal of stress with maternal stimuli. Developmental Psychobiology, 19:385–398.
109. Keller, M. C., & Nesse, R. M., (2006). The evolutionary significance of depressive symptoms:Different adverse situations lead to different depressive symptom patterns. Journal of Personality and Social Psychology, 91:316–330.
110. Kendler, K. S., Gardner, C. O., & Prescott, C. A., (2002). Toward a comprehensive developmental model for major depression in women. American Journal of Psychiatry, 159:1133–1145.
111. Kennedy, S. E., Koeppe, R. A., Young, E. A., & Zubieta, J. K., (2006). Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women. Archives of GeneralPsychiatry, 63:1199–1208.
112. Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., (2003). The epidemiology of major depressive disorder:Results from the National Comorbidity Survey Replication (NCS-R). Journal of the American Medical Association, 289 (23):3095–3105.
113. Knutson, B., Wolkowitz, O. M., Cole, S. W., Chan, T., & Moore, E. A., (1998). Selective alteration of personality and social behavior by serotonergic intervention. American Journal of Psychiatry, 348:274–282.
114. Kotlinska, J., Rafalski, P., Biala, G., Dylag, T., Rolka, K., & Silberring, J., (2003). Nociceptin inhibits acquisition of amphetamine-induced place preference and sensitization to stereotypy in rats. European Journal of Pharmacology, 474:233–239.
115. Kozisek, M. E., Middlemas, D., & Bylund, D. B., (2008). Brain-derived neurotrophic factor and its receptor tropomyosin-related kinase B in the mechanism of action of antidepressant therapies. Pharmacology & Therapeutics, 117:30–51.
116. Kramer, M. S., Cutler, N., Feighner, J., Shrinivastava, R., Carman, J., Sramek, (1998). Distinct mechanism for antidepressant activity by blockade of central substance Preceptors. Science, 281:1640–1645.
117. Krishnan, V., Han, M., Graham, D., Berton, O., Renthal, W., Russo, S., (2007). Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell, 131 (2):391–404.
118. Kroes, R. A., Burgdorf, J., Otto, N. J., Panksepp, J., & Moskal, J. R., (2007). Social defeat, a paradigm of depression in rats that elicits 22-kHz vocalizations, preferentially activates the cholinergic signaling pathway in the periaqueductal gray. Behavioral Brain Research, 182:290–300.
119. Kroes, R. A., Panksepp, J., Burgdorf, J., Otto, N. J., & Moskal, J. R., (2006). Social dominance-submission gene expression patterns in rat neocortex. Neuroscience, 137:37–49.
120. Land, B. B., Bruchas, M. R., Melief, E., Xu, M., Lemos, J., & Chavkin, C., (2008). The dysphoric component of stress is encoded by activation of the dynorphine-kappa opioid system. Journal of Neuroscience, 28:407–414.
121. Lane, R. D., & Garfield, D. A. S., (2005). Becoming aware of feelings:Integration of cognitive-developmental, neuroscientific, and psychoanalytic perspectives [with commentaries]. Neuropsychoanalysis, 7:5–70.
122. Lecrubier, Y., (2007). Widespread under-recognition and under-treatment of anxiety and mood disorders:Results from three European studies. Journal of Clinical Psychiatry, 68 (Suppl. 2):36–41.
123. LeDoux, J., (1996). The Emotional Brain. New York:Simon & Schuster.
124. Lee, A. L., Ogle, W. O., & Sapolsky, R. M., (2002). Stress and depression:Possible links to neuron death in the hippocampus. Bipolar Disorders, 4:117–128.
125. Leith, N. J., & Barrett, R. J., (1980). Effects of chronic amphetamine or reserpine on self-stimulation/responding:Animal model of depression? Psychopharmacology, 72:9–15.
126. Lemonde, S., Turecki, G., Bakish, D., Du, L., Hrdina, P. D., Bown, C. D., (2003). Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. Journal of Neuroscience, 23:8788–8799.
127. Leonard, B. E., (2006). HPA and immune axes in stress:Involvement of the serotonergic system. Neuroimmunomodulation, 13:268–276.
128. Levine, S., (2001). Primary social relationships influence the development of the hypothalamic–pituitary–adrenal axis in the rat. Physiology & Behavior, 73:255–260.
