Serotonin transporter gene, stress and raphe-raphe interactions: a molecular mechanism of depression

Trends in Neurosciences

Volumn 35, Issue 7, 2012, Pages 395-402

  Jasinska, Agnes J ^a,b   Lowry, Christopher A ^c   Burmeister, Margit ^b,d,e  

^a UNIVERSITY OF MICHIGAN   (United States)

^b UNIVERSITY OF MICHIGAN HEALTH SYSTEM   (United States)

^c UNIVERSITY OF COLORADO   (United States)

^d UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^e UNIVERSITY OF MICHIGAN   (United States)

Author keywords

5 HTTLPR; Amygdala; Dorsal raphe nucleus; Gene environment interactions; Serotonin; Stress

Indexed keywords

SEROTONIN TRANSPORTER;

AMYGDALOID NUCLEUS; DEPRESSION; DORSAL RAPHE NUCLEUS; GENOTYPE ENVIRONMENT INTERACTION; HUMAN; INTERNEURON; NEUROANATOMY; NEUROPSYCHIATRY; NONHUMAN; PRIORITY JOURNAL; REVIEW; SEROTONINERGIC TRANSMISSION; STRESS; VENTROMEDIAL PREFRONTAL CORTEX;

ANIMALS; DEPRESSION; GENE-ENVIRONMENT INTERACTION; GENETIC PREDISPOSITION TO DISEASE; HUMANS; RAPHE NUCLEI; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; STRESS, PSYCHOLOGICAL;

EID: 84862775567     PISSN: 01662236     EISSN: 1878108X     Source Type: Journal    
DOI: 10.1016/j.tins.2012.01.001     Document Type: Review

References (99)