129. Levine, S., (2005). Developmental determinants of sensitivity and resistance to stress. Psychoneuroendocrinology, 30:939–946.
130. Levinson, D. F., (2006). The genetics of depression:A review. Biological Psychiatry, 60:84–92.
131. Lifschytz, T., Segman, R., Shalom, G., Lerer, B., Gur, E., Golzer, T., (2006). Basic mechanisms of augmentation of antidepressant effects with thyroid hormone. Current Drug Targets, 7:203–210.
132. Liotti, M., & Panksepp, J., (2004). Imaging human emotions and affective feelings:Implications for biological psychiatry. In:Textbook of Biological Psychiatry, ed. J., Panksepp. Hoboken, NJ:Wiley, pp. 33–74.
133. Mague, S. D., Pliakas, A. M., Todtenkopf, M. S., Tomasiewicz, H. C., Zhang, Y, Stevens, W. C., Jr., et al. (2003). Antide-pressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats. Journal of Pharmacology and Experimental Therapeutics, 305:323–330.
134. Maier, S. F., & Watkins, R. L., (2005). Stressor controllability and learned helplessness:The roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor. Neuroscience and Biobehavioral Reviews, 29:829–841.
135. Malatynska, E., & Knapp, R. J., (2005). Dominant–submissive behavior as models of mania and depression. Neuroscience and Biobehavioral Reviews, 29:715–737.
136. Malatynska, E., Rapp, R., Harrawood, D., & Tunnicliff, G., (2005). Submissive behavior in mice as a test for antidepressant drug activity. Pharmacology, Biochemistry, and Behavior, 82 (2):306–313.
137. Mann, J. J., (2003). Neurobiology of suicidal behaviour. Nature Reviews. Neuroscience, 4:819–828.
138. Martinowich, K., & Lu, B., (2008). Interaction between BDNF and serotonin:Role in mood disorders. Neuropyschopharmacology, 33:78–83.
139. Martinowich, K., Manji, H., & Lu, B., (2007). New insights into BDNF function in depression and anxiety. Nature Neuroscience, 10:1089–1093.
140. Matsumoto, K., Puia, G., Dong, E., & Pinna, G., (2007). GABA(A) receptor neurotransmission dysfunction in a mouse model of social isolation-induced stress:Possible insights into a non-serotonergic mechanism of action of SSRIs in mood and anxiety disorders. Stress, 10:3–12.
141. Mayberg, H. S., Brannan, S. K., Tekell, J. L., Silva, J. A., Mahurin, R. K., McGinnis, S., (2000). Regional metabolic effects of fluoxetine in major depression:Serial changes and relationship to clinical response. Biological Psychiatry, 48:830–843.
142. Mayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K, Jerabek, P. A., (1999). Reciprocal limbic-cortical function and negative mood:Converging PET findings in depression and normal sadness. American Journal of Psychiatry, 156:675–682.
143. Mayberg, H. S, Lozano, A. M., Voon, V., McNeely, H. E., Seminowicz, D., Hamani, C., (2005). Deep brain stimulation for treatment-resistant depression. Neuron, 45 (5):651–660.
144. McArthur, R., & Borsini, F., (2006). Animal models of depression in drug discovery:A historical perspective. Pharmacology, Biochemistry and Behavior, 84:436–452.
145. McArthur, S., McHale, E., & Gillies, G. E., (2007). The size and distribution of midbrain dopaminergic populations are permanently altered by perinatal glucocorticoid exposure in a sex-, region-, and time-specific manner. Neuropsychopharmacology, 32 (7):1462–1476.
146. McEwen, B. S., (2000). The neurobiology of stress:From serendipity to clinical relevance. Brain Research, 886:172–189.
147. McEwen, B. S., (2004). Stress, allostasis and allostatic overload in the pathology of depression. In:Neuroplasticity:A New Approach to the Pathology of Depression. Marrickville, Australia:Science Press, pp. 51–60.
148. McEwen, B. S., (2007). Physiology and neurobiology of stress and adaptation:Central role of the brain. Physiological Reviews, 87:873–904.
149. McLaughlin, J. P., Li, S., Valdez, J., Chavkin, T. A., & Chavkin, C., (2006). Social defeat stress-induced behavioral responses are mediated by endogenous kappa opioid systems. Neuropsychopharmacology, 31:1241–1248.
150. McLaughlin, J. P., Marton-Popovici, M., & Chavkin, C., (2003). Kappa opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses. Journal of Neuroscience, 23:5674–5683.
151. Meaney, M. J., (2001). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review of Neuroscience, 24:1161–1192.
152. Mello, N. K., & Negus, S. S., (2000). Interactions between kappa opioid agonists and cocaine. Preclinical studies. Annals of the New York Academy of Sciences, 909:104–132.
153. Miklos, I. H., & Kovacs, K. J., (2002). GABAergic innervation of corticotropin-releasing hormone (CRH)-secreting parvocellular neurons and its plasticity as demonstrated by quantitative immunoelectron microscopy. Neuroscience, 113:581–592.
154. Monteggia, L. M., Barrot, M., Powell, C. M., Berton, O., Galanis, V., Gemelli, T., (2004). Essential role of BDNF in adult hippocampal function. National Academy of Sciences, USA, 101:10827–10832.
155. Muller, N., & Schwarz, M. J., (2007). The immune-mediated alteration of serotonin and glutamate:Towards an integrated view of depression. Molecular Psychiatry, 12:988–1000.
156. Neese, R. M., (2000). Is depression an adaptation? Archives of General Psychiatry, 57:14–20.
157. Nemeroff, C. B., & Vale, W. W., (2005). The neurobiology of depression:Inroads to treatment and new drug discovery. Journal of Clinical Psychiatry, 66 (Suppl. 7):5–13.
158. Nestler, E. J., (1998). Antidepressant treatments in the 21st century. Biological Psychiatry, 44:526–533.
159. Nestler, E. J., & Carlezon, W. A., Jr. (2006). The mesolimbic dopamine reward circuit in depression. Biological Psychiatry, 59:1151–1159.
160. Noble, F., & Roques, B. P., (2007). Protection of endogenous enkephalin catabolism as natural approach to novel analgesic and antidepressant drugs. Expert Opinions on Therapeutic Targets, 11:145–159.
161. Norman, T. R., & Burrows, G. D., (2007). Emerging treatments for major depression. Expert Reviews in Neurotherapeutics, 7:203–213.
162. Northoff, G., (2007). Psychopathology and pathophysiology of the self in depression:Neuropsychiatric hypothesis. Journal of Affective Disorders, 104:1–14.
163. Northoff, G., Bermpohl, F., Schoeneich, F., & Boeker, H., (2007). How does our brain constitute defense mechanisms? First-person neuroscience and psychoanalysis. Psychotherapy & Psychosomatics, 76:141–153.
164. Northoff, G., Henzel, A., de Greck, M., Bermpohl, F., Dobrowolny, H., & Panksepp, J., (2006). Self referential processing in our brain:A meta-analysis of imaging studies of the self. NeuroImage, 31:440–457.
165. Northoff, G., & Panksepp, J., (2008). The trans-species concept of self and the subcortical-cortical midline system. Trends in Cognitive Sciences, 12:259–264.
166. Ordway, G. A., Klimek, V., & Mann, J. J., (2004). Neurocircuitry of mood disorders. Neuropsychopharmacology:The Fifth Generation of Progress, ed. K. L., Davis, D., Charney, ed. J. T., Coyle C., Nemeroff. Philadelphia:Lippincott Williams & Wilkins, pp. 1051–1064.
167. Ordway, G. A., Schenk, J., Stockmeier, C. A., May, W., & Klimek, V., (2003). Elevated agonist binding to alpha2-adrenoceptors in the locus coeruleus in major depression. Biological Psychiatry, 53:315–323.
168. Overstreet, D. H., Friedman, E., Mathé, A. A., & Yadid, G., (2005). The Flinders Sensitive Line rat:A selectively bred putative animal model of depression. Neuroscience and Biobehavioral Reviews, 29:739–759.
169. Panksepp, J., (1981). Brain opioids:A neurochemical substrate for narcotic and social dependence. In:Progress in Theory in Psychopharmacology, ed. S., Cooper. London:Academic Press, pp. 149–175.