1. Wellman C.L., et al. Impaired stress-coping and fear extinction and abnormal corticolimbic morphology in serotonin transporter knock-out mice. J. Neurosci. 2007, 27:684-691.
2. Pezawas L., et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat. Neurosci. 2005, 8:828-834.
3. Holmes A. Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease. Neurosci. Biobehav. Rev. 2008, 32:1293-1314.
4. Maier S.F., Watkins L.R. Stressor controllability and learned helplessness: the roles of the dorsal raphe nucleus, serotonin, and corticotropin-releasing factor. Neurosci. Biobehav. Rev. 2005, 29:829-841.
5. Ressler K.J., Nemeroff C.B. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress. Anxiety 2000, 12(Suppl. 1):2-19.
6. Meltzer H. Serotonergic dysfunction in depression. Br. J. Psychiatry Suppl. 1989, 25-31.
7. Heils A., et al. Allelic variation of human serotonin transporter gene expression. J. Neurochem. 1996, 66:2621-2624.
8. Lesch K.P., et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996, 274:1527-1531.
9. Bradley S.L., et al. Relationship of serotonin transporter gene polymorphisms and haplotypes to mRNA transcription. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 2005, 136B:58-61.
10. Little K.Y., et al. Cocaine, ethanol, and genotype effects on human midbrain serotonin transporter binding sites and mRNA levels. Am. J. Psychiatry 1998, 155:207-213.
11. Shioe K., et al. No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by PET. Synapse 2003, 48:184-188.
12. Hranilovic D., et al. Serotonin transporter promoter and intron 2 polymorphisms: relationship between allelic variants and gene expression. Biol. Psychiatry 2004, 55:1090-1094.
13. Hu X.Z., et al. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am. J. Hum. Genet. 2006, 78:815-826.
14. Caspi A., et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003, 301:386-389.
15. Caspi A., et al. Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am. J. Psychiatry 2010, 167:509-527.
16. Karg K., et al. The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch. Gen. Psychiatry 2011, 68:444-454.
17. Risch N., et al. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 2009, 301:2462-2471.
18. Belsky J., Pluess M. Beyond diathesis stress: differential susceptibility to environmental influences. Psychol. Bull. 2009, 135:885-908.
19. Ellis B.J., et al. Differential susceptibility to the environment: an evolutionary--neurodevelopmental theory. Dev. Psychopathol. 2011, 23:7-28.
20. Homberg J.R., Lesch K.P. Looking on the bright side of serotonin transporter gene variation. Biol. Psychiatry 2010, 69:513-519.
21. Lowry C.A., et al. Serotonergic systems, anxiety, and affective disorder: focus on the dorsomedial part of the dorsal raphe nucleus. Ann. N. Y. Acad. Sci. 2008, 1148:86-94.
22. Chazal G., Ralston H.J. Serotonin-containing structures in the nucleus raphe dorsalis of the cat: an ultrastructural analysis of dendrites, presynaptic dendrites, and axon terminals. J. Comp. Neurol. 1987, 259:317-329.
23. Hale M.W., Lowry C.A. Functional topography of midbrain and pontine serotonergic systems: implications for synaptic regulation of serotonergic circuits. Psychopharmacology (Berl.) 2011, 213:243-264.
24. Jacobs B.L., Fornal C.A. Activity of serotonergic neurons in behaving animals. Neuropsychopharmacology 1999, 21:9S-15S.
25. Jankowski M.P., Sesack S.R. Prefrontal cortical projections to the rat dorsal raphe nucleus: ultrastructural features and associations with serotonin and gamma-aminobutyric acid neurons. J. Comp. Neurol. 2004, 468:518-529.
26. Celada P., et al. Control of dorsal raphe serotonergic neurons by the medial prefrontal cortex: Involvement of serotonin-1A, GABA(A), and glutamate receptors. J. Neurosci. 2001, 21:9917-9929.
27. Amat J., et al. Activation of the ventral medial prefrontal cortex during an uncontrollable stressor reproduces both the immediate and long-term protective effects of behavioral control. Neuroscience 2008, 154:1178-1186.
28. Amat J., et al. Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nat. Neurosci. 2005, 8:365-371.
29. Christianson J.P., et al. Medial prefrontal cortical activation modulates the impact of controllable and uncontrollable stressor exposure on a social exploration test of anxiety in the rat. Stress 2009, 12:445-450.
30. Maier S.F., Watkins L.R. Role of the medial prefrontal cortex in coping and resilience. Brain Res. 2010, 1355:52-60.
31. Maswood S., et al. Exposure to inescapable but not escapable shock increases extracellular levels of 5-HT in the dorsal raphe nucleus of the rat. Brain Res. 1998, 783:115-120.
32. Amat J., et al. Escapable and inescapable stress differentially and selectively alter extracellular levels of 5-HT in the ventral hippocampus and dorsal periaqueductal gray of the rat. Brain Res. 1998, 797:12-22.
33. Amat J., et al. Escapable and inescapable stress differentially alter extracellular levels of 5-HT in the basolateral amygdala of the rat. Brain Res. 1998, 812:113-120.
34. Weiss J.M. Effects of coping responses on stress. J. Comp. Physiol. Psychol. 1968, 65:251-260.
35. Crawford L.K., et al. Increased intrinsic excitability of lateral wing serotonin neurons of the dorsal raphe: a mechanism for selective activation in stress circuits. J. Neurophysiol. 2010, 103:2652-2663.
36. Roche M., et al. Circuitry underlying regulation of the serotonergic system by swim stress. J. Neurosci. 2003, 23:970-977.