170. Panksepp, J., (1988). Posterior pituitary hormones and separation distress in chicks. Neuroscience Abstracts, 14:287.
171. Panksepp, J., (1990). A role for “affective neuroscience” in understanding stress:The case of separation distress circuitry. In:Psychobiology of Stress, ed. A., Oliverio. Dordrecht:Kluwer, pp. 41–58.
172. Panksepp, J., (1998). Affective Neuroscience:The Foundations of Human and Animal Emotion. New York:Oxford University Press.
173. Panksepp, J., (2003a). Can anthropomorphic analyses of “separation cries” in other animals inform us about the emotional nature of social loss in humans? Psychological Reviews, 110:376–388.
174. Panksepp, J., (2003b). Feeling the pain of social loss. Science, 302:237–239.
175. Panksepp, J., (2005). Feelings of social loss:The evolution of pain and the ache of a broken heart. In:Consciousness & Emotions, Vol. 1, ed. R., Ellis & N., Newton. Amsterdam:John Benjamins, pp. 23–55.
176. Panksepp, J., (2006). Emotional endophenotypes in evolutionary psychiatry. Progress in Neuropsychopharmacology and Biological Psychiatry, 30:774–784.
177. Panksepp, J., & Bekkedal, M., (1997). Neuropeptides and the varieties of anxiety in the brain. Italian Journal of Psychopathology, 1:18–27.
178. Panksepp, J., Burgdorf, J., Beinfeld, M. C., Kroes, R. A., & Moskal, J. R., (2004). Regional brain cholecystokinin changes as a function of friendly and aggressive social interactions in rats. Brain Research, 1025:75–84.
179. Panksepp, J., Burgdorf, J., Beinfeld, M. C., Kroes, R. A., & Moskal, J. R., (2007). Brain regional neuropeptide changes resulting from social defeat. Behavioral Neuroscience, 121:1364–1371.
180. Panksepp, J., & Harro, J., (2004). The future of neuropeptides in biological psychiatry and emotional psychopharmacology:Goals and strategies. In:J., Panksepp (Ed.), Textbook of Biological Psychiatry. New York:Wiley, pp. 627–660.
181. Panksepp, J., Herman, B., Conner, R., Bishop, P., & Scott, J. P., (1978). The biology of social attachments:Opiates alleviate separation distress. Biological Psychiatry, 9:213–220.
182. Panksepp, J., Herman, B. H., Vilberg, T., Bishop, P., & DeEskinazi, F. G., (1980). Endogenous opioids and social behavior. Neuroscience and Biobehavioral Reviews, 4:473–487.
183. Panksepp, J., Lensing, P., & Bernatzky, G., (1989). Delta and kappa opiate receptor control of separation distress. Neuroscience Abstracts, 15:845.
184. Panksepp, J., & Moskal, J., (2008). Dopamine and SEEKING:Subcortical “reward” systems and appetitive urges. In:Handbook of Approach and Avoidance Motivation, ed. A., Elliot. Mahwah, NJ:Lawrence Erlbaum Associates, pp. 67–87.
185. Panksepp, J., Moskal, J., Panksepp, J. B., & Kroes, R., (2002). Comparative approaches in evolutionary psychology:Molecular neuroscience meets the mind. Neuroendocrinology Letters, 23 (Suppl. 4):105–115.
186. Panksepp, J., Normansell, L. A., Herman, B., Bishop, P., & Crepeau, L., (1988). Neural and neurochemical control of the separation distress call. In:The Physiological Control of Mammalian Vocalizations, ed. J. D., Newman. New York:Plenum, pp. 263–300.
187. Panksepp, J., & Northoff, G., (2009). The trans-species core self:The emergence of active cultural and neuro-ecological agents through self related processing within subcortical–cortical midline networks. Consciousness & Cognition, 18:193–215.
188. Panksepp, J., Siviy, S. M., & Normansell, L. A., (1985). Brain opioids and social emotions. In:The Psychobiology of Attachment and Separation, ed. M., Reite & T., Fields. New York:Academic Press, pp. 3–49.
189. Panksepp, J., Vilberg, T., Bean, N. J., Coy, D. H., & Kastin, A. J., (1978). Reduction of distress vocalization in chicks by opiate-like peptides. Brain Research Bulletin, 3:663–667.
190. Panksepp, J., Yates, G., Ikemoto, & Nelson, E., (1991). Simple ethological models of depression:Social-isolation induced “despair” in chicks and mice. In:Animal Models in Psychopharmacology, ed. B., Olivier & J., Moss. Holland:Duphar, pp. 161–181.
191. Pavlides, C., Niv?n, L. G., & McEwen, B. S., (2002). Effects of chronic stress on hippocampal long-term potentiation. Hippocampus, 12 (2):245–257.
192. Pezawas, L., Meyer-Lindenberg, A., Drabant, E. M., Berchinski, B. A., Munoz, K. E., Kolachana, B. S., (2005). 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions:A genetic susceptibility mechanism for depression. Nature Neuroscience, 8:828–834.
193. Preter, M., & Klein, D. F., (2008). Panic, suffocation false alarms, separation anxiety and endogenous opioids. Progress in Neuropsychopharmacology and Biological Psychiatry, 32:603–612.
194. Pryce, C. R., Ruedi-Bettschen, D., Dettling, A. C., Weston, A., Russig, H., Ferger, B., (2005). Long-term effects of early-life environmental manipulations in rodents and primates:Potential animal models in depression research Neuroscience and Biobehavioral Reviews, 29:649–674.
195. Ratey, J., (2008). Spark:The Revolutionary New Science of Exercise and the Brain. Boston:Little Brown.
196. Reite, M., Short, R., Seiler, C., & Pauley, J. D., (1981). Attachment, loss, and depression. Journal of Child Psychology and Psychiatry, 22:141–169.
197. Roffman, J. L., Marci, C. D., Glick, D. M., Dougherty, D. D., & Rauch, S. L., (2005). Neuroimaging and the functional neuroanatomy of psychotherapy. Psychological Medicine, 35:1385–1398.
198. Rosenfeld, P., Suchecki, D., & Levine, S., (1992). Multifactorial regulation of the hypothalamic–pituitary–adrenal axis during development. Neuroscience & Biobehavioral Reviews, 16:553–568.
199. Rush, A. J., (2007). STAR*D:What have we learned? American Journal of Psychiatry, 164 (2):201–204.
200. Rush, A. J., Giles, D. E., Schlesser, M. A., Orsulak, P. J., Parker, C. R., Jr., Weissenburger, J. E., (1996). The dexamethasone suppression test in patients with mood disorders. Journal of Clinical Psychiatry, 57:470–484.
201. Rush, A. J., Trivedi, M., & Fava, M., (2003). Depression IV:STAR*D treatment trial for depression. American Journal of Psychiatry, 160:237.
202. Sahay, A., & Hen, R., (2007). Adult hippocampal neurogenesis in depression. Nature Neuroscience, 10:1110–1115.
203. Sapolsky, R. M., (2003). Stress and plasticity in the limbic system. Neurochemical Research, 28:1735–1742.
204. Sargent, P. A., Kjaer, K. H., Bench, C. J., Rabiner, E. A., Messa, C., Meyer, J., (2000). Brain serotonin 1A receptor binding measured by positron emission tomography with [11C]WAY-100635:Effects of depression and antidepressant treatment. Archives of General Psychiatry, 57:174–180.
205. Schiepers, O. J., Wichers, M. C., & Maes, M., (2005). Cytokines and major depression. Progress in Neuropsychopharmacology and Biological Psychiatry, 29:201–217.
206. Schildkraut, J., (1965). The catecholamine hypothesis of affective disorders:A review of supporting evidence. American Journal of Psychiatry, 122:509–522.
207. Schore, A. N., (1994). Affect Regulation and the Origin of the Self:The Neurobiology of Emotional Development. Hillsdale, NJ:Lawrence Erlbaum Associates.
208. Schreiber, S., Bleich, A., & Pick, C. G., (2002). Venlafaxine and mirtazapine:Different mechanisms of antidepressant action, common opioid-mediated antinociceptive effects—a possible opioid involvement in severe depression? Journal of Molecular Neuroscience, 18:143–149.
209. Sheline, Y. I., Sanghavi, M., Mintun, M. A., & Gado, M. H., (1999). Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. Journal of Neuroscience, 19:5034–5043.