37. Johnson P.L., et al. Acute hypercarbic gas exposure reveals functionally distinct subpopulations of serotonergic neurons in rats. J. Psychopharmacol. 2005, 19:327-341.
38. Johnson P., et al. Disruption of GABAergic tone in the dorsomedial hypothalamus attenuates responses in a subset of serotonergic neurons in the dorsal raphe nucleus following lactate-induced panic. J. Psychopharmacol. 2008, 22:642-652.
39. Hale M.W., et al. Evidence for in vivo thermosensitivity of serotonergic neurons in the rat dorsal raphe nucleus and raphe pallidus nucleus implicated in thermoregulatory cooling. Exp. Neurol. 2011, 227:264-278.
40. Kelly K.J., et al. Swim stress activates serotonergic and nonserotonergic neurons in specific subdivisions of the rat dorsal raphe nucleus in a temperature-dependent manner. Neuroscience 2011, 197:251-268.
41. Gardner K.L., et al. Adverse experience during early life and adulthood interact to elevate tph2 mRNA expression in serotonergic neurons within the dorsal raphe nucleus. Neuroscience 2009, 163:991-1001.
42. Sidor M.M., et al. A developmental characterization of mesolimbocortical serotonergic gene expression changes following early immune challenge. Neuroscience 2010, 171:734-746.
43. Bunin M.A., Wightman R.M. Paracrine neurotransmission in the CNS: involvement of 5-HT. Trends Neurosci. 1999, 22:377-382.
44. Varnas K., et al. Autoradiographic distribution of serotonin transporters and receptor subtypes in human brain. Hum. Brain Mapp. 2004, 22:246-260.
45. Takano H., et al. Serotonergic neurotransmission in the living human brain: a positron emission tomography study using [(11) C]dasb and [(11) C]WAY100635 in young healthy men. Synapse 2011, 65:624-633.
46. Zhang Z.W., Arsenault D. Gain modulation by serotonin in pyramidal neurones of the rat prefrontal cortex. J. Physiol. 2005, 566:379-394.
47. Rainnie D.G. Serotonergic modulation of neurotransmission in the rat basolateral amygdala. J. Neurophysiol. 1999, 82:69-85.
48. Jiang X., et al. Stress impairs 5-HT2A receptor-mediated serotonergic facilitation of GABA release in juvenile rat basolateral amygdala. Neuropsychopharmacology 2009, 34:410-423.
49. Davidson R.J., et al. Depression: perspectives from affective neuroscience. Annu. Rev. Psychol. 2002, 53:545-574.
50. Mayberg H.S. Limbic-cortical dysregulation: a proposed model of depression. J. Neuropsychiatry Clin. Neurosci. 1997, 9:471-481.
51. Drevets W.C. Prefrontal cortical-amygdalar metabolism in major depression. Ann. N. Y. Acad. Sci. 1999, 877:614-637.
52. Post R.M., et al. Sensitization, kindling, and carbamazepine: an update on their implications for the course of affective illness. Pharmacopsychiatry 1992, 25:41-43.
53. Kendler K.S., et al. Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the " kindling" hypothesis. Am. J. Psychiatry 2000, 157:1243-1251.
54. Kaiser R., et al. Correlation between serotonin uptake in human blood platelets with the 44-bp polymorphism and the 17-bp variable number of tandem repeat of the serotonin transporter. Am. J. Med. Genet. 2002, 114:323-328.
55. Daws L.C. Unfaithful neurotransmitter transporters: focus on serotonin uptake and implications for antidepressant efficacy. Pharmacol. Ther. 2009, 121:89-99.
56. Rainnie D.G., et al. Corticotrophin releasing factor-induced synaptic plasticity in the amygdala translates stress into emotional disorders. J. Neurosci. 2004, 24:3471-3479.
57. Brown G.W., Harris T.O. Depression and the serotonin transporter 5-HTTLPR polymorphism: a review and a hypothesis concerning gene-environment interaction. J. Affect. Disord. 2008, 111:1-12.
58. Lenroot R.K., Giedd J.N. Brain development in children and adolescents: insights from anatomical magnetic resonance imaging. Neurosci. Biobehav. Rev. 2006, 30:718-729.
59. Griebel G., et al. Differential modulation of antipredator defensive behavior in Swiss-Webster mice following acute or chronic administration of imipramine and fluoxetine. Psychopharmacology (Berl.) 1995, 120:57-66.
60. Keers R., et al. Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project. Pharmacogenomics J. 2011, 11:138-145.
61. Fournier J.C., et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA 2010, 303:47-53.
62. Grahn R.E., et al. Activation of serotonin-immunoreactive cells in the dorsal raphe nucleus in rats exposed to an uncontrollable stressor. Brain Res. 1999, 826:35-43.
63. Lowry C.A., et al. Corticotropin-releasing factor increases in vitro firing rates of serotonergic neurons in the rat dorsal raphe nucleus: evidence for activation of a topographically organized mesolimbocortical serotonergic system. J. Neurosci. 2000, 20:7728-7736.
64. Calizo L.H., et al. Raphe serotonin neurons are not homogenous: electrophysiological, morphological and neurochemical evidence. Neuropharmacology 2011, 61:524-543.
65. Vasudeva R.K., et al. Functional organization of the dorsal raphe efferent system with special consideration of nitrergic cell groups. J. Chem. Neuroanat. 2011, 41:281-293.
66. Peyron C., et al. Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods. Neuroscience 1998, 82:443-468.
67. Lee H.S., et al. Glutamatergic afferent projections to the dorsal raphe nucleus of the rat. Brain Res. 2003, 963:57-71.
68. Lee H.S., et al. Projection patterns from the amygdaloid nuclear complex to subdivisions of the dorsal raphe nucleus in the rat. Brain Res. 2007, 1143:116-125.