210. Shelton, R. C., (2007). The molecular neurobiology of depression. Psychiatric Clinics of North America, 30:1–11.
211. Smeraldi, E., Zanardi, R., Benedetti, F., Di Bella, D., Perez, J., & Catalano, M., (1998). Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Molecular Psychiatry, 3:508–511.
212. Solomon, A., (2001). The Noonday Demon:An Atlas of Depression. New York:Scribner.
213. Steele, J. D., Currie, J., Lawrie, S. M., & Reid, I., (2007). Pre-frontal cortical functional abnormality in major depressive disorder:A stereotactic meta-analysis. Journal of Affective Disorders, 10:1–11.
214. Stone, E. A., Lin, Y., & Quartermain, D., (2008). A final common pathway for depression? Progress toward a general conceptual framework. Neuroscience & Biobehavioral Reviews, 32:508–524.
215. Stone, E. A., Lin, Y., Rosengarten, H., Kramer, H. K., & Quartermain, D., (2003). Emerging evidence for a central epinephrine-innervated alpha 1-adrenergic system that regulates behavioral activation and is impaired in depression. Neuropsychopharmacology, 28:1387–1399.
216. Sullivan, P. F., Neale, M. C., & Kendler, K. S., (2000). Genetic epidemiology of major depression:Review and meta-analysis. American Journal of Psychiatry, 157:1552–1562.
217. Swain, J. E., Lorberbaum, J. P., Korse, S., & Strathearn, L., (2007). Brain basis of early parent-infant interactions:Psychology, physiology, and in vivo function neuroimaging studies. Journal of Child and Adolescent Psychiatry, 48:262–287.
218. Szyf, M., McGowan, P., & Meaney, M. J., (2008). The social environment and the epigenome. Environmental and Molecular Mutagenesis, 49:46–60.
219. Tausk, M., (1952). Das Hormon. Hat die Nebennierrinde tatsächlich eine Verteidigungsfunktion? Vol. 3. The Netherlands:Organon International BV, Oss.
220. Teicher, M. H., Andersen, S. L., Polcari, A., Anderson, C. M., & Navalta, C. P., (2002). Developmental neurobiology of childhood stress and trauma. Psychiatric Clinics of North America, 25:397–426.
221. Teicher, M. H., Andersen, S. L., Polcari, A., Anderson, C. M., Navalta, C. P., & Kim, D. M., (2003). The neurobiological consequences of early stress and childhood maltreatment. Neuroscience Biobehavioral Reviews, 27:33–44.
222. Thomsen, A. F., Kvist, T. K., Andersen, P. K., & Kessing, L. V., (2006). The risk of affective disorders in patients with adrenocortical insufficiency. Psychoneuroendocrinology, 31 (5):614–622.
223. Todtenkopf, M. S., Marcus, J. F., Portoghese, P. S., & Carlezon, W. A., Jr. (2004). Effects of kappa-opioid receptor ligands on intracranial self-stimulation in rats. Psychopharmacology, 172:463–470.
224. Tsiouris, J. A., (2005). Metabolic depression in hibernation and major depression:An explanatory theory and an animal model of depression. Medical Hypotheses, 65:829–840.
225. Tsuno, N., Besset, A., & Ritchie, K., (2005). Sleep and depression. Journal of Clinical Psychiatry, 66 (10):1254–1269.
226. Valenstein, E. S., (1998). Blaming the Brain. New York:Free Press.
227. Vogt, B. A., & Gabriel, M., (Eds.) (1993). Neurobiology of Cingulate Cortex and Limbic Thalamus:A Comprehensive Handbook. Boston, MA:Birkhauser.
228. Vollmayr, B., & Henn, F. A., (2003). Stress models of depression. Clinical Neuroscience Research, 3:145–151.
229. von Bardeleben, U., & Holsboer, F., (1988). Human corticotropin releasing hormone:Clinical studies in patients with affective disorders, alcoholism, panic disorder and in normal controls. Progress in Neuropsychopharmacology & Biological Psychiatry, 12 (Suppl.):165–187.