69. Commons K.G., et al. A neurochemically distinct dorsal raphe-limbic circuit with a potential role in affective disorders. Neuropsychopharmacology 2003, 28:206-215.
70. Van Bockstaele E.J., et al. Topography of serotonin neurons in the dorsal raphe nucleus that send axon collaterals to the rat prefrontal cortex and nucleus accumbens. Brain Res. 1993, 624:188-198.
71. Waterhouse B.D., et al. Topographic organization of rat locus coeruleus and dorsal raphe nuclei: distribution of cells projecting to visual system structures. J. Comp. Neurol. 1993, 336:345-361.
72. Waterhouse B.D., et al. Topographical distribution of dorsal and median raphe neurons projecting to motor, sensorimotor, and visual cortical areas in the rat. J. Comp. Neurol. 1986, 249:460-476.
73. Kazakov V.N., et al. Sources of cortical, hypothalamic and spinal serotonergic projections: topical organization within the nucleus raphe dorsalis. Neuroscience 1993, 56:157-164.
74. Kirifides M.L., et al. Topographic organization and neurochemical identity of dorsal raphe neurons that project to the trigeminal somatosensory pathway in the rat. J. Comp. Neurol. 2001, 435:325-340.
75. Steinbusch H.W., et al. Serotonergic and non-serotonergic projections from the nucleus raphe dorsalis to the caudate-putamen complex in the rat, studied by a combined immunofluorescence and fluorescent retrograde axonal labeling technique. Neurosci. Lett. 1980, 19:137-142.
76. Coffield J.A., et al. Retrograde tracing of projections between the nucleus submedius, the ventrolateral orbital cortex, and the midbrain in the rat. J. Comp. Neurol. 1992, 321:488-499.
77. Hurley K.M., et al. Efferent projections of the infralimbic cortex of the rat. J. Comp. Neurol. 1991, 308:249-276.
78. Fite K.V., et al. Retinal afferents to the dorsal raphe nucleus in rats and Mongolian gerbils. J. Comp. Neurol. 1999, 414:469-484.
79. Kawano H., et al. Is there a direct retina-raphe-suprachiasmatic nucleus pathway in the rat?. Neurosci. Lett. 1996, 212:143-146.
80. Shen H., Semba K. A direct retinal projection to the dorsal raphe nucleus in the rat. Brain Res. 1994, 635:159-168.
81. Herbert H. Evidence for projections from medullary nuclei onto serotonergic and dopaminergic neurons in the midbrain dorsal raphe nucleus of the rat. Cell Tissue Res. 1992, 270:149-156.
82. Ljubic-Thibal V., et al. Origin of the serotonergic innervation to the rat dorsolateral hypothalamus: retrograde transport of cholera toxin and upregulation of tryptophan hydroxylase mRNA expression following selective nerve terminals lesion. Synapse 1999, 32:177-186.
83. Bago M., et al. Serotonergic projections to the rostroventrolateral medulla from midbrain and raphe nuclei. Brain Res. 2002, 945:249-258.
84. Beitz A.J. The organization of afferent projections to the midbrain periaqueductal gray of the rat. Neuroscience 1982, 7:133-159.
85. Underwood M.D., et al. Dorsal raphe nucleus serotonergic neurons innervate the rostral ventrolateral medulla in rat. Brain Res. 1999, 824:45-55.
86. Stezhka V.V., Lovick T.A. Projections from dorsal raphe nucleus to the periaqueductal grey matter: studies in slices of rat midbrain maintained in vitro. Neurosci. Lett. 1997, 230:57-60.
87. Chen J., et al. Serotonergic projections from the midbrain periaqueductal gray and nucleus raphe dorsalis to the nucleus parafascicularis of the thalamus. Brain Res. 1992, 584:294-298.
88. Kerman I.A., et al. Relationship of presympathetic-premotor neurons to the serotonergic transmitter system in the rat brainstem. J. Comp. Neurol. 2006, 499:882-896.
89. Hollis J.H., et al. Lipopolysaccharide has indomethacin-sensitive actions on Fos expression in topographically organized subpopulations of serotonergic neurons. Brain Behav. Immun. 2006, 20:569-577.
90. Abrams J.K., et al. Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs. Neuroscience 2005, 133:983-997.
91. Bouwknecht J.A., et al. Differential effects of exposure to low-light or high-light open-field on anxiety-related behaviors: relationship to c-Fos expression in serotonergic and non-serotonergic neurons in the dorsal raphe nucleus. Brain Res. Bull. 2007, 72:32-43.
92. Gardner K.L., et al. Early life experience alters behavior during social defeat: focus on serotonergic systems. Neuroscience 2005, 136:181-191.
93. Hale M.W., et al. Urocortin 2 increases c-Fos expression in serotonergic neurons projecting to the ventricular/periventricular system. Exp. Neurol. 2010, 224:271-281.
94. Staub D.R., et al. Urocortin 2 increases c-Fos expression in topographically organized subpopulations of serotonergic neurons in the rat dorsal raphe nucleus. Brain Res. 2005, 1044:176-189.
95. Staub D.R., et al. Evidence supporting a role for corticotropin-releasing factor type 2 (CRF2) receptors in the regulation of subpopulations of serotonergic neurons. Brain Res. 2006, 1070:77-89.
96. Valentino R.J., et al. Substance P Acts through local circuits within the rat dorsal raphe nucleus to alter serotonergic neuronal activity. J. Neurosci. 2003, 23:7155-7159.
97. Waterhouse B.D., et al. Sensorimotor-related discharge of simultaneously recorded, single neurons in the dorsal raphe nucleus of the awake, unrestrained rat. Brain Res. 2004, 1000:183-191.
98. Walther D.J., Bader M. A unique central tryptophan hydroxylase isoform. Biochem. Pharmacol. 2003, 66:1673-1680.
99. Paxinos G., Watson C. The Rat Brain in Stereotaxic Coordinates 1998, Academic Press.