230. Walsh, S. L., Strain, E. C., Abreu, M. E., & Bigelow, G. E., (2001). Enadoline, a selective kappa opioid agonist:Comparison with butorphanol and hydromorphone in humans. Psychopharmacology, 157:151–162.
231. Warner-Schmidt, J. L., & Duman, R. S., (2006). Hippocampal neurogenesis:Opposing effects of stress and antidepressant treatment. Hippocampus, 16:239–249.
232. Watt, D. F., (1990). Higher cortical functions and the ego:Explorations of the boundary between behavioral neurology, neuropsychology, and psychoanalysis. Psychoanalytic Psychology, 7:488–529.
233. Watt, D. F., (2007). Towards a neuroscience of empathy:integrating cognitive and affective perspectives. Neuropsycho-analysis, 9:119–140.
234. Watt, D. F., & Pincus, D., (2004). Neural substrates of consciousness:Implications for clinical psychiatry. In:Textbook of Biological Psychiatry, ed. J., Panksepp. New York:Wiley, pp. 75–110.
235. Weiss, M., Blier, P., & de Montigny, C., (2007). Effect of long-term administration of the antidepressant drug milnacipran on serotonergic and noradrenergic neurotransmission in the rat hippocampus. Life Science, 81:166–176.
236. Wong, M.-L., & Licinio, J., (2001). Research and treatment approaches to depression. Nature Reviews. Neuroscience, 2:343–351.
237. World Psychiatric Association (2002). WPA Bulletin on Depression. Available at www.servier.com/App_Download/Neurosciences/WPA/WPA_24.pdf
238. Young, E. A., Altemus, M., Lopez, J. F., Kocsis, J. H., Schatzberg, A. F., DeBattista, C., (2004). HPA axis activation in major depression and response to fluoxetine:A pilot study. Psychoneuroendocrinology, 29:1198–1204.
239. Young, E. A., Lopez, J. F., Murphy-Weinberg, V., Watson, S. J., & Akil, H., (2003). Mineralocorticoid receptor function in major depression. Archives of General Psychiatry, 60:24–28.
240. Zarate, C. A., Jr., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., (2006). A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Archives of General Psychiatry, 63:856–864.
241. Zhang, R., Tachibana, T., Takagi, T., Koutoku, T., Denbow, D. M., & Furuse, M., (2004). Serotonin modifies corticotropin-releasing factor-induced behaviors of chicks. Behavioral Brain Research, 151:47–52.
242. Zimmer, A., Valjent, E., Konig, M., Zimmer, A. M., Robledo, P., Hahn, H., (2001). Absence of delta-9-tetrahydrocannabinol dysphoric effects in dynorphin-deficient mice. Journal of Neuroscience, 21:9499–9505.
243. Zoebel, A. W., Nickel, T., Kunzel, H. E., Ackl, N., Sonntag, A., Ising, M., (2000). Effects of the high-affinity corticotropin-releasing hormone receptor 1 anatagonist R 121919 in major depression. The first 20 patients treated. Journal of Psychiatric Research, 34:171–181.
244. Zobel, A. W., Nickel, T., Sonntag, A., Uhr, M., Holsboer, F., & Ising, M., (2001). Cortisol response in the combined dexamethasone/CRH test as predictor of relapse in patients with remitted depression. A prospective study. Journal of Psychiatric Research, 35:83–94.
245. Zobel, A. W., Yassouridis, A., Frieboes, R. M., & Holsboer, F., (1999). Prediction of medium-term outcome by cortisol response to the combined dexamethasone-CRH test in patients with remitted depression. American Journal of Psychiatry, 6:949–951.
246. Zubieta, J. K., Ketter, T. A., Bueller, J. A., Xu, Y., Kilbourn, M. R., Young, E. A., (2003). Regulation of human affective responses by anterior cingulate and limbic mu-opioid neurotransmission. Archives of General Psychiatry, 60 (11):1145–1153.
247. Zucconi, G. S., Cipriani, S., Balgkouranidou, I., & Scattoni, R., (2006). “One night” sleep deprivation stimulates hippocampal neurogenesis. Brain Research Bulletin, 69:375–381.
248. Zupancic, M., & Guilleminault, C., (2006). Agomelatine:A preliminary review of a new antidepressant. CNS Drugs, 20:981–992.